Nova Patents
EP0807633A2

Novel 2,3-disubstituted-(5,6)- heteroarylfused-pyrimidine-4-ones

Abstract

The present invention relates to novel compounds of the formula I, described above, and their pharmaceutically acceptable salts, and pharmaceutical compositions and methods of treating neurodegenerative and CNS-trauma related conditions.

EP0807633A2, drawing sheet 1
Sheet 1 of 37

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Projected expiry passed 1 May 2017, 9.4 years ago.

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36 claims: 1 independent, 35 dependent

  1. 1
    A bicyclic compound of the formula    wherein ring A is a fused heteroaromatic ring, wherein said heteroaromatic ring is a 5 or 6 membered heteroaromatic ring, wherein said 6 membered heteroaromatic ring, taken together with the carbon atoms common to both rings of the bicyclic system, has the formula and wherein said 5 membered heteroaromatic ring, taken together with the carbon atoms common to both rings of the bicyclic system, has the formula    wherein said ring positions "A", "B", "D" and "E" may be independently selected from carbon or nitrogen;    wherein said ring positions "F", "G" and "J" may be independently selected from carbon, nitrogen, oxygen or sulfur, with the proviso that:i) if more than two of "F", "G" or "J" is a heteroatom then said 5 membered heteroaromatic ring is selected from the group consisting of (1,2,3)-triazole, (1,2,3)-thiadiazole, (1,2,5)-thiadiazole, and (1,2,5)-oxadiazole;and ii) if two of "F", "G" or "J" are heteroatoms, one of said heteroatoms may be oxygen or sulfur;wherein said fused heteroaromatic rings may optionally be independently substituted on any of the carbon or nitrogen atoms capable of forming an additional bond with a substituent selected from hydrogen, (C1-C6)alkyl, halogen, trifluoromethyl, amino-(CH2)n-, (C1-C6)alkylamino-(CH2)p-, di(C1-C6)alkyl-amino-(CH2)n-, (C1-C6)alkoxy, hydroxy(C1-C6)alkyl, (C1-C6)alkyl-O-(C1-C6)alkyl-, -CN, hydroxy, -NO2, R3-C(=O)-, R4-O-C(=O)-, di(C1-C6)alkyl-N-C(=O)-, (C1-C6)cycloalkyl, and R4-NH-C(=O)-, and phenyl optionally substituted with halo, (C1-C6) alkyl, -CN, or -CF3;R1 is substituted phenyl of the formula Ph1 or heteroaryl wherein said heteroaryl is selected from the group consisting of pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, wherein said heteroaryl may optionally be substituted on any of the atoms capable of forming an additional bond, up to a maximum of three substituents, with a substituent selected from hydrogen, (C1-C6)alkyl, halogen, trifluoromethyl, amino-(CH2)n-, (C1-C6)alkylamino-(CH2)p-, di(C1-C6)alkyl-amino-(CH2)n-, (C1-C6)alkoxy, hydroxy(C1-C6)alkyl, (C1-C6)alkyl-O-(C1-C6)alkyl-, -CN, hydroxy, H-C(=O)-, (C1-C6)alkyl-C(=O)-, HO-C(=O)-, (C1-C6)alkyl-O-C(=O)-, NH2-C(=O)-, (C1-C6)alkyl-NH-C(=O)-, and di(C1-C6)alkyl-NH-C(=O)-;wherein said Ph1 is a group of the formula R2 is disubstituted phenyl of the formula Ph2 or a five or six membered heterocycle, wherein said 6-membered heterocycle has the formula wherein "N" is nitrogen;wherein said ring positions "K", "L" and "M" may be independently selected from carbon or nitrogen, with the proviso that only one of "K", "L" or "M" can be nitrogen;wherein said five membered heterocycle has the formula wherein said ring positions "P," "Q" and "T" may be independently selected from carbon, nitrogen, oxygen or sulfur;with the proviso that only one of "P," "Q" or "T" can be oxygen or sulfur and at least one of "P," "Q" or "T" must be a heteroatom;wherein said Ph2 is a disubstituted group of the formula R3 is hydrogen or (C1-C6) alkyl;R4 is hydrogen or (C1-C6) alkyl;R5 is hydrogen (C1-C6)alkyl, halo, CF3, (C1-C6)alkoxy or (C1-C6)alkylthiol;R6 is hydrogen or halo;R7 is hydrogen or halo;R8 is hydrogen or halo;R9 is hydrogen, (C1-C6)alkyl optionally substituted with one to three halogen atoms, halo, CF3, (C1-C6)alkoxy optionally substituted with one to three halogen atoms, (C1-C6)alkylthiol, R13O-(CH2)p-, (C1-C6)alkyl-NH-(CH2)p-, di(C1-C6)alkyl-N-(CH2)n-, (C1-C5)cycloalkyl-NH-(CH2)p-, H2N-(C=O)-(CH2)p-, (C1-C6)alkyl-HN-(C=O)-(CH2)n-, di(C1-C6)alkyl-N-(C=O)-(CH2)p-, (C1-C5)cycloalkyl-NH-(C=O)-(CH2)p-R13O-(C=O)-(CH2)p-(C1-C)alkyl-(O=C)-O-(C1-C6)alkyl-, (C1-C6)alkyl-O-(O=C)-O-(C1-C6)-alkyl-, (C1-C6)alkyl-(O=C)-O-, (C1-C6)alkyl-(O=C)-NH-(CH2)p-, H(O=C)-NH-(CH2)p-, hydroxy, H-C(=O)-(CH2)p-, (C1-C6)alkyl-C(=O)-, (C1-C6)alkyl-O-C(=O)-, R4-(CH2)p-O-C(=O)-, amino-(CH2)p-, hydroxy-(C1-C6)alkyl-, (C1-C6)alkyl-O-(C1-C6)alkyl-, and -CN;R10 and R14 are hydrogen, (C1-C6)alkyl optionally substituted with one to three halogen atoms, halo, CF3, (C1-C6)alkoxy optionally substituted with one to three halogen atoms, (C1-C6)alkylthiol, R13O-(CH2)p-, (C1-C6)alkyl-NH-(CH2)n-, di(C1-C6)alkyl-N-(CH2)p-, (C1-C5)cycloalkyl-NH-(CH2)p-, H2N-(C=O)-(CH2)p-, (C1-C6)alkyl-HN-(C=O)-(CH2)p-, di(C1-C6)alkyl-N-(C=O)-(CH2)p-, (C1-C5)cycloalkyl-NH-(C=O)-(CH2)p-, R13O-(C=O)-(CH2)p-, (C1-C6)alkyl-(O=C)-O-(C1-C6)alkyl-, (C1-C6)alkyl-O-(O=C)-O-(C1-C6)-alkyl-, (C1-C6)alkyl-(O=C)-O-, (C1-C6)alkyl-(O=C)-NH-(CH2)p-, H(O=C)-NH-(CH2)p-, hydroxy, H-C(=O)-(CH2)p-, (C1-C6)alkyl-C(=O)-, (C1-C6)alkyl-O-C(=O)-, R4-(CH2)p-O-C(=O)-, amino-(CH2)p-, hydroxy-(C1-C6)alkyl, (C1-C6)alkyl-O-(C1-C6)alkyl, -CHO and -CN;R11 is hydrogen or halo;R12 is hydrogen or halo;R13 is hydrogen, (C1-C6)alkyl, (C1-C6)alkyl-(C=O)-, (C1-C6)alkyl-O-(C=O)-, (C1-C6)alkyl-NH-(C=O)-, or di(C1-C6)alkyl-N-(C=O)-;R15 is hydrogen, -CN, (C1-C6) alkyl, halo, CF3, -CHO or (C1-C6)alkoxy;R16 is hydrogen, -CN, (C1-C6)alkyl, halo, CF3, -CHO or (C1-C6)alkoxy;R17 is hydrogen, -CN, (C1-C6)alkyl, halo, CF3, CHO or (C1-C6)alkoxy;n is an integer from zero to 3;p is an integer from zero to 3;wherein the dashed bond represented an optional double bond;with the proviso that when R9 is hydrogen, then one of R11 and R12 is other than hydrogen;and the pharmaceutically acceptable salts of such compounds.