Patent ID: 6593314
Filing Date: 2003-07-15
Classification: C07C,C07D

Abstract:
A compound of formula Ia or Ib or a pharmaceutically acceptable salt, ester, or prodrug thereof, whereinR1 is selected from the group consisting of (a) â€”CO2H, (b) â€”SO3H, (c) â€”SO2H, (d) â€”PO3H2, (e) tetrazolyl, (f) â€”C(&boxH;O)â€”NHâ€”S(O)2â€”R11, and (g) â€”SO2N(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-C12 alkyl, (ii) C2-C12 alkenyl, (iii) cycloalkyl, (iv) (cycloalkyl)alkyl, (v) (cycloalkyl)alkenyl, (vi) cycloalkenyl, (vii) (cycloalkenyl)alkyl, (viii) (cycloalkenyl)alkenyl, (ix) aryl, (x) (aryl)alkyl, (xi) (aryl)alkenyl, (xii) heterocyclic, (xiii) (heterocyclic)alkyl, and (xiv) (heterocyclic)alkenyl; and R12 and R36 are independently cted 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 independently 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; R2a is selected from the group consisting of (a) hydrogen, (b) C1-C6 alkyl, (c) C2-C6 alkenyl, (d) halo C1-C6 alkyl, and (e) halo C2-C6 alkenyl; R14 and R15 are independently selected from the group consisting of (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-substituted alkyl, (xi) R37aOâ€”(O&boxH;)C-substituted alkyl, (xii) R37aSâ€”(O&boxH;)C-substituted alkyl, (xiii) R37aOâ€”(S&boxH;)C-substituted alkyl, (xiv) R37aSâ€”(S&boxH;)C-substituted alkyl, (xv) (R37aO)2â€”P(&boxH;O)-substituted alkyl, (xvi) cyanoalkyl, (xvii) C2-C12 alkenyl, (xviii) haloalkenyl, (xix) C2-C12 alkynyl, (xx) cycloalkyl, (xxi) (cycloalkyl)alkyl, (xxii) (cycloalkyl)alkenyl, (xxiii) (cycloalkyl)alkynyl, (xxiv) cycloalkenyl, (xxv) (cycloalkenyl)alkyl (xxvi) (cycloalkenyl)alkenyl, (xxvii) (cycloalkenyl)alkynyl, (xxviii) aryl, (xxxix)(aryl)alkyl, (xxx) (aryl)alkenyl, (xxxi) (aryl)alkynyl, (xxxii) heterocyclic, (xxxiii) (heterocyclic)alkyl, (xxxiv) (heterocyclic)alkenyl, (xxxv) (heterocyclic)alkynyl, (xxxvi) â€”O-alkyl, (xxxvii) â€”NHalkyl, (xxxviii) â€”NH2, (xxxix) â€”N(alkyl)2, (xxxx) â€”OH, (xxxxi) â€”Nacyl, (xxxxii) â€”Nalkylacyl, (xxxxiii) â€”NHcarbamoyl, (xxxxiv) â€”Nalkylcarbamoyl, (xxxxv) â€”NHcarbamidyl, and (xxxxvi) â€”Nalkylcarbamidyl; R37a is 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, (xxii) (heterocyclic)alkynyl, (xxiii) â€”C(&boxH;O)â€”R14, (xxiv) â€”C(&boxH;S)â€”R14, (xxv) -S(O)2-R14 and (xxvi) hydroxyalkyl; Y is selected from the group consisting of (a) C2-C5 alkenyl, (b) C2-C5 haloalkenyl, (c) C2-C5 alkynyl, (d) C5 cycloalkenyl, (e) C5 cycloalkenyl-C1-to-C3-alkyl, (f) C5 cycloalkenyl-C2-to-C3-alkenyl, (g) phenyl, (h) halo-substituted phenyl, (i) â€”(CHR39)nC(&boxH;Q2)R22 wherein R39 is hydrogen, (j) a heterocyclic ring having from 3 to 6 ring atoms, (k) OCH(CH3)2, (l) CH2CH&boxH;CH2, (m) (oxiran-2-yl)methyl, (n) CH2CH(OH)CH2OH, (o) CH2CH(OH)CH2N3, (p) CH2CH2OH, (q) CH2CH(CH3)2, (r) CH&boxH;CH2, (S) OH, (t) OCH2CH&boxH;CH2, and (u) OCH(CH3)OCH2CH3; with the proviso that Y is not when n is 0, 1, or 2; and Q2 is O, S, NR25, or CHR26; R22 is selected from the group consisting of (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, (xvil) isopropylthio, (xvii) cyclopropylthio, (xviii) vinyl, (xix) propenyl, (xx) isopropenyl, (xxi) allyl, (xxii) â€”N(R28a) (R28b), (xxiii) â€”CH2R29, (xxiv) aminomethyl, (xxv) hydroxymethyl, (xxvi) thiolmethyl, (xxvii) â€”NHNH2, (xxviii) â€”N(CH3)NH2, or (xxix) â€”NHNH(CH3); R25 is hydrogen, hydroxy, methyl, ethyl, amino, â€”CN, or â€”NO2; R26 is hydrogen, methyl or ethyl; R28a is 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 is hydrogen, hydroxy, thiol, methyl, ethyl, amino, methoxy, ethoxy, methylthio, ethylthio, methylamino or ethylamino; with 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; R6 is independently selected from the group consisting of (a) hydrogen, (b) C1C12 alkyl, (c) C2-C12 alkenyl, (d) cycloalkyl, (e) (cycloalkyl)alkyl, (f) (cycloalkyl)alkenyl, (g) cycloalkenyl, (h) (cycloalkenyl)alkyl, (i)(cycloalkenyl)alkenyl, (j) aryl, (k) (aryl)alkyl, (l) (aryl)alkenyl, (m) heterocyclic, (n) (heterocyclic)alkyl, and (o) (heterocyclic)alkenyl; and R8 and R9 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, (f) fluorine, and (g) â€”NH2, â€ƒwith the proviso that the total number of atoms, other than hydrogen, in each of R8 and R9, is 6 atoms or less; and R10 is selected from the group: consisting of (a) hydrogen, (b) C1-C6 alkyl, (c) â€”NH2, and (d) â€”OH â€ƒwith the proviso that the total number of atoms, other than hydrogen, in each of R10, is 6 atoms or less all of the foregoing with the proviso that when R*, R2a, R6, R8, R9, R10, and R14 are hydrogen, and X is â€”N(R*)â€”C(&boxH;O)â€”, the left end of which is attached to the cyclohexene ring, and R2 is C1-C2 alkyl, and Y is OH, R15 is other than R37cO-substituted alkyl or R37cO-substituted alkyl.