Patent NZ-336627-A (NZ)
Title: Atropisomers of 3-heteroaryl-4(3)-quinazolinones for the treatment of neurodegenerative and CNS-trauma related conditions
Inventor: CHENARD BERTRAND LEO
IPC: C07D417/14
Filed: 1998-02-06
Abstract: An atropisomer of the formula I a wherein: A, B and D are nitrogen or -CH-, with the proviso that only one of A, B and D can be nitrogen; n is an integer from one to four; each R5 is a substituent on any carbon atom of the A, B, D ring capable of supporting an additional bond, with the proviso that one R5 must be attached to a carbon atom ortho to the asterisked carbon of the ring; wherein each R5 may be independently selected from the group consisting of alkyl, halogen, trifluoromethyl, amino-(CH2)m-, alkylamino-(CH2)m-, di(C-C6)alkyl-amino- (CH2)m-, alkoxy, hydroxyalkyl-, alkyl-O- alkyl-, -CN, hydroxy-(CH2)m-, alkyl-(C=O)-O-alkyl-, alkyl-O-(O=C)-O-alkyl, alkyl-(O=C)-O-, H-(C=O)-(CH2)m-, alkyl-(C=O)-(CH2)m-, HO (C=O)-, alkyl-O-(C=O)-(CH2)m-, NH2-(C=O)-(CH2)m-, alkyl-NH-(C=O)(CH2)m-, and dialkyl-N-(C=O)-(CH2)m-; m is an integer from zero to four; R2 is a phenyl group of the formula Ph2 or a five or six membered heterocycle; wherein the 6-membered heterocycle has the formula (II); wherein K, L and M may be independently selected from carbon and nitrogen, with the proviso that i) only one of K, L and M can be nitrogen and ii) when K, L or M is nitrogen, then its respective R15, R16 or R17 is absent; wherein the five membered heterocycle has the formula (III) wherein T is -CH-, N, NH, O or S; wherein the ring positions P and Q may be independently selected from carbon, nitrogen, oxygen and 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 the Ph2 is a group of the formula (IV) R3 is hydrogen, halo, -CN, -NO2, CF3, alkyl or alkoxy; R9 is hydrogen, halo, CF3, alkyl optionally substituted with one to three halogen atoms, alkoxy optionally substituted with one to three halogen atoms, alkylthiol, amino-(CH2)s-, alkyl-NH-(CH2)s-, dialkyl-N-(CH2)s-, cycloalkyl-NH-(CH2)s-, H2N-(C=O)-(CH2)s-, alkyl-HN-(C=O)-(CH2)s-, dialkyl-N-(C=O)-(CH2)s-, cycloalkyl-NH-(C=O)-(CH2)s-, R13O-(CH2)s-, R13O (C=O)-(CH2)s-, H(O=C)-NH-(CH2)s-, alkyl-(O=C)-NH-(CH2)s-, alkyl-(O=C), alkyl-, alkyl-O-alkyl-, or -CN; R10 is hydrogen or halo; R11 and R14 are selected, independently, from hydrogen, halo, CF3, alkyl optionally substituted with one to three halogen atoms, alkoxy optionally substituted with one to three halogen atoms, alkylthiol, amino-(CH2)p-, alkyl-NH-(CH2)p-, dialkyl-N-(CH2)p-, cycloalkyl-NH-(CH2)p-, amino-alkyl-NH-(CH2)p-, alkyl-NH-alkyl-NH-(CH2)p-, dialkyl-N-alkyl-HN-(C=O)-(CH2)p-, dialkyl-N-(C=O)-(CH2)p, cycloalkyl-NH-(C=O) (CH2)p-, R13O-(CH2)p-, R13O-(C=O)-(CH2)p-, H(O=C)-O-, H(O=C)-O-alkyl-, H(O=C)-NH-(CH2)p-, alkyl-(O=C)-NH-(CH2)p-, -CHO, H-(C=O)-(CH2)p-, (CH2)p-, alkyl-(C=O)-O-(CH2)p-, amino-alkyl(C=O)-O-(CH2)p-,  alkyl-NH-alkyl- (C=O)-O-(CH2)p-, dialkyl-N-alkyl-(C=O)-O-(CH2)p-, amino-alkyl-O-(C=O)-(CH2)p-, alkyl-NH-alkyl-O-(C=O)-(CH2)p-, diaIkyl-N-(C, -C6)alkyl-O-(C=O)-(CH2)p-, hydroxy, hydroxy-alkyl-, hydroxy alkyl-NH-(CH2)p-, alkyl-O-alkyl-, -CN, piperidine-(CH2)p-, pyrrolidine(CH2)p-, and 3-pyrroline-(CH2)p-, wherein the piperidine, pyrrolidine and 3-pyrroline moieties of the piperidine-(CH2)p-, pyrrolidine-(CH2)p- and 3-pyrroline-(CH2)p- groups may optionally be substituted on any of the ring carbon atoms capable of supporting an additional bond, preferably zero to two substituents, with a substituent independently selected from halo, CF3, alkyl optionally substituted with one to three halogen atoms,  alkoxy optionally substituted with one to three halogen atoms, alkylthiol, amino-(CH2)p-, alkyl-NH-(CH2)p-, dialkyl-N-(CH2)p-, cycloalkyl-NH-(CH2)p-, amino-alkyl-NH-(CH2)p-, alkyl-NH-alkyl NH-(CH2)p-, dialkyl-N-alkyl-NH-(CH2)p-, alkyl-O-alkyl-, (CH2)p-, dialkyl-N-(C=O)-(CH2)p, (C3-C7)cycloalkyl-NH-(C=O)-(CH2)p-, R13O (CH2)p-, R13O-(C=O)-(CH2)p-, H(O=C)-O-, H(O=C)-O-alkyl-, H(O=C)-NH-(CH2)p-, alkyl-(O=C)-NH-(CH2)p-, -CHO, H-(C=O)-(C H2)p-, alkyl-(C=O)-, (C=O)-O-NH-(CH2)p-, amino-alkyl-(C=O)-O-(CH2)p-, alkyl-NH-alkyl (C=O)-O-(CH2)p-, dialkyl-N-alkyl-(C=O)-O-(CH2)p-, hydroxy, hydroxy-alkyl-, hydroxy- alkyl-NH-(CH2)p-, and -CN; R12 is hydrogen, -CN or halo; R13 is hydrogen, alkyl, alkyl-(C=O)-, alkyl-O-(C=O)-, alkyl-NHalkyl, di-alkyl-N-alkyl-, alkyl-NH-(C=O)-, ordialkyl-N-(C=O)-; R15 is hydrogen, -CN, alkyl, halo, CF3, -CHO or alkoxy; R16 is hydrogen, -CN, alkyl, halo, CF3, -CHO or alkoxy; R'7 is hydrogen, -CN, alkyl, amino-alkyl-, alkyl-NH-alkyl-, dialkyl-N-alkyl-, halo, CF3, -CHO or alkoxy; each p is independently an integer from zero to 4; s is an integer from zero to 4; wherein the dashed bond represented an optional double bond; and the pharmaceutically acceptable salts of such compounds.