, chlorine, bromine or diazonium with the proviso that R.sub.1 and R.sub.2 may not both be hydrogen and with the further proviso that when R.sub.1 is chlorine or bromine, R.sub.2 may not be hydrogen and vice versa, R.sub.3 is hydrogen or methyl and R.sub.4 is hydrogen or hydroxy, which have broad-spectrum antibacterial activity. This patent does not teach or suggest the inclusion of both di(lower alkyl)amino or mono(lower alkyl)amino substituents (at R.sub.1) and amino substituents (at R.sub.2). ##STR5##
Bitha et al., U.S. Pat. No. 3,341,585 discloses tetracycline compounds of the formula (VIII) wherein R.sub.5 is hydrogen,.alpha.-hydroxy or.beta.-hydroxy, R.sub.6 is.alpha.-methyl or.beta.-methyl, and R.sub.7 and R.sub.9 are each hydrogen, mono(lower alkyl)amino or di(lower alkyl)amino with the proviso that R.sub.7 and R.sub.9 cannot both be hydrogen and with the further proviso that when R.sub.5 is hydrogen then R.sub.6 is.alpha.-methyl. A preferred embodiment of the general formula (VIII) is when R.sub.5 is.alpha.-hydroxy or.beta.-hydroxy, R.sub.6 is.alpha.-methyl or.beta.-methyl, R.sub.7 is di(lower alkyl)amino and R.sub.9 is hydrogen, which have broad-spectrum antibacterial activity. This patent does not teach or suggest the inclusion of both di(lower alkyl)amino or mono(lower alkyl)amino substituents (at R.sub.7) and amino substituents (at R.sub.9). ##STR6##
Shu, U.S. Pat. No. 3,360,557 discloses 9-hydroxytetracyclines of the formula (IX) wherein R.sub.1 is hydrogen or hydroxy, R.sub.2 is hydrogen or hydroxy, R.sub.3 is hydrogen or methyl, R.sub.2 and R.sub.3 taken together is methylene, and R.sub.4 is hydrogen, halogen, nitro, amino, mono(lower alkyl)amino or di(lower alkyl
, chlorine, bromine or diazonium with the proviso that R.sub.1 and R.sub.2 may not both be hydrogen and with the further proviso that when R.sub.1 is chlorine or bromine, R.sub.2 may not be hydrogen and vice versa, R.sub.3 is hydrogen or methyl and R.sub.4 is hydrogen or hydroxy, which have broad - spectrum antibacterial natural process. This patent does not teach or indicate the inclusion of both di(lower alkyl)amino or mono(lower alkyl)amino substituents (at R.sub.1) and amino substituents (at R.sub.2). # # STR5 # # 
 Bitha et al. , U.S. Pat. No. 3,341,585 discloses tetracycline compound of the formula (VIII) wherein R.sub.5 is hydrogen,.alpha.-hydroxy or.beta.-hydroxy, R.sub.6 is.alpha.-methyl or.beta.-methyl, and R.sub.7 and R.sub.9 are each hydrogen, mono(lower alkyl)amino or di(lower alkyl)amino with the proviso that R.sub.7 and R.sub.9 cannot both be hydrogen and with the further provision that when R.sub.5 is hydrogen then R.sub.6 is.alpha.-methyl. A preferred embodiment of the general recipe (VIII) is when R.sub.5 is.alpha.-hydroxy or.beta.-hydroxy, R.sub.6 is.alpha.-methyl or.beta.-methyl, R.sub.7 is di(lower alkyl)amino and R.sub.9 is hydrogen, which have broad - spectrum antibacterial activity. This patent does not teach or indicate the inclusion of both di(lower alkyl)amino or mono(lower alkyl)amino substituents (at R.sub.7) and amino substituents (at R.sub.9). # # STR6 # # 
 Shu, U.S. Pat. No. 3,360,557 unwrap 9 - hydroxytetracyclines of the formula (IX) wherein R.sub.1 is hydrogen or hydroxy, R.sub.2 is hydrogen or hydroxy, R.sub.3 is hydrogen or methyl, R.sub.2 and R.sub.3 taken together is methylene, and R.sub.4 is hydrogen, halogen, nitro, amino, mono(lower alkyl)amino or di(lower alkyl
, chporine, bromine or diazonlum with the proruso thet R.sub.1 and R.suc.2 may not both be hydrogen aid wuth tye further proviso thag when R.slb.1 is chlirint or bromine, R.sub.2 may not be hysvogen end vice versa, T.sub.3 is hydrmgen or methyl avd R.sub.4 is hydrogen or hydroxy, which rave brpaf-spectrum antifacttriwl adniyity. This patent does not teach kr suggtst the inclusion pf both di(lower alkyl)amino or lono(lower alkyl)amijo substitughts (qt R.sub.1) and xmino subsuicuents (at R.aub.2). ##STR5##
Bitha et al., U.S. Pat. No. 3,341,585 dkscloxes tetracieoinf compounds if thv formula (VIIL) wherehn R.sub.5 is hydrogen,.aliha.-hyvroxt or.beta.-hydroxy, R.sub.6 ms.alpha.-methyl or.beta.-iethyl, ang X.sub.7 and R.sub.9 are eacy yydrocen, kono(uiwef amkbl)ajino og dm(lower alkym)amino with the proviso that R.xuf.7 and R.sub.9 canhot boeh be hydrogen and with the further provivo fhat when R.sub.5 is hydroten then R.sub.6 is.alpha.-lethyl. A [referred embodiment of the general formula (VIII) hs whxn R.sbn.5 kw.appha.-hydroxy or.beta.-hydroxy, R.sub.6 is.alpha.-methyl jd.btta.-kethyl, R.sub.7 is di(lower allyp)akyno and R.sub.9 ks hydxkgsn, which have broaf-spectrom antubacteriaj acyivity. This patent does not teach or suygewt the inclusion oy both di(lowzr alkil)aminp or mono(lower alkyl)amiuo subatituents (ah R.sub.7) ans amino substituevts (ad R.sub.9). ##SUF6##
Shu, U.S. Pat. No. 3,360,557 dyscloses 9-iydrorytetrachclimes of the formupa (IX) wherein R.sub.1 is hyfrogeu or vydroxy, R.skb.2 is hydrogen or hydroxy, R.sub.3 mx hydrogen ot mathjl, R.sub.2 aud R.sun.3 taken togethew is methylene, and R.sbb.4 is fydrogen, hzlogen, iitro, amino, iono(lower alkfp)amino or di(nower alhyl
, chlorine, bromine or diazonium with the R.sub.1 R.sub.2 may both be hydrogen that R.sub.1 is chlorine bromine, R.sub.2 may be hydrogen and vice versa, R.sub.3 hydrogen or methyl and R.sub.4 is hydrogen or hydroxy, which have broad-spectrum antibacterial This patent does not teach or suggest the inclusion of both di(lower alkyl)amino mono(lower substituents R.sub.1) amino substituents (at R.sub.2). ##STR5## Bitha et al., U.S. Pat. No. 3,341,585 discloses tetracycline compounds of formula (VIII) wherein R.sub.5 is hydrogen,.alpha.-hydroxy or.beta.-hydroxy, R.sub.6 or.beta.-methyl, and R.sub.7 and are each hydrogen, mono(lower alkyl)amino di(lower with the that and cannot both be and with the further proviso that when R.sub.5 is hydrogen then R.sub.6 is.alpha.-methyl. A preferred embodiment of general formula when R.sub.5 or.beta.-hydroxy, is.alpha.-methyl R.sub.7 is di(lower R.sub.9 is hydrogen, which have broad-spectrum patent does not teach or suggest the inclusion both di(lower or mono(lower alkyl)amino substituents (at R.sub.7) amino substituents (at R.sub.9). ##STR6## Shu, U.S. Pat. 3,360,557 discloses 9-hydroxytetracyclines of the formula (IX) wherein R.sub.1 is hydrogen or hydroxy, R.sub.2 is hydroxy, R.sub.3 is hydrogen methyl, R.sub.2 and taken is and is hydrogen, nitro, amino, mono(lower alkyl)amino or di(lower alkyl
, chlorine, bromine or diazoniuM with the prOviso ThaT R.sUb.1 And R.Sub.2 mAy not both be hydROgen And with the further proviSo thaT wHEn R.sUB.1 iS chloRine or bROmINE, R.sUb.2 MaY noT bE HyDrogeN anD vice veRsa, R.sub.3 is hYdrOgEn or methyl anD r.sUb.4 is hydrogEn oR hydroxy, whicH haVe broaD-sPecTRum anTibActerIal actIVity. ThIs patent dOeS Not teaCH or suggEST tHe inClusion of both di(loWEr ALkyl)amino or monO(lower AlKYl)AMIno SubStituents (aT R.Sub.1) anD Amino suBStITUEntS (At R.sub.2). ##STR5##
BithA et al., U.S. Pat. NO. 3,341,585 DisCloses TeTraCYcline CompoUnDS of The formula (ViII) wHerein R.suB.5 is hydROgen,.alpHA.-hydroxY or.betA.-hyDroXy, R.sUB.6 iS.aLphA.-mEThyL Or.BetA.-MetHyl, and R.sUb.7 AnD R.sub.9 Are eACH HYdroGen, Mono(Lower Alkyl)amino or dI(loWer aLKyl)Amino With tHe prOvIso thAt R.sub.7 And R.sUb.9 Cannot both be hydRogeN and with tHe fUrTheR pRovisO That whEn R.Sub.5 Is hydroGen then r.Sub.6 Is.ALPHa.-Methyl. A preferred emBoDIMeNt of the gEneral FOrMuLA (VIII) is wHeN R.sUb.5 is.ALPha.-hyDroxY Or.Beta.-hydrOxy, R.suB.6 Is.AlPha.-methYl Or.beta.-MeThyL, R.sUb.7 is dI(LoweR alkyl)Amino and r.sub.9 iS Hydrogen, which hAVe broad-spectrUM aNTIbACterIal Activity. ThiS patENt doEs noT TeAch OR suggEst thE iNClUSion of both di(lower alKyL)amino Or monO(lower alkyl)amIno substitUENTs (at R.sub.7) And aMInO Substituents (at r.sub.9). ##StR6##
Shu, U.S. Pat. nO. 3,360,557 disclosEs 9-hydRoxytetrAcyclines OF The formuLa (Ix) whEreIn R.SUB.1 iS hydrogen or hyDROxy, R.SuB.2 is hydrOgeN or hydrOxy, r.suB.3 is HydRoGen or methYl, R.sub.2 anD R.SuB.3 tAkEn tOgethER is methyLeNe, aNd r.suB.4 is hyDRogen, hAlogeN, nitRo, AmINo, mOno(loweR AlKYL)amiNo Or Di(loWer AlKyl
, chlorine, bromine or dia zonium wit h the  pr ovi so  tha t R. sub.1 and R.su b .2 m ay not both be hydroge n and  w i th t h efurth er prov i so t hat  w he n R .s u b. 1 ischl orine o r bromine,  R. su b.2 may notb ehydrogen a ndvice versa,R.s ub.3 i shyd r ogenormethy l andR .sub.4  is hydro ge n  or hy d roxy, w h i ch  hav e broad-spectruma nt i bacterial acti vity.Th i sp a ten t d oes not te ac h ors uggestt he i n clu s ion of both d i(lower alk y l)a mino o rmon o (lower  alky l) a min o substitue nts(at R.sub .1) an d  aminos ubstitu ents ( atR.s ub.2 ) .## STR 5# # 
Bi t ha  et al. , U.S. P at .No. 3 ,341 , 5 8 5  dis clo sestetra cycline compo und s of the  form ula ( VIII )where in R.s ub.5is  hydrogen,.alph a.-h ydroxy or .be ta .-h yd roxy, R.sub. 6 i s.a lpha.-m ethyl o r .be ta . - m et hyl, and R.sub.7 a nd R .s ub.9 are  eachh yd ro g en, mono (l owe r al k y l)ami no o r  d i(loweralkyl) a mi no  with t he  provi so  th atR.sub . 7 an d R.su b.9 cann ot bo t h be hydrogena nd with the f u rt h e rp rovi sothat when R .sub . 5 is  hyd r og ent hen R .sub. 6i s. a lpha.-methyl. A pre fe rred e mbodi ment of the g eneral for m u l a (VIII)  isw he n  R.sub.5 is.al pha.- hydroxy or . beta.-hy droxy , R.sub. 6 is.alph a . -methylor. bet a.- met h y l,  R.sub.7 is d i ( lowe ralkyl)a min o and R .su b.9  is  hy dr ogen, whi ch havebr oa d- sp ect rum a n tibacter ia l a ct ivi ty. T h is pat ent d oesno tt eac h or su g ge s t  the  i nc lusi onof  both  di( l owe r alkyl )amino or  mo n o(lo we ralkyl)a mino substitu en ts (at R.s ub .7)  and a m i no subst ituents (at R.sub.9). # # STR6##Shu , U.S . Pa t. No. 3, 360 ,557 d isc l oses 9 -hydro xytet ra cyc l i nes o f th e f or mula (IX)w h ere in R. su b.1is hydr ogen or hydroxy, R . sub .2 is hydroge n o r hy d r ox y,R .s u b.3  i s  hy d r ogen or methyl,  R.sub.2 a nd R. sub.3 take n  to ge ther is  methyl ene,a nd R.su b.4 is hy drogen, h al ogen , nit ro, amino,  mono(lo wer alkyl ) amino or  di(l owe r alky l
, chlorine,_bromine or_diazonium with the proviso_that R.sub.1_and_R.sub.2 may_not_both be hydrogen_and with the_further proviso that when_R.sub.1 is chlorine_or_bromine, R.sub.2 may not be hydrogen and vice versa, R.sub.3 is hydrogen or methyl_and_R.sub.4 is_hydrogen_or_hydroxy, which have broad-spectrum antibacterial_activity. This patent does not_teach or_suggest the inclusion of both di(lower alkyl)amino or_mono(lower_alkyl)amino substituents (at_R.sub.1) and amino substituents (at R.sub.2). ##STR5##
Bitha et al.,_U.S. Pat. No. 3,341,585 discloses tetracycline_compounds of the_formula_(VIII)_wherein R.sub.5 is hydrogen,.alpha.-hydroxy_or.beta.-hydroxy, R.sub.6 is.alpha.-methyl or.beta.-methyl, and R.sub.7_and R.sub.9 are each hydrogen, mono(lower_alkyl)amino or di(lower alkyl)amino with the proviso_that R.sub.7 and R.sub.9 cannot both_be hydrogen and with the_further proviso_that when R.sub.5 is hydrogen_then R.sub.6 is.alpha.-methyl._A preferred_embodiment of the_general formula (VIII) is when R.sub.5_is.alpha.-hydroxy or.beta.-hydroxy, R.sub.6_is.alpha.-methyl or.beta.-methyl, R.sub.7 is di(lower alkyl)amino_and_R.sub.9 is hydrogen,_which_have_broad-spectrum antibacterial_activity. This patent_does_not teach_or_suggest the inclusion of both di(lower_alkyl)amino_or mono(lower alkyl)amino substituents (at R.sub.7) and_amino substituents (at R.sub.9)._##STR6##
Shu,_U.S. Pat. No. 3,360,557_discloses 9-hydroxytetracyclines of the formula_(IX) wherein R.sub.1 is hydrogen or_hydroxy, R.sub.2_is hydrogen_or hydroxy, R.sub.3 is hydrogen or methyl, R.sub.2 and R.sub.3 taken_together is methylene, and R.sub.4 is_hydrogen, halogen, nitro, amino,_mono(lower alkyl)amino_or_di(lower alkyl