Patent ID: 6455571
Filing Date: 2002-09-24
Classification: A61P,C07D

Abstract:
A compound of the formula: or a pharmaceutically acceptable salt, ester or prodrug thereof,wherein R1 is selected from the group consisting of (b) â€”CO2H, (b) â€”CH2CO2H, (c) â€”SO3H, (d) â€”CH2SO3H, (e) â€”SO2H, (g) â€”CH2SO2H, (g) â€”PO3H2, (h) â€”CH2PO3H2, (i) â€”PO2H, (j) â€”CH2PO2H, (l) tetrazolyl, (l) â€”CH2-tetrazolyl, (m) â€”C(&boxH;O)â€”NHâ€”S(O)2â€”R11, (o) â€”CH2C(&boxH;O)â€”NHâ€”S(O)2â€”R11, (o) â€”SO2N(Tâ€”R11)R12 and (p) â€”CH2SO2N(Tâ€”R11)R12 wherein T is selected from the group consisting of (i) a bond, (ii) â€”C(&boxH;O)â€”, (iii) â€”C(&boxH;O)Oâ€”, (iv) â€”C(&boxH;O)Sâ€”, (v) â€”C(&boxH;O)NR36â€”, (vi) â€”C(&boxH;S)Oâ€”, (vii) â€”C(&boxH;S)Sâ€”, and (viii) â€”C(&boxH;S)NR36â€”, R11 is selected from the group consisting of (i) C1-C12alkyl, (ii) C2-C12 alkenyl, (iii) cycloalkyl, (iv) (cycloalkyl)alkyl, (w) (cycloalkyl)alkenyl, (vi) cycloalkenyl, (vii) (cycloalkenyl)alkyl, (ix) (cycloalkenyl)alkenyl, (ix) aryl, (x) (aryl)alkyl, (x) (xi) (aryl)alkenyl, (xvii) heterocyclic, (xiii) (heterocyclic)alkyl and (xviii) (xiv) (heterocyclic)alkenyl; and R12 and R36 are independently selected from the group consisting of (i) hydrogen, (ii) C1-C12 alkyl, (iii) C2-C12 alkenyl, (iv) cycloalkyl, (v) (cycloalkyl)alkyl, (vi) (cycloalkyl)alkenyl, (vii) cycloalkenyl, (viii) (cycloalkenyl)alkyl, (ix) (cycloalkenyl)alkenyl, (x) aryl, (xi) (aryl)alkyl, (xii) (aryl)alkenyl, (xiii) heterocyclic, (xiv) (heterocyclic)alkyl and (xv) (heterocyclic)alkenyl; X is selected from the group consisting of (a) â€”C(&boxH;O)â€”N(R*)â€”, (b) â€”N(R*)â€”C(&boxH;O)â€”, (c) â€”C(&boxH;S)â€”N(R*)â€”, (d) â€”N(R*)â€”C(&boxH;S)â€”, (e) â€”N(R*)â€”SO2â€”, and (f) â€”SO2â€”N(R*)â€” wherein R* is hydrogen, C1-C3 loweralkyl or cyclopropyl; R2 is selected from the group consisting of (a) hydrogen, (b) C1-C6 alkyl, (c) C2-C6 alkenyl, (d) C3-C6 cycloalkyl, (e) C5-C6 cycloalkenyl, (f) halo C1-C6 alkyl and (g) halo C2-C6 alkenyl; or R2â€”Xâ€” is â€ƒwherein Y1 is â€”CH2â€”, â€”Oâ€”, â€”Sâ€” or â€”NHâ€” and Y2 is â€”C(&boxH;O)â€” or â€”C(Raa)(Rbb)â€” wherein Raa and Rbb are indepedently selected from the group consisting of hydrogen, C1-C3 loweralkyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, aminomethyl, 1-aminoethyl, 2-aminoethyl, thiolmethyl, 1-thiolethyl, 2-thiolethyl, methoxymethyl, N-methylaminomethyl and methylthiomethyl; R3 and R4 are independently selected from the group consisting of (a) hydrogen, (b) cycloalkyl, (c) cycloalkenyl, (d) heterocyclic, (e) aryl and (f) â€”Zâ€”R14 wherein Z is (ii) â€”C(R37a)(R37bb)â€”, (ii) â€”C(R47)&boxH;C(R48)â€”, (iii) â€”Câ‰¡Câ€”, (iv) â€”C(&boxH;O)â€”, (v) â€”C(&boxH;S)â€”, (vi) â€”C(&boxH;NR15)â€”, (vii) â€”C(R37a)(OR37c)â€”, (viii) â€”C(R37a)(SR37c)â€”, (ix) â€”C(R37a)(N(R37b)(R37c))â€”, (x) â€”C(R37a)(R37b)â€”Oâ€”, (xi) â€”C(R37a)(R37b)â€”N(R37c)â€”, (xii) â€”C(R37a)(R37b)â€”N(O)(R37c)â€”, (xiii) â€”C(R37a)(R37b)â€”N(OH)â€”, (xiv) â€”C(R37a)(R37b)â€”Sâ€”, (xv) â€”C(R37a)(R37b)â€”S(O)â€”, (xvi) â€”C(R37a)(R37b)â€”S(O)2â€”, (xviii) â€”C(R37a)(R37b)â€”C(&boxH;O)â€”, (xviii) â€”C(R37a)(R37b)â€”C(&boxH;S)â€”, (xxi) â€”C(R37a)(R37b)â€”C(&boxH;NR15)â€”, (xx) â€”C(R37a)(OR37c)â€”C(&boxH;O)â€”, (xxi) â€”C(R37a)(SR37c)â€”C(&boxH;O)â€”, (xxi) â€”C(R37a)(OR37c)â€”C(&boxH;S)â€”, (xxiii) â€”C(R37a)(SR37c)â€”C(&boxH;S)â€”, (xxiv) â€”C(&boxH;O)â€”C(R37a)(OR37c)â€”, (xxv) â€”C(&boxH;O) â€”C(R37a)(OR37c)â€”, (xxvi) â€”C(&boxH;S)â€”C(R37a)(OR37c)â€”, (xxvii) â€”C(&boxH;S)â€”C(R37a)(SR37c)â€”, (xxviii) â€”C(R37a)(OR37c)â€”C(R37a)(OR37c)â€”, (xxix) â€”C(R37a)(SR37c)â€”C(R37a)(OR37c)â€”, (xxx) â€”C(R37a)(OR37c)â€”C(R37a)(SR37c)â€”, (xxxi) â€”C(R37a)(SR37c)â€”C(R37a)(SR37c)â€”, (xxxii) â€”C(&boxH;O)â€”C(&boxH;O)â€”, (xxxiii) â€”C(&boxH;S)â€”C(&boxH;S)â€”, (xxxiv) â€”C(&boxH;O)â€”Oâ€”, (xxxv) â€”C(&boxH;O)â€”Sâ€”, (xxxvi) â€”C(&boxH;S)â€”Oâ€”, (xxxvii) â€”C(&boxH;S)â€”Sâ€”, (xxxviii) â€”C(&boxH;O)â€”N(R37a)â€”, (xxxix) â€”C(&boxH;S)â€”N(R37a)â€”, (xl) â€”C(R37a)(R37b)â€”C(&boxH;O)â€”N(R37a)â€”, (xli) â€”C(R37a)(R37b)â€”C(&boxH;S)â€”N(R37a)â€”, (xlii) â€”C(R37a)(R37b)â€”C(&boxH;O)â€”Oâ€”, (xliii) â€”C(R37a)(R37b)â€”C(&boxH;O)â€”Sâ€”, (xliv â€”C(R37a)(R37b)â€”C(&boxH;S)â€”Oâ€”, (xlv) â€”C(R37a)(R37b)â€”C(&boxH;S)â€”Sâ€”, (xlvi) â€”C(R37a)(R37b)â€”N(R37b)â€”C(&boxH;O)â€”, (xlvii) â€”C(R37a)(R37b)â€”N(R37b)â€”C(&boxH;S)â€”, (xlviii) â€”C(R37a)(R37b)â€”Oâ€”C(&boxH;O)â€”, (xlix) â€”C(R37a)(R37b)â€”Sâ€”C(&boxH;O)â€”, (l) â€”C(R37a)(R37b)â€”Oâ€”C(&boxH;S)â€”, (li) â€”C(R37a)(R37b)â€”Sâ€”C(&boxH;S)â€”, (lii) â€”C(R37a)(R37b)â€”N(R37b)â€”C(&boxH;O)â€”N(R37a)â€”, (liii) â€”C(R37a)(R37b)â€”N(R37b)â€”C(&boxH;S)â€”N(R37a)â€”, (liv) â€”C(R37a)(R37b)â€”N(R37b)â€”C(&boxH;O)â€”Oâ€”, (lv) â€”C(R37a)(R37b)â€”N(R37b)â€”C(&boxH;O)â€”Sâ€”, (lvi) â€”C(R37a)(R37b)â€”N(R37b)â€”C(&boxH;S)â€”Oâ€”, (lvii) â€”C(R37a)(R37b)â€”N(R37b)â€”C(&boxH;S)â€”Sâ€”, (lviii) â€”C(R37a)(R37b)â€”Oâ€”C(&boxH;O)â€”N(R37a)â€”, (lix) â€”C(R37a)(R37b)â€”Sâ€”C(&boxH;O)â€”N(R37a)â€”, (lx) â€”C(R37a)(R37b)â€”Oâ€”C(&boxH;S)â€”N(R37a)â€”, (lxi) â€”C(R37a)(R37b)â€”Sâ€”C(&boxH;S)â€”N(R37a)â€”, (lxii) â€”C(R37a)(R37b)â€”Oâ€”C(&boxH;O)â€”Oâ€”, (lxiii) â€”C(R37a)(R37b)â€”Sâ€”C(&boxH;O)â€”Oâ€”, (lxiv) â€”C(R37a)(R37b)â€”Oâ€”C(&boxH;O)â€”Sâ€”, (lxv) â€”C(R37a)(R37b)â€”Sâ€”C(&boxH;O)â€”Sâ€”, (lxvi) â€”C(R37a)(R37b)â€”Oâ€”C(&boxH;S)â€”Oâ€”, (lxvii) â€”C(R37a)(R37b)â€”Sâ€”C(&boxH;S)â€”Oâ€”, (lxviii) â€”C(R37a)(R37b)â€”Oâ€”C(&boxH;S)â€”Sâ€”, (lxix) â€”C(R37a)(R37b)â€”Sâ€”C(&boxH;S)â€”Sâ€” or (lxx) â€”C(R37a)(R37b)â€”C(R37a)(OR37c)â€”; R14 is (i) hydrogen, (ii) C1-C12 alkyl, (iii) haloalkyl, (iv) hydroxyalkyl, (v) thiol-substituted alkyl, (vi) R37cO-substituted alkyl, (vii) R37cS-substituted alkyl, (viii) aminoalkyl, (ix) (R37c)NH-substituted alkyl, (x) (R37a)(R37c)N-susbstituted alkyl, (xi) R37aOâ€”(O&boxH;)C-substituted alkyl, (xii) R37aSâ€”(O&boxH;)C-substituted alkyl, (xiii) R37aOâ€”(S&boxH;)C-substituted alkyl, (xix) R37aSâ€”(S&boxH;)C-Substituted alkyl, (xx) (R37aO)2â€”P(&boxH;O)-substituted alkyl, (xvi) cyanoalkyl, (xxi) C2-C12 alkenyl, (xviii) haloalkenyl, (xix) C2-C12 alkynyl, (xxii) cycloalkyl, (xxi) (cycloalkyl)alkyl, (xxii) (cycloalkyl)alkenyl, (xxiv) (cycloalkyl)alkynyl, (xxiv) cycloalkenyl, (xxv) (cycloalkenyl)alkyl, (xxvii) (cycloalkenyl)alkenyl, (xxvii) (cycloalkenyl)alkynyl, (xxviii) aryl, (xxx) (aryl)alkyl, (xxx) (aryl)alkenyl, (xxxi) (aryl)alkynyl, (xxxii) heterocyclic, (xxxiii) (heterocyclic)alkyl, (xxxiv) (heterocyclic)alkenyl or (xxxv) (heterocyclic)alkynyl, â€ƒwith the proviso that R14 is other than hydrogen when Z is â€”C(R37a)(R37b)â€”N(R37b)â€”C(&boxH;O)â€”Oâ€”, â€”C(R37a)(R37b)â€”N(R37b)â€”C(&boxH;S)â€”Oâ€”, â€”C(R37a)(R37b)â€”N(R37b)â€”C(&boxH;O)â€”Sâ€”, â€”C(R37a)(R37b)â€”N(R37b)â€”C(&boxH;S)â€”Sâ€”, â€”C(R37a)(R37b)â€”Oâ€”C(&boxH;O)â€”Oâ€”, â€”C(R37a)(R37b)â€”Oâ€”C(&boxH;S)â€”Oâ€”, â€”C((R37a)(R37b)â€”Sâ€”C(&boxH;O)â€”Oâ€”, â€”C(R37a)(R37b)â€”Sâ€”C(&boxH;S)â€”Oâ€”, â€”C(R37a)(R37b)â€”Oâ€”C(&boxH;O)â€”Sâ€”, â€”C(R37a(R37b)â€”Oâ€”C(&boxH;S)â€”Sâ€”, â€”C(R37a)(R37b)â€”Sâ€”C(&boxH;O)â€”Sâ€” or â€”C(R37a)(R37b)â€”Sâ€”C(&boxH;S)â€”Sâ€”; R37a, R37b, R47, and R48 at each occurrence are independently selected from the group consisting of (i) hydrogen, (ii) C1-C12 alkyl, (iii) haloalkyl, (iv) hydroxyalkyl, (v) alkoxyalkyl, (vi) C2-C12 alkenyl, (vii) haloalkenyl, (viii) C2-C12 alkynyl, (ix) cycloalkyl, (x) (cycloalkyl)alkyl, (xi) (cycloalkyl)alkenyl, (xii) (cycloalkyl)alkynyl, (xiii) cycloalkenyl, (xiv) (cycloalkenyl)alkyl, (xv) (cycloalkenyl)alkenyl, (xvi) (cycloalkenyl)alkynyl, (xvii) aryl, (xviii) (aryl)alkyl, (xix) (aryl)alkenyl, (xx) (aryl)alkynyl, (xxi) heterocyclic, (xxii) (heterocyclic)alkyl, (xxiii) (heterocyclic)alkenyl and (xxiv) (heterocyclic)alkynyl; R37c at each occurrence is independently selected from the group consisting of (i) hydrogen, (ii) C1-C12 alkyl, (iii) haloalkyl, (iv) C2-C12 alkenyl, (v) haloalkenyl, (vi) C2-C12 alkynyl, (vii) cycloalkyl, (viii) (cycloalkyl)alkyl, (ix) (cycloalkyl)alkenyl, (x) (cycloalkyl)alkynyl, (xi) cycloalkenyl, (xii) (cycloalkenyl)alkyl, (xiii) (cycloalkenyl)alkenyl, (xiv) (cycloalkenyl)alkynyl, (xv) aryl, (xvi) (aryl)alkyl, (xvii) (aryl)alkenyl, (xviii) (aryl)alkynyl, (xix) heterocyclic, (xx) (heterocyclic)alkyl, (xxi) (heterocyclic)alkenyl, (xxiv) (heterocyclic)alkynyl, (xxiii) â€”C(&boxH;O)â€”R14, (xxiv) â€”C(&boxH;S)â€”R14, (xxv) â€”S(O)2â€”R14 and (xxvi) hydroxyalkyl; or when Z is â€”C(R37a)(R37b)â€”N(R37c)â€”, then N(R37c) and R14 when taken together are an azido group; or when Z is â€”C(R37a)(R37b)â€”N(O)(R37c)â€”, then N(O)(R37c) and R14 when taken together are an N-oxidized 3-7 membered heterocyclic ring having at least one N-oxidized ring nitrogen atom; or when Z is â€”C(R37a)(R37b)â€”, â€”C(R37a)(OR37c)â€”, â€”C(R37a)(SR37c)â€” or â€”C(R37a)(N(R37b)(R37c))â€”, then R37a, R14 and the carbon atom to which they are bonded when taken together form a cyclopentyl, cyclopentenyl, cyclohexyl or cyclohexenyl ring or then OR37c or SR37c or N(R37c) and R14 and the carbon atom to which they are bonded when taken together form a heterocyclic ring containing an O, S or N atom, respectively, and having from 4 to 8 ring atoms; R15 is selected from the group consisting of (i) hydrogen, (ii) hydroxy, (iii) amino, (iv) C1-C12 alkyl, (v) haloalkyl, (vi) C2-C12 alkenyl, (vii) haloalkenyl, (viii) cycloalkyl, (ix) (cycloalkyl)alkyl, (x) (cycloalkyl)alkenyl, (xi) cycloalkenyl, (xii) (cycloalkenyl)alkyl, (xiii) (cycloalkenyl)alkenyl, (xiv) aryl, (xv) (aryl)alkyl, (xvi) (aryl)alkenyl, (xvii) heterocyclic, (xviii) (hetcrocyclic)alkyl and (xix) (heterocyclic)alkenyl: or R3 and R4 taken together, with the atom to which they are attached, form a carbocyclic or heterocyclic ring having from 3 to 8 ring atoms; R5 is selected from the group consisting of (a) hydrogen, (b) â€”CH(R38)2, (c) â€”Oâ€”R40, (d) C2-C4 alkynyl, (e) cyclopropyl, (f) cyclobutyl, (g) â€”C(&boxH;Q1)â€”R17, and (h) â€”N(R19)2 wherein Q1 is O, S, or N(R18); R17 and R18 are independently selected, at each occurrence, from the group consisting of hydrogen, methyl, and ethyl; R19, R38, and R40 are independently selected, at each occurrence, from the group consisting of (i) hydrogen, (ii) C1-C12 alkyl, (iii) halalkyl, (iv) C2-C12 alkenyl, (v) haloalkenyl, (vi) cycloalkyl, (vii) (cycloalkyl)alkyl, (viii) (cycloalkyl)alkenyl, (ix) cylcloalkenyl, (x) (cycloakenyl)alkyl, (xi) (cycloalkenyl)alkenyl, (xii) aryl, (xiii) (aryl)alkyl, (xiv) (aryl)alkenyl, (xv) heterocyclic, (xvi) (heterocyclic)alkyl and (xvii) (heterocyclic)alkenyl; Y is selected from the group consisting of (a) hydrogen, (b) C1-C5 alkyl, (c) C1-C5 haloalkyl, (d) C2-C5 alkenyl, (e) C2-C5 haloalkenyl, (f) C2-C5 alkynyl, (g) C3-C5 cycloalkyl, (h) C3-C5 cycloalkyl-C1-to-C3-alkyl, (i) C5 cycloalkenyl, (j) C5 cycloalkenyl-C1-to-C3-alkyl, (k) C5 cycloalkenyl-C2-to-C3-alkenyl, (l) â€”(CHR39)nOR20, (m) â€”CH(OR20)â€”CH2(OR20), (n) â€”(CHR39)nSR21, (o) â€”(CHR39)nCN, (p) â€”(CHR39)nN3, (q) phenyl, (r) halo-substituted phenyl, (s) â€”(CHR39)nC(&boxH;Q2)R22, (t) â€”(CHR39)nN(&boxH;Q3), (u) â€”N(O)&boxH;CHCH3, (v) â€”(CHR39)nNR23R24 (w) halo and (x) a heterocyclic ring having from 3 to 6 ring atoms; â€ƒwherein n is 0, 1, or 2; Q2 is O, S, NR25 or CHR26; and Q3 is NR41 or CHR42; R20 at each occurrence is independently (i) hydrogen, (ii) methyl, (iii) ethyl, (iv) n-propyl, (v) isopropyl, (vi) C1-C3 haloalkyl, (vii) vinyl, (viii) propenyl, (ix) isopropenyl, (x) allyl, (xi) C2-C3 haloalkenyl, (xii) amino, (xiii) â€”NHCH3, (xiv) â€”N(CH3)2, (xv) â€”NHCH2CH3, (xvi) â€”N(CH3)(CH2CH3), (xvii) â€”N(CH2CH3)2 or (xviii) â€”N(&boxH;CH2); R21 is hydrogen, (ii) methyl, (iii) ethyl, (iv) n-propyl, (v) isopropyl, (vi) C1-C3 haloalkyl, (vii) vinyl, (viii) propenyl, (ix) isopropenyl, (x) allyl or (xi) C2-C3 haloalkenyl; R22 is (i) hydrogen, (ii) methyl, (iii) ethyl, (iv) n-propyl, (v) isopropyl, (vi) hydroxy, (vii) thiol, (viii) methoxy, (ix) ethoxy, (x) n-propoxy, (xi) isopropoxy, (xii) cyclopropyloxy, (xiii) methylthio, (xiv) ethylthio, (xv) n-propylthio, (xvi) isopropylthio, (xvii) cyclopropylthio, (xviii) vinyl, (xix) propenyl, (xx) isopropenyl, (xxi) allyl, (xxii) â€”N(R28a)(R28b), (xxv) â€”CH2R29, (xxiv) aminomethyl, (xxv) hydroxymethyl, (xxvi) thiolmethyl, (xxvii) â€”NHNH2, (xxviii) â€”N(CH3)NH2 or (xxix) â€”NHNH(CH3); R23 and R39 are independently hydrogen or methyl; R41 and R42 are independently hydrogen, methyl, or ethyl; R24 is selected from the group consisting of (i) hydrogen, (ii) C1-C4 alkyl, (iii) C2-C4 alkenyl, (iv) C2-C4 alkynyl, (v) cyclopropyl, (vi) â€”C(&boxH;Q4)â€”R30, (v) â€”OR31, and (vi) â€”N(R32)2, wherein Q4 is O, S, or N(R33); R25 is hydrogen, hydroxy, methyl, ethyl, amino, â€”CN, or â€”NO2; R26 group is hydrogen, methyl or ethyl; R28a hydrogen, hydroxy, methyl, ethyl, amino, â€”NHCH3, â€”N(CH3)2, methoxy, ethoxy, or â€”CN; R28b is hydrogen, methyl or ethyl; or R28a, R28b and the nitrogen to which they are bonded taken together represent azetidinyl; R29 group is hydrogen, hydroxy, thiol, methyl, ethyl, amino, methoxy, ethoxy, methylthio, ethylthio, methylamino or ethylamino; R30 group is hydrogen, methyl, ethyl, â€”OR34, â€”SR34, â€”N(R35)2, â€”NHOH, â€”NHNH2, â€”N(CH3)NH2, or â€”N(CH2CH3)NH2; R31 and R32, at each occurrence, are independently hydrogen, methyl or ethyl; R33 is hydrogen, hydroxy, methyl, ethyl, amino, â€”CN, or â€”NO2; R34 is methyl or ethyl; R35 is independently hydrogen, methyl or ethyl; â€ƒwith the proviso that when Q2 is CHR26 then R22 is selected from the group consisting of hydrogen, â€”CH3, â€”C2H5, â€”C3H7, â€”OCH3, â€”SCH3, â€”Oâ€”C2H5, and â€”Sâ€”C2H5, and with the proviso that when R3 and R4 are each hydrogen, then Y is other than hydrogen; R6 and R7 are independently selected from the group consisting of (c) hydrogen, (b) C1-C12 alkyl, (c) C2â€”C12 alkenyl, (d) cycloalkyl, (e) (cycloalkyl)alkyl, (f) (cycloalkyl)alkenyl, (g) cycloalkenyl, (h) (cycloalkenyl)alkyl, (j) (cycloalkenyl)alkenyl, (j) aryl, (k) (aryl)alkyl, (l) (aryl)alkenyl, (m) heterocyclic, (o) (heterocyclic)alkyl and (o) (heterocyclic)alkenyl; and R8, R9, and R10 are independently selected from the group consisting of (a) hydrogen, (b) C1-C6 alkyl, (c) C2-C6 alkenyl, (d) C3-C6 cycloalkyl, (e) C3-C6 cycloalkenyl, and (f) fluorine, with the proviso that the total number of atoms, other than hydrogen, in each of R8, R9, and R10, is 6 atoms or less.