Patent ID: 6777418
Filing Date: 2004-08-17
Classification: A61P,C07C,C07D

Abstract:
A compound according to structural formula (I): or a pharmaceutically acceptable salt, solvate, hydrate or prodrug thereof wherein:n is an integer from 0 to 2; c is 0 or 1; d is 0 or 1; A is â€”C(&boxH;O)â€”, â€”C(CH2)â€”, â€”C(&boxH;NR4)â€” or â€”CR5R6â€”; R4 is hydrogen, alkyl, hydroxy, alkoxy or amino; and R5 and R6 are independently hydrogen, alkyl or R5 and R6 together with the carbon to which they are both attached are a cyclic hydrocarbon of three to seven ring carbons; B is â€”C(O)Oâ€”, â€”OC(O)â€”, â€”C(O)NHâ€”, â€”NHC(O)â€”, â€”NHC(O)NHâ€”, â€”CR7&boxH;CR8â€”, â€”R7C&boxH;CR8â€”C(O)â€”, â€”Câ‰¡Câ€”, â€”Câ‰¡Câ€”C(O)â€”, â€”CH2Oâ€”, â€”CH2Sâ€”, â€”OCH2â€”, â€”SCH2â€”, â€”COCH2â€”, or â€”CH2COâ€”; R7 and R8 are independently hydrogen or alkyl; with the provisos that: when A is â€”C(&boxH;O)â€”, or â€”C(&boxH;NR4)â€”, then B is not â€”OC(O)â€”; and when A is â€”C(&boxH;CH2)â€”, then B is not â€”OC(O)â€”; X is aryl or a mono- or bicyclic heteroaryl radical said heteroaryl radical containing 5 to 12 ring atoms having at least one aromatic ring containing one, two, or three ring heteroatoms selected from N, O, or S, the remaining ring atoms being C, with the understanding that the attachment point of the heteroaryl radical will be on an aromatic ring, said heteroaryl ring being optionally substituted independently with one or more substituents selected from the group consisting of: (i) acyl, (ii) acylamino, (iii) alkyl, (iv) alkoxycarbonyl, (v) alkyamino, (vi) alkylsulfinyl, (vii) alkylsulfonyl, (viii) â€”SO2NRâ€²Râ€³ (where Râ€² and Râ€³ are independently hydrogen or alkyl), (ix) alkylthio, (x) alkoxy, (xi) amino, (xii) aryloxy, (xiii) carbamoyl, (xiv) cyano, (xv) dialkylamino, (xvi) ethylenedioxy, (xvii) halo, (xviii) thio, (xix) haloalkyl, (xx) a heterocycle wherein said heterocycle is a saturated or unsaturated non-aromatic cyclic radical of 3 to 8 ring atoms in which one or two ring atoms are heteroatoms selected from N, O, or S(O)n(where n is an integer from 0 to 2), the remaining ring atoms being C, where one or two C atoms may optionally be replaced by a carbonyl group, said heterocycle may be optionally substituted independently with one, two, or three substituents selected from alkyl, haloalkyl, heteroalkyl, halo, nitro, cyanoalkyl, hydroxy, alkoxy, amino, monoalkylamino, dialkylamino, arylalkyl, â€”(X)nâ€”C(O)R, -alkylene-C(O)R (where X is O or NRâ€², n is 0 or 1, R is hydrogen, alkyl, haloalkyl, hydroxy, alkoxy, amino, monoalkylamino, dialkylamino or optionally substituted phenyl) or â€”S(O)nRd (where n is an integer from 0 to 2, and Rd is hydrogen (provided that n is 0), alkyl, haloalkyl, cycloalkyl, cycloalkyl-alkyl, amino, monoalkylamino, dialkylamino, or hydroxyalkyl, (xxi) hydroxy, (xxii) hydroxyalkyl, (xxiii) methylenedioxy, (xxiv) nitro, and (xxv) heteroalkyl wherein said heteroalkyl is an alkyl radical wherein one or more hydrogen atoms have been replaced with a substituent independently selected from the group consisting of â€”ORa, â€”NRbRc, and â€”S(O)nRd (where n is an integer from 0 to 2), with the understanding that the point of attachment of the heteroalkyl radical is through a carbon atom, wherein Ra is hydrogen, acyl, alkyl, cycloalkyl, or cycloalkyl-alkyl; Rb and Rc are independently of each other hydrogen, acyl, alkyl, cycloalkyl, or cycloalkyl-alkyl; and when n is 0, Rd is hydrogen, alkyl, cycloalkyl, or cycloalkyl-alkyl, and when n is 1 or 2, Rd is alkyl, cycloalkyl, cycloalkyl-alkyl, amino, acylamino, monoalkylamino, or dialkylamino; R1 is â€”C(&boxH;O)â€”R9; R9 is (i) alkyl, (ii) cycloalkyl, (iii) cycloalkyl-alkyl radical â€”RaRb where Ra is an alkylene group and Rb is a cycloalkyl group, (iv) hydroxy, (v) alkoxy, (vi) aryloxy, (vii) cycloalkyloxy, â€”OR wherein R is a saturated monovalent cyclic hydrocarbon radical of three to seven ring carbons, (viii) cycloalkyl-alkyloxy RaORb wherein Ra is alkylene and Rb is cycloalkyl, (ix) arylalkyloxy, (x) amino, (xi) alkylamino, (xii) dialkylamino, (xiii) heteroalkyloxy, â€”OR wherein R is alkyl wherein one or more hydrogen atoms of an alkyl group have been replaced with a substituent independently selected from the group consisting of â€”ORa, â€”NRbRc, and â€”S(O)nRd (where n is an integer from 0 to 2), with the understanding that the point of attachment of the heteroalkyl radical is through a carbon atom, Ra is hydrogen, acyl, alkyl, cycloalkyl, or cycloalkyl-alkyl; Rb and Rc are independently of each other hydrogen, acyl, alkyl, cycloalkyl, or cycloalkyl-alkyl; and when n is 0, Rd is hydrogen, alkyl, cycloalkyl, or cycloalkyl-alkyl, and when n is 1 or 2, Rd is alkyl, cycloalkyl, cycloalkyl-alkyl, amino, acylamino, monoalkylamino, or dialkylamino, (xiv) heteroalkylamino, â€”NHR wherein R is as defined above for heteroalkoxy in xiii, (xv) heteroalkylthio, â€”SR wherein R is as defined above for heteroalkoxy in (xiii), (xvi) heterocycle, said heterocycle comprising a three to eight atom saturated or unsaturated non-aromatic cyclic radical in which one or two ring atoms are heteroatoms selected from N, O, or S(O)n (where n is an integer from 0 to 2), the remaining ring atoms being C, where one or two C atoms may optionally be replaced by a carbonyl group, said heterocyclyl group may be optionally substituted independently with one, two, or three substituents selected from alkyl, haloalkyl, heteroalkyl, halo, nitro, cyanoalkyl, hydroxy, alkoxy, amino, monoalkylamino, dialkylamino, arylalkyl, â€”(X)nâ€”C(O)R, -alkylene-C(O)R (where X is O or NRâ€², n is 0 or 1, R is hydrogen, alkyl, haloalkyl, hydroxy, alkoxy, amino, monoalkylamino, dialkylamino or optionally substituted phenyl and Râ€² is H or alkyl) or â€”S(O)nRd (where n is an integer from 0 to 2, and Rd is hydrogen (provided that n is 0), alkyl, haloalkyl, cycloalkyl, cycloalkyl-alkyl, amino, monoalkylamino, dialkylamino, or hydroxyalkyl), or (xvii) heterocyclylalkyl radical â€”RaRb where Ra is an alkylene group and Rb is a heterocycle as defined for (xvi) above; and, R2 is: (a) â€”(CR10R11)mâ€”Ypâ€”R12; m is an integer from 1 to 10; p is 0 or 1; R10 and R11 are independently hydrogen, alkyl, hydroxy or hydroxyalkyl; Y is â€”Oâ€”, â€”S(O)qâ€” or â€”NR13â€”; and q is an integer from 0 to 2; and R13 is hydrogen or alkyl; R12 is (i) hydrogen, (ii) alkyl, (iii) a monovalent cyclic hydrocarbon radical of three to seven ring carbons, (iv) cycloalkyl-alkyl radical RaRb where Ra is an alkylene group and Rb is a monovalent cyclic hydrocarbon radical of three to seven ring carbons, (v) aryl, (vi) arylalkyl, (vii) heteroaryl wherein said heteroaryl radical is a monocyclic or bicyclic radical of 5 to 12 ring atoms having at least one aromatic ring containing one, two, or three ring heteroatoms selected from N, O, or S, the remaining ring atoms being C, with the understanding that the attachment point of the heteroaryl radical will be on an aromatic ring, said heteroaryl radical optionally substituted independently with one or more substituents selected from acyl, acylamino, alkyl, alkoxycarbonyl, alkyamino, alkylsulfinyl, alkylsulfonyl, â€”SO2NRâ€²Râ€³ (where Râ€² and Râ€³ are independently hydrogen or alkyl), alkylthio, alkoxy, amino, aryloxy, carbamoyl, cyano, dialkylamino, ethylenedioxy, halo, haloalkyl, heteroalkyl, heterocyclyl, hydroxy, hydroxyalkyl, methylenedioxy, nitro and thio, (viii) heteroarylalkyl wherein said heteroarylalkyl is an alkyl radical wherein one of the hydrogens of an alkyl group has been replaced by a heteroaryl radical as defined in (vii), (ix) acyl, (x) alkoxycarbonyl, (xi) carbamoyl, (xii) heteroalkyl wherein said heteroalkyl is an alkyl moiety wherein wherein one or more hydrogen atoms of an alkyl moiety have been replaced with a substituent independently selected from the group consisting of â€”ORa, â€”NRbRc, and â€”S(O)nRd (where n is an integer from 0 to 2), with the understanding that the point of attachment of the heteroalkyl radical is through a carbon atom, wherein Ra is hydrogen, acyl, alkyl, cycloalkyl, or cycloalkyl-alkyl; Rb and Rc are independently of each other hydrogen, acyl, alkyl, cycloalkyl, or cycloalkyl-alkyl; and when n is 0, Rd is hydrogen, alkyl, cycloalkyl, or cycloalkyl-alkyl, and when n is 1 or 2, Rd is alkyl, cycloalkyl, cycloalkyl-alkyl, amino, acylamino, monoalkylamino, or dialkylamino, (xiii) heteroalkylsubstituted cycloalkyl wherein one, two or three hydrogen atoms of a cycloalkyl radical have been independently replaced with a heteroalkyl group with the understanding that the heteroalkyl group as defined in (xii) above is attached to the cycloalkyl radical via a carbon-carbon, (xiv) heterosubstituted cycloalkyl wherein one, two or three hydrogen atoms of a C3-7 monovalent cyclic hydrocarbon radical have been replaced with a substituent independently selected from the group consisting of hydroxy, alkoxy, amino, acylamino, monoalkylamino, dialkylamino, oxo (C&boxH;O), imino, hydroxyamino (&boxH;NOH), NRâ€²SO2Rd (where Râ€² is hydrogen or alkyl and Rd is alkyl, cycloalkyl, amino, monoalkylamino or dialkylamino) and â€”Xâ€”C(O)R (where X is O or NRâ€², R is hydrogen, alkyl, haloalkyl, hydroxy, alkoxy, amino, monoalkylamino, dialkylamino, or optionally substituted phenyl, and Râ€² is H or alkyl) or â€”S(O)nR (where n is an integer from 0 to 2) such that when n is 0, R is hydrogen, alkyl, cycloalkyl, or cycloalkyl-alkyl, and when n is 1 or 2, R is alkyl, cycloalkyl, cycloalkyl-alkyl, amino, acylamino, monoalkylamino or dialkylamino, (xv) a heterosubstituted cycloalkyl-alkyl radical â€”RaRb where Ra is an alkylene group and Rb is heterosubstituted cycloalkyl as defined in (xiv), (xvi) heterocycle, said heterocycle comprising a three to eight atom saturated or unsaturated non-aromatic cyclic radical in which one or two ring atoms are heteroatoms selected from N, O, or S(O)n (where n is an integer from 0 to 2), the remaining ring atoms being C, where one or two C atoms may optionally be replaced by a carbonyl group, said heterocyclyl group may be optionally substituted independently with one, two, or three substituents selected from alkyl, haloalkyl, heteroalkyl, halo, nitro, cyanoalkyl, hydroxy, alkoxy, amino, monoalkylamino, dialkylamino, arylalkyl, â€”(X)nâ€”C(O)R, -alkylene-C(O)R (where X is O or NRâ€², n is 0 or 1, R is hydrogen, alkyl, haloalkyl, hydroxy, alkoxy, amino, monoalkylamino, dialkylamino or optionally substituted phenyl and Râ€² is H or alkyl) or â€”S(O)nRd (where n is an integer from 0 to 2, and Rd is hydrogen (provided that n is 0), alkyl, haloalkyl, cycloalkyl, cycloalkyl-alkyl, amino, monoalkylamino, dialkylamino, or hydroxyalkyl), or (xvii) heterocyclylalkyl wherein said heterocyclylalkyl is a radical â€”RaRb where Ra is an alkylene group and Rb is heterocycle as defined in (xvi), with the proviso that when p=0, then R12is not hydrogen or alkyl; (b) heteroaryl wherein said heteroaryl radical is a monocyclic or bicyclic radical of 5 to 12 ring atoms having at least one aromatic ring containing one, two, or three ring heteroatoms selected from N, O, or S, the remaining ring atoms being C, with the understanding that the attachment point of the heteroaryl radical will be on an aromatic ring, said heteroaryl radical optionally substituted independently with one or more substituents selected from acyl, acylamino, alkyl, alkoxycarbonyl, alkyamino, alkylsulfinyl, alkylsulfonyl, â€”SO2NRâ€²Râ€³ (where Râ€² and Râ€³ are independently hydrogen or alkyl), alkylthio, alkoxy, amino, aryloxy, carbamoyl, cyano, dialkylamino, ethylenedioxy, halo, haloalkyl, heteroalkyl, heterocyclyl, hydroxy, hydroxyalkyl, methylenedioxy, nitro and thio; (c) â€”Zâ€”L; Z is â€”CR14&boxH;CR15â€”, â€”Câ‰¡Câ€”, â€”Oâ€”, â€”NR16â€”, C(&boxH;O) or â€”S(O)qâ€”; R14, R15 and R16 are independently hydrogen or alkyl; and L is (i) heteroaryl as defined in (b) above, (ii) heteroarylalkyl as defined for (viii) of R12 above, (iii) heteroalkyl as defined above for (xii) of R12, with the added proviso that when Z is O and L is heteroalkyl, Ra is other than alkyl; with the proviso that when Acâ€”Bd is â€”C(&boxH;O)â€”CR7&boxH;CR8â€”, then L is not heteroalkyl; or (d) â€”CR14&boxH;CR15â€”L1 where L1 is S(O)2R17 or SO2NR18R19 where R17 is alkyl and R19 are independently hydrogen or alkyl; each R3 is independently hydrogen, alkyl, hydroxy or oxo; and t is 1 or 2.