US 7,320,983 B2 | ||
α- and β-amino acid hydroxyethylamino sulfonamides useful as retroviral protease inhibitors | ||
Michael L. Vazquez, Gurnee, Ill. (US); Richard A. Mueller, Glencoe, Ill. (US); John J. Talley, St. Louis, Mo. (US); Daniel P. Getman, Chesterfield, Mo. (US); Gary A. DeCrescenzo, St. Peters, Mo. (US); John N. Freskos, Clayton, Mo. (US); Robert M. Heintz, Ballwin, Mo. (US); and Deborah E. Bertenshaw, Brentwood, Mo. (US) | ||
Assigned to G.D. Searle LLC, New York, N.Y. (US) | ||
Filed on Sep. 25, 2006, as Appl. No. 11/526,101. | ||
Application 10/812343 is a division of application No. 10/199481, filed on Jul. 22, 2002, granted, now 6,846,954. | ||
Application 10/199481 is a division of application No. 08/451090, filed on May 25, 1995, granted, now 6,455,581. | ||
Application 08/451090 is a division of application No. 08/204827, filed on Mar. 02, 1994, granted, now 6,060,476. | ||
Application 11/526101 is a continuation of application No. 10/812343, filed on Mar. 30, 2004, granted, now 7,115,618. | ||
Application 08/204827 is a continuation in part of application No. PCT/US93/07814, filed on Aug. 24, 1993. | ||
Application PCT/US93/07814 is a continuation in part of application No. 07/934984, filed on Aug. 25, 1992, abandoned. | ||
Prior Publication US 2007/0078173 A1, Apr. 05, 2007 | ||
This patent is subject to a terminal disclaimer. | ||
Int. Cl. A61K 31/36 (2006.01); C07D 317/50 (2006.01) |
U.S. Cl. 514—277 [514/408; 548/400; 546/314; 546/316; 546/335; 546/336] | 16 Claims |
1. A compound represented by the formula:
![]() or a pharmaceutically acceptable salt or ester thereof, wherein: R2 is a sub stituent selected from the group consisting of alkyl, aryl, cycloalkyl, cycloalkylalkyl, and aralkyl, which substituent
is optionally substituted with alkyl, halo, nitro, cyano, —CF3, —OR9, or —SR9, wherein R9 is a hydrogen radical or alkyl;
R4 is alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl,
heterocycloalkylalkyl, aryl, aralkyl, aralkenyl, heteroaralkyl, aminoalkyl, or mono- or di-substituted aminoalkyl that is
substituted with one or two substituents independently selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl,
cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl, and heterocycloalkylalkyl, or, in the case of a di-substituted
aminoalkyl, said two substituents together with the nitrogen atom to which they are bonded form a heterocycloalkyl or a heteroaryl;
R6 is a hydrogen radical or alkyl;
Y is O or S; and
A is alkoxy, alkenoxy, aralkoxy, alkyl, cycloalkyl, cycloalkylalkoxy, cycloalkylalkyl, aralkyl, aryl, aryloxy, heterocycloalkyl,
heterocycloalkoxy, heterocycloalkylalkyl, heterocycloalkylalkoxy, heteroaralkyl, heteroaralkoxy, heteroaryloxy, heteroaryl,
alkenyl, aryloxyalkyl, heteroaryloxyalkyl, hydroxyalkyl, amino, or mono- or di-substituted amino that is substituted with
one or two substituents independently selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl, cycloallcylalkyl,
heteroaryl, heteroaralkyl, heterocycloalkyl, and heterocycloalkylalkyl, or, in the case of a di-substituted amino, said two
substituents together with the nitrogen atom to which they are bonded form a heterocycloalkyl or a heteroaryl; or is A is
a radical represented by the formula
![]() wherein:
t is 0 or 1;
R is a hydrogen radical, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, cycloalkylcarbonyl, cycloalkylalkoxycarbonyl, cycloalkylalkanoyl,
carboxyalkanoyl, alkanoyl, aralkanoyl, aroyl, aryloxycarbonyl, aryloxycarbonylalkyl, aryloxyalkanoyl, heterocyclylcarbonyl,
heterocyclyloxycarbonyl, heterocyclylalkanoyl, heterocyclylalkoxycarbonyl, heteroaralkanoyl, heteroaralkoxycarbonyl, heteroaryloxycarbonyl,
heteroaroyl, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, aryloxyalkyl, heteroaryloxyalkyl, hydroxyalkyl, aminocarbonyl,
aminoalkanoyl, or mono- or di-substituted aminocarbonyl or mono- or di-substituted aminoalkanoyl, that are each substituted
with one or two sub stituents independently selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl,
heteroaryl, heteroaralkyl, heterocycloalkyl, and heterocycloalkylalkyl, or, in the case of a di-substituted aminocarbonyl
or a di-substituted aminoalkanoyl, said two substituents together with the nitrogen atom to which they are bonded form a heterocycloalkyl
or a heteroaryl;
R′ is a hydrogen radical, alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl, alkylsulfonylalkyl,
cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, heteroaralkyl, aminoalkyl,
or mono- or di-substituted aminoalkyl that is substituted with one or two substituents independently selected from the group
consisting of alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl, and heterocycloalkylalkyl,
or, in the case of a di-substituted aminoalkyl, said two substituents together with the nitrogen atom to which they are bonded
form a heterocycloalkyl or a heteroaryl; or R′ is R″SO2, wherein R″ is a hydrogen radical, alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl, alkylsulfonylalkyl,
cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, heteroaralkyl, aminoalkyl,
or mono- or di-substituted aminoalkyl that is substituted with one or two substituents independently selected from the group
consisting of alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl, and heterocycloalkylalkyl,
or, in the case of a di-substituted aminoalkyl, said two substituents together with the nitrogen atom to which they are bonded
form a heterocycloalkyl or a heteroaryl; or R and R′ together with the nitrogen to which they are bonded form a heterocycloalkyl
or a heteroaryl;
R1 is a hydrogen radical, —CO2CH3, —CH2CO2CH3, —CO2H, —CH2—CO2H, —CH2—CH2CONH2, —CH2CONH2, —CONH2, —CH2C(O)NHCH3, —CH2C(O)N(CH3)2, —CONHCH3, —CONH(CH3)2, —CH2SO2NH2, —CH2CH2SO2NH2, —CH2S[O]CH3, —CH2S [O]2CH3, —(CH3)2(SCH3), —C(CH3)2(S[O]CH3), —C(CH3)2(S[O]2CH3), alkyl, hydroxyalkyl, cyanoalkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, alkylthioalkyl, aralkyl, heteroaralkyl,
aminoalkyl, or mono- or di-substituted aminoalkyl that is substituted with one or two substituents independently selected
from the group consisting of allyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl,
and heterocycloalkylalkyl, or, in the case of a di-substituted aminoalkyl, said two substituents together with the nitrogen
atom to which they are bonded form a heterocycloalkyl or a heteroaryl; and
each of R1′ and R1″ are independently as defined for R1′; or one of R1′ and R1″ together with R1 and the carbon atoms to which R1, R1′, R1″ are bonded, forms cycloalkyl.
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