Nor-seco-himbacine derivatives, pharmaceutical composition comprising the same and their use

摘要

Heterocyclic-substituted compounds of formula (I) or a pharmaceutically acceptable salt thereof, are disclosed, wherein: Z is - (CH2)n-; (a); (b), wherein R 10 is absent; or, (c) wherein R 3 is absent; the single dotted line represents an optional double bond; the double dotted line represents an optional single bond; n is 0-2; Het is an optionally substituted mono-, bi- or tri-cyclic heteroaromatic group; B is -(CH 2 ) n3 -. wherein n 3 is 0-5, -CH 2 -O-, -CH 2 S-, -CH 2 -NR 6 -, -C(O)NR 6 -. -NR 6 C(O)-, (d), optionally substituted alkenyl or optionally substituted alkynyl; X is -O- or -NR 6 - when the double dotted line represents a single bond, or X is H, -OH or -NHR 20 when the bond is absent; Y is =O, =S, (H, H), (H, OH) or (H, C 1 -C 6 alkoxy) when the double dotted line represents a single bond or when the bond is absent, Y is =O, =NOR 17 (H, H). (H, OH), (H, SH), (H, C 1 -C 6 alkoxy) or (H, substituted-amino); R 22 and R 23 are independently -OH, -OC(O)R 30 , OC(O)NR 30 R 31 , or optionally substituted alkyl, alkenyl, alkynyl, heterocycloalkyl, aryl, cycloalkyl, cycloalkenyl, carbonyl, amino, alkoxy, alkenyloxy, alkynyloxy, heterocycloalkyloxy, cycloalkyloxy, or cycloalkenyloxy; or R 22 and R 10 , or R 23 and R 11 , can form a carbocyclic or heterocyclic ring; and the remaining variables are as described in the specification, Also disclosed are pharmaceutical compositions containing said compounds and their use as thrombin receptor antagonists and blinders to cannabinoid receptors.