Heterocyclic hydrazones for use as anti-cancer agents

摘要

The use of benzimidazole, benzoxazole or benzothiazole 2-(heteroaryl substituted)-hydrazones (I) as medicaments is new. Most compounds (I) are new. The use of benzazole derivatives of formula (I) or their salts as medicaments is new. Het = 5-(R)-pyridazin-3-yl, 6-(R)-pyrimidin-4-yl, 4- or 5-(R)-pyrimidin-2-yl, 3- or 5-(R)-pyrazin-2-yl, 3-, 4-, 5- or 6-(R)-pyridin-2-yl, quinolin-2-yl. isoquinolin-1-yl or isoquinolin-3-yl; R = H, H, Me, OMe, OH, Cl, Br, F, NO2, NH2, NHCOMe, NMe2, Ph, CN, C(=NH)NH2, C(S)NH2, C(=NH)NHOH, COOH, COOR4 or CONR5R6; R4 = aliphatic residue or Ph; R5, R6 = H, aliphatic residue or Ph; R1 = H, 1-3C alkyl, butyl, tert. butyl, cyclopropyl, cyclohexyl, Ph, benzyl or 2-pyridyl; X = O, S, NH or NR2; R2 = 1-3C alkyl, butyl, tert. butyl, allyl, cyclopropyl, Ph, benzyl, CH2CH2OMe or CH2CH2NMe2; provided that if X = S and Het = pyridinyl, then R1 is not H or Me. Independent claims are included for: (a) the preparation of (I), by reacting a ketone of formula R1-CO-Het (III) with a hydrazine of formula (II); and (b) (I) and their salts as new compounds, provided that: (i) where Het = unsubstituted 2-pyridyl, if X = S then R1 is not H, Me, Ph or 2-pyridyl, if X = O then R1 is not H; if X = N (sic) then R1 is not H; if X = NH then R1 is not Me; and if X = N(Me) then R1 is not Me; (ii) if Het = isoquinolin-1- or 3-yl and X = S, then R1 is not Me; (iii) if Het = quinolin-2-yl and X = S, then R1 is not H or Me; (iv) if Het = 5-(R)-pyrazin-2-yl, 5-(R)-pyridazin-3-yl or 6-(R)-pyrimidin-4-yl, X = S and R1 = Me, then R is not H or Me; and (v) if X = S and R1 = Me, then Het is not 3-methyl-pyrazin-2-yl, unsubstituted pyrimidin-2-yl or 6-methyl-pyridin-2-yl.