NEUROMEDIN B RECEPTOR ANTAGONISTS

摘要

A cyclic octapeptide of the formula: wherein: A1 is D-Nal or D-Trp; A3 is Phe, F5-Phe, or X-Phe wherein X is a halogen, NO2, CH3, or OH; A5 is -NH-CH(Y)-CO- wherein Y is (CH2)m-R4-N(R5)(R6) or (CH2)n-R4-NH-C(R7)-N(R5) (R6); A6 is the D- or L- isomer of Thr, Leu, Ile, Nle, Val, and Abu; A8 is Nal or Trp; m is 1, 2, or 3; n is 1, 2, 3, 4 or 5; each of R1 and R2, independently, is H, E, COE, or COOE wherein E is C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, phenyl, naphthyl, C7-12 phenylalkyl or alkylphenyl, C8-12 phenylalkenyl or alkenylphenyl, C8-12 phenylalkynyl or alkynylphenyl, C11-20 naphthylalkyl or alkylnaphthyl, C12-20 naphthylalkenyl or alkenylnaphthyl, or C12-20 naphthylalkynyl or alkynylnaphthyl, provided that when one of R1 or R2 is COE or COOE, the other must be H; R4 is C6H4 or absent; R7 is =NR8, =S, or =O; and each of R3, R5, R6, and R8, independently, is H or E.