Aryl-quinazoline/aryl-2amino-phenyl methanone derivatives

A compound of formula I

• wherein Y is O or S;
• R1 represents from 1 to 3 substituents independently selected from OH, SH, halo, NO2, optionally substituted (lower alkyl, lower alkoxy, lower alkenyl, lower alkenyloxy, lower alkynyl, lower alkynyloxy, lower alkanoyl, cycloalkyl, lower alkylsulphone, lower alkylsulphoxide or amino);
• R2 represents from 1 to 3 substituents selected from halo, optionally substituted (lower alkyl, lower alkenyl, cycloalkyl or lower alkoxy);
• R3 is
• a) lower alkyl optionally substituted by 1 to 3 substituents selected from cycloalkyl, lower alkylene, lower alkyl, Br, F, CF3, CN, COOH, lower alkyl-carboxylate, OH, lower alkoxy or —Ox—(CH2)y—SOz-lower alkyl, wherein x is 0 or 1, y is 0, 1 or 2 and z is 0, 1 or 2;
• or
• b) Benzyl which is
• a. mono-or di- (preferably mono-) substituted by —Ox—(CH2)y—SOz-lower alkyl or —Ox—(CR, R′)y—COO—R, wherein x, y and z are as defined above and R or R′ is H or lower alkyl,
• b. substituted by 1 or 2 substituents selected from morpholino-lower alkoxy, aryl-lower alkoxy, optionally N-lower alkyl substituted arylamino-lower alkoxy,
• c. substituted at the 2-position by lower alkoxy-, hydroxy-lower alkoxy- or lower alkoxy-lower alkoxy,
• d. substituted on the —CH2— group thereof;
• or
• c) optionally substituted (aryl-C2-C8-alkyl, aryl-C2-C8-alkenyl, heteroarylmethyl or 4-heteroarylbenzyl);
• or
• when R1 is 2 substituents one of which is OH, preferably at the 6-position, and the other of which is optionally substituted (lower alkyl, cycloalkyl-lower-alkyl or lower alkenyl), preferably at the 5-position, R3 is H or optionally substituted (lower alkyl, aryl, aryl-lower alkyl, arylcycloalkyl, cycloalkyl-lower alkyl, cycloalkenyl-lower alkyl, hetereoaryl-lower alkyl, hetereoaryl, or carbonyl lower alkyl);
• or
• when R1 is 2-propynyloxy and R2 is isopropyl, R3 is also benzyl which is substituted by 1 to 3 substituents selected from lower alkyl, lower alkoxy, halo, halo-lower alkyl, e.g. CF3;
• or when R1 is 2-propynyloxy and R2 is isopropyl, R3 is also benzyl which is substituted by OH and a second and optionally third substituent selected from lower alkyl, lower alkoxy, halo, —O—CH(H or lower alkyl)-COO(H or lower alkyl);
• or
• when R1 is 2-propynyloxy and R2 is cyclopropyl, R3 is also optionally substituted lower alkyl or benzyl (preferably R3 is also benzyl which is substituted by 1 to 3 substituents selected from lower alkyl, lower alkoxy, halo, —O—CH(H or lower alkyl)-COO(H or lower alkyl));
• or when Y is S and R1 is as defined above but not methoxy, R3 is also optionally substituted benzyl;
• or
• a compound selected from 4-(4-isopropyl-phenyl)-1-(3,4-diamino-benzyl)-6-prop-2-ynyloxy-1H-quinazolin-2-one, 1-(2,6-dichloro-benzyl)-4-(4-isopropyl-phenyl)-6-prop-2-ynyloxy-1H-quinazolin-2-one, 1-benzyl-4-(4-isopropyl-phenyl)-6-prop-2-ynyloxy-1H-quinazoline-2-thione;
• 1-(3,5di-tert-butyl-4-hydroxy-benzyl)-4-(4-isopropyl-phenyl)-6-prop-2-ynyloxy-1H-quinazolin-2-one, or 1-[3-(2-hydroxy-ethoxy)-benzyl]-4-(4-isopropyl-phenyl )-6-prop-2-ynyloxy-1H-quinazoline-2-thione;
• or a pharmaceutically-acceptable and -cleavable ester, or acid addition salt thereof;
• and
• provided that when Y is O and R3 is lower alkyl or cycloalkyl, R3 is not isopropyl or cyclopentyl;
• or
• provided the compound of formula I is not 4-(4-isopropyl-phenyl)-6-methoxy-1-pyridin-3-ylmethyl-1.H.-quinazolin-2-one, 4-(4-isopropyl-phenyl)-6-methoxy-1-pyridin-2-ylmethyl-1.H.-quinazolin-2-one, 1-(6-chloro-pyridin-3-ylmethyl)-4-(4-isopropyl-phenyl)-6-methoxy-1.H.-quinazolin-2-one, 4-(4-isopropyl-phenyl)-6-methoxy-1-(5-nitro-furan-2-ylmethyl)-1.H.-quinazolin-2-one or 1-[2-(1.H.-indol-2-yl)-ethyl]-4-(4-isopropyl-phenyl)-6-methoxy-1.H.-quinazolin-2-one, 4-(4-isopropyl-phenyl)-6-methoxy-1-phenethyl-1H-quinazolin-2-one, 1-(2-hydroxy-2-phenyl-ethyl)-4-(4-isopropyl-phenyl)-6-prop-2-ynyloxy-1H-quinazolin-2-one, methanesulfonic acid 2-[4-(4-isopropyl-phenyl)-2-oxo-6-prop-2-ynyloxy-2H-quinazolin-1-ylmethyl]-phenyl ester, or acetic acid 2-[4-(4-isopropyl-phenyl)-2-oxo-6-prop-2-ynyloxy-2H-quinazolin-1-yl]-1-phenyl-ethyl ester, 5-allyl-6-hydroxy-1-isopropyl-4-(4-isopropyl-phenyl)-1.H.-quinazolin-2-one, 1-cyclopropylmethyl-4-(o-tolyl)-6-nitro-2(1H)-quinazolinone, 1-ethyl-4-(o-tolyl)-6-chloro-2(1H-quinazolinone, 1-cyclopropylmethyl-4-(o-tolyl)-6-chloro-2(1H)-quinazolinone, 1-cyclopropylmethyl-4-(o-fluorophenyl)-6-chloro-2(1H)-quinazolinone, 1-cyclopropylmethyl-4-(m-chlorophenyl)-6-chloro-2(1H)-quinazolinone, 1-cyclopropylmethyl-4-(o-chlorophenyl)-6-nitro-2(1H)-quinazolinone.