.

Pharmaceutical Business Intelligence

  • Anticipate P&T budget requirements
  • Evaluate market entry opportunities
  • Find generic sources and suppliers
  • Predict branded drug patent expiration

► Plans and Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

DrugPatentWatch Database Preview

Details for Patent: 7,531,538

« Back to Dashboard

Details for Patent: 7,531,538

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. (Brentwood, MO), Getman; Daniel P. (Chesterfield, MO), DeCrescenzo; Gary A. (St. Peters, MO), Freskos; John N. (Clayton, MO), Bertenshaw; Deborah E. (Brentwood, MO), Heintz; Robert M. (Ballwin, MO)
Assignee: G.D. Searle LLC (New York, NY)
Filing Date:May 15, 2006
Application Number:11/433,797
Claims:1. A compound represented by the formula: ##STR00749## or a pharmaceutically acceptable salt thereof, wherein R.sup.2 is an alkyl, aryl, cycloalkyl, cycloalkylalkyl or aralkyl radical, which radical is optionally substituted with a radical selected from the group consisting of alkyl, halo, nitro, cyano, CF.sub.3, --OR.sup.9, and --SR.sup.9, wherein R.sup.9 is a radical selected from the group consisting of hydrogen and alkyl; R.sup.3 is a hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl, alkylsulfonylalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, heteroaralkyl, aminoalkyl or mono- or disubstituted aminoalkyl radicals, wherein said substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl and heterocycloalkylalkyl radicals; or where said aminoalkyl radical is disubstituted, said substituents along with the nitrogen atom to which they are attached, form a heterocycloalkyl or a heteroaryl radical; R.sup.4 is an alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, aralkenyl, or heteroaralkyl; R.sup.6 is a hydrogen or alkyl radical; x is 1 or 2; t is 0 or 1; and Y is O or S; and A is an 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 disubstituted amino radical, wherein the substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl and heterocycloalkyalkyl radicals; or where said amino radical is disubstituted, said substituents along with the nitrogen atom to which they are attached form a heterocycloalkyl or heteroaryl radical; or is represented by the formula ##STR00750## wherein R is a hydrogen, 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 disubstituted aminocarbonyl or mono- or disubstituted aminoalkanoyl radical, wherein the substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl and heterocycloalkyalkyl radicals; or wherein said aminocarbonyl or aminoalkanoyl radicals are disubstituted, said substituents along with the nitrogen atom to which they are attached form a heterocycloalkyl or heteroaryl radical; R' is a radical as defined for R.sup.3 or R''SO.sub.2--, wherein R'' is a radical as defined for R.sup.3; or R and R' together with the nitrogen to which they are attached form a heterocycloalkyl or heteroaryl radical; R.sup.1 is a hydrogen, --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, --C(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 disubstituted aminoalkyl radical, wherein said substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl and heterocycloalkylalkyl radicals; or where said aminoalkyl radical is disubstituted, said substituents along with the nitrogen atom to which they are attached, form a heterocycloalkyl or a heteroaryl radical; and each of R.sup.1' and R.sup.1'' are independently a radical 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' and R.sup.1'' are attached, form a cycloalkyl radical, wherein aryl is a phenyl or naphthyl radical optionally substituted with alkyl, alkoxy, halo, hydroxyl, amino, nitro, cyano, haloalkyl, carboxy, alkoxycarbonyl, cycloalkyl, heterocycloalkyl, amido, monoalkyl substituted amino, dialkyl substituted amino, monoalkyl substituted amido, or dialkyl substituted amido.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R.sup.2 is CH.sub.3SCH.sub.2CH.sub.2--, iso-butyl, n-butyl, benzyl, 4-fluorobenzyl, 2-naphthylmethyl, or cyclohexylmethyl; R.sup.3 is alkyl, cyclohexyl, iso-butyl, iso-amyl, or n-butyl; and R.sup.4 is phenyl, optionally substituted with a radical selected from the group consisting of halo, alkoxy, amino, and nitro.

3. The compound of claim 2 or a pharmaceutically acceptable salt thereof, wherein R.sup.2 is benzyl; R.sup.3 is iso-butyl; and R.sup.4 is phenyl that is substituted with a radical selected from the group consisting of halo, alkoxy, amino, and nitro.

4. A compound represented by the formula: ##STR00751## or a pharmaceutically acceptable salt thereof, wherein R.sup.2 is an alkyl, aryl, cycloalkyl, cycloalkylalkyl or aralkyl radical, which radical is optionally substituted with a radical selected from the group consisting of alkyl, halo, nitro, cyano, CF.sub.3, --OR.sup.9, and --SR.sup.9, wherein R.sup.9 is a radical selected from the group consisting of hydrogen and alkyl; R.sup.4 is an alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, aralkenyl, heteroaralkyl, aminoalkyl or mono- or disubstituted aminoalkyl radical, wherein said substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl and heterocycloalkylalkyl radicals; or where said aminoalkyl radical is disubstituted, said substituents along with the nitrogen atom to which they are attached, form a heterocycloalkyl or a heteroaryl radical; R.sup.6 is a hydrogen or alkyl radical; x is 1 or 2; t is 0 or 1; and Y is O or S; and A is an 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 disubstituted amino radical, wherein the substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl and heterocycloalkyalkyl radicals; or where said amino radical is disubstituted, said substituents along with the nitrogen atom to which they are attached form a heterocycloalkyl or heteroaryl radical; or is represented by the formula ##STR00752## wherein R is a hydrogen, 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 disubstituted aminocarbonyl or mono- or disubstituted aminoalkanoyl radical, wherein the substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl and heterocycloalkyalkyl radicals; or wherein said aminocarbonyl or aminoalkanoyl radicals are disubstituted, said substituents along with the nitrogen atom to which they are attached form a heterocycloalkyl or heteroaryl radical; R' is a radical as defined for R.sup.3 or R''SO.sub.2--, wherein R'' is a radical as defined for R.sup.3; or R and R' together with the nitrogen to which they are attached form a heterocycloalkyl or heteroaryl radical; R.sup.1 is a hydrogen, --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, --C(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 disubstituted aminoalkyl radical, wherein said substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl and heterocycloalkylalkyl radicals; or where said aminoalkyl radical is disubstituted, said substituents along with the nitrogen atom to which they are attached, form a heterocycloalkyl or a heteroaryl radical; and each of R.sup.1' and R.sup.1'' are independently a radical 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' and R.sup.1'' are attached, form a cycloalkyl radicals, wherein aryl is a phenyl or naphthyl radical optionally substituted with alkyl, alkoxy, halo, hydroxyl, amino, nitro, cyano, haloalkyl, carboxy, alkoxycarbonyl, cycloalkyl, heterocycloalkyl, amido, monoalkyl substituted amino, dialkyl substituted amino, monoalkyl substituted amido, or dialkyl substituted amido.

5. The compound of claim 4 or a pharmaceutically acceptable salt thereof, wherein R.sup.2 is an alkyl, aryl, cycloalkyl, cycloalkylalkyl or aralkyl radical, which radical is optionally substituted with a radical selected from the group consisting of alkyl, halo and --OR.sup.9, wherein R.sup.9 is a radical selected from the group consisting of hydrogen and alkyl; R.sup.4 is an alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, aralkenyl or heteroaralkyl radical; R.sup.6 is a hydrogen or alkyl radical; x is 1 or 2; t is 0 or 1; and Y is O or S; and A is an alkoxy, alkenoxy, aralkoxy, alkyl, cycloalkyl, cycloalkylalkoxy, cycloalkylalkyl, aralkyl, aryl, aryloxy, heterocycloalkyl, heterocycloalkoxy, heterocycloalkylalkyl, heterocycloalkylalkoxy, heteroaralkyl, heteroaralkoxy, heteroaryloxy, heteroaryl, hydroxyalkyl, amino, or mono- or disubstituted amino radical, wherein the substituents are selected from the group consisting of alkyl, aralkyl, heteroaryl, heteroaralkyl, heterocycloalkyl and heterocycloalkyalkyl radicals; or where said amino radical is disubstituted, said substituents along with the nitrogen atom to which they are attached form a heterocycloalkyl radical; or is represented by the formula ##STR00753## wherein R is a hydrogen, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, carboxyalkanoyl, alkanoyl, aralkanoyl, aroyl, heterocyclylcarbonyl, heterocyclyloxycarbonyl, heterocyclylalkanoyl, heterocyclylalkoxycarbonyl, heteroaralkanoyl, heteroaralkoxycarbonyl, heteroaryloxy-carbonyl, heteroaroyl, alkyl, cycloalkyl, aralkyl, hydroxyalkyl, aminocarbonyl, aminoalkanoyl, or mono- or disubstituted aminocarbonyl or mono- or disubstituted aminoalkanoyl radical, wherein the substituents are selected from the group consisting of alkyl, aralkyl, heteroaryl, heteroaralkyl, heterocycloalkyl and heterocycloalkyalkyl radicals; or wherein said aminocarbonyl or aminoalkanoyl radicals are disubstituted, said substituents along with the nitrogen atom to which they are attached form a heterocycloalkyl or heteroaryl radical; R' is a hydrogen, alkyl or aralkyl radical or R''SO.sub.2--, wherein R'' is a radical as defined for R.sup.3; or R and R' together with the nitrogen to which they are attached form a heterocycloalkyl or heteroaryl radical; R.sup.1 is a hydrogen, --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, --C(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 disubstituted aminoalkyl radical, wherein said substituents are selected from the group consisting of alkyl, aralkyl, heteroaryl, heteroaralkyl, heterocycloalkyl and heterocycloalkylalkyl radicals; or where said aminoalkyl radical is disubstituted, said substituents along with the nitrogen atom to which they are attached, form a heterocycloalkyl or a heteroaryl radical; and each of R.sup.1' and R.sup.1'' are independently a radical 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' and R.sup.1'' are attached, form a cycloalkyl radical.

6. The compound of claim 5 or a pharmaceutically acceptable salt thereof, wherein R.sup.2 is an alkyl, aryl, cycloalkyl, cycloalkylalkyl or aralkyl radical, which radical is optionally substituted with a radical selected from the group consisting of alkyl, halo and --OR.sup.9, wherein R.sup.9 is a radical selected from the group consisting of hydrogen and alkyl; R.sup.4 is an alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, aralkenyl or heteroaralkyl radical; R.sup.6 is a hydrogen or alkyl radical; x is 1 or 2; t is 0 or 1; and Y is O or S; and A is an alkoxy, alkenoxy, aralkoxy, alkyl, cycloalkyl, aryl, heterocycloalkyl, heterocycloalkoxy, heterocycloalkylalkyl, heteroaralkoxy, heteroaryl, amino, or mono- or disubstituted amino radical, wherein the substituents are selected from the group consisting of alkyl and aralkyl radicals; or is represented by the formula ##STR00754## wherein R is a hydrogen, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, carboxyalkanoyl, alkanoyl, aroyl, heteroaroyl, alkyl, aralkyl, aminocarbonyl, aminoalkanoyl, or mono- or disubstituted aminocarbonyl or mono- or disubstituted aminoalkanoyl radical, wherein the substituents are selected from the group consisting of alkyl and aralkyl radicals; R' is a hydrogen, alkyl or aralkyl radical or R''SO.sub.2--, wherein R'' is a radical as defined for R.sup.3; or R and R' together with the nitrogen to which they are attached form a heterocycloalkyl or heteroaryl radical; R.sup.1 is a hydrogen, --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, --C(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 disubstituted aminoalkyl radical, wherein said substituents are selected from the group consisting of alkyl and aralkyl radicals; and R.sup.1' is a hydrogen, alkyl or aralkyl; and R.sup.1'' is a hydrogen, 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' and R.sup.1'' are attached, form a cycloalkyl radical.

7. The compound of claim 6 or a pharmaceutically acceptable salt thereof, wherein R.sup.2 is an alkyl, cycloalkylalkyl or aralkyl radical, which radical is optionally substituted with a radical selected from the group consisting of alkyl, halo and --OR.sup.9, wherein R.sup.9 is a radical selected from the group consisting of hydrogen and alkyl; R.sup.4 is an alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, aralkenyl or heteroaralkyl radical; R.sup.6 is a hydrogen or alkyl radical; x is 1 or 2; t is 0 or 1; and Y is O or S; and A is an alkoxy, alkenoxy, aralkoxy, alkyl, cycloalkyl, aryl, heterocycloalkyl, heterocycloalkoxy, heterocycloalkylalkyl, heteroaralkoxy, heteroaryl, amino, or mono- or disubstituted amino radical, wherein the substituents are selected from the group consisting of alkyl and aralkyl radicals; or is represented by the formula ##STR00755## wherein R is a hydrogen, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, carboxyalkanoyl, alkanoyl, aroyl, heteroaroyl, alkyl, aralkyl, aminocarbonyl, aminoalkanoyl, or mono- or disubstituted aminocarbonyl or mono- or disubstituted aminoalkanoyl radical, wherein the substituents are selected from the group consisting of alkyl and aralkyl radicals; R' is a hydrogen, alkyl or aralkyl radical or R''SO.sub.2--, wherein R'' is a radical as defined for R.sup.3; or R and R' together with the nitrogen to which they are attached form a heterocycloalkyl or heteroaryl radical; R.sup.1 is a hydrogen, --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 radical; and R.sup.1' is a hydrogen, alkyl or aralkyl; and R.sup.1'' is a hydrogen, 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' and R.sup.1'' are attached, form a cycloalkyl radical; with the proviso that alkyl, alone or in combination, is a straight-chain or branched-chain hydrocarbon radical containing 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 containing 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 containing from two to ten carbon atoms; and cycloalkyl, alone or in combination, is a hydrocarbon ring containing from three to eight carbon atoms.

8. The compound of claim 7 or a pharmaceutically acceptable salt thereof, wherein R.sup.2 is an alkyl, cycloalkylalkyl or aralkyl radical, which radical is optionally substituted with a radical selected from the group consisting of alkyl, halo and --OR.sup.9, wherein R.sup.9 is a radical selected from the group consisting of hydrogen and alkyl; R.sup.4 is an alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, aralkenyl or heteroaralkyl radical; R.sup.6 is a hydrogen or alkyl radical; x is 1 or 2; t is 0 or 1; and Y is O or S; and A is an alkoxy, alkenoxy, aralkoxy, alkyl, cycloalkyl, aryl, heterocycloalkyl, heterocycloalkoxy, heterocycloalkylalkyl, heteroaralkoxy, heteroaryl, amino, or mono- or disubstituted amino radical, wherein the substituents are selected from the group consisting of alkyl and aralkyl radicals; or is represented by the formula ##STR00756## wherein R is a hydrogen, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, carboxyalkanoyl, alkanoyl, aroyl, heteroaroyl, alkyl, aralkyl, aminocarbonyl, aminoalkanoyl, or mono- or disubstituted aminocarbonyl or mono- or disubstituted aminoalkanoyl radical, wherein the substituents are selected from the group consisting of alkyl and aralkyl radicals; R' is a hydrogen, alkyl or aralkyl radical or R''SO.sub.2--, wherein R'' is a radical as defined for R.sup.3; or R and R' together with the nitrogen to which they are attached form a heterocycloalkyl or heteroaryl radical; R.sup.1 is a hydrogen, --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 radical; and R.sup.1' is a hydrogen, alkyl or aralkyl; and R.sup.1'' is a hydrogen, 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' and R.sup.1'' are attached, form a cycloalkyl radical; with the proviso that alkyl, alone or in combination, is a straight-chain or branched-chain hydrocarbon radical containing 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 containing 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 containing from two to five carbon atoms; and cycloalkyl, alone or in combination, is a hydrocarbon ring containing from three to eight carbon atoms.

9. The compound of claim 8 or a pharmaceutically acceptable salt 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, acetamidophenyl, methoxycarbonylphenyl, dimethylaminophenyl, nitrophenyl, trifluoromethylphenyl, benzyl, 2-phenylethenyl or thienyl; R.sup.6 is hydrogen; x is 2; t is or 1; and Y is O; R' is hydrogen, benzyl or methyl; or R and R' together with the nitrogen to which they are attached form pyrrolyl; and R.sup.1' is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, benzyl, phenylethyl, phenylpropyl, phenylbutyl or 4,4-diphenylbutyl; and R.sup.1'' is hydrogen, 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' and R.sup.1'' are attached, form cyclobutyl, cyclopentyl or cyclohexyl.

10. The compound of claim 4 or a pharmaceutically acceptable salt thereof, wherein, in said formula, the stereochemistry of the carbon atom bonded to the hydroxyl radical is designated as (R).

11. The compound of claim 10, represented by the formula ##STR00757## or a pharmaceutically acceptable salt thereof.

12. A compound represented by the formula: ##STR00758## or a pharmaceutically acceptable salt thereof, wherein P.sup.1 and P.sup.2 independently represent hydrogen, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, cycloalkylcarbonyl, cycloalkylalkoxycarbonyl, cycloalkylalkanoyl, alkanoyl, aralkanoyl, aroyl, aryloxycarbonyl, aryloxycarbonylalkyl, aryloxyalkanoyl, heterocyclylcarbonyl, heterocyclyloxycarbonyl, heterocyclylalkanoyl, heterocyclylalkoxycarbonyl, heteroaralkanoyl, heteroaralkoxycarbonyl, heteroaryloxycarbonyl, heteroaroyl, alkyl, alkenyl, cycloalkyl, aryl, aralkyl, aryloxyalkyl, heteroaryloxyalkyl, hydroxyalkyl, aminocarbonyl, aminoalkanoyl, or mono- or disubstituted aminocarbonyl or mono- or disubstituted aminoalkanoyl radical, wherein the substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl and heterocycloalkyalkyl radicals; or where said aminoalkanoyl radical is disubstituted, said substituents along with the nitrogen atom to which they are attached form a heterocycloalkyl or heteroaryl radical; R.sup.2 is an alkyl, aryl, cycloalkyl, cycloalkylalkyl or aralkyl radical, which radicals are optionally substituted with a group selected from alkyl and halogen radicals, nitro, cyano, CF.sub.3, --OR.sup.9, and --SR.sup.9, wherein R.sup.9 is a hydrogen or alkyl radical; R.sup.3 is a hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heteroaryl, heterocycloalkylalkyl, aryl, aralkyl, heteroaralkyl, aminoalkyl or mono- or disubstituted aminoalkyl radical, wherein said substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl and heterocycloalkylalkyl radicals; or where the aminoalkyl radical is disubstituted, said substituents along with the nitrogen atom to which they are attached, form a heterocycloalkyl or a heteroaryl radical; and R.sup.4 is a radical as defined by R.sup.3 except for hydrogen, wherein aryl is a phenyl or naphthyl radical optionally substituted with alkyl, alkoxy, halo, hydroxyl, amino, nitro, cyano, haloalkyl, carboxy, alkoxycarbonyl, cycloalkyl, heterocycloalkyl, amido, monoalkyl substituted amino, dialkyl substituted amino, monoalkyl substituted amido, or dialkyl substituted amido, and wherein at least one of P.sup.1 and P.sup.2 is other than hydrogen.

13. The compound of claim 12 or a pharmaceutically acceptable salt thereof, wherein R.sup.2 is CH.sub.3SCH.sub.2CH.sub.2--, iso-butyl, n-butyl, benzyl, 4-fluorobenzyl, 2-naphthylmethyl, or cyclohexylmethyl; R.sup.3 is alkyl, cyclohexyl, iso-butyl, iso-amyl, or n-butyl; and R.sup.4 is phenyl, optionally substituted with a radical selected from the group consisting of halo, alkoxy, amino, and nitro.

14. The compound of claim 13 or a pharmaceutically acceptable salt thereof, wherein R.sup.2 is benzyl; R.sup.3 is iso-butyl; and R.sup.4 is phenyl that is substituted with a radical selected from the group consisting of halo, alkoxy, amino, and nitro.

15. A compound represented by the formula: ##STR00759## or a pharmaceutically acceptable salt thereof, wherein P.sup.1 and P.sup.2 independently represent hydrogen, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, cycloalkylcarbonyl, cycloalkylalkoxycarbonyl, cycloalkylalkanoyl, alkanoyl, aralkanoyl, aroyl, aryloxycarbonyl, aryloxycarbonylalkyl, aryloxyalkanoyl, heterocyclylcarbonyl, heterocyclyloxycarbonyl, heterocyclylalkanoyl, heterocyclylalkoxycarbonyl, heteroaralkanoyl, heteroaralkoxycarbonyl, heteroaryloxycarbonyl, heteroaroyl, alkyl, alkenyl, cycloalkyl, aryl, aralkyl, aryloxyalkyl, heteroaryloxyalkyl, hydroxyalkyl, aminocarbonyl, aminoalkanoyl, or mono- or disubstituted aminocarbonyl or mono- or disubstituted aminoalkanoyl radical, wherein the substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroaralkyl, heterocycloalkyl and heterocycloalkyalkyl radicals; or where said aminoalkanoyl radical is disubstituted, said substituents along with the nitrogen atom to which they are attached form a heterocycloalkyl or heteroaryl radical; R.sup.2 is an alkyl, aryl, cycloalkyl, cycloalkylalkyl or aralkyl radical, which radicals are optionally substituted with a group selected from alkyl and halogen radicals, nitro, cyano, CF.sub.3, --OR.sup.9, and --SR.sup.9, wherein R.sup.9 is a hydrogen or alkyl radical; and R.sup.4 is phenyl that is optionally substituted with a radical selected from the group consisting of halo, alkoxy, amino, and nitro, wherein at least one of P.sup.1 and P.sup.2 is other than hydrogen.

16. The compound of claim 15 or a pharmaceutically acceptable salt thereof, wherein P.sup.1 and P.sup.2 independently represent a hydrogen, alkoxycarbonyl, aralkyloxycarbonyl, heteroaralkoxycarbonyl, aroyl, heteroaroyl, alkanoyl or cycloalkanoyl radical; R.sup.2 is a cycloalkylalkyl, aralkyl or alkyl radical.

17. The compound of claim 15, wherein R.sup.2 is benzyl, and whereby said compound is represented by the formula: ##STR00760## or a pharmaceutically acceptable salt thereof.

18. The compound of claim 15 or a pharmaceutically acceptable salt thereof, wherein, in said formula, the stereochemistry of the carbon atom bonded to the hydroxyl radical is designated as (R).

19. The compound of claim 18, represented by the formula: ##STR00761## or a pharmaceutically acceptable salt thereof.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

`abc