Heterocyclic-substituted tricyclics of the formula ##STR00001## or a pharmaceutically acceptable salt thereof, wherein: the dotted line represents an optional single bond; represents an optional double bond; n is 0 2; Q is cycloalkyl, optionally substituted by R.sup.13 and R.sup.14; R.sup.13 and R.sup.14 are independently selected from (C.sub.1 C.sub.6)alkyl, (C.sub.3 C.sub.8)cycloalkyl, --OH, (C.sub.1 C.sub.6)alkoxy, R.sup.27-aryl(C.sub.1 C.sub.6)alkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halogen and haloalkyl; or R.sup.13 and R.sup.14 together form a spirocyclic or a heterospirocyclic ring of 3 6 atoms; Het is a mono- or bi-cyclic optionally substituted heteroaryl group; and B is a bond, alkylene, or optionally substituted alkenylene or alkynylene, wherein the remaining substituents are as defined in the specification, are disclosed, as well as pharmaceutical compositions containing them and a method of treating diseases associated with thrombosis, atherosclerosis, restenosis, hypertension, angina pectoris, arrhythmia, heart failure, and cancer by administering said compounds. Combination therapy with other cardiovascular agents is also claimed.
The present application claims priority under 35 USC section 119(e) of U.S. Provisional application Ser. No. 60/373,072, filed Apr. 16, 2002, the complete text, claims and figures of which are incorporated by reference herein as if fully set forth.
The present invention relates to an improved process for preparing himbacine analogs. The compounds are useful as thrombin receptor antagonists. The improved process may allow for at least one of easier purification by crystallization, easier scalability, and improved process yield on the desired enantiomer.An example of a step in the synthesis of such a himbacine analog is as follows: ##STR00001##
A compound represented by the structural formula ##STR00001## and pharmaceutically acceptable salts and solvents thereof is disclosed, wherein: the single-dashed line ##STR00002## between the ring carbons to which R.sup.10 and R.sup.34 are attached represents either a single bond or a double bond; the double-dashed line ##STR00003## between X and the carbon to which Y is attached represents either a single bond or an absent bond; X is --O-- or --NR.sup.6-- when the double-dashed line represents a single bond; X is H, --OH or --NHR.sup.20 when the double-dashed line represents an absent bond; and other parameters are as defined herein. Also disclosed are pharmaceutical compositions and combinations containing said compounds and their uses as thrombin receptor antagonists and binders to cannabinoid receptors.
