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Details for Patent: 6,455,581

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Details for Patent: 6,455,581

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 & Co. (Chicago, IL)
Filing Date:May 25, 1995
Application Number:08/451,090
Claims:1. A compound represented by the formula (A): ##STR470##

or a pharmaceutically acceptable salt, or ester 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, aryl, aralkyl, aminoalkyl or mono- or disubstituted aminoalkyl radicals, wherein said substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl and cycloalkylalkyl radicals; R.sup.4 is an alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, aralkenyl, aminoalkyl or mono- or disubstituted aminoalkyl radical, wherein said substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl and cycloalkylalkyl radicals; R.sup.6 is a hydrogen or alkyl radical; x is 1 or 2; Y is 0 or S; and A is an alkoxy, alkenoxy, aralkoxy, alkyl, cycloalkyl, cycloalkylalkoxy, ##STR471##

cycloalkylalkyl, aralkyl, aryl, aryloxy, alkenyl, aryloxyalkyl, hydroxyalkyl, amino, or mono- or disubstituted amino radical, wherein the substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl and cycloalkylalkyl radicals; or is represented by the formula (B): ##STR472## t is 0or 1; wherein R is a hydrogen, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, cycloalkylcarbonyl, cycloalkylalkoxycarbonyl, cycloalkylalkanoyl, carboxyalkanoyl, alkanoyl, aralkanoyl, aroyl, aryloxycarbonyl, aryloxycarbonylalkyl, aryloxyalkanoyl, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, aryloxyalkyl, hydroxyalkyl, aminocarbonyl, aminoalkanoyl, or mono- or disubstituted aminocarbonyl or mon- or disubstituted aminoalkanoyl radical, wherein the substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl and cycloalkylalkyl radicals; 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 ; R.sup.1 is a hydrogen, --CO.sub.2 CH.sub.3, --CH.sub.2 CO.sub.2 CH.sub.3, --CO.sub.2 H, --CH.sub.2 CO.sub.2 H, --CH.sub.2 CH.sub.2 CONH.sub.2, --CH.sub.2 CONH.sub.2, --CONH.sub.2, --CH.sub.2 C(O)NHCH.sub.3, --CH.sub.2 C(O)N(CH.sub.3).sub.2, --CONHCH.sub.3, --CONH(CH.sub.3).sub.2, --CH.sub.2 SO.sub.2 NH.sub.2, --CH.sub.2 CH.sub.2 SO.sub.2 NH.sub.2, --CH.sub.2 S(O)CH.sub.3, --CH.sub.2 S(O).sub.2 CH.sub.3, --C(CH.sub.3).sub.2 (S(O)CH.sub.3), --C(CH.sub.3).sub.2 (S(O).sub.2 CH.sub.3), alkyl, hydroxyalkyl, cyanoalkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, alkylthioalkyl, aralkyl, aminoalkyl or mono- or disubstituted aminoalkyl radical, wherein said substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl and cycloalkylalkyl radicals; 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.

2. The compound of claim 1 or a pharmaceutically acceptable salt, prodrug or ester 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.3 is a hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl, alkylsulfonylalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, aminoalkyl or mono- or disubstituted aminoalkyl radicals, wherein said substituents are selected from the group consisting of alkyl, aralkyl, cycloalkyl and cycloalkylalkyl radicals; R.sup.4 is an alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, or aralkyl, aralkenyl; R.sup.6 is a hydrogen or alkyl radical; x is 1 or 2; t is 0 or 1; and Y is 0 or S; and A is an alkoxy, alkenoxy, aralkoxy, alkyl, cycloalkyl, cycloalkylalkoxy, cycloalkylalkyl, aralkyl, aryl, aryloxy, amino, or mono- or disubstituted amino radical, wherein the substituents are selected from the group consisting of alkyl, and aralkyl, represented by the formula ##STR473## wherein R is a hydrogen, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, carboxyalkanoyl, alkanoyl, aralkanoyl, aroyl, 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, and aralkyl; 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.2 CH.sub.3, --CH.sub.2 CO.sub.2 CH.sub.3, --CO.sub.2 H, --CH.sub.2 CO.sub.2 H, --CH.sub.2 CH.sub.2 CONH.sub.2, --CH.sub.2 CONH.sub.2, --CONH.sub.2, --CH.sub.2 C(O) NHCH.sub.3, --CH.sub.2 C(O)N(CH.sub.3).sub.2, --CONHCH.sub.3, --CONH(CH.sub.3).sub.2, --CH.sub.2 SO.sub.2 NH.sub.2, --CH.sub.2 CH.sub.2 SO.sub.2 NH.sub.2, --CH.sub.2 S[O]CH.sub.3, --CH.sub.2 S [O].sub.2 CH.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.2 CH.sub.3), alkyl, hydroxyalkyl, cyanoalkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, alkylthioalkyl, aralkyl, aminoalkyl or mono- or disubstituted aminoalkyl radical, wherein said substituents are selected from the group consisting of alkyl, and aralkyl, radicals; 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.

3. The compound of claim 2 or a pharmaceutically acceptable salt, prodrug or ester 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.3 is a hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl, alkylsulfonylalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, aminoalkyl or mono- or dialkyl substituted aminoalkyl radical; R.sup.4 is an alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, or aralkenyl radical; R.sup.6 is a hydrogen or alkyl radical; x is 1 or 2; t is 0 or 1; and Y is 0 or S; and A is an alkoxy, alkenoxy, aralkoxy, alkyl, cycloalkyl, aryl, 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 ##STR474## wherein R is a hydrogen, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, carboxyalkanoyl, alkanoyl, aroyl, 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 ; R.sup.1 is a hydrogen, --CO.sub.2 CH.sub.3, --CH.sub.2 CO.sub.2 CH.sub.3, --CO.sub.2 H, --CH.sub.2 CO.sub.2 H, --CH.sub.2 CH.sub.2 CONH.sub.2, --CH.sub.2 CONH.sub.2, --CONH.sub.2, --CH.sub.2 C(O)NHCH.sub.3, --CH.sub.2 C(O)N(CH.sub.3).sub.2, --CONHCH.sub.3, --CONH(CH.sub.3).sub.2, --CH.sub.2 SO.sub.2 NH.sub.2, --CH.sub.2 CH.sub.2 SO.sub.2 NH.sub.2, --CH.sub.2 S[O]CH.sub.3, --CH.sub.2 S[O].sub.2 CH.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.2 CH.sub.3), alkyl, hydroxyalkyl, cyanoalkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, alkylthioalkyl, aralkyl, 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.2 CH.sub.3 or --CONH.sub.2 ; or one of R.sup.1 ' and R.sup.1 " tog ther 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.

4. The compound of claim 3 or a pharmaceutically acceptable salt, prodrug or ester 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.3 is a hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl, alkylsulfonylalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, aminoalkyl or mono- or dialkyl substituted aminoalkyl radical; R.sup.4 is an alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, or aralkenyl or radical; R.sup.6 is a hydrogen or alkyl radical; x is 1 or 2; t is 0 or 1; and Y is 0 or S; and A is an alkoxy, alkenoxy, aralkoxy, alkyl, cycloalkyl, aryl, 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 ##STR475## wherein R is a hydrogen, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, carboxyalkanoyl, alkanoyl, aroyl, 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.2 H, --CH.sub.2 CO.sub.2 H, --CH.sub.2 CH.sub.2 CONH.sub.2, --CH.sub.2 CONH.sub.2, --CONH.sub.2, --CH.sub.2 C(O)NHCH.sub.3, --CH.sub.2 C(O)N(CH.sub.3).sub.2, --CONHCH.sub.3, --CONH(CH.sub.3).sub.2, --CH.sub.2 SO.sub.2 NH.sub.2, --CH.sub.2 CH.sub.2 SO.sub.2 NH.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.2 CH.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.

5. The compound of claim 4 or a pharmaceutically acceptable salt, prodrug or ester 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.3 is a hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl, alkylsulfonylalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaralkyl, aminoalkyl or mono- or dialkyl substituted aminoalkyl radical; R.sup.4 is an alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, or aralkenyl radical; R.sup.6 is a hydrogen or alkyl radical; x is 1 or 2; t is 0 or 1; and Y is 0 or S; and A is an alkoxy, alkenoxy, aralkoxy, alkyl, cycloalkyl, aryl, 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 ##STR476## 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 ; R.sup.1 is a hydrogen, --CO.sub.2 H, --CH.sub.2 CO.sub.2 H, --CH.sub.2 CH.sub.2 CONH.sub.2, --CH.sub.2 CONH.sub.2, --CONH.sub.2, --CH.sub.2 C(O)NHCH.sub.3, --CH.sub.2 C(O)N(CH.sub.3).sub.2, --CONHCH.sub.3, --CONH(CH.sub.3).sub.2, --CH.sub.2 SO.sub.2 NH.sub.2, --CH.sub.2 CH.sub.2 SO.sub.2 NH.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.2 CH.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; and with the proviso that when R.sup.2 is cycloalkylalkyl and t is 0, R' is a group other than alkoxycarbonyl.

6. The compound of claim 5 or a pharmaceutically acceptable salt, prodrug or ester thereof, wherein R.sup.2 is butyl, cyclohexylmethyl, benzyl, 4-fluorobenzyl or naphthylmethyl; R.sup.3 is methyl, ethyl, propyl, butyl, pentyl, hexyl, iso-butyl, iso-amyl, 3-methoxypropyl, 3-methylthiopropyl, 4-methylthiobutyl, 4-methylsulfonylbutyl, 2-dimethylaminoethyl, 2-(1-morpholino)ethyl, 4-hydroxybutyl, allyl, propargyl, cyclohexylmethyl, cyclopropylmethyl, phenyl, benzyl, 4-fluorobenzyl, 4-methoxybenzyl, 1-phenylethyl, 2-phenylethyl, 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; x is 2; t is 0 or 1; and Y is 0; and A is methyl, cyclohexyl, cyclopentyl, cycloheptyl, 1,2,3,4-tetrahydronaphthyl, naphthyl, quinolinyl, thiophenyl, phenyl, methylphenyl, ethylphenyl, dimethylphenyl, iso-propylphenyl, chlorophenyl, hydroxyphenyl, methoxyphenyl, methylsulfonylphenyl, methylsulfonylmethylphenyl, carboxyphenyl, aminocarbonylphenyl, methylhydroxyphenyl, methylnitrophenyl, methylaminophenyl, methyl-N,N-dimethylaminophenyl, t-butoxy, benzyloxy, 3-propenoxy, methylamino, benzylamino or isopropylamino; or is represented by the formula ##STR477## wherein R is hydrogen, acetyl, phenoxyacetyl, methoxyacetyl, naphthaloxyacetyl, succinoyl, 2-methylpropionoyl, 2-hydroxypropionoyl, t-butoxycarbonyl, benzyloxycarbonyl, methoxybenzyloxycarbonyl, aminocarbonyl, quinolinylcarbonyl, N-methylglycinyl or N,N-dimethylglycinyl; R' is hydrogen, benzyl or methyl; or R.sup.1 is hydrogen, --CO.sub.2 H, --CH.sub.2 CO.sub.2 H, --CH.sub.2 CH.sub.2 CONH.sub.2, --CH.sub.2 CONH.sub.2, --CONH.sub.2, --CH.sub.2 C(O)NHCH.sub.3, --CH.sub.2 C(O)N(CH.sub.3).sub.2, --CONHCH.sub.3, --CONH(CH.sub.3).sub.2, --CH.sub.2 SO.sub.2 NH.sub.2, --CH.sub.2 CH.sub.2 SO.sub.2 NH.sub.2, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, 3-methylbutyl, cyclohexylmethyl, benzyl, hydroxybenzyl, imidazoyl, imidazoylmethyl, cyanomethyl, methylthiomethyl, propargyl or hydroxyethyl; 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.2 CH.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; with the proviso that when R.sup.2 is cyclohexylmethyl and t is 0, R' is a group other than t-butoxycarbonyl.

7. The compound of claim 1 which is: Phenylmethyl[2R-hydroxy-3-[(3-methylbutyl)(methylsulfonyl)amino]-1S-(phenyl methyl)propyl]carbamate; Phenylmethyl[2R-hydroxy-3-[(3-methylbutyl)(phenylsulfonyl)amino]-1S-(phenyl methyl)propyl]carbamate; N1-[2R-hydroxy-3-[(3-methylbutyl)(methylsulfonyl)amino]-1S-(phenylmethyl)pr opyl]-2S-[(2-quinolinylcarbonyl)amino]butanediamide; N1-[2R-hydroxy-3-[(3-methylbutyl)(methylsulfonyl)amino]-1S-(phenylmethyl)pr opyl]-2S-[(phenylmethyloxycarbonyl)amino]butanediamide; N1-[2R-hydroxy-3[(3-methylbutyl)(phenylsulfonyl)amino]-1S-(phenylmethyl)pro pyl]-2S-[(2-quinolinylcarbonyl)amino]butanediamide; N1-[2R-hydroxy-3[(3-methylbutyl)(phenylsulfonyl)amino]-1S-(phenylmethyl)pro pyl]-2S-[(phenylmethyloxycarbonyl)amino]butanediamide; 2S-[[(dimethylamino)acetyl]amino]-N-[2R-hydroxy-3-[(3-methyl-butyl)(phenyls ulfonyl)amino]-1S-(phenylmethyl)propyl]-3,3-dimethylbutaneamide; 2S-[[(methylamino)acetyl]amino]-N-[2R-hydroxy-3-[(3-methyl-butyl)(phenylsul fonyl)amino]-1S-(phenylmethyl)propyl]-3,3-dimethylbutaneamide; N1-[2R-hydroxy-3-[(3-methylbutyl)(phenyl-sulfonyl)amino]-N4-methyl-1S-(phen ylmethyl)propyl]-2S-[(2-quinolinylcarbonyl)amino]butanediamide; [3-[[2-hydroxy-3-[N-(3-methylbutyl)-N-(phenylsufonyl)amino]-1-(phenylmethyl )propyl]amino]-2-methyl-3-oxopropyl]-, (4-methoxyphenyl)methyl ester, [1S-[1R*(S*),2S*]]-; Carbamic acid, [2R-hydroxy-3-[[(4-hydroxyphenyl)sulfonyl](2-methylpropyl)amino]-1S-(pheny lmethyl)propyl]-, 5-(thiazolyl)methyl ester; Benzamide, N-[2R-hydroxy-3-[[(4-hydroxyphenyl)sulfonyl](2-methylpropyl)amino]-1S-(phe nylmethyl)propyl]-2-methyl; Carbamic acid, [2R-hydroxy-3-[[(4-methoxyphenyl)sulfonyl](2-methylpropyl)amino]-1S-(pheny lmethyl)propyl]-, 3-(6-aminopyridyl)methyl ester; Carbamic acid, [2R-hydroxy-3-[[(4-hydroxyphenyl)sulfonyl](2-methylpropyl)amino]-1S-(pheny lmethyl)propyl]-, 3-(6-aminopyridyl)methyl ester; Carbamic acid, [2R-hydroxy-3-[[(4-methoxyphenyl)sulfonyl](2-methylpropyl)amino]-1S-(pheny lmethyl)propyl]-, 3-(6-hydroxypyridyl)methyl ester; Carbamic acid, [2R-hydroxy-3-[[(4-hydroxyphenyl)sulfonyl](2-methylpropyl)amino]-1S-(pheny lmethyllpropyl]-, 5-pyrimidylmethyl ester; or Benzamide, N-[2R-hydroxy-3-[[(4-methoxyphenyl)sulfonyl] (2-methylpropyl) amino]-1S-(phenylmethyl)propyl]-2-methyl.

8. A compound represented by the formula (I): ##STR478##

or a pharmaceutically acceptable salt, or ester thereof, wherein: each of P.sup.1 and P.sup.2 independently represent hydrogen, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, cycloalkylcarbonyl, cycloalkylalkoxycarbonyl, cycloalkylalkanoyl, alkanoyl, aralkanoyl, aroyl, aryloxycarbonyl, aryloxycarbonylalkyl, aryloxyalkanoyl, alkyl, alkenyl, cycloalkyl, aryl, aralkyl, aryloxyalkyl, 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 and cycloalkylalkyl radicals; R.sup.2 is an alkyl, aryl, cycloalkyl cycloalkylalkyl or aralkyl radical, which radicals are optionally substituted with a group selected from allyl 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,aryl, aralkyl, aminoalkyl or mono- or disubstituted aminoalkyl radical, wherein said substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl and cycloalkylalkyl radicals; and R.sup.4 is a radical as defined by R.sup.3 except for hydrogen.

9. The compound of claim 8, wherein each of P.sup.1 and P.sup.2 independently represent a hydrogen, alkoxycarbonyl, aralkyloxycarbonyl, aroyl, alkanoyl or cycloalkanoyl radical; R.sup.2 is a cycloalkylalkyl, aralkyl or alkyl radical; R.sup.3 is an alkyl, cycloalkyl or cycloalkylalkyl radical; and R.sup.4 is an aryl, alkyl, or aryl radical.

10. The compound of claim 9, wherein P.sup.1 and P.sup.2 independently represent 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-fluorobenzyl, para-methoxybenzyl, isobutyl or n-butyl; R.sup.3 is isobutyl, isoamyl, cyclohexyl, cyclohexylmethyl, n-butyl or n-propyl; and R.sup.4 is phenyl, para-methoxyphenyl, para-cyanophenyl, para-chlorophenyl, para-hydroxyphenyl, para-nitrophenyl, para-fluorophenyl, or 2naphthyl; 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. A compound of claim 8 which is: Phenylmethyl[2R-hydroxy-3-[(2-methylpropyl)(phenylsulfonyl)amino]-1S-(pheny lmethyl)propyl]carbamate; Phenylmethyl[2R-hydroxy-3-[(2-methylpropyl)(4-methoxyphenyl sulfonyl)amino]-1S-(phenylmethyl)propyl]carbamate; Phenylmethyl[2R-hydroxy-3-[(2-methylpropyl)(4-fluorophenyl sulfonyl)amino]-1S-(phenylmethyl)propyl]carbamate; Phenylmethyl[2R-hydroxy-3-[(2-methylpropyl)(4-nitrophenylsulfonyl)amino]-1S -(phenylmethyl)propyl]carbamate; Phenylmethyl[2R-hydroxy-3-[(2-methylpropyl)(4-chlorophenyl sulfonyl)amino]-1S-(phenylmethyl)propyl]carbamate; Phenylmethyl[2R-hydroxy-3-[(2-methylpropyl)(4-acetamidophenyl sulfonyl)amino]-1S-(phenylmethyl)propyl]carbamate; Phenylmethyl[2R-hydroxy-3-[(2-methylpropyl)(4-aminophenylsulfonyl)amino]-1S -(phenylmethyl)propyl]carbamate; Phenylmethyl[2R-hydroxy-3-[(3-methylbutyl)(4-methoxyphenyl sulfonyl)amino]-1S-(phenylmethyl)propyl]carbamate; Phenylmethyl[2R-hydroxy-3-[(3-methylbutyl)(4-fluorophenyl sulfonyl)amino]-1S-(phenylmethyl)propyl]carbamate; Phenylmethyl[2R-hydroxy-3-[(3-methylbutyl)(4-nitrophenylsulfonyl)amino]-1S- (phenylmethyl)propyl]carbamate; Phenylmethyl[2R-hydroxy-3-[(3-methylbutyl)(4-chlorophenyl sulfonyl)amino]-1S-(phenylmethyl)propyl]carbamate; Phenylmethyl[2R-hydroxy-3-[(2-methylpropyl)(4-methoxyphenyl sulfonyl)amino]-1S-(4-fluorophenylmethyl)propyl]carbamate; Phenylmethyl[2R-hydroxy-3-[(2-methylpropyl)(4-fluorophenyl sulfonyl)amino]-1S-(4-fluorophenylmethyl)propyl]carbamate; Phenylmethyl[2R-hydroxy-3-[(butyl)(phenylsulfonyl)amino]-1S-(phenylmethyl)p ropyl]carbamate; Phenylmethyl[2R-hydroxy-3-[(cyclohexyimethyl)(phenylsulfonyl)amino]-1S-(phe nylmethyl)propyl]carbamate; Phenylmethyl[2R-hydroxy-3-[(cyclohexyl)(phenylsulfonyl)amino]-1S-(phenylmet hyl)propyl]carbamate; Phenylmethyl[2R-hydroxy-3-[(propyl)(phenylsulfonyl)amino]-1S-(phenylmethyl) propyl]carbamate; Pentanamide, 2S-[[(dimethylamino)acetyl]amino]-N-2R-hydroxy-3-[(3-methylpropyl)(4-metho xyphenylsulfonyl)amino]-1S-(phenylmethyl)propyl]-3S-methyl; Pentanamide, 2S-[[(methylamino)acetyl]amino]-N-2R-hydroxy-3-[(4-methylbutyl)(phenylsulf onyl)amino]-1S-(phenylmethyl)propyl]-3S-methyl; Pentanamide, 2S-[[(dimethylamino)acetyl]amino]-N-2R-hydroxy-3-[(4-methylbutyl)(phenylsu lfonyl)amino]-1S-(phenylmethyl)propyl]-3S-methyl; [2R-hydroxy-3-[[4-methoxyphenyl)sulfonyl](2-methylpropyl)amino]-1S-(phenylm ethyl)propylamine; 2R-hydroxy-3-[(2-methylpropyl)(4-hydroxyphenyl)sulfonyl]amino-1S-(phenylmet hyl)propylamine; [2R-hydroxy-3-[(phenylsulfonyl)(3-methylbutyl)amino]-1S-(phenylmethyl)propy lamine; [2R-hydroxy-3-[(phenylsulfonyl)(2-methylpropyl)amino]-1S-(phenylmethyl)prop ylamine; [2R-hydroxy-3-[(phenylsulfonyl)(cyclohexylmethyl)amino]-1S-(phenylmethyl)pr opylamine; [2R-hydroxy-3-[(phenylsulfonyl)(cyclohexyl)amino]-1S-(phenylmethyl)propylam ine; Benzamide, N-[2R-hydroxy-3-[[(4-methoxyphenyl)sulfonyl](2-methylpropyl)amino]-1S-(phe nylmethyl)propyl]-2,6-dimethyl; Benzamide, N-[2R-hydroxy-3-[[(4-methoxyphenyl)sulfonyl](2-methylpropyl)amino]-1S-(phe nylmethyl)propyl]-2-methyl; Benzamide, N-[2R-hydroxy-3-[[(4-methoxyphenyl)sulfonyl](2-methylpropyl)amino]-1S-(phe nylmethyl)propyl]-2-ethyl; Benzamide, N-[2R-hydroxy-3-[[(4-methoxyphenyl)sulfonyl](2-methylpropyl)amino]-1S-(phe nylmethyl)propyl]-2-chloro; Carbamic acid, [2R-hydroxy-3-[[(4-methoxyphenyl)sulfonyl](2-methylpropyl)amino]-1S-(pheny lmethyl)propyl]-, 5- pyrimidylmethyl ester.

12. A compound represented by formula (A): ##STR479##

or a pharmacputically acceptable salt or ester thereof, wherein: R.sup.2 is an alkyl, aryl cycloalkyl, cycycloalkylalkyl or aralkyl radical, which radical is optionally submitted with a radical selected from the group consisting of alkyl, halo, nitro cyano, CE.sub.3, --OR.sup.0, and --SR.sup.9, wherein R.sup.9 is a radical selectcd from the group consisting of hydrogen and alkyl; R.sup.3 is is a hydrogen, alkyl haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl, alkylsulfonylalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, aminoalkyl or mono- or disubstituted aminoalkyl radicals, wherein said substitutents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl and cycloalkylalkyl radicals; R.sup.4 is an alkyl, haloalkyl, alkenyl alklynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, aralkenyl, aminoalkyl or mono- or disubstituted aminoalkyl radical, wherein said substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl and cycloalkylalkyl radicals; R.sup.6 is a hydrogen or alkyl radical; x is 1 or 2: Y is 0 or S; and A is an alkoxyl, alkenoxy, aralkoxy, alkyl, cycloalkyl, cycloalkylalkoxy, cycloalkylalkyl, aralkyl, aryl, aryloxy, alkenyl, aryloxyalkyl, hydroxyalkyl, amino, or mono- or disubstituted amino radical, wherein the substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl and cycloalkylalkyl radicals; or is represented by the formula (B): ##STR480## wherein R is a hydrogen, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, cycloalkylcarbonyl, cycloalkylalkoxycarbonyl, cycloalkylalkanoyl, carboxyalkanoyl, alkanoyl, aralkanoyl, aroyl, aryloxycarbonyl, aryloxycarbonylalky, aryloxyalkanoyl, alkyl, alkenyl, alkynl, cycloalkyl, aryl, aralkyl, aryloxyalkyl, hydroxyalkyl, aminocarbonyl, aminoalkanoyl, or mono- disubstituted aminocarbonyl or mono- or disubstituted aminoalkanoyl radical, wherein the substitutents are selected from the group consisting of alkyl, aryl, aralkyl, cycoalkyl and cycloalkylalkyl radicals; 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, R.sup.1 is a hydrogen, --CO.sub.2 CH.sub.3, --CH.sub.2 CO.sub.2 CO.sub.3, --CO.sub.2 H, --CH.sub.2 CO.sub.2 H, --CH.sub.2 CH.sub.2 CONH.sub.2, --CH.sub.2 CONH.sub.2, --CONH.sub.2, --CH.sub.2 C(O)NHCH.sub.3, --CH.sub.2 C(O)N(CH.sub.3).sub.2, --CONHCH.sub.3,CONH(CH.sub.3).sub.2, --CH.sub.2 SO.sub.2 NH.sub.2, --CH.sub.2 CH.sub.2 SO.sub.2 NH.sub.2, --CH.sub.2 S(O)CH.sub.3, --CH.sub.2 S(O).sub.2 CH.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.2 CH.sub.3), alkyl, hydroxyalkyl, cyanoalkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, alkythioalkyl, aralkyl, aminoalkyl or mono- or disubstituted aminoalkyl radical, wherein said substitutients are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl and cycloalkylalkyl radicals; 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 and a pharmacrutically acceptable carrier.

13. A composition comprising a compound represented by the formula (J): ##STR481##

or a pharmaceutically acceptable salt or ester thereof, wherein: each of P.sup.1 and P.sup.2 independently represent hydrogen, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, cycloalkylcarbonyl, cycloalkylalkoxycarbonyl, cycloalkelalkanoyl, alkanoyl, aralkanoyl, aroyl, aryloxycarbonyl, arloxycarbonylalkyl, aryloxyalkanoyl, alkyl, alkenyl, cycloalkyl, aryl, aralkyl,aryloxyalkyl, hydroxyalkyl, aminocarbonyl, aminoalkanoyl, or mono- or disubstituted aminocarbonyl or mono- or disubstituted aminoalkanoyl radical, wherein the substitutents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl and cycloalkylalkyl radicals; R.sup.2 is an alkyl, aryl, cycloalkyl, cycloalkylalkyl or aralkyl radicals, which radicals are optionally substituted with a group selected from alkyl and halogen radicals, nitro, cyano, CH.sub.3, OR.sup.9, and --SR.sup.9, wherein R.sup.9 is a hydrogen or alkyl radical; R.sup.5 is a hydrogen alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylakyl, aryl, aralkyl, aminoalkyl or mono- or disubstituted aminoalkyl radical, wherein said substitutents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl and cycloalkylalkyl radicals; and R.sup.4 is a radical as defined by R.sup.3 except for hydrogen and a pharmaceutically acceptable carrier.

14. Method of inhibiting a retroviral protease in a mammal comprising administering to said mammal an effective amount of a compound of claim 1.

15. Method of inhibiting a retroviral protease in a mammal comprising administrating to said mammal an effective amount of a compound of claim 8.

16. Method of treating a retoviral infection in a mammal comprising administering to said mammal an effective amount of a composition of claim 12.

17. Method of treating a retroviral infection in a mammal comprising administering to said mammal an effective amount of composition of claim 13.

18. Method of preventing replication of a retrovirus suspected of being present in a solution comprising administering to said solution an effective amount of a compound of claim 1.

19. Method of preventing replication of a retrovirus suspected of being present in a solution comprising administering to said solution an effective amount of a compound of claim 8.

20. The method of claim 14 further comprising selecting said mammal from the group consisting of a human, a simian and a feline.

21. The method of claim 15 further comprising selecting said mammal from the group consisting of a human, a simian and a feline.

22. The method of claim 16 further comprising selecting said mammal from the group consisting of a human, a simian and a feline.

23. The method of claim 17 further comprising selecting said mammal from the group consisting of a human, a simian and a feline.

24. A compound represented by the formula (A): ##STR482##

or a pharmaceutically acceptable salt, prodrug or ester 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, aryl, aralkyl, aminoalkyl or mono- or disubstituted aminoalkyl radicals, wherein said substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl and cycloalkylalkyl radicals; R.sup.4 is an alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, aralkenyl, aminoalkyl or mono- or disubstituted aminoalkyl radical, wherein said substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl and cycloalkylalkyl radicals; R.sup.6 is a hydrogen or alkyl radical; x is 1 or 2; Y is 0 or S; and A is an alkoxy, alkenoxy, aralkoxy, alkyl, cycloalkyl, cycloalkylalkoxy, cycloalkylalkyl, aralkyl, aryl, aryloxy, alkenyl, aryloxyalkyl, hydroxyalkyl, amino, or mono- or disubstituted amino radical, wherein the substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl and cycloalkylalkyl radicals; or is represented by the formula (B): ##STR483## t is 0 or 1; wherein R is a hydrogen, alkoxycarbonyl, aralkoxycarbonyl, alkylcarbonyl, cycloalkylcarbonyl, cycloalkylalkoxycarbonyl, cycloalkylalkanoyl, carboxyalkanoyl, alkanoyl, aralkanoyl, aroyl, aryloxycarbonyl, aryloxycarbonylalkyl, aryloxyalkanoyl, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, aryloxyalkyl, hydroxyalkyl, aminocarbonyl, aminoalkanoyl, or mono- or disubstituted aminocarbonyl or mon- or disubstituted aminoalkanoyl radical, wherein the substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl and cycloalkylalkyl radicals; 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 ; R.sup.1 is a hydrogen, --CO.sub.2 CH.sub.3, --CH.sub.2 CO.sub.2 CH.sub.3, --CO.sub.2 H, --CH.sub.2 CO.sub.2 H, --CH.sub.2 CH.sub.2 CONH.sub.2, --CH.sub.2 CONH.sub.2, --CONH.sub.2, --CH.sub.2 C(O)NHCH.sub.3, --CH.sub.2 C(O)N(CH.sub.3).sub.2, --CONHCH.sub.3, --CONH(CH.sub.3).sub.2, --CH.sub.2 SO.sub.2 NH.sub.2, --CH.sub.2 CH.sub.2 SO.sub.2 NH.sub.2, --CH.sub.2 S(O)CH.sub.3, --CH.sub.2 S(O).sub.2 CH.sub.3, --C(CH.sub.3).sub.2 (SCH.sub.3), --C(CH.sub.3).sub.2 (S(O).sub.2 CH.sub.3), --C(CH.sub.3).sub.2 (S(O).sub.2 CH.sub.3), alkyl, hydroxyalkyl, cyanoalkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, alkylthioalkyl, aralkyl, aminoalkyl or mono- or disubstituted aminoalkyl radical, wherein said substituents are selected from the group consisting of alkyl, aryl, aralkyl, cycloalkyl and cycloalkylalkyl radicals; 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; and wherein when R.sup.3 is hydrogen or alkyl, t of said formula (B) is 1.

25. The compound of claim 1, wherein said formula (A) is: ##STR484##

26. The compound of claim 8, wherein said formula (J) is: ##STR485##
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