Patent ID: 6586459
Filing Date: 2003-07-01
Classification: A61K,A61P,C07D

Abstract:
A compound of formula I whereinA3, A4, A5 and A6, together with the two carbons to which they are attached, complete a substituted indole ring in which A3 and A4 together form a fused benz ring, and A5 and A6 together form â€”NHâ€”; whereinL1 is â€”COâ€”NHâ€” such that â€”L1â€”Q1 is â€”COâ€”NHâ€”Q1; Q1 is phenyl, 2-furanyl, 2-thienyl, 4-thiazolyl, 2-pyridyl, 2-naphthyl, 1,2-dihydrobenzofuran-5-yl, 1,2-dihydrobenzofuran-6-yl or 1,2-benzisoxazol-6-yl in which the phenyl may bear a 2-fluoro substituent or may bear one, two or three substituents at the 3-, 4- or 5-position(s) independently selected from halo, cyano, carbamoyl, aminomethyl, methyl, methoxy, difluoromethoxy, hydroxymethyl, formyl, vinyl, amino, hydroxy and 3,4-methylenedioxy, the 2-furanyl or 2-thienyl may bear a chloro or methyl substituent at the 5-position, the 4-thiazolyl may bear an amino substituent at the 2-position, the 2-pyridyl may bear an amino substituent at the 6-position, and the 1,2-benzisoxazol-6-yl may bear a chloro or methyl substituent at the 3-position; or â€”COâ€”Q1 is cyclopentenylcarbonyl or cyclohexenylcarbonyl; R2 is â€”L2Aâ€”Q2A, â€”L2Bâ€”Q2B, â€”L2Câ€”Q2C or â€”L2Dâ€”Q2D wherein L2A is a direct bond; and Q2A is in which D is carbonyl or â€”CHRkâ€” in which Rk is hydrogen, hydroxy, (1-6C)alkoxy or â€”CH2â€”Rj in which Rj is carboxy, [(1-4C)alkoxy]carbonyl or carbamoyl which may bear one or two (1-2C)alkyl substituents on the nitrogen; and one of Rm and Rn is hydrogen and the other is amino, bromo, (1-4C)alkyl or (1-4C)alkoxy, or Rm and Rn together form a benz ring;L2B is â€”NHâ€”COâ€” such that â€”L2Bâ€”Q2B is â€”NHâ€”COâ€”Q2B; and Q2B is in which Ro is hydrogen, halo, (1-6C)alkyl, (1-4C)alkoxy, benzyloxy or (1-4C)alkylthio; and Rp is 1-hydroxyethyl, 1-hydroxy-1-methylethyl, 1-methoxy-1-methylethyl, 4-piperidinyl, 4-pyridinyl, dimethylaminosulfonyl or â€”Jâ€”Rq in which J is a single bond, methylene, carbonyl, oxo, â€”S(O)qâ€” (wherein q is 0, 1 or 2), or â€”NRrâ€” (wherein Rr is hydrogen or methyl); and Rq is (1-6C)alkyl, phenyl, 3-pyridyl or 4-pyridyl;L2C is â€”NRvâ€”COâ€”Xâ€” or â€”NRvâ€”CSâ€”Yâ€” such that â€”L2Câ€”Q2C is â€”NRvâ€”COâ€”Xâ€”Q2C or â€”NRvâ€”CSâ€”Yâ€”Q2C in which X is â€”(CH2)xâ€” (wherein x is 0, 1 or 2), â€”NRwâ€”, NRwâ€”CH2â€”, â€”Oâ€”, â€”Oâ€”CH2â€” or â€”Sâ€”CH2â€”; Y is â€”NRwâ€”CH2â€” or â€”Oâ€”CH2â€”; and each of Rv and Rw is independently hydrogen, benzyl or (1-6C)alkyl which is not branched at the &agr;-position; and Q2C is 1-(4-pyridyl)piperidin-4-yl, 1-(4-pyridyl)piperidin-3-yl or 1-(4-pyridyl)pyrrolidin-3-yl in which the pyridyl may bear a substituent at its 2-position selected from cyano, aminomethyl, carboxy, hydroxymethyl and (1-2C) alkyl; L2D is â€”NHâ€”COâ€” such that â€”L2Dâ€”Q2D is â€”NHâ€”COâ€”Q2D; and Q2D is selected from 4-(4-pyridinyl)benzyloxy, 9-oxo-9H-fluoren-3-yl, benzo[b]thiophen-2-yl (which may bear a chloro, methyl or methoxy substituent), benzofuran-2-yl (which may bear a chloro, methyl or methoxy substituent), 4-(4-morpholinyl)-4-oxobutyl, and 4-piperidinyl or 3,4-didehydropiperidin-4-yl (either one bearing a substituent at the 1-position selected from methylsulfonyl, phenylsulfonyl, (1-5C)alkyl, (4-7C)cycloalkyl, tetrahydropyran-4-yl, 4-thiacyclohexyl and â€”CH2â€”Rz in which Rz is isopropyl, cyclopropyl, phenyl, furyl, thienyl, 2-thiazolyl, or pyridyl in which the phenyl may bear one or two substituents independently selected from halo, cyano, hydroxy, methoxy, acetoxy, benzyloxy, amino, acetylamino, nitro and 3,4-methylenedioxy, and the thienyl or furyl may bear a methyl or nitro substituent); or a prodrug of the compound of formula I; or a pharmaceutically acceptable salt of the compound of formula I or prodrug thereof.