META-SUBSTITUTED PHENYL SULPHONYLAMIDES OF SECONDARY AMINO ACID AMIDES AS MATERIALS OF MATRIPTASE TO INHIBIT TUMOR GROWTH AND / OR METASTASIS OF TUMORS

摘要

N-Phenylsulfonyl-3-amidino-phenylalanine piperidide derivatives (I) are new. N-Phenylsulfonyl-3-amidinophenylalanine piperidide derivatives of formula (I) are new. R 1optionally substituted, optionally hydrogenated aryl or heteroaryl; R 2, R 2' : 1-6C (hetero)alkyl, 1-6C aminoalkyl, 1-6C guanidinoalkyl or (CH 2) mCONHR 4, or form a ring; R 1aminoalkyl, 1-6C hydroxyalkyl or 3-azetidinecarboxamido; R 2, R 2' : 1-6C aminoalkyl or 1-6C guanidinoalkyl, or R 2 is (CH 2) mCONHR 4; R 1H 2N(CH 2) nCONH, HO(CH 2) nCONH or 3-azetidinecarboxamido; R 2, R 2' : (CH 2) mCONHR 4 or (CH 2) oCOOR 5 or form a ring; R 3H, OH, alkoxy, acetoxy or 1-6C alkoxycarbonyl; R 4H or 1-4C n-alkyl; m : 0-4; n : 1-4; o : 1-6; R 5H or 1-4C alkyl. Independent claims are also included for: (1) N-phenylsulfonyl-3-aminomethyl-phenylalanine piperidide derivatives of formula (II); (2) N-phenylsulfonyl-phenylalanine piperazide derivatives of formula (III); (3) four processes for preparing (I)-(III). R 7optionally substituted, optionally hydrogenated aryl or heteroaryl, 1-8C (hetero)alkyl, H 2N(CH 2) rCONH, HO(CH 2) rCONH, H 2N(CH 2) q, HO(CH 2) q or 3-azetidinecarboxamido; r : 1-4; q : 1-5; R 6, R 6' : 1-8C (hetero)alkyl, 1-6C aminoalkyl, 1-6C guanidinoalkyl or (CH 2) mCONHR 4, or form a ring. R 11H 2N(CH 2) nCONH, 3-azetidinecarboxamido or optionally substituted, optionally hydrogenated aryl or heteroaryl; R 12H, 1-6C aminoalkyl, COOR 14, COR 14, CONHR 14; R 141-6C alkyl, aralkyl or heteroaralkyl; R 13aminomethyl or C(NR 15)NH 2; R 15H, OH, alkoxy, acetoxy or 1-6C alkoxycarbonyl. [Image] [Image] [Image] ACTIVITY : Cytostatic. MECHANISM OF ACTION : Matriptase inhibitor. N-(3-(3,4-dimethoxyphenyl)phenylsulfonyl)-3-amidino-L-phenylalanine 4-(2-aminoethyl)piperidide had a Ki for matripase inhibition of 5.4 nM.