US 5,541,206 AGranted

Retroviral protease inhibiting compounds

AssigneeAbbott Laboratories

InventorsDale J. Kempf, Daniel W. Norbeck, Hing Leung Sham, Chen Zhao

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Abstract

A retroviral protease inhibiting compound of the formula: ##STR1## is disclosed.

Claims19

Dependent claims

A compound of the formula:

##STR18## wherein R.sub.1 is monosubstituted thiazolyl or monosubstituted oxazolyl wherein the substituent is selected from (i) C.sub.1 -C.sub.6 -loweralkyl, (ii) C.sub.2 -C.sub.6 -loweralkenyl, (iii) C.sub.3 -C.sub.7 -cycloalkyl, (iv) C.sub.3 -C.sub.7 -cycloalkyl-C.sub.1 -C.sub.6 -alkyl, (v) C.sub.5 -C.sub.7 -cycloalkenyl, (vi) C.sub.5 -C.sub.7 -cycloalkyl-C.sub.1 -C.sub.6 -alkyl, (vii) C.sub.1 -C.sub.6 -alkoxy-C.sub.1 -C.sub.6 -alkyl or benzyloxy-C.sub.1 -C.sub.6 -alkyl, (viii) C.sub.1 -C.sub.6 -thioalkoxy-C.sub.1 -C.sub.6 -alkyl or benzyl- S--C.sub.1 -C.sub.6 -alkyl, (ix) C.sub.1 -C.sub.6 -alkylamino, (x) di-C.sub.1 -C.sub.6 -alkylamino, (xi) phenyl wherein the phenyl ring is unsubstituted or substituted with a substituent selected from halo, C.sub.1 -C.sub.6 -loweralkyl, hydroxy, C.sub.1 -C.sub.6 -alkoxy, benzyloxy, C.sub.1 -C.sub.6 -thioalkoxy and benzyl-S--, (xii) phenyl-C.sub.1 -C.sub.6 -alkyl wherein the phenyl ring is unsubstituted or substituted as defined above, (xiii) di-C.sub.1 -C.sub.6 -alkylamino-C.sub.1 -C.sub.6 -alkyl, (xiv) C.sub.1 -C.sub.6 -alkoxy or benzyloxy and (xv) C.sub.1 -C.sub.6 -thioalkoxy or benzyl-S--;
n is 1,2or 3;
R.sub.2 is hydrogen or C.sub.1 -C.sub.6 -loweralkyl;
R.sub.3 is C.sub.1 -C.sub.6 -loweralkyl;
R.sub.4 and R.sub.4a are independently selected from phenyl and substituted phenyl wherein the phenyl ring is substituted with a substituent selected from (i) halo, (ii) C.sub.1 -C.sub.6 -loweralkyl, (iii) hydroxy, (iv) C.sub.1 -C.sub.6 -alkoxy or benzyloxy and (v) C.sub.1 -C.sub.6 -thioalkoxy or benzyl-S--;
R.sub.6 is hydrogen or C.sub.1 -C.sub.6 -loweralkyl;
R.sub.7 is thiazolyl or oxazolyl wherein the thiazolyl or oxazolyl ring is unsubstituted or substituted with C.sub.1 -C.sub.6 -loweralkyl;
X is hydrogen and Y is --OH ;
and
Z is absent, --O--, --S--, --CH.sub.2 -- or --N(R.sub.8)-- wherein R.sub.8 is C.sub.1 -C.sub.6 -loweralkyl, C.sub.3 -C.sub.7 -cycloalkyl, --OH or --NHR.sub.8a wherein R.sub.8a is hydrogen, C.sub.1 -C.sub.6 -loweralkyl or an N-protecting group selected from the group consisting of formyl, acetyl, propionyl, pivaloyl, t-butylacetyl, 2-chloroacetyl, 2-bromoacetyl, trifluoroacetyl, trichloroacetyl, phthalyl, o-nitrophenoxyacetyl, .alpha.-chlorobutyryl, benzoyl, 4-chlorobenzoyl, 4-bromobenzoyl, 4-nitrobenzoyl, benzenesulfonyl, p-toluenesulfonyl, benzyloxycarbonyl, p-chlorobenzyloxycarbonyl, p-methoxybenzyloxycarbonyl, p-nitrobenzyloxycarbonyl, 2-nitrobenzyloxycarbonyl, p-bromobenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, 3,5-dimethoxybenzyloxycarbonyl, 2,4-dimethoxybenzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 2-nitro-4,5-dimethoxybenzyloxycarbonyl, 3,4,5-trimethoxybenzyloxycarbonyl, 1-(p-biphenylyl)-1-methylethoxycarbonyl, .alpha..alpha.-dimethyl-3,5-dimet hoxybenzyloxycarbonyl, benzhydryloxycarbonyl, t-butyloxycarbonyl, diisopropylmethoxycarbonyl, isopropyloxycarbonyl, ethoxycarbonyl, methoxycarbonyl, allyloxycarbonyl, 2,2,2,-trichloroethoxycarbonyl, phenoxycarbonyl, 4-nitrophenoxycarbonyl, fluorenyl-9-methoxycarbonyl, cyclopentyloxycarbonyl, adamantyloxycarbonyl, cyclohexyloxycarbonyl, phenylthiocarbonyl, benzyl, triphenylmethyl, benzyloxymethyl and trimethylsilyl;
or a pharmaceutically acceptable salt thereof.

8 more elements

A compound of the formula:

##STR19## wherein R.sub.1 is monosubstituted thiazolyl or monosubstituted oxazolyl wherein the substituent is selected from (i) C.sub.1 -C.sub.6 -loweralkyl, (ii) C.sub.2 -C.sub.6 -loweralkenyl, (iii) C.sub.3 -C.sub.7 -cycloalkyl, (iv) C.sub.3 -C.sub.7 -cycloalkyl-C.sub.1 -C.sub.6 -alkyl, (v) C.sub.5 -C.sub.7 -cycloalkenyl, (vi) C.sub.5 -C.sub.7 -cycloalkenyl-C.sub.1 -C.sub.6 -alkyl, (vii) C.sub.1 -C.sub.6 -alkoxy -C.sub.1 -C.sub.6 -alkyl or benzyloxy-C.sub.1 -C.sub.6 -alkyl, (viii) C.sub.1 -C.sub.6 -thioalkoxy-C.sub.1 -C.sub.6 -alkyl or benzyl-S--C.sub.1 -C.sub.6 -alkyl, (ix) C.sub.1 -C.sub.6 -alkylamino, (x) di-C.sub.1 -C.sub.6 -alkylamino, (xi) phenyl wherein the phenyl ring is unsubstituted or substituted with a substituent selected from halo, C.sub.1 -C.sub.6 -loweralkyl, hydroxy, C.sub.1 -C.sub.6 -alkoxy, benzyloxy, C.sub.1 -C.sub.6 -thioalkoxy and benzyl-S--, (xii) phenyl -C.sub.1 -C.sub.6 -alkyl wherein the phenyl ring is unsubstituted or substituted as defined above, (xiii) di-C.sub.1 -C.sub.6 -alkylamino -C.sub.1 -C.sub.6 -alkyl, (xiv) C.sub.1 -C.sub.6 -alkoxy or benzyloxy and (xv) C.sub.1 -C.sub.6 -thioalkoxy or benzyl-S--;
n is 1;
R.sub.2 is hydrogen or C.sub.1 -C.sub.6 -loweralkyl;
R.sub.3 is C.sub.1 -C.sub.6 -loweralkyl;
R.sub.4 is phenyl wherein the phenyl ring is unsubstituted or substituted with a substituent selected from (i) halo, (ii) C.sub.1 -C.sub.6 -loweralkyl, (iii) hydroxy, (iv) C.sub.1 -C.sub.6 -alkoxy or benzyloxy and (v) C.sub.1 -C.sub.6 -thioalkoxy or benzyl-S--:
R.sub.5 is hydrogen, halo, C.sub.1 -C.sub.6 -loweralkyl, hydroxy, C.sub.1 -C.sub.6 -alkoxy, benzyloxy, C.sub.1 -C.sub.6 -thioalkoxy or benzyl-S--;
R.sub.6 is hydrogen or C.sub.1 -C.sub.6 -loweralkyl;
R.sub.7 is thiazolyl or oxazolyl wherein the thiazolyl or oxazolyl ring is unsubstituted or substituted with C.sub.1 -C.sub.6 -loweralkyl;
X is hydrogen and Y is --OH;
Z is absent, --O--, --S--, --CH.sub.2 -- or --N(R.sub.8)-wherein R.sub.8 is C.sub.1 -C.sub.6 -loweralkyl, C.sub.3 -C.sub.7 -cycloalkyl, --OH or --NHR.sub.8a wherein R.sub.8a is hydrogen or C.sub.1 -C.sub.6 -loweralkyl;
or a pharmaceutically acceptable salt thereof.

8 more elements

A compound of the formula:

##STR20## wherein R.sub.1 is monosubstituted thiazolyl or monosubstituted oxazolyl wherein the substituent is selected from (i) C.sub.1 -C.sub.6 -loweralkyl, (ii) C.sub.2 -C.sub.6 -loweralkenyl, (iii) C.sub.3 -C.sub.7 -cycloalkyl, (iv) C.sub.3 -C.sub.7 -cycloalkyl-C.sub.1 -C.sub.6 -alkyl, (v) C.sub.5 -C.sub.7 -cycloalkenyl, (vi) C.sub.5 -C.sub.7 -cycloalkenyl-C.sub.1 -C.sub.6 -alkyl, (vii) C.sub.1 -C.sub.6 -alkoxy-C.sub.1 -C.sub.6 -alkyl or benzyloxy-C.sub.1 -C.sub.6 -alkyl, (viii) C.sub.1 -C.sub.6 -thioalkoxy -C.sub.1 -C.sub.6 -alkyl or benzyl-S--C.sub.1 -C.sub.6 -alkyl, (ix) C.sub.1 -C.sub.6 -alkylamino, (x) di-C.sub.1 -C.sub.6 -alkylamino, (xi) phenyl wherein the phenyl ring is unsubstituted or substituted with a substituent selected from halo, C.sub.1 -C.sub.6 loweralkyl, hydroxy, C.sub.1 -C.sub.6 -alkoxy, benzyloxy, C.sub.1 -C.sub.6 -thioalkoxy and benzyl-S--, (xii) phenyl -C.sub.1 -C.sub.6 -alkyl wherein the phenyl ring is unsubstituted or substituted as defined above, (xiii) di-C.sub.1 -C.sub.6 -alkylamino-C.sub.1 -C.sub.6 -alkyl, (xiv) C.sub.1 -C.sub.6 -alkoxy or benzyloxy and (xv) C.sub.1 -C.sub.6 -thioalkoxy or benzyl-S--;
n is 1,2 or 3;
R.sub.2 is hydrogen or C.sub.1 -C.sub.6 -loweralkyl;
R.sub.4 and R.sub.4a are independently selected from phenyl and substituted phenyl wherein the phenyl ring is substituted with a substituent selected from (i) halo, (ii) C.sub.1 -C.sub.6 -loweralkyl, (iii) hydroxy, (iv) C.sub.1 -C.sub.6 -alkoxy or benzyloxy and (v) C.sub.1 -C.sub.6 -thioalkoxy or benzyl-S--;
R.sub.6 is hydrogen or C.sub.1 -C.sub.6 -loweralkyl;
R.sub.7 is thiazolyl or oxazolyl wherein the thiazolyl or oxazolyl ring is unsubstituted and R.sub.3 is C.sub.2 -C.sub.6 -loweralkyl and Z is absent, --O--, --S-- or --CH.sub.2 --;
or
R.sub.7 is thiazolyl or oxazolyl wherein the thiazolyl or oxazolyl ring is substituted with C.sub.1 -C.sub.6 -loweralkyl and R.sub.3 is C.sub.1 -C.sub.6 -loweralkyl and Z is absent, --O--, --S--, --CH.sub.2 --Nor --(R.sub.8)-- wherein R.sub.8 is C.sub.1 -C.sub.6 -loweralkyl, C.sub.3 -C.sub.7 -cycloalkyl, --OH or --NHR.sub.8a wherein R.sub.8a is hydrogen, C.sub.1 -C.sub.6 -loweralkyl or an N-protecting group selected from the group consisting of formyl, acetyl, propionyl, pivaloyl, t-butylacetyl, 2-chloroacetyl, 2-bromoacetyl, trifluoroacetyl, trichloroacetyl, phthalyl, o-nitrophenoxyacetyl, .alpha.-chlorobutyryl, benzoyl, 4-chlorobenzoyl, 4-bromobenzoyl, 4-nitrobenzoyl, benzenesulfonyl, p-toluenesulfonyl, benzyloxycarbonyl, p-chlorobenzyloxycarbonyl, p-methoxybenzyloxycarbonyl, p- nitrobenzyloxycarbonyl, 2- nitrobenzyloxycarbonyl, p-bromobenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, 3,5-dimethoxybenzyloxycarbonyl, 2,4-dimethoxybenzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 2-nitro-4,5-dimethoxybenzyloxycarbonyl, 3,4,5-trimethoxybenzyloxycarbonyl, 1-(p-biphenylyl)-1-methylethoxycarbonyl, .alpha.,.alpha.-dimethyl-3,5-dime thoxybenzyloxycarbonyl, benzhydryloxycarbonyl, t-butyloxycarbonyl, diisopropylmethoxycarbonyl, isopropyloxycarbonyl, ethoxycarbonyl, methoxycarbonyl, allyloxycarbonyl, 2,2,2,-trichloroethoxycarbonyl, phenoxycarbonyl, 4-nitrophenoxycarbonyl, fluorenyl-9-methoxycarbonyl, cyclopentyloxycarbonyl, adamantyloxycarbonyl, cyclohexyloxycarbonyl, phenylthiocarbonyl, benzyl, triphenylmethyl, benzyloxymethyl and trimethylsilyl;
and
X is --OH and Y is hydrogen;
or a pharmaceutically acceptable salt thereof.

8 more elements

A compound of the formula:

##STR21## wherein R.sub.1 is monosubstituted thiazolyl or monosubstituted oxazolyl wherein the substituent is selected from (i) C.sub.1 -C.sub.6 -loweralkyl, (ii) C.sub.2 -C.sub.6 -loweralkenyl, (iii) C.sub.3 -C.sub.7 -cycloalkyl, (iv) C.sub.3 -C.sub.7 -cycloalkyl-C.sub.1 -C.sub.6 -alkyl, (v) C.sub.5 -C.sub.7 -cycloalkenyl, (vi) C.sub.5 -C.sub.7 -cycloalkenyl-C.sub.1 -C.sub.6 -alkyl, (vii) C.sub.1 -C.sub.6 -alkoxy-C.sub.1 -C.sub.6 -alkyl or benzyloxy-C.sub.1 -C.sub.6 -alkyl, (viii) C.sub.1 -C.sub.6 -thioalkoxy-C.sub.1 -C.sub.6 -alkyl or benzyl-S--C.sub.1 -C.sub.6 -alkyl, (ix) C.sub.1 -C.sub.6 -alkylamino, (x) di-C.sub.1 -C.sub.6 -alkylamino, (xi) phenyl wherein the phenyl ring is unsubstituted or substituted with a substituent selected from halo, C.sub.1 -C.sub.6 -loweralkyl, hydroxy, C.sub.1 -C.sub.6 -alkoxy, benzyloxy, C.sub.1 -C.sub.6 -thioalkoxy and benzyl-S--, (xii) phenyl -C.sub.1 -C.sub.6 -alkyl wherein the phenyl ring is unsubstituted or substituted as defined above, (xiii) di-C.sub.1 -C.sub.6 -alkylamino -C.sub.1 -C.sub.6 -alkyl, (xiv) C.sub.1 -C.sub.6 -alkoxy or benzyloxy and (xv) C.sub.1 -C.sub.6 -thioalkoxy or benzyl-S--;
n is 1;
R.sub.2 is hydrogen or C.sub.1 -C.sub.6 -loweralkyl;
R.sub.4 is phenyl or substituted phenyl wherein the phenyl ring is substituted with a substituent selected from (i) halo, (ii) C.sub.1 -C.sub.6 -loweralkyl, (iii) hydroxy, (iv) C.sub.1 -C.sub.6 -alkoxy or benzyloxy and (v) C.sub.1 -C.sub.6 -thioalkoxy or benzyl-S--;
R.sub.6 is hydrogen or C.sub.1 -C.sub.6 -loweralkyl;
R.sub.7 is thiazolyl or oxazolyl wherein the thiazolyl or oxazolyl ring is unsubstituted and R.sub.3 is C.sub.2 -C.sub.6 -loweralkyl and Z is absent, --O--, --S-- or --CH.sub.2 --;
or
R.sub.7 is thiazolyl or oxazolyl wherein the thiazolyl or oxazolyl ring is substituted with C.sub.1 -C.sub.6 -loweralkyl and R.sub.3 is C.sub.1 -C.sub.6 -loweralkyl and Z is absent, --O--, --S--, --CH.sub.2 -- or --N(R.sub.8)-- wherein R.sub.8 is C.sub.1 -C.sub.6 -loweralkyl, C.sub.3 -C.sub.7 -cycloalkyl, --OH or --NHR.sub.8 a wherein R.sub.8a is hydrogen or C.sub.1 -C.sub.6 -loweralkyl;
and
X is --OH and Y is hydrogen;
or a pharmaceutically acceptable salt thereof.

8 more elements

A compound selected from the group consisting of:

(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-cyclohexyl-4-thiazolyl)methyl)amino)-ca rbonyl)valinyl)amino)-2-(N-((5-thiazolyl) methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane;
(2S,3S, 5S)-5-(N-(N-((N-Methyl-N-((2-(1,1-dimethyl)ethyl-4-thiazolyl)methyl)amino) carbonyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphe nyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-ethenyl-4-thiazolyl)methyl)amino)-carbo nyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3 -hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(2-propenyl)-4-thiazolyl)methyl)amino)c arbonyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphen yl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(1-cyclopentenyl)-4-thiazolyl)methyl)am ino)carbonyl)valinyl)amino)-2-(N-((5-thiazolyl)-methoxycarbonyl)amino)-1,6- diphenyl-3hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(1-cyclohexenyl)-4-thiazolyl)methyl)ami no)carbonyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-di phenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((4-(cyclopentenyl-4-thiazolyl)methyl)amino )carbonyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diph enyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((4-cyclohexenyl-4-thiazolyl)methyl)amino)c arbonyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphen yl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(1-propenyl)-4-thiazolyl)methyl)amino)c arbonyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphen yl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(1-methyl-1-propenyl)-4-thiazolyl)methy l)amino)carbonyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1 ,6-diphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(1-methyl-2-propenyl)-4-thiazolyl)methy l)amino)carbonyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)-amino)- 1,6-diphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(1,2-dimethyl-1-propenyl)-4-thiazolyl)m ethyl)amino)carbonyl)valinyl)amino)-2-(N-((5-thiazolyl)-methoxycarbonyl)ami no)-1,6-diphenyl-3hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(1,2-(cyclopentyl)methyl-4-thiazolyl)me thyl)amino)carbonyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino )-1,6-diphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(cyclohexyl)methyl-4-thiazolyl)methyl)a mino)carbonyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6- diphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-phenyl-4-thiazolyl)methyl)amino)-carbon yl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3- hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-benzyl-4-thiazolyl)methyl)amino)-carbon yl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3- hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(2-phenyl)ethyl-4-thiazolyl)methyl)amin o)carbonyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-dip henyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(2-(4-fluoro)phenyl-4-thiazolyl)methyl) amino)carbonyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6 -diphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(2-chloro)phenyl-4-thiazolyl)methyl)ami no)carbonyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-di phenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(2-methoxy)phenyl-4-thiazolyl)methyl)am ino)carbonyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-d iphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-methoxy-4-thiazolyl)methyl)amino)-carbo nyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3 -hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-ethoxy-4-thiazolyl)methyl)amino)-carbon yl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3- hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-isoproploxy-4-thiazolyl)methyl)amino)ca rbonyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-dipheny l-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(N,N-dimethylamino)methyl-4-thiazolyl)m ethyl)amino)carbonyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)-ami no)-1,6-diphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-propyl-4-thiazolyl)methyl)amino)-carbon yl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3- hydroxyhexane;
(2S,3S,5S,)-5-(N-(N-(N-Methyl-N-((2-(methyl)propyl-4-thiazolyl)methyl)amino )carbonyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diph enyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(1-methyl)propyl-4-thiazolyl)methyl)ami no)carbonyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-di phenyl-3hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(1-ethyl)propyl-4-thiazolyl)methyl)amin o)carbonyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-dip henyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)carb onyl)analinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl -3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-Isopropyl-4-thiazolyl)methyl)amino)carb onyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl- 3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((2-Isopropyl-4-thiazolyl)methoxycarbonyl)valinyl)amino) -2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane;
(2S,3S,5S)-2-(N-(N-((2-Isopropyl-4-thiazolyl)methoxycarbonyl)valinyl)amino) -5-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((2-Isopropyl-4-thiazolyl)methoxycarbonyl)alaninyl)amino )-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((2-(N,N-Dimethylamino)-4-thiazolyl)methoxycarbonyl)vali nyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3- hydroxyhexane;
(2S,3S,5S)-2-(N-(N-((2-(N,N-Dimethylamino)-4-thiazolyl)methoxycarbonyl)vali nyl)amino)-5-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxy hexane;
(2S,3S,5S)-5-(N-(N-((N-Cyclopropyl-N-((2-isopropyl-4-thiazolyl)methyl)amino )carbonyl)alaninyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-dip henyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-(1-(2-Isopropyl-4-thiazolyl)ethoxycarbonyl)valinyl)amino )-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Cyclopropyl-N-((2-isopropyl-4-thiazolyl)methyl)amino )carbonyl)valinyl)amino-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphe nyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-isopropyl-4-oxazolyl)methyl)amino)carbo nyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3 -hydroxyhexane;
(2S, 3S, 5S) -5-(N-(N-((N-Methyl-N-((2-isopropyl-4-oxazolyl)methyl)amino)carbonyl)valin yl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhe xane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)carb onyl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3 -hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((4-Isopropyl-2-thiazolyl)methoxycarbonyl)valinyl)amino) -2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((2-(N,N-Diethylamino)-4-thiazolyl)methoxycarbonyl)valin yl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyh exane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-(((N,N-dimethylamino)-4-thiazolyl)methyl)am ino)carbonyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-d iphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((2-Isopropyl-4-thiazolyl)methoxycarbonyl)valinyl)amino) -2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(methoxymethyl)-4-thiazolyl)methyl)amin o)carbonyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-dip henyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N,N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)carbo nyl)valinyl)amino)-2-(N-((2-methyl-5-thiazolyl)methoxycarbonyl)amino)-1,6-d iphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N,N-((2-Isopropyl-4-thiazolyl)thiomethoxycarbonyl)valinyl)ami no)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-(3-(2-Isopropyl-4-thiazolyl)propanoyl)valinyl)amino)-2-( N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)carb onyl)valinyl)amino)-2-(N-(1-(5-thiazolyl)ethoxycarbonyl)amino)-1,6-diphenyl -3-hydroxyhexane;
(2S,3S,5S)-2-(N-(N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)carb onyl)valinyl)amino)-5-(N-((2-methyl-5-thiazolyl)methoxycarbonyl)amino)-1,6- diphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-cyclopentyl-4-thiazolyl)methyl)amino)-c arbonyl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-dipheny l-3-hydroxyhexane;
(2S,3S,5S)-5-(N,N-((N-Methyl-N-((2-cyclohexyl-4-thiazolyl)methyl)amino)-car bonyl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-diphenyl- 3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(1,1-dimethyl)ethyl-4-thiazolyl)methyl) amino)carbonyl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6- diphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N,N-((N-Methyl-N-((2-cyclobutyl-4-thiazolyl)methyl)amino)-car bonyl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-diphenyl- 3-hydroxyhexane;
(2S,3S,5S)-5-(N,N-((N-Methyl-N-((2-cyclopropyl-4-thiazolyl)methyl)amino)-ca rbonyl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-diphenyl -3-hydroxyhexane;
(2S,3S,5S)-5-(N,N-((N-Methyl-N-((2-ethyl-4-thiazolyl)methyl)amino)-carbonyl )valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hyd roxyhexane:
(2S,3S,5S)-5-(N,N-((N-Methyl-N-((2-ethenyl-4-thiazolyl)methyl)amino)-carbon yl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-h ydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(2-propenyl)-4-thiazolyl)methyl)amino)- carbonyl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-diphen yl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(1-cyclopentenyl)-4-thiazolyl)methyl)am ino)carbonyl)valinyl)amino)-2-(N-((5-oxazolyl)-methoxycarbonyl)amino)-1,6-d iphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(1-cyclohexenyl)-4-thiazolyl)methyl)ami no)carbonyl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-dip henyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((4-cyclopentenyl-4-thiazolyl)methyl)amino) carbonyl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-diphen yl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((4-cyclohexenyl-4-thiazolyl)methyl)amino)c arbonyl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-dipheny l-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(3-propenyl)-4-thiazolyl)methyl)amino)c arbonyl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-dipheny l-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(1-propenyl)-4-thiazolyl)methyl)amino)c arbonyl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-dipheny l-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(1-methyl-1-propenyl)-4-thiazolyl)methy l)amino)carbonyl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1, 6-diphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(2-methyl-1-propenyl)-4-thiazolyl)methy l)amino)carbonyl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)-amino)-1 ,6-diphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(1,2-dimethyl-1-propenyl)-4-thiazolyl)m ethyl)amino)carbonyl)valinyl)amino)-2-(N-((5-oxazolyl)-methoxycarbonyl)amin o)-1,6-diphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(cyclopentyl)methyl-4-thiazolyl)methyl) amino)carbonyl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6- diphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(cyclohexyl)methyl-4-thiazolyl)methyl)a mino)carbonyl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-d iphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N,N-((N-Methyl-N-((2-phenyl-4-thiazolyl)methyl)amino)-carbony l)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hy droxyhexane;
(2S,3S,5S)-5-(N,N-((N-Methyl-N-((2-benzyl-4-thiazolyl)methyl)amino)-carbony l)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hy droxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(2-phenyl)ethyl-4-thiazolyl)methyl)amin o)carbonyl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-diph enyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(2-phenyl-1-ethenyl)-4-thiazolyl)methyl )amino)carbonyl)valinyl)amino-2-(N-((5-oxazolyl)-methoxycarbonyl)amino)-1,6 -diphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(4-fluoro)phenyl-4-thiazolyl)methyl)ami no)carbonyl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-dip henyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(2-chloro)phenyl-4-thiazolyl)methyl)ami no)carbonyl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-dip henyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(3-methoxy)phenyl-4-thiazolyl)methyl)am ino)carbonyl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-di phenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(2-thiazolyl)methyl)amino)-carbonyl)val inyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxy hexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(2-thiazolyl)methyl-4-thiazolyl)methyl) amino)carbonyl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6- diphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-methoxy-4-thiazolyl)methyl)amino)-carbo nyl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3- hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-ethoxy-4-thiazolyl)methyl)amino)-carbon yl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-h ydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-isopropyloxy-4-thiazolyl)methyl)amino)c arbonyl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-dipheny l-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(N,N-dimethylamino)methyl-4-thiazolyl)m ethyl)amino)carbonyl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)-amin o)-1,6-diphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-propyl-4-thiazolyl)methyl)amino)-carbon yl)valinyl)amino)-2-((5-oxazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydr oxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(2-methyl)propyl-4-thiazolyl)methyl)ami no)carbonyl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-dip henyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(1-methyl)propyl-4-thiazolyl)methyl)ami no)carbonyl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-dip henyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(1-ethyl)propyl-4-thiazolyl)methyl)amin o)carbonyl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-diph enyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)carb onyl)alaninyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-diphenyl- 3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Ethyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)carbo nyl)valinyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3- hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((2-Isopropyl-4-thiazolyl)methoxycarbonyl)valinyl)amino) -2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane;
(2S,3S,5S)-2(N-(N-((2-Isopropyl-4-thiazolyl)methoxycarbonyl)valinyl)amino)- 5-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((2-Isopropyl-4-thiazolyl)methoxycarbonyl)alaninyl)amino )-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((2-(N,N-Dimethylamino)-4-thiazolyl)methoxycarbonyl)vali nyl)amino)-2-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyh exane;
(2S,3S,5S)-2-(N-(N-((2-(N,N-Dimethylamino)-4-thiazolyl)methoxycarbonyl)vali nyl)amino)-5-(N-((5-oxazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyh exane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-ethyl-4-oxazolyl)methyl)amino)carbonyl) valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hyd roxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-methyl-4-oxazolyl)methyl)amino)carbonyl )valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hy droxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-(3-pentyl)-4-thiazolyl)methyl)amino)car bonyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl -3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)carb onyl)valinyl)amino)-2-(N-(((2-isopropyl)-5-thiazolyl)methoxycarbonyl)amino) -1,6-diphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((2-(2-Isopropyl-4-thiazolyl)ethoxy)carbonyl)valinyl)ami no)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane;
(2S,3S,5S)-2-(N-(N-((2-(2-Isopropyl-4-thiazolyl)ethoxy)carbonyl)valinyl)ami no)-5-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((2-Isopropyl-4-thiazolyl)acetyl)valinyl)amino)-2-(N-((5 -thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N,N-((N-Methyl-N-((2-cyclopropyl-4-thiazolyl)methyl)amino)car bonyl)valinyl)amino)-2-(N -((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-cyclobutyl-4-thiazolyl)methyl)amino)car bonyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl -3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-ethyl-4-thiazolyl)methyl)amino)carbonyl )valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hy droxyhexane;
(2S,3S,5S)-5-(N-(N-((N-(1-Propyl)-N-((2-isopropyl-4-thiazolyl)methyl)amino) carbonyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphe nyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N,N-((N-(Isobutyl)-N-((2-isopropyl-4-thiazolyl)methyl)amino)c arbonyl)valinyl)amino)-2-(N -((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-isopropyl-4-oxazolyl)methyl)amino)carbo nyl)-L-alaninyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphen yl-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-cyclopentyl-4-thiazolyl)methyl)amino)ca rbonyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-dipheny l-3-hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-Methyl-N-((2-isobutyl-4-thiazolyl)methyl)amino)carbo nyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3 -hydroxyhexane;
(2S,3S,5S)-5-(N,N-((N-Ethyl-N-((2-cyclopentyl-4-thiazolyl)methyl)amino)carb onyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl- 3-hydroxyhexane;
(2S,3S,5S)-5-(N-((N-Methyl-N-(2-(2-isopropyl-4-thiazolyl)ethyl)amino)carbon yl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3- hydroxyhexane;
(2S,3S,5S)-5-(N-(N-((N-(tert-Butyloxycarbonylamino)-N-((2-isopropyl-4-thiaz olyl)methyl)amino)carbonyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbony l)amino)-1,6-diphenyl-3-hydroxyhexane;
and
(2S,3S,5S)-5-(N-(N-((N-(Amino)-N-((2-isopropyl-4-thiazolyl)methyl)amino)car bonyl)valinyl)amino)-2-(N-((5-thiazolyl)methoxycarbonyl)amino)-1,6-diphenyl -3-hydroxyhexane Hydrochloride;
or a pharmaceutically acceptable salt thereof.

112 more elements

Dependencies are inferred from the claim text.

Facts

Application: 08/423,387Filed 25 Apr 1995 · continuation
Priority: 23 May 1989
Granted: 30 Jul 1996
Term ends: Not estimatedThe source records don’t support an estimate.

Classification104 codes

C07D 207/08
Having no double bonds between ring members or between ring members and non-ring members: with hydrocarbon radicals, substituted by hetero atoms,…
A61K 31/425
Having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole: thiazoles
A61K 31/427
Thiazoles: not condensed and containing further heterocyclic rings
A61K 45/06
Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00: mixtures of active ingredients without…

Family

Serial355,945Parent of this continuation-in-part · filed 23 May 1989
Serial405,604Parent of this continuation-in-part · filed 8 Sep 1989
Serial456,124Parent of this continuation-in-part · filed 22 Dec 1989
Serial518,730Parent of this continuation-in-part · filed 9 May 1990
Serial616,170Parent of this continuation-in-part · filed 20 Nov 1990
Serial746,020Parent of this continuation-in-part · filed 15 Aug 1991
Serial777,626Parent of this continuation-in-part · filed 23 Oct 1991
Serial998,114Parent of this continuation-in-part · filed 29 Dec 1992
Serial158,587Parent of this continuation · filed 2 Dec 1993
US 5,142,056 AParent of this continuation-in-part
US 5,541,206 AThis patent

From the US filing history. Foreign family members aren’t listed.

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A compound of the formula:

##STR18## wherein R.sub.1 is monosubstituted thiazolyl or monosubstituted oxazolyl wherein the substituent is selected from (i) C.sub.1 -C.sub.6 -loweralkyl, (ii) C.sub.2 -C.sub.6 -loweralkenyl, (iii) C.sub.3 -C.sub.7 -cycloalkyl, (iv) C.sub.3 -C.sub.7 -cycloalkyl-C.sub.1 -C.sub.6 -alkyl, (v) C.sub.5 -C.sub.7 -cycloalkenyl, (vi) C.sub.5 -C.sub.7 -cycloalkyl-C.sub.1 -C.sub.6 -alkyl, (vii) C.sub.1 -C.sub.6 -alkoxy-C.sub.1 -C.sub.6 -alkyl or benzyloxy-C.sub.1 -C.sub.6 -alkyl, (viii) C.sub.1 -C.sub.6 -thioalkoxy-C.sub.1 -C.sub.6 -alkyl or benzyl- S--C.sub.1 -C.sub.6 -alkyl, (ix) C.sub.1 -C.sub.6 -alkylamino, (x) di-C.sub.1 -C.sub.6 -alkylamino, (xi) phenyl wherein the phenyl ring is unsubstituted or substituted with a substituent selected from halo, C.sub.1 -C.sub.6 -loweralkyl, hydroxy, C.sub.1 -C.sub.6 -alkoxy, benzyloxy, C.sub.1 -C.sub.6 -thioalkoxy and benzyl-S--, (xii) phenyl-C.sub.1 -C.sub.6 -alkyl wherein the phenyl ring is unsubstituted or substituted as defined above, (xiii) di-C.sub.1 -C.sub.6 -alkylamino-C.sub.1 -C.sub.6 -alkyl, (xiv) C.sub.1 -C.sub.6 -alkoxy or benzyloxy and (xv) C.sub.1 -C.sub.6 -thioalkoxy or benzyl-S--;
n is 1,2or 3;
R.sub.2 is hydrogen or C.sub.1 -C.sub.6 -loweralkyl;
R.sub.3 is C.sub.1 -C.sub.6 -loweralkyl;
R.sub.4 and R.sub.4a are independently selected from phenyl and substituted phenyl wherein the phenyl ring is substituted with a substituent selected from (i) halo, (ii) C.sub.1 -C.sub.6 -loweralkyl, (iii) hydroxy, (iv) C.sub.1 -C.sub.6 -alkoxy or benzyloxy and (v) C.sub.1 -C.sub.6 -thioalkoxy or benzyl-S--;
R.sub.6 is hydrogen or C.sub.1 -C.sub.6 -loweralkyl;
R.sub.7 is thiazolyl or oxazolyl wherein the thiazolyl or oxazolyl ring is unsubstituted or substituted with C.sub.1 -C.sub.6 -loweralkyl;
X is hydrogen and Y is --OH ;
and
Z is absent, --O--, --S--, --CH.sub.2 -- or --N(R.sub.8)-- wherein R.sub.8 is C.sub.1 -C.sub.6 -loweralkyl, C.sub.3 -C.sub.7 -cycloalkyl, --OH or --NHR.sub.8a wherein R.sub.8a is hydrogen, C.sub.1 -C.sub.6 -loweralkyl or an N-protecting group selected from the group consisting of formyl, acetyl, propionyl, pivaloyl, t-butylacetyl, 2-chloroacetyl, 2-bromoacetyl, trifluoroacetyl, trichloroacetyl, phthalyl, o-nitrophenoxyacetyl, .alpha.-chlorobutyryl, benzoyl, 4-chlorobenzoyl, 4-bromobenzoyl, 4-nitrobenzoyl, benzenesulfonyl, p-toluenesulfonyl, benzyloxycarbonyl, p-chlorobenzyloxycarbonyl, p-methoxybenzyloxycarbonyl, p-nitrobenzyloxycarbonyl, 2-nitrobenzyloxycarbonyl, p-bromobenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, 3,5-dimethoxybenzyloxycarbonyl, 2,4-dimethoxybenzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 2-nitro-4,5-dimethoxybenzyloxycarbonyl, 3,4,5-trimethoxybenzyloxycarbonyl, 1-(p-biphenylyl)-1-methylethoxycarbonyl, .alpha..alpha.-dimethyl-3,5-dimet hoxybenzyloxycarbonyl, benzhydryloxycarbonyl, t-butyloxycarbonyl, diisopropylmethoxycarbonyl, isopropyloxycarbonyl, ethoxycarbonyl, methoxycarbonyl, allyloxycarbonyl, 2,2,2,-trichloroethoxycarbonyl, phenoxycarbonyl, 4-nitrophenoxycarbonyl, fluorenyl-9-methoxycarbonyl, cyclopentyloxycarbonyl, adamantyloxycarbonyl, cyclohexyloxycarbonyl, phenylthiocarbonyl, benzyl, triphenylmethyl, benzyloxymethyl and trimethylsilyl;
or a pharmaceutically acceptable salt thereof.

8 more elements

Facts

Application

08/423,387Filed 25 Apr 1995 · continuation

Priority

23 May 1989

Granted

30 Jul 1996

Term ends

Not estimatedThe source records don’t support an estimate.

Classification104 codes

C07D 207/08
Having no double bonds between ring members or between ring members and non-ring members: with hydrocarbon radicals, substituted by hetero atoms,…
A61K 31/425
Having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole: thiazoles
A61K 31/427
Thiazoles: not condensed and containing further heterocyclic rings
A61K 45/06
Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00: mixtures of active ingredients without…

Family

Serial355,945Parent of this continuation-in-part · filed 23 May 1989

Serial405,604Parent of this continuation-in-part · filed 8 Sep 1989

Serial456,124Parent of this continuation-in-part · filed 22 Dec 1989

Serial518,730Parent of this continuation-in-part · filed 9 May 1990

Serial616,170Parent of this continuation-in-part · filed 20 Nov 1990

Serial746,020Parent of this continuation-in-part · filed 15 Aug 1991

Serial777,626Parent of this continuation-in-part · filed 23 Oct 1991

Serial998,114Parent of this continuation-in-part · filed 29 Dec 1992

Serial158,587Parent of this continuation · filed 2 Dec 1993

US 5,142,056 AParent of this continuation-in-part

US 5,541,206 AThis patent

From the US filing history. Foreign family members aren’t listed.