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Details for Patent: 7,320,983

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Details for Patent: 7,320,983

Title:.alpha.- and .beta.-amino acid hydroxyethylamino sulfonamides useful as retroviral protease inhibitors
Abstract: .alpha.- and .beta.-amino acid hydroxyethylamino sulfonamide compounds are effective as retroviral protease inhibitors, and in particular as inhibitors of HIV protease.
Inventor(s): Vazquez; Michael L. (Gurnee, IL), Mueller; Richard A. (Glencoe, IL), Talley; John J. (St. Louis, MO), Getman; Daniel P. (Chesterfield, MO), DeCrescenzo; Gary A. (St. Peters, MO), Freskos; John N. (Clayton, MO), Heintz; Robert M. (Ballwin, MO), Bertenshaw; Deborah E. (Brentwood, MO)
Assignee: G.D. Searle LLC (New York, NY)
Filing Date:Sep 25, 2006
Application Number:11/526,101
Claims:1. A compound represented by the formula: ##STR00494## or a pharmaceutically acceptable salt or ester thereof, wherein: R.sup.2 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, --CF.sub.3, --OR.sup.9, or --SR.sup.9, wherein R.sup.9 is a hydrogen radical or alkyl; R.sup.4 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; R.sup.6 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 ##STR00495## 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''SO.sub.2, 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; R.sup.1 is a hydrogen radical, --CO.sub.2CH.sub.3, --CH.sub.2CO.sub.2CH.sub.3, --CO.sub.2H, --CH.sub.2--CO.sub.2H, --CH.sub.2--CH.sub.2CONH.sub.2, --CH.sub.2CONH.sub.2, --CONH.sub.2, --CH.sub.2C(O)NHCH.sub.3, --CH.sub.2C(O)N(CH.sub.3).sub.2, --CONHCH.sub.3, --CONH(CH.sub.3).sub.2, --CH.sub.2SO.sub.2NH.sub.2, --CH.sub.2CH.sub.2SO.sub.2NH.sub.2, --CH.sub.2S[O]CH.sub.3, --CH.sub.2S [O].sub.2CH.sub.3, --(CH.sub.3).sub.2(SCH.sub.3), --C(CH.sub.3).sub.2(S[O]CH.sub.3), --C(CH.sub.3).sub.2(S[O].sub.2CH.sub.3), 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 R.sup.1' and R.sup.1'' are independently as defined for R.sup.1'; or one of R.sup.1' and R.sup.1'' together with R.sup.1 and the carbon atoms to which R.sup.1, R.sup.1', R.sup.1'' are bonded, forms cycloalkyl.

2. The compound of claim 1 or a pharmaceutically acceptable salt or ester thereof, wherein: R.sup.4 is alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, aralkenyl, 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, and cycloalkylalkyl.

3. The compound of claim 1 or a pharmaceutically acceptable salt or ester thereof, wherein: R.sup.2 is a substituent selected from the group consisting of alkyl, aryl, cycloalkyl, cycloalkylalkyl, and aralkyl, which substituent is optionally substituted with alkyl, halo, or --OR.sup.9, wherein R.sup.9 is a hydrogen radical or alkyl; R.sup.4 is alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, aralkenyl, or heteroaralkyl; A is alkoxy, alkenoxy, aralkoxy, alkyl, cycloalkyl, cycloalkylalkoxy, cycloalkylalkyl, aralkyl, aryl, aryloxy, heterocycloalkyl, heterocycloalkoxy, heterocycloalkylalkyl, heterocycloalkylalkoxy, heteroaralkyl, heteroaralkoxy, heteroaryloxy, heteroaryl, hydroxyalkyl, amino, or mono- or di-substituted amino that is substituted with one or two substituents independently selected from the group consisting of alkyl, aralkyl, 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 is A is a radical represented by the formula ##STR00496## wherein: R is a hydrogen radical, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, carboxyalkanoyl, alkanoyl, aralkanoyl, aroyl, heterocyclylcarbonyl, heterocyclyloxycarbonyl, heterocyclylalkanoyl, heterocyclylalkoxycarbonyl, heteroaralkanoyl, heteroaralkoxycarbonyl, heteroaryloxycarbonyl, heteroaroyl, alkyl, cycloalkyl, aralkyl, hydroxyalkyl, aminocarbonyl, aminoalkanoyl, or mono- or di-substituted aminocarbonyl or mono- or di-substituted aminoalkanoyl, that are each substituted with one or two substituents independently selected from the group consisting of alkyl, aralkyl, 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, aralkyl, or R''SO.sub.2--, wherein R'' is a hydrogen radical, alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl, alkylsulfonylalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylailcyl, 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, aralkyl, cycloalkyl, and cycloalkylalkyl, 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; R.sup.1 is a hydrogen radical, --CO.sub.2CH.sub.3, --CH.sub.2CO.sub.2CH.sub.3, --CO.sub.2H, --CH.sub.2CO.sub.2H, --CH.sub.2CH.sub.2CONH.sub.2, --CH.sub.2CONH.sub.2, --CONH.sub.2, --CH.sub.2C(O)NHCH.sub.3, --CH.sub.2C(O)N(CH.sub.3).sub.2, --CONHCH.sub.3, --CONH(CH.sub.3).sub.2, --CH.sub.2SO.sub.2NH.sub.2, --CH.sub.2CH.sub.2SO.sub.2NH.sub.2, --CH.sub.2S[O]CH .sub.3, --CH.sub.2S[O].sub.2CH.sub.3, --(CH.sub.3).sub.2(SCH.sub.3), --C(CH.sub.3).sub.2(S[O]CH.sub.3), --C(CH.sub.3).sub.2(S[O].sub.2CH.sub.3), 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 alkyl, aralkyl, heteroaryl, heteroaralkyl, heterocycloalkyl, and heterocycloalkylalkyl, or, in the case of a di-substituted aminoalkyl, said two sub stituents together with the nitrogen atom to which they are bonded form a heterocycloalkyl or a heteroaryl; and each of R.sup.1' and R.sup.1'' are independently as defined for R.sup.1; or one of R.sup.1' and R.sup.1'' together with R.sup.1 and the carbon atoms to which R.sup.1, R.sup.1', R.sup.1'' are bonded, forms cycloalkyl.

4. The compound of claim 3 or a pharmaceutically acceptable salt or ester thereof, wherein: A is alkoxy, alkenoxy, aralkoxy, alkyl, cycloalkyl, aryl, heterocycloalkyl, heterocycloalkoxy, heterocycloalkylalkyl, heteroaralkoxy, heteroaryl, amino, or mono- or di-substituted amino that is substituted with one or two substituents independently selected from the group consisting of alkyl and aralkyl; or is A is a radical represented by the formula ##STR00497## wherein: R is a hydrogen radical, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, carboxyalkanoyl, alkanoyl, aroyl, heteroaroyl, alkyl, aralkyl, aminocarbonyl, aminoalkanoyl, or mono- or di-substituted aminocarbonyl or mono- or di-substituted aniinoalkanoyl, that are each substituted with one or two substituents independently selected from the group consisting of alkyl, and aralkyl; R' is a hydrogen radical, alkyl, aralkyl, or R''SO.sub.2--, 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-alkyl or di-alkyl substituted aminoalkyl; or R and R' together with the nitrogen to which they are bonded form a heterocycloalkyl or a heteroaryl; R.sup.1 is a hydrogen radical, --CO.sub.2CH.sub.3, --CH.sub.2CO.sub.2CH.sub.3, --CO.sub.2H, --CH.sub.2CO.sub.2H, --CH.sub.2CH.sub.2CONH.sub.2, --CH.sub.2CONH.sub.2, --CONH.sub.2, --CH.sub.2C(O)NHCH.sub.3, -CH.sub.2C(O)N(CH.sub.3).sub.2, --CONHCH.sub.3, --CONH(CH.sub.3).sub.2, --CH.sub.2SO.sub.2NH.sub.2, --CH.sub.2CH.sub.2SO.sub.2NH.sub.2, --CH.sub.2S[O]CH .sub.3, --CH.sub.2S[O].sub.2CH.sub.3, --(CH.sub.3).sub.2(SCH.sub.3), --C(CH.sub.3).sub.2(S[O]CH.sub.3), --C(CH.sub.3).sub.2(S[O].sub.2CH.sub.3), 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 alkyl and aralkyl; R' is a hydrogen radical, alkyl, or aralkyl; and R'' is a hydrogen radical, alkyl, --CO.sub.2CH.sub.3, or --CONH.sub.2; or one of R.sup.1' and R.sup.1'' together with R.sup.1 and the carbon atoms to which R.sup.1, R.sup.1', R.sup.1'' are bonded, forms cycloalkyl.

5. The compound of claim 4 or a phannaceutically acceptable salt or ester thereof, wherein: R.sup.2 is a substituent selected from the group consisting of alkyl, cycloalkylalkyl, and aralkyl, which substituent is optionally substituted with alkyl, halo, or --OR.sup.9, wherein R.sup.9 is a hydrogen radical or alkyl; R' is a hydrogen radical, alkyl, aralkyl, or R''SO.sub.2--, wherein R'' is a hydrogen radical, alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl, alkylsulfonylalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkylalkyl, aryl, aralkyl, heteroaralkyl, aminoalkyl, or mono-alkyl or di-alkyl substituted aminoalkyl; or R and R' together with the nitrogen to which they are bonded form a heterocycloalkyl or a heteroaryl; and R.sup.1 is a hydrogen radical, --CO.sub.2H, --CH.sub.2CO.sub.2H, --CH.sub.2CH.sub.2CONH.sub.2, --CH.sub.2CONH.sub.2 , --CONH.sub.2, --CH.sub.2C(O)NHCH.sub.3, --CH.sub.2C(O)N(CH.sub.3).sub.2, --CONHCH.sub.3, --CONH(CH.sub.3).sub.2, --CH.sub.2SO.sub.2NH.sub.2, --CH.sub.2CH.sub.2SO.sub.2NH.sub.2, alkyl, hydroxyalkyl, cyanoalkyl, alkynyl, cycloalkylalkyl, alkylthioalkyl, aralkyl, or heteroaralkyl; with the proviso that alkyl, alone or in combination, is a straight-chain or branched-chain hydrocarbon radical having from one to eight carbon atoms; alkenyl, alone or in combination, is a straight-chain or branched-chain hydrocarbon radical having at least one double bond and from two to eight carbon atoms; alkynyl, alone or in combination, is a straight-chain or branched-chain hydrocarbon radical having at least one triple bond and from two to ten carbon atoms; and cycloalkyl, alone or in combination, is a hydrocarbon ring radical having from three to eight carbon atoms.

6. The compound of claim 5 or a pharmaceutically acceptable salt or ester thereof, with the proviso that alkyl, alone or in combination, is a straight-chain or branched-chain hydrocarbon radical having from one to five carbon atoms; alkenyl, alone or in combination, is a straight-chain or branched-chain hydrocarbon radical having at least one double bond and from two to five carbon atoms; alkynyl, alone or in combination, is a straight-chain or branched-chain hydrocarbon radical having at least one triple bond and from two to five carbon atoms; and cycloalkyl, alone or in combination, is a hydrocarbon ring radical having from three to eight carbon atoms; and with the further proviso that when R.sub.2 is cycloalkylalkyl and t is 0, R' is a group other than alkoxycarbonyl.

7. The compound of claim 6 or a pharmaceutically acceptable salt or ester thereof, wherein: R.sup.2 is butyl, cyclohexylmethyl, benzyl, 4-fluorobenzyl or naphthylmethyl; R.sup.4 is methyl, ethyl, propyl, butyl, ethenyl, chloromethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, naphthyl, chlorophenyl, fluorophenyl, hydroxyphenyl, methylphenyl, methoxyphenyl, ethoxyphenyl, methylthiophenyl, methylsulfoxyphenyl, methylsulfonylphenyl, acetamidophenyl, methoxycarbonylphenyl, dimethylaminophenyl, nitrophenyl, trifluoromethylphenyl, benzyl, 2-phenylethenyl or thienyl; R.sup.6 is hydrogen; A is methyl, cyclohexyl, cyclopentyl, cycloheptyl, 1,2,3,4-tetrahydronaphthyl, naphthyl, quinolinyl, indolyl, pyridyl, methylpyridyl, furanyl, thiophenyl, oxazolyl, thiazolyl, phenyl, methylphenyl, ethylphenyl, dimethylphenyl, isopropylphenyl, chlorophenyl, hydroxyphenyl, methoxyphenyl, methylsulfonylphenyl, methylsulfonylmethylphenyl, carboxyphenyl, aminocarbonylphenyl, methylhydroxyphenyl, methylnitrophenyl, methylaminophenyl, methyl-N,N-dimethylaminophenyl, t-butoxy, benzyloxy, pyridylmethoxy, 3-propenoxy, hydroxypyridylmethoxy, aminopyridylmethoxy, pyrimidinylinethoxy, N-oxo-pyrimidinylmethoxy, thiazolylmethoxy, tetrahydrothiophenoxy, methylamino, benzylamino, or isopropylamino; or is A is a radical represented by the formula ##STR00498## wherein: R is a hydrogen radical, acetyl, phenoxyacetyl, methoxyacetyl, naphthaloxyacetyl, succinoyl, 2-methylpropionoyl, 2-hydroxypropionoyl, t-butoxycarbonyl, benzyloxycarbonyl, methoxybenzyloxycarbonyl, aminocarbonyl, quinolinylcarbonyl, N-methylglycinyl or N,N-dimethylglycinyl; R.sup.'is a hydrogen radical, benzyl or methyl; or R and R' together with the nitrogen to which they are attached form pyrrolyl; R.sup.1 is a hydrogen radical, --CO.sub.2H, --CH.sub.2CO.sub.2H, --CH.sub.2CH.sub.2CONH.sub.2, --CH.sub.2CONH.sub.2, --CONH.sub.2, --CH.sub.2C(O)NHCH.sub.3, --CH.sub.2C(O)N(CH.sub.3).sub.2, --CONHCH.sub.3, --CONH(CH.sub.3).sub.2, --CH.sub.2SO.sub.2NH.sub.2, --CH.sub.2CH.sub.2SO.sub.2NH.sub.2, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, 3-methylbutyl, cyclohexylmethyl, benzyl, hydroxybenzyl, imidazoyl, imidazoylmethyl, cyanomethyl, methylthiomethyl, propargyl or hydroxyethyl; R.sup.1' is a hydrogen radical, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, benzyl, phenylethyl, phenylpropyl, phenylbutyl or 4,4-diphenylbutyl; R.sup.1'' is a hydrogen radical, methyl, --CO.sub.2CH.sub.3, or CONH.sub.2; or one of R.sup.1' and R.sup.1'' together with R.sup.1 and the carbon atoms to which R.sup.1, R.sup.1', R.sup.1'' are bonded, forms cyclobutyl, cyclopenyl, or cyclohexyl.

8. A compound represented by the formula: ##STR00499## or a pharmaceutically acceptable salt or ester thereof, wherein: each of P.sup.1 and P.sup.2 independently represents a hydrogen radical, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, cycloalkylcarbonyl, cycloalkylalkoxycarbonyl, cycloalkylalkanoyl, alkanoyl, aralkanoyl, aroyl, aryloxycarbonyl, aryloxycarbonylalkyl, aryloxyalkanoyl, heterocyclylcarbonyl, heterocyclyloxycarbonyl, heterocyclylalkanoyl, heterocyclylalkoxycarbonyl, heteroaryloxycarbonyl, heteroaralkanoyl, heteroaralkoxycarbonyl, heteroaryloxycarbonyl. heteroaroyl, alkyl, alkenyl, 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 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 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.sup.2 is a substituent selected from the group consisting of alkyl, aryl, cycloalkyl, cycloalkylalkyl, and aralkyl, which substituent is optionally substituted with alkyl, halo, nitro, cyano, --CF.sub.3, --OR.sup.9, or --SR.sup.9, wherein R.sup.9 is a hydrogen radical or alkyl; and R.sup.4 is alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, 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.

9. The compound of claim 8 or a pharmaceutically acceptable salt or ester thereof, wherein: each of P.sup.1 and P.sup.2 independently represents a hydrogen radical, alkoxycarbonyl, aralkyloxycarbonyl, heteroaralkoxycarbonyl, aroyl, heteroaroyl, alkanoyl, or cycloalkanoyl; R.sup.2 is cycloalkylalkyl, aralkyl or alkyl; and R.sup.4 is alkyl, heteroaryl, or aryl.

10. The compound of claim 9 or a pharmaceutically acceptable salt or ester thereof, wherein: each of P.sup.1 and P.sup.2 independently represents 3-pyridylmethyloxycarbonyl, 3-pyridylmethyloxycarbonyl N-oxide,4-pyridylmethyloxycarbonyl, 4-pyridylmethyloxycarbonyl N-oxide, 5-pyridylmethyloxycarbonyl, tert-butyloxycarbonyl, allyloxycarbonyl, 2-propyloxycarbonyl, benzyloxycarbonyl, cycloheptylcarbonyl, cyclohexylcarbonyl, cyclopentylcarbonyl, benzoyl, 4-pyridylcarbonyl, 2-methylbenzoyl, 3-methylbenzoyl, 4-methylbenzoyl, 2-chlorobenzoyl, 2-ethylbenzoyl, 2,6-dimethylbenzoyl, 2,3-dimethylbenzoyl, 2,4-dimethylbenzoyl or 2,5-dimethylbenzoyl; R.sup.2 is benzyl, cyclohexylmethyl, 2-naphthylmethyl, para-fiuorobenzyl, para-methoxybenzyl, isobutyl or n-butyl; R.sup.4 is phenyl, para-methoxyphenyl, para-cyanophenyl, para-chlorophenyl, para-hydroxyphenyl, para-nitrophenyl, para-fluorophenyl, 2-naphthyl, 3-pyridyl, 3-pyridyl N-oxide, 4-pyridyl, or 4-pyridyl N-oxide with the proviso that when R.sup.2 is cyclohexylmethyl, each of P.sup.1 and P.sup.2 independently represent a group other than tert-butyloxycarbonyl.

11. The compound of claim 1 represented by the formula: ##STR00500## or a pharmaceutically acceptable salt or ester thereof, wherein A, Y, R.sup.2, R.sup.4, and R.sup.6 are as defined in claim 1.

12. The compound of claim 8 represented by the formula: ##STR00501## or a phannaceutically acceptable salt or ester thereof, wherein P.sup.1, P.sup.2, R.sup.2 and R.sup.4 are as defined in claim 8.

13. The compound of claim 1, wherein said pharmaceutically acceptable salt is selected from the group consisting of an acetate salt, an adipate salt, an alginate salt, a citrate salt, an aspartate salt, a benzoate salt, a benzenesulfonate salt, a bisulfate salt, a butyrate salt, a camnhorate salt, a camphorsulfonate salt, a digluconate salt, a cyclopentanepropionate salt, a dodecylsulfate salt, an ethanesulfonate salt, a glucoheptanoate salt, a glycerophosphate salt, a hemisulfate salt, a heptanoate salt, a hexanoate salt, a fumarate salt, a hydrochloride salt, a hydrobromide salt, a hydroiodide salt, a 2-hydroxy-ethanesulfonate salt, a lactate salt, a maleate salt, a methanesulfonate salt, a nicotinate salt, a 2-naphthalenesulfonate salt, an oxalate salt, a palmoate salt, a pectinate salt, a persulfate salt, a 3-phenylpropionate salt, a picrate salt, a pivalate salt, a propionate salt, a succinate salt, a tartrate salt, a thiocyanate salt, a tosylate salt, a mesylate salt, and an undecanoate salt.

14. The compound of claim 8 wherein said pharmaceutically acceptable salt is selected from the group consisting of an acetate salt, an adipate salt, an alginate salt, a citrate salt, an aspartate salt, a benzoate salt, a benzenesulfonate salt, a bisulfate salt, a butyrate salt, a camphorate salt, a camphorsulfonate salt, a digluconate salt, a cyclopentanepropionate salt, a dodecylsulfate salt, an ethanesulfonate salt, a glucoheptanoate salt, a glycerophosphate salt, a hemisulfate salt, a heptanoate salt, a hexanoate salt, a fumarate salt, a hydrochloride salt, a hydrobromide salt, a hydroiodide salt, a 2-hydroxy-ethanesulfonate salt, a lactate salt, a maleate salt, a methanesulfonate salt, a nicotinate salt, a 2-naphthalenesulfonate salt, an oxalate salt, a palmoate salt, a pectinate salt, a persulfate salt, a 3-phenylpropionate salt, a picrate salt, a pivalate salt, a propionate salt, a succinate salt, a tartrate salt, a thiocyanate salt, a tosylate salt, a mesylate salt, and an undecanoate salt.

15. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt or ester thereof.

16. A pharmaceutical composition comprising a compound of claim 8 or a pharmaceutically acceptable salt or ester thereof.
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