Compounds which are acryloyl substituted distamycin derivatives of formula (I) wherein: n is 2, 3 or 4; m is 1 or 2; X and Y are the same or different and are selected, independently for each heterocyclic ring of the polyetherocyclic chain, from N and CH; R1 and R2, which are the same or different, are selected from hydrogen, halogen, and C1-C4 alkyl; R3 is hydrogen or halogen; B is selected from (a), (b), (c), (d), (e), (f), (g) and xe2x80x94Cxe2x89xa1N; wherein R4, R5, R6, R7, R8, R10, R11, and R12 are, independently from each other, hydrogen or C1-C4 alkyl; and R9 is hydrogen or hydroxy, or pharmaceutically acceptable salt thereof; provided that a) at least one of R4, R5 and R6 is alkyl b) at least one of the heterocyclic rings within the polyheterocyclic chain is other than pyrole; and c) X and Y are not both N for the same heterocyclic ring; are useful as antitumor agents.

The present invention relates to new peptidic compounds analogous to Distamycin A, to a process for their preparation, to pharmaceutical compositions containing them and to their use as therapeutic agents.
Distamycin A is an antibiotic substance with antiviral and oncolytic properties, having a polypyrrole framework (Nature 203, 1064 (1964); J. Med. Chem. 32, 774-778 (1989)).
Several compunds analogous to Distamycin A and derivatives thereof are known in the art.
The international patent application WO 97/43258, in the name of the applicant, discloses acryloyl distamycin derivatives wherein the amidino moiety is replaced by different nitrogen-containing ending groups such as, for instance, cyanamidino, N-methylamidino, ethylguanidino, amido, amidoximo, nitrile and the like.
Distamycin derivatives wherein at least one pyrrole ring of the aforementioned polypyrrole framework is substituted by an imidazole or pyrazole ring are also reported in the literature.
See, for a general reference, Anti-Cancer Drug Design 8, 173-192 (1993); J. Am. Chem. Soc. Vol. 114, 5911-5919 (1992); Anti-Cancer Drug Design 6, 501-517 (1991); patent applications EP-A-0246868 and WO 96/05196, both in the name of the applicant.
It has now been found that a new class of distamycin derivatives as defined hereinunder, wherein at least one ring of the polypyrrole framework is other than pyrrole, the formyl group is substituted by an acryloyl moiety and the amidino group is substituted by different nitrogen-containing ending groups, shows valuable biological properties.
Therefore, the present invention provides compounds which are acryloyl substituted distamycin derivatives of formula
wherein:
n is 2, 3 or 4;
m is 1 or 2;
X and Y are the same or different and are selected, independently for each heterocyclic ring of the polyhetherocyclic chain, from N and CH;
R1 and R2, which are the same or different, are selected from hydrogen, halogen, and C1-C4 alkyl;
R3 is hydrogen or halogen;
B is selected from
wherein R4, R5, R6, R7, R8, R10, R11 and R12 are, independently from each other, hydrogen or C1-C4 alkyl; and R9 is hydrogen or hydroxy;
or a pharmaceutically acceptable salt thereof;
provided that
a) at least one of R4, R5 and R6 is alkyl;
b) at least one of the heterocyclic rings within the polyheterocyclic chain is other than pyrrole; and
c) X and Y are not both N for the same heterocyclic ring.
The present invention includes within its scope also all the possible isomers covered by the compounds of formula (I), both separately and in admixture, as well as the metabolites and the pharmaceutically acceptable bio-precursors (otherwise known as pro-drugs) of the compounds of formula (I).
In the present description, unless otherwise specified, the term alkyl includes straight or branched alkyl, for instance C1-C4 alkyl such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl; the term halogen includes fluorine, chlorine, bromine and iodine.
Preferably, the alkyl groups are selected from methyl and ethyl and the halogen atoms are selected from fluorine, chlorine or bromine.
Pharmaceutically acceptable salts of the compounds of formula (I) are the salts with pharmaceutically acceptable, inorganic or organic, acids. Examples of inorganic acids are hydrochloric, hydrobromic, sulphuric and nitric acid; examples of organic acids are acetic, propionic, succinic, malonic, citric, tartaric, methanesulfonic and p-toluenesulfonic acid.
As above reported, X and Y are selected, independently for each heterocyclic ring of the polyheterocyclic chain, between N and CH. This means that within the compounds of formula (I) and for different heterocyclic rings, X can be either N as well as CH; the same applies for Y provided that X and Y are not contemporaneously N for a single heterocycle.
Examples for the said heterocycles are pyrrole, pyrazole and imidazole.
A preferred class of compounds according to the present invention is represented by the compounds of formula (I) wherein R4, R5, R6, R7, R8, R10, R11 and R12 are, independently from each other, hydrogen, methyl, or ethyl.
Even more preferred are the compounds of formula (I) wherein
n is 3 or 4;
m is 1;
R1 and R2 are hydrogen;
R3 is chlorine or bromine;
B is selected from
wherein R4, R5, R6, R7, R8, R10, R11 and R12 are, independently from each other, hydrogen or methyl; R9 is hydrogen.
Another class of preferred compounds of formula (I) are those wherein the acrylamido moiety is directly linked to a pyrazole or imidazole ring.
Examples of specific compounds according to the present invention, especially in the form of salts, preferably with hydrochloric acid, are the following:
(1) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propioncyanamidine;
(2) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-N-methylamidine;
(3) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-chloroacrylamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-N-methylamidine;
(4) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-N,Nxe2x80x2-dimethylamidine;
(5) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-chloroacrylamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-N,Nxe2x80x2-dimethylamidine;
(6) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-N,N,Nxe2x80x2-trimethylamidine;
(7) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propionamide;
(8) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-N-methylamide;
(9) 2-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)ethylguanidine;
(10) 2-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-chloroacrylamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)ethylguanidine;
(11) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propyl-N,N-dimethylamine;
(12) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propionamidoxime;
(13) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-chloroacrylamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propionamidoxime;
(14) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-O-methylamidoxime;
(15) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-chloroacrylamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-O-methylamidoxime;
(16) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propionitrile;
(17) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-chloroacrylamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propionitrile;
(18) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propioncyanamidine;
(19) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-N-methylamidine;
(20) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-N,Nxe2x80x2-dimethylamidine;
(21) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-N,N,Nxe2x80x2-trimethylamidine;
(22) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido propionamide;
(23) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-N-methylamide;
(24) 2-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)ethylguanidine;
(25) 2-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-chloroacrylamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)ethylguanidine;
(26) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propyl-N,N-dimethylamine;
(27) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propionamidoxime;
(28) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-chloroacrylamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propionamidoxime;
(29) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-O-methylamidoxime;
(30) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-chloroacrylamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-O-methylamidoxime;
(31) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido) propionitrile;
(32) 3-(1-methyl-4-(1-methyl-4-(1-methyl-3-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-N-methylamidine;
(33) 3-(1-methyl-4-(1-methyl-4-(1-methyl-3-(1-methyl-3-(xcex1-chloroacrylamido)pyrazole-5-carboxamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-N-methylamidine;
(34) 3-(1-methyl-4-(1-methyl-4-(1-methyl-3-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-N,Nxe2x80x2-dimethylamidine;
(35) 3-(1-methyl-4-(1-methyl-4-(1-methyl-3-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-N,N,Nxe2x80x2-trimethylamidine;
(36) 3-(1-methyl-4-(1-methyl-4-(1-methyl-3-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-N-methylamide;
(37) 2-(1-methyl-4-(1-methyl-4-(1-methyl-3-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)ethylguanidine;
(38) 2-(1-methyl-4-(1-methyl-4-(1-methyl-3-(1-methyl-3-(xcex1-chloroacrylamido)pyrazole-5-carboxamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)ethylguanidine;
(39) 3-(1-methyl-4-(1-methyl-4-(1-methyl-3-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propionamidoxime;
(40) 3-(1-methyl-4-(1-methyl-4-(1-methyl-3-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propionitrile;
(41) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)imidazole-2-carboxamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propioncyanamidine;
(42) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)imidazole-2-carboxamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-N-methylamide;
(43) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)imidazole-2-carboxamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-N,N-dimethylamine;
(44) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)imidazole-2-carboxamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-O-methylamidoxime;
(45) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)imidazole-2-carboxamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propionitrile;
(46) 3-(1-methyl-3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrazole-5-carboxamido)propion-N-methylamidine;
(47) 3-(1-methyl-3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrazole-5-carboxamido)propion-N,Nxe2x80x2-dimethylamidine;
(48) 2-(1-methyl-3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrazole-5-carboxamido)ethylguanidine;
(49) 3-(1-methyl-3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrazole-5-carboxamido)propionamidoxime;
(50) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)imidazole-2-carboxamido)propion-N-methylamidine;
(51) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)imidazole-2-carboxamido)propionamide;
(52) 2-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)imidazole-2-carboxamido)ethylguanidine;
(53) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)imidazole-2-carboxamido)propionamidoxime;
(54) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-N-methylamidine;
(55) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-N,Nxe2x80x2-dimethylamidine;
(56) 2-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)ethylguanidine;
(57) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propionamidoxime;
(58) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propionitrile;
(59) 3-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propioncyanamidine;
(60) 3-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-N-methylamidine;
(61) 3-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-chloroacrylamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-N-methylamidine;
(62) 3-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-N,Nxe2x80x2-dimethylamidine,
(63) 3-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-N,N,Nxe2x80x2-trimethylamidine;
(64) 3-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propionamide;
(65) 2-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)ethylguanidine;
(66) 2-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-chloroacrylamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)ethylguanidine;
(67) 3-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propionamidoxime;
(68) 3-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-chloroacrylamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propionamidoxime;
(69) 3-(1-methyl-4-(1-methyl-4-(1-methyl-3-(xcex1-bromoacrylamido)pyrazole-5-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propionitrile;
(70) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propioncianamidine;
(71) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-N-methylamidine;
(72) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-N,Nxe2x80x2-dimethylamidine;
(73) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-N,N,Nxe2x80x2-trimethylamidine;
(74) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propionamide;
(75) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-N-methylamide;
(76) 2-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)ethylguanidine;
(77) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)imidazole-2-carboxamido)pyrrcle-2-carboxamido)pyrrole-2-carboxamido)propion-N,N-dimethylamine;
(78) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propionamidoxime;
(79) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propion-O-methylamidoxime;
(80) 3-(1-methyl-4-(1-methyl-4-(1-methyl-4-(xcex1-bromoacrylamido)imidazole-2-carboxamido)pyrrole-2-carboxamido)pyrrole-2-carboxamido)propionitrile.
The compounds of the present invention can be prepared according to one of the following processes, which comprise:
(a) reacting a compound of formula:
wherein n, m, X, Y and B are as defined above;
p is 0 or 1;
with a compound of formula:
wherein R1, R2, R3, X, Y and p are as defined above;
Z is hydroxy or a leaving group;
or:
(b) when B is equal to xe2x80x94Cxe2x89xa1N, reacting a compound of formula:
wherein n, m, R1, R2, R3, X and Y are as defined above;
with succinic anhydride; and
(c) if desired, converting a compound of formula (I) into a pharmaceutically acceptable salt thereof.
In the compounds of formula (III), Z is hydroxy or a suitable leaving group selected, for instance, among chloro, 2,4,5-trichlorophenoxy, 2,4-dinitro-phenoxy, succinimido-N-oxy, imidazolyl group, and the like.
The reaction of process (a) as above between a compound of formula (II) and a compound of formula (III) can be carried out according to known methods, for instance those described in the aforementioned EP-A-246,868 and WO 96/05196.
It is clear to the man skilled in the art that when preparing the compounds of formula (I) according to the process object of the present invention, optional amino groups, i.e. R10 and/or R11 of the compound of formula (II) equal to hydrogen, need to be properly protected according to conventional techniques, so as to avoid unwanted side reactions.
Likewise, the conversion of the said protected amino group into the free amine may be carried out according to known procedures. See, for a general reference, J. Org. Chem. 43, 2285, (1978); J. Org. Chem. 44, 811 (1979); J. Am. Chem. Soc. 78, 1359 (1956); Ber. 65, 1192 (1932); and J. Am Chem. Soc. 80, 1154, (1958).
The compounds of formula (II) may be prepared by converting the compounds of formula (V)
wherein T is a nitro group or an amino group properly protected with a group such as, for instance, t-butyloxycarbonyl, triphenylmethyl or, preferably, carbobenzyloxy or formyl; X, Y, B, n, m and p are as defined above; into the desired amino derivative of formula (II).
The conversion of the nitro group into amino group may be carried out according to known procedures such as, for instance, hydrogenation under hydrogen pressure in the presence of suitable catalysts, e.g., palladium on charcoal, into a suitable solvent such as dioxane, methanol, ethanol and mixtures thereof, at room temperature.
The compounds of formula (V) wherein B is other than
can be obtained, in their turn, from the compounds of formula:
wherein T, X, Y, n, p and m are as defined above; by using:
(i) H2Nxe2x80x94CN, so obtaining a compound of formula (V) having B equal to:
(ii) H2Nxe2x80x94OR12 wherein R12 has the above reported meanings, so obtaining a compound of formula (V) having B equal to:
(iii) H2Nxe2x80x94NH2, so obtaining a compound of formula (V) having B equal to:
(iv) HNR4R5, so obtaining a compound of formula (V) having B equal to:
and then optionally with H2NR6, so obtaining a compound of formula (V) having B equal to:
wherein R4, R5, and R6 are as defined above;
(v) succinic anhydride, so obtaining a compound of formula (V) having B equal to xe2x80x94Cxe2x89xa1N;
(vi) water in an alkaline medium, so obtaining a compound of formula (V) having B equal to xe2x80x94COxe2x80x94NR7R8 wherein R7 and R8 are both hydrogen;
(vii) HNR7R8, so obtaining a compound of formula (V) having B equal to:
and then with water in an alkaline medium, so obtaining a compound of formula (V) having B equal to xe2x80x94COxe2x80x94NR7R8, wherein R7 and R8 are as defined above.
The reaction between a compound of formula (VI) and one of the reactants as set forth in points (i)-(vii) as above can be carried out according to known methods, for instance those reported in WO97/43258; Chem. Revs. 1961; 155; J. Med. Chem. 1984, 27, 849-857; Chem. Revs. 1970, 151; and xe2x80x9cThe Chemistry of Amidines and Imidatesxe2x80x9d, edited by S. Patai, John Wiley and Sons, N.Y. (1975).
Alternatively, the compounds of formula (V) wherein B is other than
can be prepared from a compound of formula:
wherein n, p, X, Y, T and Z are as defined above, by reaction with a compound of formula:
wherein m is as defined above and B is selected from:
wherein R4, R5, R6, R7, R8, R9, R10, R11 and R12 are as defined above.
Finally, the compounds of formula (V) wherein B is other than
can be prepared through the so-called Pinner reaction, by reacting a compound of formula (V) wherein B is equal to CN with a suitable amino compound as set forth above under points (i), (ii), (iii) or (iv).
Also the compounds of formula (III) are known or easily prepared according to conventional methods.
See, for a general reference, WO96/05196; J.C.S. 1947-1032 and JACS 62, 3495 (1940).
The reaction of process (b) is carried out according to the method reported in WO 97/43258.
The compounds of formula (IV), (VI), (VII) and (VIII) are known compounds, or may be obtained by known methods (see, for a general reference, Tetrahedron, 34, 2389-2391, 1978; J. Org. Chem., 46, 3492-3497, 1981; J. Org. Chem., 52, 3493-3501, 1987; WO96/05196 and WO97/43258.
The optional conversion of a compound of formula (I) into a pharmaceutically acceptable salt, as well as the preparation of a free compound starting from a salt, may be carried out by known standard methods.
Well known procedures such as, e.g., fractional crystallization or chromatography, may also be followed for separating a mixture of isomers of formula (I) into the single isomers.
The compounds of formula (I) may be purified by conventional techniques such as, e.g., silica gel or alumina column chromatography, and/or by recrystallization from an organic solvent such as, e.g., a lower aliphatic alcohol, e.g. methyl, ethyl or isopropyl alcohol, or dimethylformamide.
The compounds of the invention show cytotoxic properties towards tumor cells so that they can be useful as antineoplastic agents, e.g. to inhibit the growth of various tumors such as, for instance, carcinomas, e.g. mammary carcinoma, lung carcinoma, bladder carcinoma, colon carcinoma, ovary and endometrial tumors. Other neoplasias in which the compounds of the invention could find application are, for instance, sarcomas, e.g. soft tissue and bone sarcomas, and the hematological malignancies such as, e.g., leukemias.
The antitumor activity of the compounds of formula (I) was evaluated in vitro by cytotoxicity studies carried out on murine L1210 leukemia cell. Cells were derived from in vivo tumors and established in cell culture. Cells were used until the tenth passage. Cytotoxicity was determined by counting surviving cells after 4 hours treatment and 48 hours growth in drug-free medium.
The percentage of cell growth in the treated cultures was compared with that of controls. Doses inhibiting 50% of the cellular growth in respect to controls, expressed as ID50 values, were calculated on dose-response curves.
The compounds of the invention can be administered by the usual routes, for example, parenterally, e.g. by intravenous injection or infusion, intramuscularly, subcutaneously, topically or orally.
The dosage depends on the age, weight and conditions of the patient and on the administration route.
For example, a suitable dosage for administration to adult humans may range from about 0.05 to about 100 mg pro dose 1-4 times a day.
The pharmaceutical compositions of the invention contain a compound of formula (I) as the active substance, in association with one or more pharmaceutically acceptable excipients.
The pharmaceutical compositions of the invention are usually prepared following conventional methods and are administered in a pharmaceutically suitable form.
For instance, solutions for intravenous injection or infusion may contain sterile water as a carrier or, preferably, they may be in the form of sterile aqueous isotonic saline solutions.
Suspensions or solutions for intramuscular injections may contain, together with the active compound, a pharmaceutically acceptable carrier, e.g. sterile water, olive oil, ethyl oleate, glycols, e.g. propylene glycol and, if desired, a suitable amount of lidocaine hydrochloride.
In the form for topical application, e.g. creams, lotions or pastes for use in dermatological treatment, the active ingredient may be mixed with conventional oleaginous or emulsifying excipients.
The solid oral forms, e.g. tablets and capsules, may contain, together with the active compound, diluents, e.g. lactose, dextrose, saccharose, cellulose, corn starch and potato starch; lubricants, e.g. silica, talc, stearic acid, magnesium or calcium stearate, and/or polyethylene glycols; binding agents, e.g. starches, arabic gums, gelatin, methylcellulose, carboxymethyl-cellulose, polyvinylpyrrolidone; disaggregating agents, e.g. a starch, alginic acid, alginates, sodium starch glycolate; effervescing mixtures; dyestuffs; sweeteners; wetting agents, for instance, lecithin, polysorbates, laurylsulphates; and, in general, non-toxic and pharmacologically inactive substances used in pharmaceutical formulations. Said pharmaceutical preparations may be manufactured in a known manner, for example by means of mixing, granulating, tabletting, sugar-coating, or film-coating processes.
Furthermore, according to the present invention, there is provided a method of treating tumors in a patient in need of it, comprising administering to the said patient a composition of the invention.
The following examples illustrate but do not limit the invention.
The abbreviations DMF and DMSO-d6 stand for dimethylformamide and deutero-dimethylsulfoxide, respectively.

Acryloyl derivatives analogous to distamycin, process for preparing them, and their use as antitumor agents


Provided are a display panel, a preparation method thereof and a display apparatus. The display panel includes a display substrate and a cover plate oppositely disposed. The display substrate includes an array substrate, pixel define layers on the array substrate, pixel support layers on a side of the pixel define layers away from the array substrate, and second electrodes each located on a side of each of the pixel support layers away from each pixel define layers. The cover plate includes a first substrate, a touch sensor layer and protective layer disposed on the first substrate, wherein multiple openings are disposed on the touch sensor layer and covered by the protective layer. An orthographic projection of each of the openings on the array substrate at least partially overlaps with that of a surface on a side of each of the pixel support layers away from the array substrate.

An Organic Light Emitting Diode (OLED) is an active light emitting display device, and has advantages of self-emission, wide angle of view, high contrast, low power consumption, extremely high response speed, etc. With the continuous development of display technology, the OLED technology is increasingly applied in flexible display apparatuses.
The incell touch screen has a touch sensor structure disposed within the display panel, which has advantages of simple structure, lightness, thinness, and low cost and the like, and has increasingly become the mainstream technology of the touch screen. However, in the incell OLED panel, there is a large parasitic capacitance between a touch sensor layer and a cathode of the display panel, causing a current passing through the cathode greatly affects the capacitance value and thereby affecting the sensitivity of the touch sensor to external touch signals.

Display panel, preparation method thereof, and display apparatus

Ordos Yuansheng Optoelectronics Co., Ltd.

Beijing BOE Technology Development Co., Ltd.


In a dual belt conveyor for multi-ply continuous paper tubing having upper and lower endless conveyor belts between which the tubing is fed, turning point pulleys and backing rollers for the respective conveyor belts are longitudinally offset so that the tubing is moved through the conveyor along an undulating path. The inlet turning point pulley for the upper conveyor belt is positioned in front of the equivalent pulley for the lower conveyor belt so that the upper belt will contact the incoming tubing before the lower belt. A brake plate is provided under the inlet pulley of the upper belt over which plate the tubing is fed. The arrangement avoids the formation of undesirable waves and wrinkles in the tubing.

1. Field of the Invention
This invention relates to a dual belt conveyor for continuous paper tubing which may have adhesive-bonded longitudinal seams in the middle portions of the upper plies, and which conveyor preferably precedes a tear-off dual belt conveyor moving at a higher speed serving to retain the last but one length section of the paper tubing, when a transverse perforation line at which the tubing is to be severed is disposed between the two dual belt conveyors, and wherein reversing pulleys and backing rollers for the conveyor belt or belts on the underside of the path of the continuous paper tubing are longitudinally offset from reversing pulleys and backing rollers on the upper side of said path, so that the paper tubing is moved through the dual belt conveyor along an undulating path.
2. Description of the Prior Art
In a dual belt conveyor as disclosed, for example, in European Patent No. 0 96 223, a wave may form in the top ply of the continuous paper tubing before the entry gap of the dual belt conveyor. The wave can be subsequently pulled into the nip of the conveyor and compressed by the belts so that sacks made from the paper tubing have a poor appearance and considerable difficulties can arise in further processing.
The formation of a wave before the entry gap of the dual belt conveyor is due to the fact that flat continuous paper tubing unwound from a roll may be somewhat longer at its edge portions than its intermediate portion. The difference in length may be about 1 mm per 1000 mm length of the continuous paper tubing.

Dual belt conveyor for multi-ply continuous paper tubing


Several embodiments of a tunneling transistor are disclosed. In one embodiment, a tunneling transistor includes a semiconductor substrate, a source region formed in the semiconductor substrate, a drain region formed in the semiconductor substrate, a gate stack including a metallic gate electrode and a gate dielectric, and a tunneling junction that is substantially parallel to an interface between the metallic gate electrode and the gate dielectric. As a result of the tunneling junction that is substantially parallel with the interface between the metallic gate electrode and the gate dielectric, an on-current of the tunneling transistor is substantially improved as compared to that of a conventional tunneling transistor. In another embodiment, a tunneling transistor includes a heterostructure that reduces a turn-on voltage of the tunneling transistor.

The maximum integration density of modern integrated circuits (ICs) is limited by the amount of power or heat dissipated per unit area. In order to increase the device integration density, the power dissipation per device must be reduced steadily with time. An important method of reducing the device power consumption is to reduce the power supply voltage (VDD). Reducing VDD can decrease both the dynamic power consumption and the standby power consumption of future ICs. Device on-state current must be sufficiently large in order to achieve good circuit speed. Device off-current must be sufficiently small in order to suppress the standby power consumption. It is well known to those skilled in the art that the Metal Oxide Semiconductor Field Effect Transistor (MOSFET), the device driving today's ICs, is limited in the ratio of on-state to off-state currents, ION/IOFF, when VDD is small. When VDD is small, a new transistor requiring smaller changes in the input voltage to effect a tenfold increase in the transistor current, a quantity called "swing" or "S" and measured in millivolts (mV)/decade, is highly desirable because the maximum change in the input voltage is normally equal to VDD. This requires an operating principle other than the passage of charge carriers over a potential barrier—the operating principle behind both MOSFETs and bipolar transistors. This operating principal behind both MOSFETs and bipolar transistors sets a floor of 60 mV/decade to the swing achievable at room temperature.
Various researchers have explored tunneling transistors. Tunneling transistors are transistors that operate based on a principle involving charge carriers tunneling under or passing through, rather than over, a potential barrier. Therefore, tunneling transistors are not subject to the 60 mV/decade limitation to swing. FIG. 1 illustrates a conventional tunneling transistor 10. In general, the conventional tunneling transistor 10 includes a substrate 12, an N+ source 14 and a P+ drain 16 formed in the substrate 12, and a gate stack 18 arranged as shown. The gate stack 18 may also be referred to as a gate. The gate stack 18 is generally formed of a metallic gate electrode 20 and a gate dielectric 22 arranged as shown. A p-type channel (a portion of the p-type substrate 12 between the N+ source 14 and the P+ drain 16) and the N+ source 14 form a gated PN diode. When this gated PN diode is reverse biased by applying a negative gate-to-source voltage (VGS), a tunneling current occurs at a vertical tunneling junction 24.
The conventional tunneling transistor 10 has at least two issues. First, best on-current (ION) reports for the conventional tunneling transistor 10 have been withdrawn. Remaining valid experiments have all shown that the on-current NO of the conventional tunneling transistor 10 is too low for general applications. Second, a large gate voltage is needed to turn on the conventional tunneling transistor 10. As such, there is a need for a new tunneling transistor having a suitable on-current (ION) for modern applications. There is also a need for a new tunneling transistor having a reduced turn-on voltage and is therefore capable of operating at lower supply voltage, or VDD, levels.

Tunneling transistor suitable for low voltage operation

The Regents of the University of California


A transmission ratio variable mechanism includes an input member and an output member arranged to rotate around a first axis, an intermediate member arranged to connect the input member and the output member so as to be differentially rotatable, and a motor arranged to drive the intermediate member. The motor includes a cylindrical rotor arranged to rotate around the first axis. An inner periphery of the rotor is arranged to support the intermediate member and arranged to rotatably support the input member and the output member via bearings, respectively.

Examples of a transmission include one using a swing gear (see. e.g., Patent Documents 1 and 2). Patent Document 1 discusses a reduction gear mechanism for obtaining a great reduction gear ratio. Patent document 2 discusses a steering angle ratio variable steering apparatus capable of changing a steering angle ratio.

Transmission ratio variable mechanism and vehicle steering apparatus including the same


The inventive device for fixing a seat belt winder is fixed to the part of a motor vehicle. The plate of the housing of the winder is provided with at lest one fixing hole for receiving a screw connection which maintains the vehicle part embodied therein. The housing of said seat belt winder is arranged in such a way that it is rotatable with respect to the fixing hole of the vehicle part, thereby enabling the winder to be automatically oriented in a direction of a force of a belt which moves at an angle with respect to the axis of the shaft. Said fixing device is characterised in that the housing (10) of the winder is rotationally maintained on the holder part (13, 19, 25) which can be firmly connected to the vehicle part (40). Said housing (10) is supported by the holder part (13, 19, 25) at a distance to the fixing hole (41) of the vehicle part (40) and is fixed to said holder part (13, 19, 25) in such away that the housing (10) of the seat belt winder is rotatable with respect the holder part (13, 19, 25) in an opposite direction to the action of a pre-set resistance.

The invention relates to a fixing device for a seat belt retractor to be attached to a motor vehicle part, whereby the housing plate of the seat belt retractor housing has at least one fixing opening formed on the motor vehicle part for receiving a screw connection and the seat belt retractor is arranged in such a way that it is rotatable relative to the fixing opening of the motor vehicle part, thereby enabling the retractor to be automatically oriented in a direction of a force of a belt which moves at an angle with respect to the axis of the shaft.
A fixing device with the above-noted features is disclosed in FR 28 14 415. Specifically, it relates in detail to the fixing of a seat belt retractor to the rear storage area of a motor vehicle, whereby the belt unwound from the belt retractor extends from the rear shelf to the shoulder of the strapped-in occupants without interposition of a return device. Because of this, a skewed belt progression results, taking into. consideration the storage position of the belt mounted in the seat belt retractor. This problem is encountered by the fixing device described in FR 28 14 415, in that the seat belt retractor housing is not fixed, but is connected with the vehicle to be pivotable about an axis defined by its attachment screw, whereby a two-leg spring via one spring end is suspended on the vehicle part and presses with the other spring end against the seat belt retractor housing, so that the seat belt retracting is pre-stressed in its starting position and pivots, respectively, against the spring action. The known fixing device is expensive with regard to its mounting, since the seat belt retractor housing is fixed to the vehicle part in such a way that a smooth-running rotation about the axis of the fixing screw is possible. In addition, the mounting of the additionally required spring denotes an additional assembly step.
In addition, it turned out that a practical post-guiding of the seat belt retractor that practically occurs with each fastening or storage process is not necessary; it sufficed, in fact, for protection of the seat belt as well as the seat belt retractor itself, if the seat belt retractor is oriented to the adjusted belt tension under a load. In this manner, in particular, damage to the seat belt and the seat belt retractor under the effect of a load can be avoided.
The invention is based on the object of forming a fixing device having the general features in such a way that the seat belt retractor is mounted in a simple manner and, with a load on the seat belt, rotates relative to its attachment on the motor vehicle part and orients itself with the occurring belt tension.


The invention relates to a test area of an electronic circuit comprising a contact point formed in the surface of a substrate. The test area also includes spaced apart radially extending bosses adjacent the contact point for guiding a test probe positioned on the surface of the substrate to the contact point.

Test areas, generally formed on the surface of substrates are electrically connected to different parts of circuits in order to carry out checks on the correct operation of these circuits. The checks typically include measuring continuous control voltages at the test area and are carried out by means of microprobes. These microprobes are connected to suitable measurement equipment and are temporarily applied to contact points on the test area to carry out the measurements.
The known type of test areas for electronic circuits are in the form of metal contact points. These contact points, generally square in shape, have dimensions of the order of 20 .mu.m.times.20 .mu.m and are arranged on the surface of a substrate in which one or more electronic circuits are formed. The contact points are surrounded by an insulating layer called a passivation layer which forms a slight rounded mass in the surface of the substrate.
The contact points or pads can be connected to parts of an electronic circuit formed in the surface of the substrate, but also to parts of a circuit formed deep in the substrate. This is notably the case when the substrate is a multi-layer substrate comprising a stack of conducting layers separated by insulating layers. In this case, a contact point of a test area is formed in the surface of the substrate and is connected to a component of a deep conducting layer by means of conductor filled vias which pass through the insulating layers.
In order to carry out the control measurements on the electronic circuits, a tool fitted with one or more microprobes is brought to the surface of the substrate to a distance close enough for the ends of the microprobes to make contact with the substrate. The microprobes take the form of fine metal strips which are pressed onto the surface of the substrate. These fine metal strips are generally flexible and are comparable to hair.
A micrometric displacement device, such as a micropositioner, is then actuated to cause a relative displacement of the probes and the substrate along the plane of the substrate. This displacement is intended to bring the ends of the probes into coincidence with the contact points on the test areas. The relative displacement movement of the probes and the substrate can be controlled by various devices, such as optical location systems or viewing systems that use a CCD camera.
The main difficulty that is apparent during the control operation of the circuits described above is positioning the ends of the probes exactly on the contact points. Incorrect positioning of the probes can cause erroneous control measurements. Another difficulty is to keep the ends of the probes on the contact points. This is attributed to the fact that the contact points protrude from the surface of the substrate.
To facilitate the positioning and holding of the microprobes on the contact points, the dimensions of the contact points are commonly increased. However, increasing the dimensions, and hence the area of metal contact points on the surface of the substrate, is accompanied by the creation of or the increase of parasitic capacitances.
In effect, the contact points of the test areas define capacitors with the other conductive parts of the integrated circuits of the substrate. These capacitors have a capacitance that increases with the area of the contact points. These capacitances are parasitic capacitances which modify and impair the behavior of electronic circuits. This problem is a particular nuisance for electronic circuits operating at high frequency.
On the other hand, when the dimensions of the contact points are reduced so as to limit the parasitic capacitances, expensive equipment for adjusting the probes on the contact points must be installed and good electrical contact between the probes and the contact points is not always guaranteed. Furthermore, location of contact points of small dimensions on the surface of the substrate proves to be difficult.

Test area with automatic positioning of a microprobe and a method of producing such a test area


A rotational vibration test system and method of a storage system set storage devices of the storage system, fan speeds of an electric fan of the storage system, and access patterns of the storage system. The electric fan is controlled to run at the fan speeds. The storage system is accessed according to the access patterns. Accordingly, the storage devices are input/output performance tested. Test results of the storage devices are output to an output device.

1. Technical Field
Embodiments of the present disclosure relate to storage systems and methods, and particularly to a rotational vibration test system and method of a storage system.
2. Description of Related Art
Due to the mechanical nature of storage devices (e.g., hard disks) and electric fans of a storage system, rotational vibration is generated in the storage system when the storage system is accessed. The rotational vibration can degrade input/output (IO) performance of the storage system. Therefore, it is desirable to perform rotational vibration tests on the storage system.

Rotational vibration test system and method


An LED ceiling lamp includes a primary illumination unit and at least one subsidiary illumination unit. The primary illumination includes a base and a connecting member to fix the base to a ceiling. Each of the at least one subsidiary illumination unit is fixed to the base and faces the ceiling. Each of the at least one subsidiary illumination unit comprises a circuit board with an LED unit, a lens and a reflector. The lens covers the circuit board. The circuit board and the lens are received in the reflector. The lens is configured for dividing the light beams from the LED units into several light groups. An aphotic area is formed between each two adjacent light groups. The reflector is configured for reflecting the several light groups on the ceiling.

1. Technical Field
The present disclosure relates to LED illumination devices, especially to an LED ceiling lamp.
2. Description of Related Art
Compared to traditional light sources, light emitting diodes (LEDs) have many advantages, such as high luminous efficiency, low power consumption, and long service life. LED lights are widely used in many applications, such as LED ceiling lamp. Because the light emitting diodes are small and have a narrow light emitting angle, the LED ceiling lamp does not form a shaped light beam on a ceiling board such as quartz lamps.


A radiation generating tube includes a vacuum envelope formed by an insulating tube, a cathode and an anode. At least one of the cathode and the anode is bonded to the insulating tube via a conductive bonding material disposed between bonded surfaces facing each other. The conductive bonding material is partially protruding from between the bonded surfaces to an outer peripheral surface or an inner peripheral surface of the insulating tube. A concave portion is formed on the outer peripheral surface or the inner peripheral surface of the insulating tube adjacent to a bonded surface on an insulating tube side, and a distal end of a conductive bonding material protruding from between bonded surfaces is accommodated in the concave portion.

1. Field of the Invention
The present disclosure relates to a radiation generating tube, a radiation generating unit provided with the radiation generating tube as a radiation source, and a radiation image taking system using the radiation generating unit.
2. Description of the Related Art
In the related art, a vacuum envelope including an insulating tube and a conductive electrode is used as a radiation generating tube used as a radiation source of a radiation generating unit. US Patent Application Publication No. 2007/0076849 A1 (U.S. Pat. No. 7,382,862) discusses a brazing material that is used for joining an insulating tube and an electrode of a radiation generating unit.
The vacuum envelope of the radiation generating tube requires sealing properties which maintain an internal vacuum atmosphere. Therefore, joining between the insulating tube and the electrode may be performed using a sufficient required amount of a conductive bonding material such as brazing material in order to enhance reliability by achieving a stable sealed state.
However, when the sufficient required amount of the conductive bonding material is used to join the insulating tube and the electrode, the conductive bonding material is easily protruding from between a bonded surface of the insulating tube and a bonded surface of the electrode facing each other (hereinafter, referred to as "between bonded surfaces" in this specification). When the conductive bonding material is protruding from between the bonded surfaces, an electric field tends to concentrate on a distal end of the protruding conductive bonding material when the radiation generating tube is driven, and hence, depending on the shape of the protruding conductive bonding material, there is a risk of induction of abnormal emission in the radiation generating apparatus in which the radiation generating tube is used.
In the radiation generating unit and the radiation image taking system, improvement of a voltage withstand property of the radiation generating tube to be used is required for accommodating size reduction or power increase of radiation to be emitted. In addition, operation stability increases and high voltage application is enabled with the improvement of the voltage withstand property, whereby improvement of performance is expected. As regards the vacuum envelope of the radiation generating tube, reliability and performance of the radiation generating unit and the radiation image taking system using the same may be improved by the improvement of the voltage withstand property simultaneously with a stable sealing property.

Radiation generating tube, radiation generating unit, and radiation image taking system


A firefighter tracking system is provided for use in conjunction with a fire truck to track firefighters at the scene of a fire. The system a plurality of portable wireless transceiver tags each carried by a respective firefighter, an accelerometer within each of the plurality of portable wireless transceiver tags, a motion processor within each of the plurality of portable wireless transceiver tags coupled to the accelerometer, the motion processor processes information from the accelerometer, detects an immobilized state of the respective firefighter and wirelessly transmits information including a notification of the detected immobilized state, a gateway carried by the fire truck that receives the transmitted information from each of the plurality of portable wireless transceivers and a status processor coupled to the gateway within the fire truck programmed to determine and display a status of at least some of the firefighters at the location of the fire via the received information including at least the immobilized state of the at least some of the firefighters.

Communication among public safety personnel, such as firemen, is an important aspect of safely fighting fires. In large buildings, firefights are often required to attack fires from multiple directions in order to prevent the fire from spreading. In such cases, different teams of firefighters are often assigned to attack the fire from the different directions. Often the efforts of the teams to fight the fire are made more difficult by smoke that obscures the flames or avenues for accessing a fire.
In addition to fighting the actual fire, firefighters may encounter situations where the buildings occupants are still present within the building. In such cases, occupants may feel trapped by the smoke or flames or from fear of becoming lost within a smoke-filled building.
Where occupants are present, firefighters are often required to search for and lead occupants to safety before they can begin to fight the fire. In large structures, the very size of the structures may require that individual firefights fan out within the structure to search for occupants or victims of the fire.
In some cases, a great deal of time may be lost searching for occupants. Where the structure or number of occupants is large, a great deal of time may be spent looking for occupants while the fire continues to spread. Alternatively, a fire may not be discovered and firefighters may not be notified until the fire is well developed.
In either case, the search for occupants may be curtailed by the possibility that parts of the structure may be unstable and subject to collapse. Because of such risks, firefighters may only have a very limited time to search for occupants. Because of the danger to firefighters, better methods are needed to monitor firefighters.

Wireless transceiver for firefighter safety


A number of modified nucleosides are disclosed composed of modified sugar moieties which contain substituents at C1 and C4 positions, or branched substituents at C3 and C5 positions of deoxyribose or ribose. Each nucleoside is converted to or properly protected and then converted to the corresponding phosphoramidites. These phosphoramidites are used to assemble oligonucleotides in which there is at least one of the forenoted nucleosides. These sugar modified oligonucleotides have the potential to be used as antisense therapies since they are expected to enhance nuclease resistance and cellular uptake while they maintain sequence-specificity and affinity to nucleic acid targets in vitro or in vivo.

The invention is in the field of polynucleotide analogs containing modified sugars.
The therapeutic use of oligonucleotides is a field of great significance and is described, for example, in, (1) Zamecnik, P. C. and Stephenson, M. L. Proc. Natl. Acad. Sci. U.S.A. 1978, 75, 280, 285.xe2x80x9d; (2) Uhlmann, E. and Peyman, A. Chemical Reviews, 1990, 90, 543-584; (3) Goodchild, J. Bioconjugate chemistry, 1990, 1, 165-187; and (4) Crooke, S. T. and Lebleu, B. xe2x80x9cAntisense Research and Applicationsxe2x80x9d, CRC Press (1993)). The specific binding of antisense polynucleotides to the DNA or RNA targets of interest may inactivate the functions associated with the DNA or RNA such as replication, transcription, or translation, thereby providing a mechanism for controlling diseases such as cancer and viral infection. Therefore, the binding of an antisense oligonucleotide to a target can be used to alter gene expression, in a variety of circumstances, e.g., to interfere with viral life cycles, or the growth of cancerous cells (Stein, C. A., Cheng, Y. C. Science, 1993, 261, 1004-1012). In addition, some oligonucleotides also bind tightly to protein targets, thereby acting as enzyme inhibitors. Bock et al. describes oligonucleotides that inhibit human thrombin-catalyzed fibrin-clot formation in vitro (Bock, L. C., Griffin, L. C., Latham, J. A., Vermaas, E. H., Toole, J. J. Nature, 1992, 355, 564-566). Ecker et al describes several oligonucleotides that inhibit human herpes simplex virus at below 1.0 xcexcmol. Polynucleotides that have enzyme inhibiting properties can readily be found by using combinatorial technology (Ecker, D. J., Vickers, T. A., Hanecak, R., Driver, V., Anderson, K. Nucleic Acids Res. 1993, 21, 1853-1856).
An oligonucleotide containing a 5xe2x80x2-C-methyl branched nucleoside has been reported to show enhanced nuclease resistance (Saha, A. K. et al., a poster in 206th ACS Meeting, Chicago, 1993). An oligonucleotide containing 2xe2x80x2-O-methyl nucleosides has also been reported to show improved stability to nucleases and enhanced binding affinity to RNA (a. Inoue, H., Hayase, Y., Imura, A., Iwai, S., Miura, K., Ohtsuka, E., Nucleic Acids Res. 1987, 15, 6131; b. Shibahara, S., Mukai, S., Morisawa, H., Nakashima, H., Cobayashi, S., Yamamoto, N. Nucleic Acids Res. 1989, 17, 239). An oligonucleotide containing 1xe2x80x2-substituted nucleoside has been reported to show some nuclease resistance (Ono, A., Dan, A., Matsuda, A. Bioconjugate Chemistry, 1993, 4, 499-508).
Besides having a specific binding affinity to a complementary target polynucleotide sequence, antisense oligonucleotides desirably meet the requirements for therapeutic purposes, e.g., potency, bioavailability, low toxicity, and low cost. Since oligonucleotides having the natural phosphodiester backbone are labile to nucleases and do not readily penetrate the cell membrane, researchers have attempted to make polynucleotide backbone modifications that improve nuclease resistance and cellular uptake. A major shortcoming of oligonucleotides analogs used for antisense is that the modified internucleotide linkages eliminate the RNase H activation of antisense oligonucleotides, which degrades the RNA strand to which the oligonucleotide analog binds. Therefore, it is desirable to provide polynucleotide analogs with enhanced nuclease resistance and cellular uptake, while retaining the property of activating RNase H.
The present invention provides various novel sugar modified nucleosides and corresponding sugar modified oligonucleotides that have properties superior to natural RNA and DNA oligonucleotides when used for antisense, diagnostic, or other purposes.
The compounds of the invention include various nucleosides that have been modified so as to comprise substitutions at positions C1xe2x80x2, C3xe2x80x2, C4xe2x80x2 or C5xe2x80x2 of the sugar moiety of the nucleoside.
Another aspect of the invention is to provide oligonucleotides that comprise one or more of the sugar modified nucleosides of the invention.
Another aspect of the invention is to provide conjugates of oligonucleotides that comprise one or more of the sugar modified nucleosides of the invention.


An IoT service of a provider network may be used to increase the edge device address space while complying with a radio communication protocol. This may allow a service provider to manage a much larger number of client devices that use a particular radio communication protocol that specifies a limited address space (e.g., LoRaWAN). When the IoT service receives a join request via a private gateway of the client network, the service determines, based on the private gateway ID, the client ID of the client that owns the private gateway/client network. The service may generate a unique internal ID for the edge device by combining the client ID with an assigned device ID. The internal ID identifies the edge device as an activated device of the edge network.

The Internet of Things (IoT) is a phrase given for the interconnection of computing devices scattered around the globe within the existing internet infrastructure. Clients of a remote service provider may leverage the internet-based connectivity of IoT devices (also referred to herein as edge devices) by using a service offered by the service provider. For example, temperature sensors at a client site may collect temperature values for different equipment and transmit them to the service provider for analysis, such as determining whether a machine needs servicing.
A client's network may include edge devices that communicate wirelessly using radios. A service provider may provide a service that manages edge devices for many different clients, resulting in an edge network that includes a very large number of edge devices. However, the size of the device address space that is available for assigning to edge devices may be limited based on the radio communication protocol used by the edge devices. For example, a low-power wide-area network ("LoRaWAN") protocol may specify a limited number of bits that may be used to assign a network address to each of the client edge devices, resulting in a limited number of available unique network addresses. The number of available unique network addresses may not be sufficient to meet the client demand.
While embodiments are described herein by way of example for several embodiments and illustrative drawings, those skilled in the art will recognize that the embodiments are not limited to the embodiments or drawings described. It should be understood, that the drawings and detailed description thereto are not intended to limit embodiments to the particular form disclosed, but on the contrary, the intention is to cover all modifications, equivalents and alternatives falling within the spirit and scope as defined by the appended claims. The headings used herein are for organizational purposes only and are not meant to be used to limit the scope of the description or the claims. As used throughout this application, the word "may" is used in a permissive sense (i.e., meaning having the potential to), rather than the mandatory sense (i.e., meaning must). Similarly, the words "include", "including", and "includes" mean including, but not limited to.

Increasing edge device address space while complying with a radio communication protocol


Novel DC-89 derivatives represented by general formula (I): ##STR1## wherein X represents Cl or Br; R.sup.1 represents hydrogen, CONR.sup.2 R.sup.3 (in which R.sup.2 and R.sup.3 independently represent hydrogen, a straight-chain or branched alkyl group having 1 to 4 carbon atoms or phenyl group), ##STR2## (in which n represents an integer of 4 to 7), ##STR3## (in which R.sup.4 represents oxygen, N--CH.sub.3 or N--CH.sub.2 CH.sub.2 NH.sub.2), ##STR4## (in which R.sup.5 R.sup.6 and R.sup.7 independently represent a straight-chain or branched alkyl group having 1 to 4 carbon atoms); and ##STR5## (in which Y represents hydrogen or CO.sub.2 CH.sub.3); provided that when R.sup.1 is hydrogen, CONR.sup.2 R.sup.3 or SiR.sup.5 R.sup.6 R.sup.7, ##STR6## and pharmaceutically acceptable salts thereof have an excellent anti-tumor activity and are expected to be useful as anti-tumor compositions.

The present invention relates to DC-89 derivatives. The compounds have an excellent anti-tumor activity and are expected to be useful as anti-tumor agents.
As compounds similar to the DC-89 derivatives of the present invention, DC-89A1, DC-89A2, DC-89B1 and DC-89B2 represented by the following structural formula are known. These compounds exhibit an antibacterial activity against various bacteria and also show an anti-tumor activity against melanoma B-16, etc. ##STR7## DC-89A1: X.sup.0 =--CH.sub.2 --, Y.sup.0 =Cl DC-89A2: X.sup.0 =single bond, Y.sup.0 =CH.sub.2 Cl
DC-89B1: X.sup.0 =--CH.sub.2 --, Y.sup.0 =Br PA1 DC-89B2: X.sup.0 =single bond, Y.sup.0 =CH.sub.2 Br
DC-89A1 is disclosed in WO 87/06265 (EP-A-0271581); and DC-89A2, DC-89B1 and DC-89B2 are disclosed in Japanese Published Unexamined Patent Application No. 119787/90 (EP-A-0351865) and Japanese Published Unexamined Patent Application No. 139590/89 (EP-A-0318056). Further, DC-88A which has the following structure is disclosed in WO 87/06265 (EP-A-0271581). DC-88A not only shows an antibacterial activity against a variety of bacteria but also exhibits an anti-tumor activity against melanoma B-16, etc. ##STR8##
DC-88A derivatives are disclosed in Japanese Published Unexamined Patent Application No. 128379/91 (EP-A-0406749), Japanese Published Unexamined Patent Application No. 288879/90 (EP-A-0354583) and Japanese Published Unexamined Patent Application No. 7287/91 (EP-A-0365041).
Further, as compounds which are structurally similar-to the compounds of the present invention, derivatives of SF2582C are disclosed in Japanese Published Unexamined Patent Application No. 275581/89 (EP-A-0339681) and CC-1065 and its derivatives are disclosed in Japanese Published Unexamined Patent Application No. 64695/79 (U.S. Pat. No. 4,169,888), Japanese Published Unexamined Patent Application No. 193989/85 (EP-A-0154445) and WO 88/04659.


Polymers for extreme ultraviolet and 193 nm photoresists are disclosed. The polymers comprise a photoacid generator (PAG) residue, an acid cleavable residue and a diacid joined by ester linkages. The polymers include a photoacid generating diol, a diacid and an acid table diol.

Extreme Ultraviolet (EUV, 13.5 nm) imaging technology continues to be the primary option for the 22 nm microelectronics node. However, EUV resist performance remains one of the largest barriers to EUV technology implementation, because it is difficult to simultaneously meet performance targets for resolution, line width roughness (LWR) and sensitivity. For example, low concentrations of acid during imaging will yield rough lines (high LWR), but good sensitivity; high concentrations of acid will give smoother lines, but poor sensitivity. To break through to a new level of performance, new materials must be developed that will make improvements toward one performance target without compromising the performance of the other two.
Photoacid generators have been known in the polymer art for decades. Typical first-generation ionic PAGs are sulfonium and iodonium salts. In an early approach to a deep ultraviolet (DUV or 248 nm) photoresist or a 193 nm photoresist, the PAG is randomly dissolved within the polymer film. The polymer has an ester with a side-chain blocking group (e.g. t-butyl) that can be removed with catalytic acid, yielding a developer-soluble carboxylic acid. The advantage of this approach is that these resists are relatively inexpensive and simple to prepare using standard formulation methods. The resists have high sensitivity because acids are free to diffuse through the film, catalyzing acidolysis reactions (removal of ester blocking group) with large turnover numbers. The disadvantage of this approach is that the acid's rapid diffusion limits the ultimate resolution that can be achieved because the acid can diffuse into the unexposed regions of the resist—blurring the aerial image. In a second approach, the chromophore end of the PAG is bound to the polymer and the acid is free to diffuse in the film. The advantage of this approach is that the high acid diffusion rate gives these resists relatively high sensitivity, however, the disadvantage is that the high acid diffusion rate limits resolution. In a third possible approach the photogenerated acid is bound to the middle of a polymer chain and cannot diffuse very far. The advantage of this approach is that the resist's resolution will not be limited by acid diffusion. The disadvantage, however, is that the resist will have low photosensitivity, as the acid's limited movement will keep turnover numbers low.

Chain scission polyester polymers for photoresists

The Research Foundation of State University of New York


A method of debugging within an integrated circuit (IC) that includes an embedded processor can include detecting an event within a circuit of the IC that is external to the processor and, responsive to detecting the event, initiating a debug function within the processor. Similarly, responsive to detecting an event within the processor, a debug function within a circuit block of the IC that is external to the processor can be initiated. Trace data generated within the processor and trace data generated within the programmable fabric further can be merged to generate combined trace data.

Integrated circuits (ICs) can be implemented to perform a variety of functions. One type of IC is a programmable IC such as, e.g., a field programmable gate array (FPGA). An FPGA typically includes an array of programmable tiles. These programmable tiles can include, for example, input/output blocks (IOBs), configurable logic blocks (CLBs), dedicated random access memory blocks (BRAM), multipliers, digital signal processing blocks (DSPs), processors, clock managers, delay lock loops (DLLs), and so forth.
Each programmable tile typically includes both programmable interconnect circuitry and programmable logic circuitry. The programmable interconnect circuitry typically includes a large number of interconnect lines of varying lengths interconnected by programmable interconnect points (PIPs). The programmable logic circuitry implements the logic of a user design using programmable circuit elements that can include, for example, function generators, registers, arithmetic logic, and so forth.
The programmable interconnect circuitry and programmable logic circuitry are typically programmed by loading a stream of configuration data into internal configuration memory cells that define how the programmable elements are configured. The configuration data can be read from memory (e.g., from an external PROM) or written into the FPGA by an external device. The collective states of the individual memory cells then determine the function of the FPGA. Accordingly, the loading of first configuration data specifying a first circuit design into the programmable IC results in implementation of first physical circuitry within the programmable IC. The loading of second configuration data specifying a second circuit design that is different from the first circuit design results in implementation of second physical circuitry within the programmable IC that is different from the first physical circuitry.
Another type of programmable IC is the complex programmable logic device, or CPLD. A CPLD includes two or more "function blocks" connected together and to input/output (I/O) resources by an interconnect switch matrix. Each function block of the CPLD includes a two-level AND/OR structure similar to those used in programmable logic arrays (PLAs) and programmable array logic (PAL) devices. In CPLDs, configuration data is typically stored on-chip in non-volatile memory. In some CPLDs, configuration data is stored on-chip in non-volatile memory, then downloaded to volatile memory as part of an initial configuration (programming) sequence.
For all of these programmable ICs, the functionality and physical circuitry that is implemented within the device is controlled by data bits provided to the device for that purpose. The data bits can be stored in volatile memory (e.g., static memory cells, as in FPGAs and some CPLDs), in non-volatile memory (e.g., FLASH memory, as in some CPLDs), or in any other type of memory cell.
Other programmable ICs are programmed by applying a processing layer, such as a metal layer, that programmably interconnects the various elements on the device. These programmable ICs are known as mask programmable devices. Programmable ICs can also be implemented in other ways, e.g., using fuse or antifuse technology. The phrase "programmable IC" can include, but is not limited to these devices and further can encompass devices that are only partially programmable. For example, one type of programmable IC includes a combination of hard-coded transistor logic and a programmable switch fabric that programmably interconnects the hard-coded transistor logic.
Some modern ICs, including programmable ICs, can include embedded processors that are capable of executing program code. For example, some models of the Virtex 5 type of programmable IC available from Xilinx Inc. of San Jose, Calif., can include a PowerPC® 440 type of processor. The processor is fabricated as part of the same die that includes the programmable logic circuitry and the programmable interconnect circuitry, also referred to as the programmable fabric. Despite the incorporation of a processor, the systems available for testing and debugging the processor and the circuits implemented within the programmable fabric are separate and independent systems. For example, the system available to debug the processor exists as a separate and independent entity from the system available to debug the circuit design implemented within the programmable fabric of the IC.

Integrated debugging within an integrated circuit having an embedded processor


A method for securing a semiconductor device component to another element is provided. An adhesive material includes a pressure-sensitive component and a curable component is used to at least temporarily secure the semiconductor device component and the other element to each other. The pressure-sensitive component of the adhesive material temporarily secures the semiconductor device component and the other element to one another. When the semiconductor device component and the other element are properly aligned, the curable component of the adhesive material may be cured to more permanently secure them to one another. For example, when a thermoset material is used as the curable component, it may be cured by heating, such as at a temperature of lower than about 200° C. and as low as about 120° C. or less.

1. Field of the Invention
The present invention relates to methods for using adhesive materials to secure two or more semiconductor device components to one another. Particularly, the present invention relates to the use of pressure-sensitive adhesive materials to secure semiconductor device components to each other. The present invention also relates to assemblies including semiconductor device components that are secured to one another with adhesive materials that include a pressure-sensitive component with sufficient bonding strength to at least temporarily secure the semiconductor device components to one another and a thermoset component for more permanently securing the semiconductor device components to one another.
2. State of the Art

This patent is subject to a terminal disclaimer.

Methods for securing components of semiconductor device assemblies to each other with adhesive materials that include pressure-sensitive and curable components


A method and apparatus for handoff to a rescue channel is introduced without the need to send and receive handoff control messages. In the preferred embodiment of the present invention, coordination of the rescue procedure at the infrastructure and mobile station is provided first by disabling the mobile transmitter followed by subsequent detection of signal loss and frame erasures at the serving cells, then by enabling the mobile transmitter followed by subsequent detection of signal by a rescue cell, and finally by enabling the rescue cell channel transmitter followed by subsequent detection and reception of signal and frames by the mobile.

The present invention relates generally to wireless communications systems and, more particularly, to a method for autonomous handoff from a first fixed communication unit to a second fixed communication unit in a wireless communication system.
In a cellular communication system, signaling and voice or data communications between mobile communication units and fixed communication units (such as the infrastructure which is composed of cells) are carried over an RF channel. In a TDMA system such as GSM, the RF channel is an RF carrier and timeslot combination. In a CDMA system such as described by IS-95, IS-2000, or WCDMA, the RF channel is an RF carrier with signals from many communications independently spread with the use of orthogonal Walsh codes and other unique identifiers. As a mobile unit moves through a cellular system, it becomes necessary to support a handoff of the mobile unit from the first fixed communication unit to a second fixed communication unit. In the case of CDMA, this handoff might be a soft handoff that allows the first fixed communication unit to remain connected with the mobile unit along with the second fixed communication unit. Soft handoff then permits cell site diversity to improve the communication paths by combining the best signals from each fixed communication unit connection.
Cellular systems have always been faced with the challenge of reducing or eliminating dropped calls. However, in an interference-limited environment, when the traffic channel degrades, the ability for the mobile and the infrastructure to exchange signaling messages for the purpose of handover is severely hampered. If this message exchange cannot take place, then the necessary handover cannot occur to move the mobile out of its current degraded traffic channel condition. This ultimately results in a dropped call.
A partial solution to this problem is described in U.S. Pat. No. 5,913,167, METHOD FOR TRANSFERRING A COMMUNICATION LINK IN A WIRELESS COMMUNICATION SYSTEM, by Bonta, et al. The ""167 patent provides the mobile with list of reserved channels that can be used for handoff from the first fixed communication unit to the second fixed communication unit when communication between the mobile unit and a first fixed communication unit is interrupted. Although the ""167 patent provides a partial solution to this problem, no mechanism exists to insure that the mobile unit and the first fixed communication unit are time coordinated to perform what amounts to a blind handoff. If the mobile unit and the infrastructure are not time-coordinated, the mobile unit may attempt to perform a handoff to infrastructure equipment that is unprepared to accept the handoff. In addition, the prior art does not provide a mechanism for handling simultaneous communication breakdowns that would lead to simultaneous dropped calls. This is particularly a problem when trying to efficiently utilize equipment resources. Therefore, a need exists for efficiently performing an autonomous handoff within a wireless communication system that reduces the chances that infrastructure will be unprepared to accept the handoff when it occurs.

Method for autonomous handoff in a wireless communication system


A curable sealant composition is provided. The composition includes a polymer including at least conjugated diene contributed monomer units in a backbone of the polymer and terminal groups including silicon. The composition also includes additional sealant ingredients selected from the group consisting of plasticizers, filler, reinforcing agents, modifiers, curing catalysts/hardeners, stabilizers, and mixtures thereof.

The present invention is generally directed to a curable sealant composition. It is more specifically directed to a poly(conjugated diene) curable sealant composition.
Polymers, such as polyisobutylene, have found applications in building sealants due to inherent moisture impermeability. To function as a sealant, a curable group is usually combined with the isobutylene units, resulting in, for example, alkoxy-silane functionalized polyisobutylene. Current polyisobutylene building sealants are often formed using a two-step process. The polymer backbone is formed and endcapped with a reactive functional group. The reactive functional group is then reacted, often in the presence of a metal catalyst, resulting in the presence of a curable group on the polymer backbone. In one specific example, the polymer is endcapped with allyl groups through the use of allyltrimethylsilane. Then, the allyl group is hydrosilylated using a platinum catalyst and an appropriate silane. In another method, the reactive functional groups are dispersed throughout the polymer backbone, followed by the reaction of the functional groups to form curable siloxane groups within the polymer backbone. This two-step process is both expensive and cumbersome.
Accordingly, polyisobutylene-based sealants may suffer from several drawbacks. Moreover, such sealants are (i) often expensive to prepare and (ii) strongly influenced by the relatively high cost of isobutylene monomer. Furthermore, they are often limited to use as a two-part building sealant, requiring combination of the sealant with a catalyst immediately prior to use. If the catalyst is added to the sealant too soon, premature curing may occur, resulting in difficult, and inconsistent, application of the sealant. The requirement for end-user mixing may also result in inconsistencies in the building sealants due to carelessness on the part of the end-user.
It would be desirable to have available a less expensive, more efficient process to directly prepare alkoxysilane functionalized sealant compositions with low polydispersity.
In one embodiment of the present invention, a curable sealant composition is provided. The composition includes a polymer including at least conjugated diene contributed monomer units in a backbone of the polymer and terminal groups including silicon. The composition further includes additional curable sealant ingredients selected from the group consisting of plasticizers, fillers, reinforcing agents, modifiers, curing catalysts/hardeners, stabilizers, and mixtures thereof.
In a second embodiment of the present invention, a process for forming a curable sealant is provided. The process comprises initiating a living polymerization of conjugated diene monomer units with a multifunctional substituted initiator, and terminating the polymerization with a tetra-substituted silicon group.
In another embodiment of the present invention, a curable sealant is provided. The curable sealant includes a poly(conjugated diene) backbone having a Mw between about 5,000 and 60,000, and at least one alkoxysilane end group. The composition further includes additional curable sealant ingredients selected from the group consisting of plasticizers, fillers, reinforcing agents, modifiers, curing catalysts/hardeners, stabilizers, and mixtures thereof.
The present invention is directed to a curable sealant comprised of polymers with conjugated diene monomer units and curing groups. The curing groups may be terminal groups, resulting in a telechelic polymer composition. The polymer compositions of the present invention preferably have a polydispersity ratio less than about 1.8, more preferably less than about 1.7, and most preferably less than about 1.6. The polydispersity ratio is represented by the ratio of Mw to Mn, with a ratio of about one representing a composition that is substantially monodisperse. If the polydispersity is too high, the resultant sealants may demonstrate poor tensile properties and poor workability. xe2x80x9cWorkabilityxe2x80x9d refers to the rate at which the viscosity of the sealant increases as it begins to cure.
The polymer composition of the present invention includes a polymer backbone with monomer units selected from the group consisting of C4-C8 conjugated dienes, and mixtures thereof. Preferred conjugated dienes include 1,3-butadiene, isoprene, 1,3-pentadiene, 2,3-dimethyl-1,3-butadiene, 1,3-hexadiene, 2-methyl-1,3-pentadiene, 3,4-dimethyl-1,3-hexadiene 4,5-diethyl-1,3-octadiene, 3-butyl-1,3-octadiene, phenyl-1,3-butadiene, and mixtures thereof. An especially preferred conjugated diene is 1,3-butadiene.
The conjugated diene backbone preferably has a weight average molecular weight (Mw) between about 5,000 and 60,000, more preferably between about 10,000 and 35,000. While the backbone is preferably linear, it may be crosslinked to form branched structures.
The polymer composition may also include additional monomer units in the polymer backbone. Suitable additional monomer units may include vinyl aromatic hydrocarbon monomers, ethylene oxide, propylene oxide, styrene oxide, ethylene sulfide, propylene sulfide, styrene sulfide, acetaldehyde, propionaldehyde, isobutyraldehyde, n-caproaldehyde, acetthioaldehyde, propionthioaldehyde, isbutyrthioaldehyde, n-caprothioaldehyde, 3-dimethyl-oxycyclobutane, 3-diethyloxycyclobutane, 3-methylethyl-oxycyclobutane, 3-diemethylthiocycylobutane, 3-diethyl-thiocyclobutane, 3-methylethylthiocyclobutane, methylethyl thioketone, methyl isopropyl thioketone and diethyl thioketone, heterocyclic nitrogen containing monomers, and mixtures thereof Exemplary vinyl aromatic hydrocarbon monomers for use in the present invention include one or more of styrene, xcex1-methyl styrene, 1-vinyl naphthalene, 2-vinyl naphthalene, 1-xcex1-methyl vinyl naphthalene, 2-xcex1-methyl vinyl naphthalene, as well as alkyl, cycloalkyl, aryl, alkaryl, and aralkyl derivatives thereof, in which the total number of carbon atoms in the combined hydrocarbon is not greater than about 18, and mixtures thereof. Exemplary heterocyclic nitrogen containing monomers include pyridine and quinoline derivatives containing at least 1 vinyl or alphamethylvinyl group such as 2-vinylpyridine, 3-vinylpyridine, 4-vinylpyridine, 3-ethyl-5-vinylpyridine, 3-methyl-5-vinylpyridine, 3,5-diethyl-4-vinylpyridine and similar mono- and di-substituted alkenyl pyridines and like quinolines such as 2-vinylquinoline, 3-vinylquinoline, 4-vinylquinoline and mixtures thereof.
In the event additional monomer units are employed, the polymer composition preferably includes between about 1 and 99 wt % conjugated diene contributed monomer units, more preferably between about 50 and 99 wt %, and most preferably between about 70 and 99 wt %. The polymer composition further preferably includes between about 1 and 99 wt % additional 20 contributed monomer units, e.g., vinyl aromatic hydrocarbon, more preferably between about 1 and 50 wt %, most preferably between about 1 and 30 wt %.
The sealant can be formed by any polymerization technique known to the skilled artisan. Preferably, the polymerization is initiated via addition of anionic initiators that are known in the art as useful in the polymerization of diene monomers and/or copolymerization of diene monomers and vinyl aromatic hydrocarbons. A multi-functionalized lithium initiator may be used to initiate the preferred living polymerization reaction. Lithium initiators with two or more active initiation sites will initiate a living polymerization with at least two living polymerization sites on each living polymer chain. The polymer backbone may have an initiator residue derived from the multi- or di-functional lithium initiator remaining at the initiation site. Especially preferred initiators include 1,3-bis(1-lithio-1,3-dimethylpentyl)benzene, 1,3-phenylenebis(3-methyl-1-phenylpentylidene)dilithium, 1,3-phyenylenebis[3-methyl-1(methylphenyl)pentylidene]dilithium, initiators derived from reaction of two molar equivalents of sec-butyllithium with 1,3-diisopropenylbenzene 1,3-di(1-phenylethenyl)benzene, 13-di[1-(methylphenyl)ethenyl)] benzene, bis[4-(1-phenylethenyl)phenyl] ether, 1,4-bis(1-phenylethenyl)-1, 1xe2x80x2-biphenyl, and 2, 2xe2x80x2-bis[4-(1-phenylethenyl)phenyl] propane, and mixtures thereof.
The polymerization is preferably carried out at moderate temperatures, such as those between about 23xc2x0 C. and about 70xc2x0 C., and most preferably between about 40xc2x0 C. and 60xc2x0 C., under an inert atmosphere, such as N2 or Ar. The initiator, conjugated diene monomer, and any additional monomer that may be inlcuded, are added to a polymerization vessel, and polymerization is initiated. Living polymerization is a preferred polymerization method, although other polymerization techniques known in the art are contemplated. The initiator is added in an amount of about 0.001 to 0.1 mol initiator per 100 grams conjugated diene, more preferably between about 0.0017 and 0.02 mol initiator per 100 grams conjugated diene monomer, most preferably between about 0.0029 and 0.01 mole per 100 grams conjugated diene monomer. The polymerization is allowed to continue until substantially 100% of monomer conversion has been achieved.
The polymerization can be terminated by the addition of tetra-substituted silicon group. A preferred terminator is of the general formula:
wherein R1, R2, R3, and R4 are independently selected from the group consisting of hydrocarbon, alkoxy groups and mixtures thereof. No more than three of R1, R2, R3, and R4 may be hydrocarbon. At least one of R1, R2, R3, and R4 is preferably an alkoxy group. Suitable alkoxy groups include methoxy, ethoxy, propoxy, butoxy, pentoxy, alkoxy groups with up to about 10 carbons, and mixtures thereof Suitable hydrocarbon groups include methyl, ethyl, propyl, butyl, pentyl-, hexyl-, heptyl-, octyl-, nonyl-, decyl-, and mixtures thereof. Hydrocarbon groups may be linear or branched, and are preferably saturated. At least one of R1, R2, R3, or R4 should be capable of terminating the living polymerization of conjugated diene monomers.
A 1,2-microstructure controlling agent or randomizing modifier is optionally used to 15 control the 1,2-microstructure in the conjugated diene contributed monomer units, such as 1,3-butadiene, of the polymer composition. Suitable modifiers include hexamethylphosphoric acid triamide, N,N,Nxe2x80x2,Nxe2x80x2-tetramethylethylene diamine, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tri ethylene glycol dimethyl ether, tetraethylene glycol dimethyl ether, tetrahydrofuran, 1,4-diazabicyclo [2.2.2] octane, diethyl ether, triethylamine, tri-n-butylamine, tri-n-butylphosphine, p-dioxane, 1,2-dimethoxy ethane, dimethyl ether, methyl ethyl ether, ethyl propyl ether, di-n-propyl ether, di-n-octyl ether, anisole, dibenzyl ether, diphenyl ether, dimethylethylamine, bis-oxalanyl propane, tri-n-propyl amine, trimethyl amine, triethyl amine, N,N-dimethyl aniline, N-ethylpiperidine, N-methyl-N-ethyl aniline, N-methylmorpholine, tetramethylenediamine, oligomeric oxolanyl propanes (OOPs), 2,2-bis-(4-methyl dioxane), and bistetrahydrofuryl propane.
A mixture of one or more randomizing modifiers can also be used. The ratio of the modifier to the monomers can vary from a minimum as low as about 0 to a maximum as great as about 4000 millimoles, preferably about 0.01 to 3000 millimoles, of modifier per hundred grams of monomer currently being charged into the reactor. As the modifier charge increases, the percentage of 1,2-microstructure (vinyl content) increases in the conjugated diene contributed monomer units in the polymer backbone. The 1,2-microstructure content of the conjugated diene units is preferably between about 10 and 90%, more preferably between about 40 and 70%.
The polymer composition will preferably have a room temperature (about 23xc2x0 C.) viscosity between about 10 poise and 200 poise, more preferably between about 20 poise and 70 poise.
It may be desirable to include additional additives known in the art to the present curable sealant composition.
For example, hardeners (also known as curing catalysts), plasticizers, fillers, stabilizers, other miscellaneous ingredients known in the art, and mixtures thereof may preferably be added in an amount between about 60 and 80 wt % of the total composition. Exemplary hardeners/curing catalysts include for instance, a titanate such as tetrabutyl titanate or tetrapropyl titanate; an organotin compound such as dibutyl tin dilaurate, dibutyl tin maleate, dibutyl tin diacetate, tin octylate or tin naphthenate; lead octylate; an amine compound such as butylamine, octylamine, dibutylamine, monoethanolamine, diethanolamine, triethanolamine, diethylenetriamine, triethylenetetramine, oleylamine, cyclohexylamine, benzylamine, diethylaminopropylamine, xylylenediamine, triethylenediamine, guanidine, diphenylguanidine, 2,4,6-tris(dimethylaminomethyl)phenol, morpholine, N-methylmorpholine or 1,3-diazabicyclo-(5,4,6)undecene-7(DBU), and its salt with a carboxylic acid or the like; a polyamide having a low molecular weight obtained by the reaction of an excess polyamine with a polybasic acid; a reaction product of an excess polyamine with an epoxy compound; and a silane couping agent having an amino group, e.g. a silanol condensation catalyst such as xcex3-aminopropyltrimethoxysilane or N-(beta-aminoethyl)aminopropyl-methyl-dimethoxysilane; and the like. The curing catalysts may be employed alone or as an admixture thereof.
Exemplary plasticizers include, for instance, a hydrocarbon oil such as an alkyl diphenyl or a partially hydrogenated terphenyl; chlorinated paraffin or a phthalic acid ester such as dibutyl phthalate, diheptyl phthalate, di-(2-ethylhexyl)phthalate, butylbenzyl phthalate or butylphthalylbutyl glycolate; a non-aromatic dibasic acid ester such as dioctyl adipate or dioctyl sebacate; an ester of polyalkylene glycol such as diethylene glycol dibenzoate or triethylene glycol dibenzoate; a phosphoric acid ester such as tricresyl phosphate or tributyl phosphate; and the like, and mixtures thereof. The plasticizers are used alone or as an admixture thereof. It is possible to admix the placticizers at the time when preparing the organic polymer. Plasticizers typically constitute between about 10% to 40% of the total composition
As the modifier, various silane coupling agents are used, as occasion demands. Examples of the silane coupling agents are, for instance, alkylalkoxysilanes such as methyltrimethoxysilane, dimethyldimethoxysilane such as dimethyldiisopropenoxysilane, methltriisopropenoxysilane and xcex3-glycidoxypropylmethyldiisopropenoxysilane; alkoxysilanes having a functional group such as xcex3-glycidoxypropylmethyldimethoxysilane, xcex3-glycidoxypropyltrimethoxysilane, vinyltrimethoxysilane, vinyldimethylmethoxysilane, xcex3-aminopropyltrimethoxysilane, N-(beta-aminoethyl)aminopropylmethyldimethoxysilane, xcex3-mercapto-propyltrimethoxysilane and y-mercaptopropylmethyldimethoxysilane; silicone varnish; polysiloxanes; and mixtures thereof By employing the above-mentioned modifiers, it is possible to increase the hardness of the cured product or to decrease the hardness to give better elongation property. Modifiers typically constitute about 0.5% to 2% of the total composition
Examples of fillers and reinforcing agents are, for instance, heavy or light calcium carbonate; calcium carbonate the surface of which is treated with a fatty acid, a resin acid, a cationic surface active agent, or an anionic surface active agent; magnecium carbonate, talc, titanium oxide, barium sulfate, alumina, metal powder such as aluminum powder, zinc powder or iron powder, bentonite, kaoline clay, fumed silica, quartz powder, carbon black, and mixtures thereof. The fillers or reinforcing agents are employed alone or as an admixture thereof. When using the filler or the reinforcing agent capable of giving transparency to the composition such as filmed silica, scaling compositions having excellent transparency can be obtained. Fillers and/or reinforcing agents typically constitute between about 20% and 50% of the total composition.
Examples of typical stabilizers known in the art are antioxidants, radical chain terminators, ultraviolet absorbers, sequestrants, ozone degradation inhibitors, light stabilizers, and phosphorus type peroxide decomposers and mixtures thereof. Stabilizers typically constitute between about 0.5% and 2% of the total composition.
Examples of miscellaneous ingredients known in the art include, but are not limited to, lubricants, pigments, blowing agents, photocurable resins, thixotropic agents and mixtures thereof. Miscellaneous ingredients typically constitute about 0.5% to 2% of the total composition.
Although the curable composition of the present invention itself has good adhesion to glass, ceramics or metals, the composition of the invention can be widely adhered to various materials by employing primers. The adhesion property of the curable composition to various materials can be further improved by incorporation of adhesion accelerators such as epoxy resins, phenol resins, various silane coupling agents, alkyltitanates or aromatic polyisocyanates. The accelerators may be used alone or as an admixture thereof.
The curable polymer composition formed in accordance with the present invention is suitable for use as a one-part building sealant. The resultant sealant may be applied at building sites to prevent moisture permeation. The alkoxysilane groups of the polymer composition form crosslinks upon exposure to moisture, resulting in cured building sealants. Cure times of between about 1 day and 7 days may be achieved by exposing the polymers to moisture in the air.