Novel 3-amino/hydroxy-4- 4-benzoylphenylcarboxylamino/oxy -azepanes and their homologies as protein kinase inhibitors.

摘要

Benzyloxy-, benzoyloxy- and benzoylamino-azepanes of formula (I) and their salts are new: A = opt. substd. 2-, 3- or 4-pyridyl or 2- or 3-piperazinyl; X, Y = O or NH, but not both NH; Z = O or, when X = O, O or (H, H); n = 1-3; R<1> = H or F; R<2> = H; lower alkoxy; or F; R<3> = H; OH; lower alkoxy; F; CF3, lower alkoxycarbonyl; or opt. substd. tetrazolyl; R<4> = H; OH, lower alkoxy; lower alkyl; Cl; F; CF3; COCH3; di(lower alkyl)amino; lower alkoxy-lower alkyl; etc.; R<5> = H, lower alkoxy, F, or CF3; or R<3>+R<4> = -CH=CH-CH=CH- or ethylenedioxy; or R<4>+R<5> = -CH=CH-CH=CH-; -(CH2)4-; methylenedioxy; ethylenedioxy; -N=CH-CH=CH-; etc.; R6 = H, OH; lower alkoxy; F; 2,4-di-fluoro-Ph; lower alkoxy-lower alkyl; etc.; R<7> = H; OH, lower alkoxy; COOH; NH2 or F; or R<6>+R<7> = -N=CH-CH=N- or -N(Me)CH2CH2N(Me)-; R<8> = H; lower alkoxy; lower alkyl or F; R<9> = H or F; R<10> = H; OH; lower alkoxy; or lower alkyl; R<11> = H; lower alkoxy; lower alkyl; F; or Br; R<12> = H; OH; lower alkoxy; COOH; lower alkoxycarbonyl; or NH2; R<13> = H; OH; lower alkoxy; lower alkyl; COCH3; or F; or R<12>+R<13> = -CH=CH-CH=CH-; or -C(OH)=CH-CH=CH- with the C(OH) gp. bonded to R<12>; R<14> = H; lower alkyl; or F; R<15> = H or amidino. Also claimed are n-protected intermediates (II).