A medicament for the therapeutic treatment of diabetes which comprises as an active ingredient a compound represented by the general formula (I):

The present invention relates to an enhancer of insulin secretion and a medicament for the treatment of diabetes, which comprise a condensed purine derivative as an active ingredient.
Diabetes is a metabolic abnormality mainly of glycometabolism, resulting from insufficient insulin secretion, decreased sensitivity of target cells of insulin and so forth, and principally characterized by noticeable hyperglycemia. If the hyperglycemia continues for a long period of time, serious complications arise in various organs and nerves such as retinopathy, nephropathy and neuropathy, which are caused mainly by vascular lesion. Therefore, for the treatment of diabetes, it is extremely important to control and maintain blood glucose level at a normal level, and methods for that purpose have been studied since old days.
For a type of diabetes where onset is gradual and insulin therapy is not necessarily required for life support (non-insulin dependent diabetes: NIDDM), blood glucose level can be controlled by combination of exercise therapy and drug therapy. As the drugs, insulin secretion enhancers, one of orally available hypoglycemic agents, have widely been used clinically. However, since currently available insulin secretion enhancers all promote insulin secretion non-dependently on glucose level, they cause problems of severe hypoglycemia or insufficient control of blood glucose if doses are not appropriate, and are not fully satisfactory drugs. If a hypoglycemic agent can be provided that is capable of enhancing insulin secretion dependently on a blood glucose level, the agent is expected to be extremely useful for blood glucose control of patients suffering from diabetes because the risk of hypoglycemia due to an excess dosage can be avoided.
As purine derivatives, the compounds of the following formula (I) having diuretic action, antiasthmatic action, anti-dementia action, bronchodilatation action, antiallergic action, antiulcer action and so forth are known (Japanese Patent Unexamined Publication (Kokai) No.3-204880/1991; Journal of Medicinal Chemistry, vol. 35, p.3578, 1992; Journal of Medicinal Chemistry, vol. 36, p.2508, 1993; International Publication WO98/15555). Journal of Medicinal Chemistry, vol. 23, p.1188, 1980 discloses that the compounds represented by the formula (A) have bronchodilatation action. Furthermore, Journal of Medicinal Chemistry, vol. 40, p.3248, 1997 discloses that the compounds represented by the formula (B) have inhibitory action against type IV phosphodiesterase (bronchodilatation action).
An object of the present invention is to provide a medicament useful for the therapeutic treatment of diabetes and the prophylactic and/or therapeutic treatment of complications of diabetes. More specifically, the object of the present invention is to provide a medicament having action of enhancing insulin secretion in a blood glucose level-dependent manner.
The inventors of the present invention conducted various studies to achieve the foregoing object. As a result, we found that the compounds represented by the following general formula (I) have insulin secretion enhancing action, and that the compounds are useful as an active ingredient of a medicament for the treatment of diabetes. The present invention was achieved on the basis of these findings.
The present invention thus provides medicaments for the therapeutic treatment of diabetes which comprise compound represented by the general formula (I) or a physiologically acceptable salt thereof as an active ingredient:
wherein R1 represents a hydrogen atom, a lower alkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted aromatic heterocyclic group; R2 represents a hydrogen atom, a lower alkyl group, a substituted or unsubstituted aralkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted aromatic heterocyclic group; R3 represents a hydrogen atom, a lower alkyl group, or a substituted or unsubstituted aralkyl group; X1 and X2 independently represent a hydrogen atom, a lower alkyl group, a substituted or unsubstituted aralkyl group, or a substituted or unsubstituted aryl group; and n represents an integer of from 0 to 3. The invention also provides medicaments for the prophylactic and/or therapeutic treatment of a complication of diabetes which comprise the aforementioned compound or a physiologically acceptable salt thereof as an active ingredient.
According to other aspects of the present invention, there are provided hypoglycemic agents comprising a compound represented by the aforementioned formula (I) or a physiologically acceptable salt thereof as an active ingredient, and insulin secretion enhancers comprising a compound represented by the aforementioned formula (I) or a physiologically acceptable salt thereof as an active ingredient. These medicaments are preferably provided in the form of a pharmaceutical composition which comprises a compound represented by the aforementioned formula (I) or a physiologically acceptable salt thereof and one or more of pharmaceutical additives.
According to other aspects of the present invention, there are provided use of a compound represented by the aforementioned formula (I) or a physiologically acceptable salt thereof for the manufacture of the aforementioned medicaments; a method for the therapeutic treatment of diabetes which comprises the step of administering a therapeutically effective amount of a compound represented by the aforementioned formula (I) or a physiologically acceptable salt thereof to a mammal including human; a method for enhancing insulin secretion which comprises the step of administering a therapeutically effective amount of a compound represented by the aforementioned formula (I) or a physiologically acceptable salt thereof to a mammal including human; and a method for decreasing blood glucose level which comprises the step of administering a therapeutically effective amount of a compound represented by the aforementioned formula (I) or a physiologically acceptable salt thereof to a mammal including human.
The compounds represented by the general formula (I) will be hereinafter referred to as Compound (I).
Meanings of terms used herein are as follows. As the lower alkyl group or a lower alkyl moiety of a functional group containing the lower alkyl moiety (for example, an aralkyl group), an alkyl group having about 1 to 10 carbon atoms can be used, and the term xe2x80x9calkyl groupxe2x80x9d includes linear, branched and cyclic alkyl groups as well as those consisting of a combination thereof. A cyclic alkyl group or a cyclic alkyl moiety of an alkyl group may have one or more rings, and may have, for example, a bicyclic ring or tricyclic ring system.
Examples of the linear or branched lower alkyl group include a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a n-pentyl group, a neopentyl group, a n-hexyl group, a n-heptyl group, a n-octyl group, a n-nonyl group and so forth. Examples of the cyclic lower alkyl group include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group, a noradamantyl group, an adamantyl group and so forth.
Preferred examples of the lower alkyl group represented by R1 include a linear or branched lower alkyl group (for example, a tert-butyl group, etc.), a monocyclic to tricyclic lower cycloalkyl group (for example, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a 3-noradamantyl group, etc.) and a lower alkyl group substituted with a lower cycloalkyl group (for example, a cyclopropylmethyl group, a cyclopentylmethyl group, etc.). Among them, a 3-noradamantyl group and a cyclopentyl group are more preferred. As the lower alkyl group represented by R2, a linear or branched lower alkyl group (for example, a methyl group, an ethyl group, a n-propyl group, etc.), a monocyclic lower cycloalkyl group or a lower alkyl group substituted with a lower cycloalkyl group (for example, a cyclopropylmethyl group etc.) is preferred. Among them, a n-propyl group is more preferred. As the lower alkyl group represented by R3, a linear or branched lower alkyl group (for example, a methyl group, an ethyl group, etc.) is preferred, and a methyl group is more preferred. As the lower alkyl group represented by X1 or X2, a linear or branched lower alkyl group (for example, an ethyl group, an isopropyl group, a n-butyl group, an isobutyl group, a tert-butyl group, etc.), a monocyclic lower cycloalkyl group, or a lower alkyl group substituted with a lower cycloalkyl group (for example, a cyclohexylmethyl group etc.) is preferred. Among them, an ethyl group, an isopropyl group, an isobutyl group, and a tert-butyl group are more preferred.
As the aryl group or an aryl moiety of a functional group containing the aryl moiety (for example, an aralkyl group), an aromatic group consisting of a single ring or two or more condensed rings can be used. More specifically, an aryl group having 6 to 14 ring-membered carbon atoms is preferred. For example, a phenyl group, a naphthyl group, an indenyl group, an anthranyl group or the like may preferably be used. As the aralkyl group, for example, an aralkyl group having 7 to 15 carbon atoms can be used. More specifically, a benzyl group, a phenethyl group, a diphenylmethyl group, a naphthylmethyl group or the like may be used.
As the aromatic heterocyclic group, an aromatic heterocyclic group consisting of a single ring or two or more condensed rings can be used. The kind and number of hetero atom(s) contained in the aromatic heterocyclic group are not particularly limited. For example, one or more hetero atoms selected from the group consisting of a nitrogen atom, a sulfur atom, and an oxygen atom may be contained. More specifically, an aromatic heterocyclic group containing about 6 to 14 ring-membered carbon atoms is preferred. For example, a furyl group, a thienyl group, a pyrrolyl group, an imidazolyl group, a pyrazolyl group, a triazolyl group, a tetrazolyl group, an oxazolyl group, a thiazolyl group, a pyridyl group, a pyrazinyl group, a pyrimidinyl group, a pyridazinyl group, a triazinyl group, an indolyl group, an indazolyl group, a benzimidazolyl group, a benzoxazolyl group, a benzothiazolyl group, a quinolyl group, an isoquinolyl group, a phthalazinyl group, a naphthylidinyl group, a quinoxalinyl group, a quinazolinyl group, a cinnolinyl group, a purinyl group or the like may preferably be used.
When the aryl ring (including the aryl ring of an aralkyl group) or the aromatic heterocyclic ring has substituent(s), the kind, number and substitution position of the substituent(s) are not particularly limited. When two or more substituents exist, they may be the same or different. For example, the rings may have about 1 to 3 substituents. Examples of the substituents on the aryl ring or the aromatic heterocyclic ring include a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower alkenyl group, a substituted or unsubstituted lower alkynyl group, a substituted or unsubstituted aralkyl group, a substituted or unsubstituted aryl group, a hydroxyl group, a substituted or unsubstituted lower alkoxy group, a substituted or unsubstituted aralkyloxy group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted aroyl group, a lower alkoxycarbonyl group, a substituted or unsubstituted lower alkylthio group, a substituted or unsubstituted lower alkylsulfonyl group, a carboxyl group, a substituted or unsubstituted carbamoyl group, a substituted or unsubstituted lower alkanoyl group, a halogen atom (the xe2x80x9chalogen atomxe2x80x9d used in the present specification may be any of a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom), a nitro group, an amino group, a mono- or di(lower alkyl)-substituted amino group, a cyano group, a methylenedioxy group, an ethylenedioxy group and the like.
In the aforementioned functional groups, the above-explained groups may be used as the lower alkyl or a lower alkyl moiety of the functional groups containing a lower alkyl moiety (for example, the aralkyl group, the lower alkoxy group, the aralkyloxy group, the lower alkoxycarbonyl group, the lower alkylthio group, the lower alkylsulfonyl group, the lower alkanoyl group, the mono- or di(lower alkyl)-substituted amino group and the like). When the lower alkyl group or the lower alkyl moiety has substituent(s), the kind, number, and substitution position of the substituent(s) are not particularly limited. When two or more substituents exist, they may be the same or different. For example, the lower alkyl group or the lower alkyl moiety may have about 1 to 3 substituents. Examples of such substituents include a hydroxyl group, a halogen atom, a carboxyl group, a sulfo group, a phosphono group, ester groups derived from these acidic groups (a lower alkyl ester, an aralkyl ester, an aryl ester, etc.) and the like. More specific examples of the substituted alkyl group include a hydroxyethyl group, a trifluoromethyl group and the like. The two lower alkyl groups in the di(lower alkyl)-substituted amino group may be the same or different.
In the aforementioned functional groups, the aralkyl group or an aralkyl moiety of the aralkyloxy group has the same meaning as the aforementioned aralkyl group, and the aryl moiety of the aryl group, the aryloxy group, or the aroyl group has the same meaning as the aforementioned aryl group. As the lower alkenyl group, a linear or branched alkenyl group having 2 to 6 carbon atoms can be used. For example, a vinyl group, an allyl group, a 1-propenyl group, a methacryl group, a butenyl group, a crotyl group, a pentenyl group, a hexenyl group or the like may be used. As the lower alkynyl group, a linear or branched alkynyl group having 2 to 6 carbon atoms can be used. For example, an ethynyl group, a propynyl group, a butynyl group, a pentynyl group, a hexynyl group or the like may be used. The number of unsaturated bond in the alkenyl group or the alkynyl group is not particularly limited, and the number may preferably be 1.
When the aforementioned lower alkenyl group, lower alkynyl group, aralkyl group, aryl group, aralkyloxy group, aryloxy group, or aroyl group has substituent(s), the kind, number, and substitution position of the substituent(s) are not particularly limited. When two or more substituents exist, they may be the same or different. For example, the lower alkenyl group, lower alkynyl group, aralkyl group, aryl group, aralkyloxy group, aryloxy group, or aroyl group may have about 1 to 3 substituents. As the substituents, those exemplified as the substituents of the lower alkyl group may be used.
As the aryl group represented by R1, a phenyl group, a 4-bromophenyl group and the like are preferred. As the aromatic heterocyclic group represented by R1, a furyl group, a thienyl group and the like are preferred. As the aryl group represented by R2, a phenyl group is preferred. As the aralkyl group represented by R2, a benzyl group is preferred. As the aralkyl group represented by R3, a benzyl group is preferred. As the aralkyl group represented by X1 or X2, a phenyl group is preferred. Examples of the aralkyl group represented by X1 or X2 include a benzyl group, a halogenated benzyl group (a 4-fluorobenzyl group, a 3-fluorobenzyl group, a 2-fluorobenzyl group, a 2,3-difluorobenzyl group, a 2,5-difluorobenzyl group, a 4-chlorobenzyl group, a 3-chlorobenzyl group, a 2,5-dichlorobenzyl group, a 4-bromobenzyl group, a 3-bromobenzyl group, an 3-iodobenzyl group, etc.), a 4-tert-butylbenzyl group, a 2-phenylbenzyl group, a 3-trifluoromethylbenzyl group, a 3-trifluoromethoxybenzyl group, a 3,5-bis(trifluoromethyl)benzyl group, a 4-hydroxybenzyl group, a 4-methoxybenzyl group, a 4-nitrobenzyl group, a 3-cyanobenzyl group, a 3-carboxybenzyl group, a 3-phenoxybenzyl group, a 3-(2-fluorophenoxy)benzyl group, a 4-benzyloxybenzyl group, a diphenylmethyl group, a phenethyl group, an xcex1, xcex1-dimethylbenzyl group and the like. When X1 is a group other than a hydrogen atom, X2 is preferably a hydrogen atom. A combination of a lower alkyl group as X1 (for example, a methyl group) and an aralkyl group as X2 (for example, a benzyl group) is also preferred.
In the aforementioned general formula (I), the substitution positions of X1 and X2 are not particularly limited, and they may substitute at any positions on the ring. When X1 or X2 is a substituent other than a hydrogen atom, the absolute configuration of the carbon atom to which it binds may be in either a S- or R-configuration. The symbol xe2x80x9cnxe2x80x9d may preferably be 0.
As the active ingredient of the medicament of the present invention, physiologically acceptable salts of Compound (I) may be used. Such physiologically acceptable salts include acid addition salts such as inorganic acid salts and organic acid salts; base addition salts such as metal salts, ammonium salts and organic amine addition salts; amino acid addition salts and the like. Examples of the physiologically acceptable acid addition salts include inorganic acid salts such as hydrochlorides, sulphates and phosphates, and organic acid salts such as acetates, maleates, fumarates, tartrates, and citrates. Examples of the physiologically acceptable metal salts include alkali metal salts such as sodium salts and potassium salts, alkaline earth metal salts such as magnesium salts and calcium salts, as well as aluminum salts, zinc salts and the like. Examples of the physiologically acceptable organic amine addition salts include addition salts of organic amines such as morpholine, piperidine and the like. Examples of the physiologically acceptable amino acid addition salts include addition salts of lysine, glycine, phenylalanine and the like.
As the active ingredient of the medicament of the present invention, the aforementioned compounds in free forms or physiologically acceptable salts thereof, as well as any hydrates and solvates thereof may be used. The kind of solvents forming the solvates is not particularly limited so long as they are physiologically acceptable. For example, ethanol, acetone and the like may be used. The compounds represented by the formula (I) may have one or more asymmetric carbons. As the active ingredient of the medicament of the present invention, any substances falling within the scope of the general formula (I) may be used, including optical isomers or diastereoisomers in pure forms, any mixtures of isomers, racemates and the like. When the compounds represented by the general formula (I) contain one or more double bonds, each configuration thereof may be in either a Z- or E-configuration.
The methods for the preparation of typical compounds falling within the compounds represented by the formula (I) are specifically disclosed in International Publication WO98/15555, and are also explained in Japanese Patent Unexamined Publication No. 3-204880/1991; Journal of Medicinal Chemistry, vol. 35, p.3578, 1992; Journal of Medicinal Chemistry, vol. 36, p.2508, 1993; Journal of Heterocyclic Chemistry, vol. 30, p.241, 1993 and the like. Furthermore, the methods for preparing preferred compounds shown below will be specifically explained in detail in the examples of the present specification. Therefore, those skilled in the art can prepare any compounds falling within the scope of the general formula (I) according to the processes disclosed in the aforementioned references or the manufacturing processes specifically described in the present specification, or by suitably changing regents and starting materials, and further by appropriately modifying or altering these processes, if necessary.
The intermediate compounds and target compounds obtained in these manufacturing processes can be isolated and purified by methods for purification conventionally used in the field of synthetic organic chemistry, for example, neutralization, filtration, extraction, washing, drying, concentration, recrystallization, various kinds of chromatography and the like. The intermediate compounds can also be used in subsequent reactions without particular purification. When salts of the compounds represented by the general formula (I) are prepared, the compounds in a free form may be dissolved or suspended in a suitable solvent, and a suitable acid or base is added to the mixture to form a salt, and then the resulting salts may be isolated and purified as required. It is also possible to convert a target substance obtained in a form of salt into a free form, and their converted into a desired salt.
Preferred examples of the active ingredient of the medicament of the present invention include:
(1) those wherein R1 represents a hydrogen atom, a lower alkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted aromatic heterocyclic group, R2 represents a lower alkyl group, a substituted or unsubstituted aralkyl group or a substituted or unsubstituted aryl group, R3 represents a hydrogen atom, a lower alkyl group, or a substituted or unsubstituted aralkyl group, X1 and X2 independently represent a hydrogen atom, a lower alkyl group, a substituted or unsubstituted aralkyl group or a substituted or unsubstituted aryl group, and the symbol xe2x80x9cnxe2x80x9d represents 0, or physiologically acceptable salts thereof; more preferred examples include:
(2) those wherein R1 represents a lower alkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted aromatic heterocyclic group, R2 represents a lower alkyl group or a substituted or unsubstituted aryl group, R3 represents a hydrogen atom or a substituted or unsubstituted aralkyl group, X1 represents a hydrogen atom, a lower alkyl group, or a substituted or unsubstituted aralkyl group, X2 represents a hydrogen atom, and the symbol xe2x80x9cnxe2x80x9d represents 0, or physiologically acceptable salts thereof; and further preferred examples include
(3) those wherein R1 represents a n-propyl group, a n-butyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cyclopropylmethyl group, a cyclopentylmethyl group, an isopropyl group, or a tert-butyl group, R2 represents a n-propyl group or an ethyl group, R3 represents a hydrogen atom, X1 represents a lower alkyl group or a substituted or unsubstituted aralkyl group, X2 represents a hydrogen atom, and the symbol xe2x80x9cnxe2x80x9d represents 0, or physiologically acceptable salts thereof.
More specifically, the followings can be exemplified as preferred compounds or physiologically acceptable salts thereof suitable as the active ingredient of the medicament of the present invention. Among them, Compound 16, Compounds 18-20, Compound 23, Compound 31, Compound 35, Compound 37, Compound 43, and Compound 55 are particularly preferred. The compounds in free forms or other physiologically acceptable salts of these salts are also preferred. References disclosing each corresponding compound are indicated in the parentheses after the names of compounds. As for Compound 6, a racemate thereof is disclosed in Japanese Patent Unexamined Publication No.3-204880/1991. It should be understood that the active ingredients of the medicaments of the present invention are not limited to the compounds or physiologically acceptable salts thereof listed below. The compounds specifically disclosed in Japanese Patent Unexamined Publication No. 3-204880/1991 or International Publication WO98/15555 or physiologically acceptable salts thereof, as well as those listed below, are preferred as the active ingredient of the medicament of the present invention.
Compound 1: (R)-8-ethyl-7,8-dihydro-2-(3-noradamantyl)-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one L-tartrate (Journal of Medicinal Chemistry, vol.36, p.2508, 1993)
Compound 2: (S)-8-ethyl-7,8-dihydro-2-(3-noradamantyl)-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one D-tartrate (Journal of Medicinal Chemistry, vol. 36, p.2508, 1993)
Compound 3: (R)-7,8-dihydro-8-isopropyl-2-(3-noradamantyl)-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 4: (S)-7,8-dihydro-8-isopropyl-2-(3-noradamantyl)-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 5: 7,8-dihydro-2-(3-noradamantyl)-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 6: (R)-2-cyclopentyl-7,8-dihydro-8-methyl-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 7: (R)-2-cyclopentyl-8-ethyl-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one L-tartrate (Japanese Patent Unexamined Publication No. 3-204880/1991)
Compound 8: (S)-2-cyclopentyl-8-ethyl-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one D-tartrate (Japanese Patent Unexamined Publication No. 3-204880/1991)
Compound 9: (R)-2-cyclopentyl-7,8-dihydro-8-isopropyl-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride (Japanese Patent Unexamined Publication 3-204880/1991)
Compound 10: (S)-2-cyclopentyl-7,8-dihydro-8-isopropyl-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride (Japanese Patent Unexamined Publication No. 3-204880/1991)
Compound 11: (R)-2-cyclopentyl-7,8-dihydro-8-isobutyl-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one L-tartrate
Compound 12: (S)-8-tert-butyl-2-cyclopentyl-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 13: 8-butyl-2-cyclopentyl-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 14: (S)-8-cyclohexylmethyl-2-cyclopentyl-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 15: (R)-2-cyclopentyl-7,8-dihydro-8-phenyl-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride (Japanese Patent Unexamined Publication No. 3-204880/1991)
Compound 16: (R)-8-benzyl-2-cyclopentyl-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride (Japanese Patent Unexamined Publication No. 3-204880/1991)
Compound 17: (S)-8-benzyl-2-cyclopentyl-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride (Japanese Patent Unexamined Publication No. 3-204880/1991)
Compound 18: 2-cyclopentyl-8-(4-fluorobenzyl)-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 19: 2-cyclopentyl-8-(3-fluorobenzyl)-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 20: 8-(4-chlorobenzyl)-2-cyclopentyl-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 21: 8-(3-chlorobenzyl)-2-cyclopentyl-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 22: 2-cyclopentyl-8-(2,6-dichlorobenzyl)-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 23: 8-(4-bromobenzyl)-2-cyclopentyl-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 24: 8-(3-bromobenzyl)-2-cyclopentyl-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 25: 2-cyclopentyl-7,8-dihydro-8-(4-methoxybenzyl)-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 26: 2-cyclopentyl-7,8-dihydro-8-(4-nitrobenzyl)-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 27: (R)-8-(4-benzyloxybenzyl)-2-cyclopentyl-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 28: (S)-8-(4-benzyloxybenzyl)-2-cyclopentyl-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 29: (R)-8-benzyl-2-cyclopentyl-7,8-dihydro-1-methyl-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 30: 2-cyclopentyl-7,8-dihydro-8-diphenylmethyl-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 31: 2-cyclopentyl-7,8-dihydro-8-phenethyl-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 32: (R)-4,8-dibenzyl-2-cyclopentyl-7,8-dihydro-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 33: (R)-8-benzyl-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 34: (R)-1,8-dibenzyl-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 35: (R)-8-benzyl-7,8-dihydro-2,4-dipropyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 36: (R)-8-benzyl-2-cyclopropyl-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 37: (R)-8-benzyl-2-cyclobutyl-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 38: (R)-8-benzyl-2-cyclohexyl-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 39: (R)-8-benzyl-7,8-dihydro-2-(3-noradamantyl)-4-propyl-1-H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 40: (R)-8-benzyl-2-cyclopentylmethyl-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 41: (R)-8-benzyl-7,8-dihydro-2-isopropyl-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 42: (R)-8-benzyl-2-(3-furyl)-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 43: (R)-8-benzyl-2-tert-butyl-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 44: (R)-8-benzyl-7,8-dihydro-4-propyl-2-(3-thienyl)-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 45: 8-(4-bromobenzyl)-2-cyclohexyl-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 46: 8-(4-chlorobenzyl)-7,8-dihydro-2,4-dipropyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 47: 8-(4-chlorobenzyl)-2-cyclohexyl-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 48: 8-(4-chlorobenzyl)-2-cyclobutyl-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 49: 8-(4-fluorobenzyl)-7,8-dihydro-2,4-dipropyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 50: 2-cyclohexyl-8-(4-fluorobenzyl)-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 51: (R)-2-cyclobutyl-8-(4-fluorobenzyl)-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 52: 2-butyl-8-(4-fluorobenzyl)-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 53: 8-(4-fluorobenzyl)-2-(2-furyl)-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 54: (R)-8-(4-fluorobenzyl)-2-(3-furyl)-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one
Compound 55: (R)-2-tert-butyl-8-(4-fluorobenzyl)-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 56: 8-(3-fluorobenzyl)-7,8-dihydro-2,4-dipropyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 57: 2-cyclobutyl-8-(3-fluorobenzyl)-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 58: 8-(3-fluorobenzyl)-7,8-dihydro-2-isobutyl-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one
Compound 59: 2-(4-bromophenyl)-8-(3-fluorobenzyl)-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 60: 8-(2-fluorobenzyl)-7,8-dihydro-2-isobutyl-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one
Compound 61: 2-cyclopentyl-7,8-dihydro-8-(3-methylbenzyl)-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one
Compound 62: 2-cyclopentyl-7,8-dihydro-8-(3-iodobenzyl)-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 63: 2-cyclopentyl-8-(2,3-difluorobenzyl)-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 64: 2-cyclopentyl-8-(2,5-difluorobenzyl)-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 65: 2-cyclopentyl-8-(2,5-dichlorobenzyl)-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 66: (S)-8-tert-butyl-7,8-dihydro-2-(3-noradamantyl)-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 67: (S)-8-tert-butyl-2-(3-furyl)-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one
Compound 68: (S)-8-tert-butyl-2-(3,5-dimethylisoxazol-4-yl)-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 69: (S)-7,8-dihydro-2,8-diisopropyl-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 70: 8-(3-cyanobenzyl)-2-cyclopentyl-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one
Compound 71: (R)-8-benzyl-2-cyclopentyl-4-ethyl-7,8-dihydro-1H-imidazo[2,1-i]purin-5(4H)-one hydrochloride
Compound 72: (R)-8-benzyl-2-cyclopentyl-4-cyclopropylmethyl-7,8-dihydro-1H-imidazo[2,1-i]purin-5(4H)-one
Compound 73: (R)-8-benzyl-2-cyclopropylmethyl-7,8-dihydro-4-propyl-1H-imidazo-[2,1-i]purin-5(4H)-one hydrochloride
Compound 74: 8-(3-carboxybenzyl)-2-cyclopentyl-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one
Compound 75: 2-cyclopentyl-8-(xcex1, xcex1-dimethylbenzyl)-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one
Compound 76: (R)-2-cyclopentyl-7,8-dihydro-8-(4-hydroxybenzyl)-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one
Compound 77: (R)-8-benzyl-7,8-dihydro-4-propyl-2-(3-pyridyl)-1H-imidazo[2,1-i]purin-5(4H)-one
Compound 78: (R)-8-benzyl-7,8-dihydro-2-phenyl-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one
Compound 79: (R)-8-benzyl-7,8-dihydro-4-propyl-2-(2,2,3,3-tetramethylcyclopropyl)-1H-imidazo[2,1-i]purin-5(4H)-one
Compound 80: (R)-8-benzyl-7,8-dihydro-2-(3,4-methylenedioxyphenyl)-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one
Compound 81: (R)-8-benzyl-7,8-dihydro-4-propyl-2-(4-pyridyl)-1H-imidazo[2,1-i]purin-5(4H)-one
Compound 82: (R)-8-benzyl-7,8-dihydro-4-propyl-2-(2-pyrazyl)-1H-imidazo[2,1-i]purin-5(4H)-one
Compound 83: (R)-8-benzyl-7,8-dihydro-4-propyl-2-(2-thienyl)-1H-imidazo[2,1-i]purin-5(4H)-one
Compound 84: (R)-8-benzyl-2-cyclopentyl-7,8-dihydro-4-methyl-1H-imidazo[2,1-i]purin-5(4H)-one
Compound 85: (R)-8-benzyl-2-cyclopentyl-7,8-dihydro-4-phenyl-1H-imidazo[2,1-i]purin-5(4H)-one
Compound 86: 8-(4-tert-butylbenzyl)-2-cyclopentyl-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one
Compound 87: 2-cyclopentyl-7,8-dihydro-8-(2-phenylbenzyl)-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one
Compound 88: 2-cyclopentyl-7,8-dihydro-4-propyl-8-(3-trifluoromethylbenzyl)-1H-imidazo[2,1-i]purin-5(4H)-one
Compound 89: 2-cyclopentyl-8-[3-(2-fluorophenoxy)benzyl]-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one
Compound 90: 2-cyclopentyl-7,8-dihydro-8-(3-phenoxybenzyl)-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one
Compound 91: 2-cyclopentyl-7,8-dihydro-4-propyl-8-(3-trifluoromethoxybenzyl)-1H-imidazo[2,1-i]purin-5(4H)-one
Compound 92: 8-[3,5-bis(trifluoromethyl)benzyl]-2-cyclopentyl-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one
Compound 93: 8-benzyl-2-cyclopentyl-7,8-dihydro-8-methyl-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one
The compounds represented by the general formula (I) or physiologically acceptable salts thereof have insulin secretion enhancing action in cultured xcex2-cells and hypoglycemic action in rats, and accordingly, they are useful as an active ingredient of the medicament for the treatment of diabetes. Further, they are useful as an active ingredient of the medicament for the prophylactic and/or therapeutic treatment of various complications of diabetes, for example, retinopathy, nephropathy, neurosis and the like. As the active ingredient of the medicament of the present invention, one or more substances selected from the group consisting of the compounds represented by the general formula (I) and physiologically acceptable salts thereof, and hydrates thereof and solvates thereof can be used. Although the aforementioned substances, per se, may be administered, it is generally desirable to provide the medicament in a form of a pharmaceutical composition comprising the aforementioned substance as the active ingredient and one or more pharmaceutical additives. The medicament of the present invention can be administered to human and other mammals.
The form of the pharmaceutical composition is not particularly limited, and an appropriate form most suitable for a purpose of the prophylactic or therapeutic treatment can be selected from forms of pharmaceutical preparations for oral or parenteral administration. Examples of pharmaceutical preparations suitable for oral administration include tablets, capsules, powders, granules, subtilized granules, syrups, solutions, emulsions, suspensions, chewable formulations and the like. Examples of pharmaceutical preparations suitable for parenteral administration include injections (for subcutaneous injection, intramuscular injection, intravenous injection or the like), drip infusions, inhalants, sprays, suppositories, transdermal or transmucosal preparations in the forms of gel, ointment or the like, transdermal preparations in the forms of patch, tape or the like. However, the preparations are not limited to these examples.
Liquid preparations suitable for oral administration such as solutions, emulsions and syrups can be prepared by using water, saccharides such as sucrose, sorbitol and fructose, glycols such as polyethylene glycol and propylene glycol, oils such as sesame oil, olive oil and soybean oil, preservatives such as p-hydroxybenzoic acid esters, flavors such as strawberry flavor and peppermint or the like. For the preparation of solid preparations such as capsules, tablets, powders and granules, excipients such as lactose, glucose, sucrose and mannitol, disintegrating agents such as starch and sodium alginate, lubricants such as magnesium stearate and talc, binders such as polyvinyl alcohol, hydroxypropylcellulose and gelatin, surface active agents such as fatty acid esters, plasticizers such as glycerin or the like may be used.
Pharmaceutical preparations for injection or drip infusion, which are suitable for parenteral administration, contain the aforementioned substance as the active ingredient preferably in a sterilized aqueous medium isotonic with blood of a recipient in a dissolved or suspended state. For example, as for injections, a solution can be prepared by using an aqueous medium consisting of saline, a glucose solution, or a mixture of saline and a glucose solution. Preparations for enteral administration can be prepared, for example, by using a carrier such as cacao butter or hard fat, and are provided as suppositories. Further, for the preparation of sprays, a carrier may be used which can disperse the aforementioned substance as the active ingredient as fine particles, and facilitate adsorption of the active ingredient without stimulating mucosae of oral cavity and respiratory tract of recipients. Specifically, examples of the carrier include lactose and glycerol. Depending on the properties of the substance as the active ingredient and the carrier, pharmaceutical preparations in forms of aerosol, dry powder and the like can be prepared. To these pharmaceutical preparations for parenteral administration, one or more auxiliary ingredients selected from glycols, oils, flavors, preservatives, excipients, disintegrating agents, lubricants, binders, surface active agents, plasticizers and the like may also be added.
Dose and frequency of administration of the medicament of the present invention may preferably be increased or decreased depending on various factors such as type and severity of diseases, dosage form, conditions of patients such as age and body weight, and presence or absence of complications. In general, the medicament may preferably be administered in an amount of 1 to 1000 mg/kg per day for an adult dividedly as three or four times of administrations.
According to another aspect of the present invention, there are provided the compounds of the general formula (I):
(1) wherein R1 represents a 3-noradamantyl group, R2 represents a n-propyl group, R3 represents a hydrogen atom, X1 represents a hydrogen atom, a tert-butyl group, an isopropyl group, or a benzyl group, X2 represents a hydrogen atom, and the symbol xe2x80x9cnxe2x80x9d represents 0;
(2) wherein R1 represents a cyclopentyl group, R2 represents a n-propyl group, R3 represents a hydrogen atom, X1 represents a n-butyl group, an isobutyl group, a tert-butyl group, a cyclohexylmethyl group, an aralkyl group whose alkyl moiety is substituted or an unsubstituted aralkyl group (except for a benzyl group), or an aralkyl group (preferably a benzyl group) having one or more substituents (preferably one or two, more preferably one) selected from the group consisting of a halogen atom, a substituted or unsubstituted lower alkyl group, a lower alkoxyl group (preferably a methoxy group), an aralkyloxy group (preferably a benzyloxy group), a carboxyl group, a cyano group, a hydroxyl group, and a nitro group on the ring, X2 represents a hydrogen atom, and the symbol xe2x80x9cnxe2x80x9d represents 0;
(3) wherein R1 represents a cyclopentyl group, R2 represents a n-propyl group, R3 represents a lower alkyl group (preferably a methyl group), X1 represents a substituted or unsubstituted aralkyl group (preferably a benzyl group), X2 represents a hydrogen atom, and the symbol xe2x80x9cnxe2x80x9d represents 0;
(4) wherein R1 represents a cyclopentyl group, R2 represents a substituted or unsubstituted aralkyl group (preferably a benzyl group), a lower alkyl group (except for a n-propyl group; preferably a cyclopropylmethyl group or a linear lower alkyl group) or a substituted or unsubstituted aryl group (preferably a phenyl group), R3 represents a hydrogen atom, X1 represents a substituted or unsubstituted aralkyl group (preferably a benzyl group), X2 represents a hydrogen atom, and the symbol xe2x80x9cnxe2x80x9d represents 0;
(5) wherein R1 represents a hydrogen atom, R2 represents a n-propyl group, R3 represents a hydrogen atom, or a substituted or unsubstituted aralkyl group (preferably a benzyl group), X1 represents a substituted or unsubstituted aralkyl group (preferably a benzyl group), X2 represents a hydrogen atom, and the symbol xe2x80x9cnxe2x80x9d represents 0;
(6) wherein R1 represents a lower alkyl group (except for a cyclopentyl group), a substituted or unsubstituted aromatic heterocyclic group, or a substituted or unsubstituted aryl group, R2 represents a n-propyl group, R3 represents a hydrogen atom, X1 represents a substituted or unsubstituted aralkyl group (preferably a benzyl group), X2 represents a hydrogen atom, and the symbol xe2x80x9cnxe2x80x9d represents 0;
(7) wherein R1 represents a linear or branched lower alkyl group (preferably an isopropyl group) or a substituted or unsubstituted aromatic heterocyclic group, R2 represents a n-propyl group, R3 represents a hydrogen atom, X1 represents a lower alkyl group (except for a methyl group; preferably an isopropyl group, or an isobutyl group, a t-butyl group), X2 represents a hydrogen atom, and the symbol xe2x80x9cnxe2x80x9d represents 0; and
(8) wherein R1 represents a cyclopentyl group, R2 represents a n-propyl group, R3 represents a hydrogen atom, X1 represents a methyl group, X2 represents a substituted or unsubstituted aralkyl group, and the symbol xe2x80x9cnxe2x80x9d represents 0.
Specific examples of these compounds include, for example, Compounds 3-5, Compounds 11-14, and Compound 18 to Compound 93.
As preferred compounds, there are provided:
the aforementioned compounds wherein R1 represents a cyclopentyl group, R2 represents a n-propyl group, R3 represents a hydrogen atom, X1 represents an aralkyl group (preferably a benzyl group) having one or more (preferably one) halogen atoms on the ring or an unsubstituted aralkyl group (except for a benzyl group), X2 represents a hydrogen atom, and the symbol xe2x80x9cnxe2x80x9d represents 0;
the aforementioned compounds wherein R1 represents a cyclopentyl group, R2 represents a linear or branched lower alkyl group (except for a n-propyl group), R3 represents a hydrogen atom, X1 represents a substituted or unsubstituted aralkyl group (preferably a benzyl group), X2 represents a hydrogen atom, and the symbol xe2x80x9cnxe2x80x9d represents 0; and
the aforementioned compounds wherein R1 represents a lower alkyl group (except for a cyclopentyl group), R2 represents a n-propyl group, R3 represents a hydrogen atom, X1 represents a substituted or unsubstituted aralkyl group (preferably a benzyl group), X2 represents a hydrogen atom, and the symbol xe2x80x9cnxe2x80x9d represents 0;
Particularly preferred compounds are:
the aforementioned compounds where R1 represents a cyclopentyl group, R2 represents an ethyl group, R3 represents a hydrogen atom, X1 represents a substituted or unsubstituted aralkyl group (preferably a benzyl group), X2 represents a hydrogen atom, and the symbol xe2x80x9cnxe2x80x9d represents 0; and
the aforementioned compounds wherein R1 represents a tert-butyl group, R2 represents a n-propyl group, R3 represents a hydrogen atom, X1 represents a substituted or unsubstituted aralkyl group (preferably a benzyl group), X2 represents a hydrogen atom, and the symbol xe2x80x9cnxe2x80x9d represents 0.
As salts of the aforementioned compounds, those explained above can be used. It should be understood that, besides the aforementioned compounds in free forms and physiologically acceptable salts thereof, any hydrates and solvates thereof fall within the scope of the present invention. Further, any isomers, mixtures of isomers, racemates and the like also fall within the scope of the present invention. These compounds and salts thereof are useful as, for example, the active ingredient of the medicament of the present invention. However, utilities of the compounds of the present invention and salts thereof are not limited to said particular utility.

Abstract: wherein R1 represents a hydrogen atom, a lower alkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted aromatic heterocyclic group, R2 represents a hydrogen atom, a lower alkyl group, a substituted or unsubstituted aralkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted aromatic heterocyclic group, R3 represents a hydrogen atom, a lower alkyl group or a substituted or unsubstituted aralkyl group, X1 and X2 independently represent a hydrogen atom, a lower alkyl group, a substituted or unsubstituted aralkyl group, or a substituted or unsubstituted aryl group, and the symbol xe2x80x9cnxe2x80x9d represents an integer of from 0 to 3, or a physiologically acceptable salt thereof.


A bicycle component position correcting device is basically provided with a first sensor, a second sensor, a comparison unit and a position adjuster. The first sensor detects a current absolute value of a positioning angle of a movable part of a bicycle component. The second sensor detects both a movement direction of the movable part and an amount of movement of the movable part. The comparison unit compares the current absolute value of the positioning angle of the movable part to a prestored reference value of the positioning angle of the movable part in response to a component operation command. The position adjuster selectively outputs an adjustment command to the movable part that adjusts the absolute value of the positioning angle of the movable part in accordance with both detected results of the first and second sensors.

1. Field of the Invention
This invention generally relates to a bicycle component position correcting device. More specifically, the present invention relates to a bicycle component position correcting device for correcting a position of electrical controlled bicycle component.
2. Background Information
Bicycling is becoming an increasingly more popular form of recreation as well as a means of transportation. Moreover, bicycling has become a very popular competitive sport for both amateurs and professionals. Whether the bicycle is used for recreation, transportation or competition, the bicycle industry is constantly improving the various components of the bicycle. In particular, the bicycle transmission has been significantly changed over the years.
Derailleur operated bicycle transmissions typically comprise a plurality of sprockets that rotate with another rotating member (e.g., the front crank and/or the rear wheel of the bicycle) and a derailleur that is used to shift a chain among the plurality of sprockets. Conventional derailleur transmissions were manually controlled by a hand operated actuator such as a lever or twist-grip attached to the bicycle handlebar, wherein the derailleur is connected to the actuator by a Bowden cable.
Recently, bicycles have been equipped with electrical components to make riding easier and more enjoyable for the rider. Some bicycles are equipped with electrically controlled shifting systems. In particular, in theses electrically controlled shifting systems, the front and rear derailleurs are provided with motors that move the chain guide to obtain the various gear positions. A common operating parameter is the position of the derailleur relative to the plurality of sprockets. In the past, potentiometers that cooperated with various moving components of the derailleur were used to ascertain the position of the derailleur. Since derailleurs usually have a relatively small range of motion, high precision potentiometers were required for this purpose. That was especially true when the information provided by the potentiometer is used by an electronic device to shift the chain among the plurality of sprockets. Unfortunately, high precision potentiometers are relatively expensive, thus making electronically controlled derailleurs using high precision potentiometers unsuitable for mass production. Inexpensive potentiometers have nonlinear characteristics, and such characteristics vary from one potentiometer to another. Thus, the actual derailleur position is difficult to ascertain with such potentiometers, and the unpredictability from one potentiometer to another also makes derailleurs using such potentiometers unsuitable for mass production. Some examples of electrical controlled bicycle derailleurs are disclosed in U.S. Pat. No. 6,945,888 to Fukuda et al. (assigned to Shimano Inc.) and U.S. Pat. No. 7,306,531 to Ichida et al. (assigned to Shimano Inc.). In these conventional electrically controlled bicycle derailleurs, an analog position sensor and a digital position sensor are used to control the shift position of the derailleur.
In particular, in U.S. Pat. No. 7,306,531, the electrical controlled bicycle derailleur uses an analog position sensor formed by a potentiometer in order to detect a position of the an output shaft of a motor drive train of a motor, and a digital position sensor formed by a shutter wheel and a photo interrupter in order to detect both the rotational direction and the angular position of the output shaft of the motor drive train of the motor.
In generally, with the electrical controlled bicycle derailleur disclosed in U.S. Pat. No. 7,306,531, the analog sensor functions only during a calibration mode in order to detect a top or a low end gear ranges. At each shifting operations, the digital sensor only functions. So, sometimes the derailleur may be out of alignment by hitting something. Since these sensors would not detect if an absolute value of starting or stopping position of the motor is correct or incorrect during shifting, the shifting position can be incorrect.
In view of the above, it will be apparent to those skilled in the art from this disclosure that there exists a need for an improved bicycle derailleur position adjusting device. This invention addresses this need in the art as well as other needs, which will become apparent to those skilled in the art from this disclosure.

Bicycle component position correcting device


Provided are methods of producing 2,5-furandicarboxylic acid (FDCA) from renewable sources such as seaweed, alginate, oligoalginate, pectin, oligopectin, polygalacturonate, galacturonate, and/or oligogalacturonate. The sugars in the renewable sources can be converted into one or more intermediates such as 4-deoxy-L-erythro-5-hexoseulose uronate (DEHU), 4-deoxy-L-threo-5-hexosulose uronate (DTHU), 5-hydroxymethyl furfural (HMF), 2,5-dihydroxymethyl furan (DHMF), and 5-formyl-2-furancarboxylic acid (FFA), which can be converted into FDCA by dehydration and cyclization to produce 5-formyl-2-furancarboxylic acid (FFA), followed by oxidation to produce FDCA. DEHU or DTHU may also be converted into FDCA by oxidation to produce 2,3-dihydroxy-5-oxohexanedioic acid (DOHA), which then undergoes dehydration and cyclization to produce FDCA.

There exists a high demand to produce 2,5-furandicarboxylic acid (FDCA) from renewable sources. FDCA is an attractive alternative to terephthalic acid in producing polyethylene terephthalate (PET), which is used to manufacture polyester fabrics. Additionally, FDCA may also serve as a precursor for adipic acid, which in turn may be used to produce nylons. FDCA may also serve as a precursor for jet fuels (e.g., Jet-A), as well as other diol-, diamine-, or dialdehyde-based chemicals.
Currently, several methods are known for synthesizing FDCA. For example, FDCA may be produced by dehydration of hexose derivatives. Hexose such as fructose or glucose can undergo acid-catalyzed dehydration to form 5-hydroxymethylfurfural (HMF), which is then oxidized to produce FDCA. These reactions, however, are generally not selective and yield a number of side products, such as humin, levulinic acid and formic acid. Furthermore, HMF may undergo polymerization under the oxidation reaction conditions to produce FDCA. Due to these various side product reactions, the yields for FDCA from hexose derivatives are typically quite low.
FDCA may also be produced by oxidation of 2,5-disubstituted furans, and by catalytic conversion of various furan derivatives. Yields for these reactions are also typically low, or may require harsh reaction conditions that are not suitable for commercial production.
Thus, what is needed in the art is a commercially-viable method of producing FDCA from renewable resources, such as seaweed, alginate or pectin.

Methods for preparing 2,5-furandicarboxylic acid

BOARD OF TRUSTEES OF MICHIGAN STATE UNIVERSITY


A long-term memory network method and system for text comprehension. A recurrent neural network can be provided, which includes an external memory module and a long-short term memory unit, wherein said recurrent neural network encodes raw text information into vector representations, forms memories, finds relevant sentences to answer questions, and generates multi-word answers to said questions utilizing the long short term memory unit.

Knowledge extraction from documents such as PubMed articles is crucial to, for example, healthcare analytics tasks such as disease progression modeling and intervention modeling. This problem can be cast into a question answering problem with a fixed set of questions related to the disease or intervention being studied, whose answers can be found in the given article.
Question answering (QA), a challenging problem which requires an ability to understand and analyze the given unstructured text, is one of the core tasks in natural language understanding and processing. Many problems in natural language processing, such as reading comprehension, machine translation, entity recognition, sentiment analysis, and dialogue generation can be cast as question answering problems.
Traditional question answering approaches can be categorized as: IR-based question answering where the question is formulated as a search query and a short text segment is found on the Web or similar corpus for the answer; and knowledge-based question answering, which aims to answer a natural language question by mapping it to a semantic query over a database. The main drawback of traditional question answering approaches is that they cannot fully understand the meaning of the text information.
Traditional question answering approaches, which include IR-based and Knowledge based methods, thus formulate the question as a query over a corpus or a database. They cannot fully comprehend the meaning of the input text before generating the answer. Deep neural network architectures, like end-to-end memory networks, developed recently to understand, memorize, and reason over the text information, require a large amount of data, high supervision, and are limited to single-word answers.
To address these challenges, a Long-Term Memory Network (LTMN) is described herein, which can be configured to incorporate both an external memory (e.g., an external memory module) and a Long Short-Term Memory (LSTM) (e.g., LSTM module) to comprehend the input data, and generate multi-word answers. The LTMN discussed herein can be trained end-to-end using back-propagation and requires minimal supervision.
FIG. 1 illustrates an example of a question-answering task 10, in accordance with an example embodiment. The question-answering task 10 depicted in FIG. 1 includes a number of statements of facts and questions. The sentences in standard black are facts that may be relevant to the questions, the questions 12, 16, 20 are shown bolded, and the correct answers 14, 18, 22 are shown in grey. In order to correctly answer the question "What did Steve Jobs offer Xerox to visit and see their latest technology?", the model should have the ability to recognize that the sentence "After hearing of the pioneering GUI technology being developed at Xerox PARC, Jobs had negotiated a visit to see the Xerox Alto computer and its Smalltalk development tools in exchange for Apple stock option" is a supporting fact and completely understand its meaning. In addition, the model should have the ability to memorize all the facts that have been presented to it until the current time and deduce the answer.
A new class of learning models named Memory Networks (MemNN) was proposed, which use a long-term memory component to store information and an inference component for reasoning. Additionally, a Dynamic Memory Network (DMN) has been proposed for general question answering tasks, which processes input sentences and questions, forms episodic memories, and generates answers. These two approaches are strongly supervised, i.e., only the supporting facts (factoids) are fed to the model as inputs for training the model for each type of question. These methods require a large amount of training data. To tackle this issue, a weakly supervised approach called End-to-End Memory Network (MemN2N) has been proposed. MemN2N is trained end-to-end and uses an attention mechanism to calculate the matching probabilities between the input sentences and questions. The sentences, which match the question with high probability, are used as the factoids for answering the question.
However, this model is capable of generating only single word answers. For example, the answer of the question "According to Andy Hertzfeld, whose idea is the final Mac design closer to?" in FIG. 1 is only one word "Jobs." Since the answers of many questions contain multiple words (for instance, the question labeled 4 in FIG. 1), this model cannot be directly applied to the general question answering tasks.

Long-term memory networks for knowledge extraction from text and publications


A catheter assembly for draining and collecting fluid from a body cavity has a container having an inner containment space defined therewith. An elongate tubular catheter extends longitudinally through the container. A tip member/lubricant reservoir is mounted to the catheter passage opening. A quantity of lubricant is disposed within a tip member/lubricant reservoir and lubricate the catheter as it is extended from the container.

Various self-contained drainage catheter assemblies have been known in the prior art. Such drainage catheter assemblies typically comprise flexible catheters having plastic collection bags connected thereto. The flexible catheter is insertable into a body orifice or passageway (e.g., urethra) such that fluid may drain through the lumen of the catheter and into the attendant collection bag.
Examples of drainage catheter assemblies of the prior art are found in U.S. Pat. Nos. 4,652,259 (O'Neill) and 5,147,341 (Starke et al).
Although the self-contained drainage catheter assemblies of the prior art have become commonly used in clinical practice, especially for intermittent or long term catheterization of the urinary bladder, these prior art-drainage catheter assemblies have been of designs and configurations which are less than optimal for all applications. Accordingly, there remains a need in the art for the development of improved self-contained drainage catheter assemblies which incorporate modified designs and configurations to provide improved operability and ease of use, at least in certain patient types and/or certain clinical situations.


Methods and apparatus, including computer program products, implementing and using techniques for masking and extracting a foreground portion from a background portion of a digital video. An input defining an initial border region is received, which includes a border between a foreground portion and a background portion of an initial digital image in a digital video. A border region for another digital image in the digital video is generated. The initial and automatically generated border regions are used for masking the foreground portion from the background portion in the digital video.

A common task in the manipulation of digital images is to extract one or more foreground objects from a background scene. There are a number of difficulties associated with extracting the object in an accurate way, especially when the background is complex and contains several different colors.
One difficulty is that the object can blend in with the background scene, i.e. A pixel at the edge of an object can have contributions from both the foreground and background and the color of the pixel then becomes a blend of the foreground and background colors. Another difficulty relates to object complexity, i.e. An object border may contain substantial detail that requires tedious effort to identify. Furthermore, there may be combinations of these problems, which for example is the case when the object has hair or fur. The hair or fur shapes are complex, and regions with thin fibers lead to substantial color blending. This makes it difficult to correctly extract the object from the background, since it both has to be masked (i.e. It has to be determined which pixels in the border region belong to the object) and it has to be color decontaminated (i.e. Pixels having colors from both the object and the background need to be "cleaned up" so they only contain colors of the object).
Several conventional systems and methods addressing these difficulties have been developed, but all of them have various problems as will be discussed below.
One conventional method for extracting an object from a background in a still image is to use a software product, such as Adobe® Photoshop® 5.5 and 6.0. Photoshop provides an image extract feature that enables highlighting of a fuzzy border of an object in a still image. Photoshop performs the image extraction, producing both an opacity mask and modified colors which remove the background contamination from the object. This method has been described in "METHOD FOR DETERMINING A BORDER IN A COMPLEX SCENE WITH APPLICATIONS TO IMAGE MASKING," application Ser. No. 09/566,632, filed May 8, 2000, which is incorporated herein by reference. The image extract feature can also be applied to a video clip consisting of a series of digital images. However, the image extract feature requires a manual process of highlighting and extracting the object in each frame in the video clip.
Conventional systems that perform image extraction in digital video use a background having a constant, or almost constant, background color (usually blue). Despite the techniques that have been developed in this area, problems still remain with extracting objects whose edges contain substantial detail or have contributions from both the background and the foreground. Blue spill or blue flare (reflection of blue light from the blue screen on the foreground object), backing shadows on the blue screen (shadows of the foreground object on the backing that one wishes to preserve as part of the foreground object), and backing impurities (departures of a supposedly pure blue backing from pure blue) are examples of problems. An analytical approach to overcome some of these problems was presented by A. Ray Smith and J. F. Blinn in "Blue Screen Matting" (Computer Graphics Proceedings, Annual Conference Series, 1996, 259-268) [hereinafter Smith]. Smith proposed a "triangulation solution" where, in addition to a shot of the object against a blue background, another shot of the object is taken against a background having a second color. However, this method cannot be used for moving foreground objects because the method performs a pixel-by-pixel comparison, and the object therefore needs to be in the exact same position in the two shots. Consequently, even though the proposed method may reduce the problems associated with blue screens, it cannot be used when there are moving objects present in a scene with a more realistic background.
It would thus be desirable to have a method similar to the image extract feature in Adobe® Photoshop® that permits accurate object extractions from non-uniform backgrounds, and that also can be applied to a digital video clip without manually having to mark the object to be extracted in every digital image in the video sequence.

Image extraction from complex scenes in digital video


A washing machine includes an external cabinet, an outer tub installed inside the external cabinet, a spin basket rotatably installed inside the outer tub and a plurality of suspension units for suspending the outer tub with respect to the external cabinet. Each of the suspension units comprises: a suspension bar for connecting the outer tub to the external cabinet; a main damper combined with one end of the suspension bar; and an auxiliary damper combined with the one end of the suspension bar, adjacent to said main damper. Accordingly, vibrations and noises of the outer tub can be reduced effectively.

The present invention relates to a washing machine including an external cabinet, an outer tub installed inside the external cabinet, a spin basket rotatably installed inside the outer tub and a plurality of suspension units for suspending the outer tub with respect to the external cabinet, particularly, to a washing machine designed to effectively reduces.
A washing machine is generally provided with an external cabinet and vibratory system, which being constituted an outer tub and spin basket, suspended inside the external cabinet. The spin basket is rotatably installed in the outer tub for containing the laundry. The outer tub containing the spin basket is suspended inside the external cabinet by a plurality of suspension units.
During washing, rinsing and dehydrating operations of the washing machine, there are generated vibrations due to the rotation of the spin basket. The vibrations are severe especially when the load of the laundry is distributed in the spin basket in an unbalanced way. The vibrations of the spin basket are transmitted to the outer tub, to thereby generate vibrations and noises in the outer tub. Thus, the suspension units of the washing machine are provided with a damper for reducing the vibrations of the outer tub.
FIG. 10 shows a conventional washing machine. As shown in FIG. 10, a vibratory system 3 including an outer tub 4 and a spin basket 5 is elastically suspended inside an external cabinet 2 by a plurality of suspension units 61, each being installed at respective corners of the external cabinet 2. A pulsator (not shown) is installed inside the spin basket 5 to rotate washing water. A power transmission unit 9 having a driving motor (not shown) and a shaft assembly (not shown) is installed below the vibratory system. 3 to rotate the spin basket 5 or the pulsator selectively. The driving motor is operated according to a program stored in a controller (not shown) to make the washing machine perform washing, rinsing and dehydrating operations.
As shown in FIG. 10, the conventional suspension unit 61 includes a suspension bar 63 for connecting the outer tub 4 to the external cabinet 2 and a damper 65 installed at the lower end of the suspension bar 63 for supporting the outer tub 4. The damper 65 has a hollow cylinder (not shown) and a piston (not shown) frictionally slidable inside the cylinder, and the piston is combined with the lower end of the suspension bar 63. A balancer 6 is installed at the upper portion of the spin basket 5 to balance a rotation of the spin basket 5. In the above-described structure, when a vibration is generated to the vibratory system 3, that is, the outer tub 4 due to the rotation of the spin basket 5, the piston slides along up and down inside the cylinder, to thereby reduce the vibrations transmitted to the outer tub 4 by the frictional force between the cylinder and the piston.
The vibration of the vibratory system 3 and a cause thereof will be described in detail with reference to FIG. 11. The vibration of the vibratory system 3 may be divided into a translational movement and a rotational movement. The translational movement includes X-, Y- and Z-directional components, and the rotational movement includes pitching (P) with respect to the X-axis, yawing (Y) with respect to the Y-axis and rolling (R) with respect to the Z-axis, respectively. Here, since the Z-directional component of the translational movement and the rolling (R) with respect to the Z-axis, which are basic movement elements according to the operation of the vibratory system 3, are negligible with respect to the vibration of the vibratory system 3. On the other hand, the X- and Y-directional components of the translational movement and the pitching (P) and yawing (Y) with respect to the X- and Y-axes are unnecessary movement elements, which cause a noise and affect the endurance of the washing machine.
The vibration of the vibratory system 3 may be classified into a vibration generated at an initial stage of the dehydrating operation and a vibration generated at the time of an intermittent dehydration during the washing operation. Here, the vibration at the initial stage of the dehydrating operation is of translational movement, while the vibration at the time of the intermittent dehydration is of the rotational movement. Natural frequencies of the vibratory system with respect to the translational and rotational movements are 1.7 Hz (102 rpm) and 4.5 Hz (270 rpm), respectively.
The vibration at the initial stage of the dehydrating operation is caused by an unbalanced rotation of the spin basket 5. That is, when the load of the laundry is unbalanced inside the spin basket 5, the spin basket 5 rotates at an unbalanced state at a frequency range lower than a rotational frequency of 1.7 Hz. At this time, balancing balls (not shown) and a viscous fluid (not shown) in the balancer 6 may move toward the unbalanced load of the laundry. Accordingly, the spin basket 5 adds its unbalanced rotation so that the vibration of the spin basket 5 is increased to cause the noise.
On the other hand, at the time of the intermittent dehydration, the balancing balls and the viscous fluid start to move when the rotational frequency of the spin basket 5 exceeds 1.7 Hz, and the amplitude of the vibration depends on the location of the balancing balls and the viscous fluid at the frequency of 4.5 Hz. For example, if the balancing balls and the viscous fluid moving independently of the rotation of the spin basket 5 are located at the same side of the unbalanced laundry, the vibration becomes severe.
The vibration of the spin basket 5 which is transmitted to the outer tub 4 is decreased by the suspension unit 61.
However, the conventional suspension unit 61 is generally installed to the washing machine 60, based on a washing capacity of the washing machine 60 and experimental data under a no-load test. Thus, the vibration of the vibratory system 3, that is, of the outer tub 4 which is transmitted from the translational and rotational movements of the spin basket 5 can not be suitably decreased, thereby generating the noise to the washing machine. Also, the vibratory system 3 may collide with the external cabinet 2, to thereby obstruct a normal operation of the washing machine or to cause damage to the components of the washing machine.


A semiconductor memory device includes a first active region formed having a first portion extending laterally and second portion extendedly vertically upward from a central portion of the first portion; a second active region formed spaced from the first active region, the second active region having a third portion extending laterally, fourth and fifth portions extending vertically downwardly at distal end portions of the third portion, and a sixth portion extending vertically downwardly at a central portion of the third portion; a first gate formed extending vertically and overlapping the first portion of the first active region and the third portion of the second active regions; a second gate formed extending vertically and overlapping the first portion of the first active region and the third portion of the second active regions; a third gate formed extending in a direction perpendicular to the first and second gates and overlapping of the fourth and fifth portions of the second active region; and a plurality of contacts spaced apart predetermined distances from the gates.

A cell array scheme of a semiconductor memory device is an important technology determining a specification of the device, together with a structure of a semiconductor layer and a process condition. The semiconductor memory device of such a cell array scheme has a stack-type gate structure, and shares a line contact with electrode lines in a plurality of cells, thereby making it possible to realize high integration. Also, since it is possible to connect in parallel and layer the electrode lines and the contact, it may implement a high function of the device.
However, the semiconductor memory device of the cell array scheme has a problem that wiring density becomes high, and it is difficult to secure an accurate process margin so that yield is deteriorated. Particularly, in a case where a sufficient process margin is not secured in a distance between the contact and a gate line, the yield may be largely deteriorated. However, in this aspect, a study on the process margin is not sufficient, for example, a probe test cannot be performed.


The arithmetic device configured to perform a calculation for controlling a motion of a grasping apparatus that performs work involving a motion of sliding a grasped object includes: an acquisition unit configured to acquire a state variable indicating a state of the grasping apparatus during the work; a storage unit storing a learned neural network that has been learned by receiving a plurality of training data sets composed of a combination of the state variable acquired in advance and correct answer data corresponding to the state variable; an arithmetic unit configured to calculate a target value of each of various actuators related to the work of the grasping apparatus by inputting the state variable to the learned neural network read from the storage unit; and an output unit configured to output the target value of each of the various actuators to the grasping apparatus.

The present disclosure relates to an arithmetic device that performs a calculation for controlling a motion of a grasping apparatus that performs work involving a motion in which a grasping part or a grasped object grasped by the grasping part is brought into contact with a target object to slide the grasped object.
Robots that perform a desired motion by teaching them the motion of a manipulator are known. For example, Japanese Unexamined Patent Application Publication No. 2017-121649 discloses a robot that performs a welding operation by teaching it the motion of a manipulator.

Arithmetic device, control program, machine learner, grasping apparatus, and control method


A resin composition comprising (a) an epoxy compound, (b) a curing agent comprising a polysiloxane resin having a phenolic hydroxyl group on its side chain, and (c) an inorganic filler. The mixing ratio of the inorganic filler should preferably be 10 to 95% by weight based on the entire resin composition.

This invention relates to a resin composition which is excellent in moldability and heat resistance and hence suited for use in encapsulating a semiconductor device, and to a resin-encapsulated semiconductor device which is sealed with the resin composition.
With the current trend to further increasing the integration of semiconductor elements, the miniaturization of various function units of the elements and the enlargement of the elements per se are rapidly progressing now. For the purpose of sealing such semiconductor element with a resin composition, an epoxy resin composition comprising a thermosetting epoxy resin as a main component and a phenol resin as a curing agent has been extensively employed.
For example, a gate array of so-called ASIC (Application Specific IC) or a surface mount type package represented by a standard cell type LSI has been produced by making use of the aforementioned epoxy resin composition as a sealing resin. In the process of mounting these semiconductor devices on a substrate, various processes such as a vapor phase reflow, an infra-violet ray reflow and a solder dipping have been adopted. In this mounting process, the package is exposed to a high temperature in the order of 215 to 260.degree. C., so that a trace of water which has been penetrated into the package is suddenly vaporized, thus often giving rise to the generation of a crack in the sealing resin.
When the crack is extended to the external surface of the sealing resin, the moisture resistance reliability of resin-encapsulated semiconductor device will be damaged raising a serious problem. Moreover, when a crack is generated in the sealing resin, the resin will be caused to swell resulting in the deformation of the package, thus possibly making it difficult to mount the package on a substrate.
Furthermore, when such a package is mounted on a substrate, various problems including a cracking may be brought about even in the interior of the semiconductor element sealed with a resin. For example, PSG (phosphosilicate glass) or SiN (silicon nitride) which is used as a passivation film for a metallic interconnecting wiring layer formed of aluminum for example may be cracked, or the breakage of a gold bonding wire may be caused.
To solve these problems, there have been various demands as described below in the manufacture of a resin-encapsulated semiconductor device in particular of large size, these demands being mainly related to the sealing resin.
(1) The stress to be laid upon inner devices by the sealing resin should be minimized, and the adhesion between the sealing resin and a lead frame or a film such as PSG film, SiN film or polyimide film which is formed on a semiconductor element should be improved.
(2) The sealing resin should be excellent in heat resistance, i.e., sufficiently high in high temperature strength or in high temperature strength under moisture absorption so as to enable it to withstand the mounting temperature of the package. At the same time, the hygroscopicity of the sealing resin should be as low as possible.
On the other hand, in order to minimize the mounting area of a semiconductor chip in view of the popularization of a notebook type personal computer and a potable telephone, a flip chip mounting which enables a bare chip to be directly adhered onto a substrate has been widely adopted. In order to perform this flip chip mounting, a liquid sealing resin which is excellent in reliability, i.e. low in hygroscopicity and excellent in adhesivity is required to be employed.
In view of these demands, there has been developed a method of using a resin composition containing a silicone oil, the addition of which is intended to minimize the stress to be laid upon inner devices by the sealing resin and to improve the adhesion between the sealing resin and a lead frame, etc. However, the addition of silicone oil is accompanied with the problems that the silicone may oozed out to the surface of the molded product, thereby making the product defective in outer appearance or soiling a metal mold.
The conventional epoxy resin composition generally contains an acid anhydride or an amine compound as a curing agent. However, the resin composition containing such a curing agent is high in hygroscopicity, thus making it difficult to obtain a sealing resin having a highly reliable moisture resistance.
As explained above, a resin composition which is not only provided with every kinds of features demanded when it is to be used as a sealing resin, but also capable of exhibiting a low water absorption and avoiding the soiling of a metal mold is not yet available up to date.

Resin composition and semiconductor device employing the same


An improved method and apparatus for adjusting the flow of a diaphragm pump. The thickness of the diaphragm itself is capable of being adjusted. Full stroke output is thereby reduced in inverse proportion to the increased volume occupied by the diaphragm. Adjusting the thickness of the diaphragm while the pump is operating provides a means of varying pump output without stopping the pump for adjustments or modifications.

There are two major divisions into which pumps may be classified; Non-positive displacement and Positive displacement.
Non-positive displacement pumps induce flow by means of a device such as a propeller or centrifugal impeller. Such pumps are well suited for bulk transport but their flow output is difficult to predict as the flow output of non-positive displacement pumps is substantially dependent on fluid and system parameters such as discharge pressure and viscosity.
Positive displacement pumps move fluids by means of a displacement element sealed to retard or altogether prevent fluid leakage. A motive force applied to the displacement element regulates the flow rate. There are several types of such displacement elements or liquid ends, including piston, disc diaphragm, and tubular diaphragm. The liquid output of a positive displacement pump is accurate and predictable over a wide range of conditions, being governed only by the stroke rate and displacement volume of the piston.
The simplest such type is a piston sealed within a cylinder by a packing or sealing ring. Liquid, an incompressible fluid, contained between the housing and piston will discharge from the pump at a rate governed by the rate of the motive force resulting from advancement of the piston into the cylinder. Fluid is delivered at this rate in a manner essentially independent of fluid or discharge conditions.
"Milton Roy Meter Pump Technology," Bulletin 210, page 7 and 8 discloses a variety of disc diaphragm liquid ends, which builds upon the piston pump previously described. These disc diaphragm liquid ends have a diaphragm which acts as a barrier between the piston and the process fluid. The piston's pumping motion is applied to hydraulic fluid which communicates the piston action to the diaphragm and causes the diaphragm to flex back and forth as the piston reciprocates. The diaphragm, in turn acts upon the process fluid.
Typically a disc diaphragm liquid end uses discharge and suction contour plates to restrain the maximum suction and discharge position of the disk diaphragm. The volume contained between the contour plates minus the volume occupied by the diaphragm is generally set to be slightly greater than the volume displaced by the piston at full stroke. The diaphragm thereby oscillates between the confines of the contour plates without contacting said contour plates during normal pump operation. Slight piston leakage over time or other physical changes such as temperature induced expansion of working fluid or starved suction operation may cause the diaphragm to contact the suction or discharge contour plates.
Contact with the discharge contour plate, prior to completion of the piston discharge stroke, causes a pressure increase in the working fluid. The pressure increase is a result of the constraint on the discharge motion by the contour plate while the piston continues to force the diaphragm in the discharge direction. This pressure increase causes a relief valve to open, effectively bypassing the piston working fluid back to the supply reservoir. In a similar manner, contact with the suction contour plate prior to completion of a suction stroke causes a decrease in working fluid pressure opening the vacuum breaker relief valve. Contour plates serve to both describe the maximum allowable volume delivered per stroke and to keep the diaphragm synchronized with the piston.
It is possible to replace the piston and working fluid with an external source of air pressure and vacuum and a suitable valving arrangement. Here air pressure is directed to the diaphragm to effect a discharge stroke. The valve is switched to vent the air pressure and direct a vacuum to the diaphragm initiating a suction stroke. Here the delivered volume is equal to the volume captured between the contour plates minus the thickness of the diaphragm so long as the valve is maintained in pressure or vacuum for sufficient time to assure full contact with each respective plate.
"Milton Roy Metering Pump Technology," Bulletin 210, page 7 discloses a tubular diaphragm liquid end, which places two different flexible, sealed members between the piston and the process fluid. In this liquid end, the piston forces hydraulic fluid to flex a disc diaphragm. The disc diaphragm then transfers the pumping action to an intermediate fluid which surrounds an elastomeric tubular diaphragm, through which the process fluid passes. A tubular diaphragm liquid end has been primarily used for pumping slurries and viscous applications.
These types of positive displacement pumps use a piston, and the more advanced liquid ends also use some sort of diaphragm. The flow rates for such positive displacement pumps are generally adjusted by modulating the stroking rate and the stroke length of the piston. Two patents which disclose methods used to adjust the stroke length of a displacement element are U.S. Pat. No. 2,856,857 to Salfrank and U.S. Pat. No. 3,769,879 to Loftquist. A variable speed motor is a common method of adjusting stroking rate. In a diaphragm type liquid end, the stroke length has also been modified by bypassing the working fluid for a portion of the piston stroke to remove motive force from the diaphragm. Bypassing is an effective and inexpensive stroke adjustment means but imposes shock on the mechanism and process fluid plumbing. These mechanical stroke adjustments tend to be complex, expensive and difficult to economically miniaturize.

Method and apparatus for diaphragm pumping with adjustable flow


Devices for restraining tubular segments and methods for storing and accessing tubular segments may include a frame arrangement that has a plurality of parallel cradles for holding tubular segments and movable restraining handles for securing the tubular segments. A spring retention assembly may also be provided that has a spring force to hold the restraining handles against the tubular segments. A vehicle can be equipped to have a device for storing and accessing tubular segments, wherein the device is movable between a storage position and an access position.

Underground storm sewer systems often require periodic maintenance or service. One such instance is when a pipeline becomes clogged with debris, such as leaves, and ceases to function. To clear the obstruction, mobile vehicles have been developed which can vacuum the debris out of the piping system and into a debris collection tank. Generally, a variety of hoses, tubes and pipes are utilized to ensure vacuuming occurs at an appropriate location for debris removal, such as the bottom of a catch basin. These types of tubes may also be used to assist in debris removal from a hard surface, such as a street or parking lot. When these hoses, tubes and pipes are not in use, they are usually stored somewhere on the exterior of the vehicle. To date various storage methods have been used for this purpose such as racks, storage tubes and rotatable frames.


An optical pickup actuator includes focus coils, track coils, and tilt coils disposed on opposite sides of a bobbin to drive the bobbin in a focus direction, a track direction, and a tilt direction and leaves the other opposite sides of the bobbin as empty sides on which the focus, track, and tilt coils are not disposed. The optical pickup actuator includes a base, a bobbin, a holder, and a magnetic driver. The bobbin is movably disposed on the base since supporting units support the bobbin above the base. The holder is disposed on one side of the base and connected to one ends of the supporting units. The magnetic driver has the focus coils driving the bobbin in the focus direction, the track coils driving the bobbin in the track direction, the tilt coils driving the bobbin in a tilt direction, and magnets installed to face the focus coils, the track coils, and the tilt coils. Since the other opposite sides are not mounted with the focus, track, and tilt coils, wires of the support units can easily be installed on the other opposite sides of the bobbin.

1. Field of the Invention
The present invention relates to an optical pickup actuator, and more particularly, to an optical pickup actuator having a bobbin having first opposite sides and second opposite sides, focus coils, track coils, and tilt coils disposed on the first opposite sides of the bobbin, to drive the bobbin in a focus direction, a track direction, and a tilt direction, and a support disposed on the second opposite sides of the bobbin to support the bobbin on the optical pickup actuator.
2. Description of the Related Art
In general, optical pickup actuators have been used in optical recording/reproducing devices and control an optical pickup to move in a non-contact way in a radial direction of a recording medium (disc) mounted on a turntable to record/reproduce data on/from the optical medium.
The optical pickup includes an objective lens condensing light emitted from a light source to form a light spot on the optical medium and an actuator controlling the objective lens in a track direction, a focus direction, and a tilt direction to accurately position the light spot on the optical medium.
The optical pickup actuator includes a 2-axis driving actuator driving the objective lens in the track and focus directions. However, as the number of numeral apertures of the objective lens increases for high density recording and a wavelength of a laser beam is reduced, a tilt margin of the optical pickup actuator decreases. To compensate for this, a 3-axis or 4-axis driving actuator driving in the tilt direction as well as the track and focus directions is required. The 3-axis driving actuator allows the objective lens to move in the focus, track, and tilt radial directions. The 4-axis actuator allows the objective lens to move in the focus, track, tilt radial, and tilt tangential directions. In FIG. 1, the focus, track, tilt radial, and tilt tangential directions are represented as L–L′, M–M′, N, and O, respectively.
Referring to FIG. 1, a conventional optical pickup actuator includes a base 100, a holder 103 fixed on the base 100, a bobbin 107 having an objective lens 105, wires 109 connecting the holder 103 to the bobbin 107, and a magnetic driver (not shown) driving the bobbin 107 in the track and focus directions or the tilt direction.
As shown in FIGS. 1, 2A and 2B, the magnetic driver includes focus coils 110 and tilt coils 112 both forming two pairs, track coils 115, first magnets 117, and second magnets 119. The focus coils 110 and the tilt coils 112 are disposed on first opposite sides 107a of the bobbin 107. The track coils 115 are disposed on second opposite sides 107b of the bobbin 107. The first magnets 117 and the second magnets 119 are installed on the base 100 to be spaced-apart from the focus coils 110, the tilt coils 112, and the track coils 115. Outer yokes 118 and 120 are installed on the base 100 and support corresponding ones of the first magnets 117 and the second magnets 119. Inner yokes 122 are installed on the base 100 to correspond to the first magnets 117 to guide the bobbin 107. The outer and inner yokes 118, 120; and 122 induce a magnetic field created by the first and second magnets 117 and 119 in a desired direction.
The wires 109 are soldered on two second opposite sides of the bobbin 107 and coupled to the holder 103 to electrically connect the magnetic driver to a circuit unit (not shown), which supplies current to the magnetic driver having the focus coils 110, the tilt coils 112, and the track coils 115.
FIG. 2A schematically shows a polarity of the first magnets 117 and directions of the current to observe a relationship of interaction forces between the focus and tilt coils 110 and 112, and the first magnets 117. Here, the focus coils 110 on two first opposite sides 107a of the bobbin 107 receive a focusing force Ff] according to Fleming's left-hand law so that the bobbin 107 moves in the focus direction L. The focus coils 110 receive an opposite focusing force in an opposite focus direction L′ if the direction of the supplied current is changed.
The tilt coils 112 form pairs with the focus coils 110 on the first opposite sides 107a of the bobbin 107 to interact with the first magnets 117. Here, if the tilt coils 112 on the first opposite sides 107a of the bobbin 107 are supplied with the current having the same intensity and opposite direction as those of the focus coils 110, the tilt coils 112 receive one of tilting forces Fti with opposite directions. Thus, the bobbin 107 is driven in the tilt direction and particularly in the radial tilt direction N.
FIG. 2B schematically shows the polarity of the second magnets 117 and the directions of the current to observe the relationship of the interaction forces between the track coils 115 and the second magnets 117. The directions and magnitudes of the interaction forces between magnets and coils are determined based on Fleming's left-hand law. Thus, the track coils 115 on the second opposite sides 107b of the bobbin 107 receive a tracking force Ft in the track direction due to the second magnets 119 so that the bobbin 107 moves in the track direction M. Here, if the direction of the supplied current is changed, the track coils 115 receive an opposite tracking force in the opposite track direction M′.
The wires 109 of the optical pickup actuator generally include six wires driving the bobbin 107 in the focus, track, and tilt directions. The 4-axis driving actuator may require more wires. However, since the optical pickup actuator is very small in size, there is not enough space to install the wires 109 on the bobbin 107 if the four first and second opposite sides 107a, 107b of the bobbin 107 are used to install the focus coils, track coils; and tilt coils. Also, if the number of wires 109 increases, it is difficult to adhere the wires to corresponding sides 107a, 107b of the bobbin 107 in such a narrow space. As a result, the poor adhesion of the wires 109 on the bobbin 107 increases.
Moreover, if the four first and second opposite sides 107a, 107b of the bobbin 107 are all used to be mounted with the focus, tilt, and track coils 110, 112, and 115, a connection between the focus, tilt, and track coils 110, 112, and 115 becomes complicated. Also, since each of the focus, tilt, and track coils 110,112, and 115 requires a magnet, the number of parts increases, and thus, productivity of the optical pick actuator decreases. Also, since the first magnets 117 for the focus coils 110 disposed on the first opposite sides of the bobbin 107 may interfere with a spindle motor (not shown) rotating the optical medium, the control of the spindle motor can be obstructed.

Optical pickup actuator with a magnetic driver having focus, track and tilt coils


A moving image compression (or encoding) device including: a hardware processing section which compresses moving image data by hardware; a data storage section which stores the moving image data processed by the hardware processing section; and a software processing section which compresses the moving image data from the data storage section by software. The hardware processing section includes a plurality of processing sections which perform processing including a discrete cosine transform and quantization of the moving image data. The software processing section performs variable-length coding of the quantized moving image data.

The present invention relates to a decompression device which decompresses a moving image compressed by Moving Picture Experts Group (MPEG) technology or the like, and an image display device using the same.
In a conventional MPEG-4 compression (encode)/decompression (decode) device, the entire encode/decode processing is performed by hardware.
In the case where the entire encode/decode processing is performed by hardware, since the circuit scale is inevitably increased, reduction of the IC size is hindered. This makes it impossible to satisfy a demand for reduction of the size of a portable instrument such as a portable telephone.
In the case where the entire encode/decode processing is performed by software, the load imposed on the CPU increases. Therefore, the time necessary for the CPU to perform other processing is limited, whereby the performance of the instrument cannot be realized. Moreover, power consumption is increased due to an increase in operation time of the CPU. Therefore, a demand for reduction of power consumption of a portable instrument such as a portable telephone in order to maintain battery life cannot be satisfied.

Compressed moving image decompression device and image display device using the same