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US 5,512,560 AGranted
Conformationally restricted HIV-1 protease inhibitors
AssigneeMerck & Co., Inc.
InventorsByeong M. Kim, Joseph P. Vacca
Life of this patent
Estimating the term…
Abstract
HIV protease inhibitors containing hydroxypyrrolidine or hydroxypiperidine with one or more basic amines are disclosed.
Claims16
A compound of the Formula I ##STR171## m=0,1;
- n=0,1;
- R.sub.1 and R.sub.2 are independently
- a) aryl unsubstituted or substituted with one or more of C.sub.1-4 lower alkyl, hydroxy, C.sub.1-3 alkoxy or halo;
- b) C.sub.5 -C.sub.7 cycloalkyl;
- or
- c) heterocycle unsubstituted or substituted with one or more of C.sub.1-4 lower alkyl, hydroxy, C.sub.1-3 alkoxy or halo;
- R.sub.3 is
- a) hydrogen;
- b) C.sub.1-6 alkyl, unsubstituted or substituted with one or more of hydroxy, C.sub.1-3 alkoxy, aryl, heterocycle or halo;
- c) aryl unsubstituted or substituted with one or more of C.sub.1-4 lower alkyl, hydroxy, C.sub.1-3 alkoxy or halo;
- d) heterocycle unsubstituted or substituted with one or more of C.sub.1-4 lower alkyl, hydroxy, C.sub.1-3 alkoxy or halo;
- or
- e) a 5 to 7 membered carbocyclic or 7-10 membered bicyclic carbocyclic ring, the carbocyclic ring being unsubstituted or substituted with one or more of C.sub.1-4 lower alkyl, hydroxy, C.sub.1-3 alkoxy or halo;
- and
- T is R.sub.4 OC(O), R.sub.4 C(O) or R.sub.4 NR.sub.5 C(O) wherein R.sub.4 is
- a) C.sub.1-5 alkyl unsubstituted or substituted with one or more of aryl, heterocycle, hydroxy, halo or C.sub.1-3 alkoxy;
- b) a 5- to 7-membered carbocycle or carbocycle-C.sub.1-4 alkyl wherein the carbocycle is either saturated, partially saturated or unsaturated, any of which carbocycle is unsubstituted or substituted with one or more of C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.1-3 alkoxy, halo-C.sub.1-3 alkyl, aryl-C.sub.1-3 alkyl, or C.sub.3-5 cycloalkyl;
- c) a 5- to 7-membered heterocycle or heterocycle-C.sub.1-4 alkyl wherein the heterocycle has one or two heteroatoms selected from O, N or S, any of which heterocycle is unsubstituted or substituted with one or more of C.sub.1-4 alkyl, C.sub.2-4 alkenyl, oxo, C.sub.3-5 cycloalkyl, or C.sub.1-3 alkoxy;
- d) aryl unsubstituted or substituted with one or more of C.sub.1-4 lower alkyl, hydroxy, C.sub.1-3 alkoxy or halo;
- or
- e) heterocycle;
- and
- R.sub.5 is
- a) hydrogen, or
- b) C.sub.1-4 alkyl unsubstituted or substituted with one or more of C.sub.2-4 alkenyl, C.sub.1-3 alkoxy, halo-C.sub.1-3 alkyl, hydroxy-C.sub.2-4 alkyl, aryl-C.sub.1-3 alkyl, or C.sub.3-5 cycloalkyl;
- and
- A is absent or
- a) an L-amino acid residue chosen from valine, isoleucine, leucine, alanine, asparagine or serine;
- or
- b) 5- to 7-membered heterocycle or heterocycle-C.sub.1-4 alkyl wherein the heterocycle has one or two heteroatoms selected from O, N or S, any of which heterocycle is unsubstituted or substituted with one or more of C.sub.1-4 alkyl, C.sub.2-4 alkenyl, oxo, C.sub.3-5 cycloalkyl, or C.sub.1-3 alkoxy, or pharmaceutically acceptable salt thereof.
27 more elements
The compound:
- ##STR172## named:
- N-(1'(S)-(2'(R)-hydroxyindanyl))-2(S)-(1'-(3'(S)-hydroxy-3'(S)-(1"(S)-tert -butyloxycarbonylamino-2"-phenylethyl)pyrrolidinyl))-3-phenylpropane amide;
- or pharmaceutically acceptable salt thereof.
The compound:
- ##STR173## named:
- N-(1'(S)-(2'(R)-hydroxyindanyl))-2(S)-(1'-(3'(R)-hydroxy-3'(R)-(1"(S)-tert -butyloxycarbonylamino-2"-phenylethyl)pyrrolidinyl))-3-phenylpropane-amide;
- or pharmaceutically acceptable salt thereof.
The compound:
- ##STR174## named:
- N-(1'(S)-(2'(R)-hydroxyindanyl))-2(S)-(4'(S)-hydroxy-4'(S)-(1"(S)-tert-but yloxycarbonylamino-2"-phenylethyl)piperidinyl)-3-phenylpropane-amide;
- or pharmaceutically acceptable salt thereof.
The compound:
- ##STR175## named:
- N-(1'(S)-(2'(R)-hydroxyindanyl))-2(S)-(4'-hydroxy-4'(1"(S)-(3"'(S)-tetrahy drofuryloxycarbonyl)amino-2"-phenyl)ethyl-1'-piperidinyl)-3-phenylpropane-a mide;
- or pharmaceutically acceptable salt thereof.
The compound:
- ##STR176## named:
- N-(1'(S)-(2'(R)-hydroxyindanyl))-2(S)-(3'(S)-hydroxy-3'(S)-(1"(S)-tert-but yloxycarbonylamino-2"-phenylethyl)-1'-piperidinyl)-3-phenylpropane-amide;
- or pharmaceutically acceptable salt thereof.
The compound:
- ##STR177## named:
- N-(1',1'-dimethylethyl)-2(S)-(3'(R)-hydroxy-3'(R)-(1"(S)-tert-butyloxycarb onylamino-2"-phenylethyl)-1'-piperidinyl)-3-cyclohexylpropane-amide
- or pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.