Constrained himbacine analogs as thrombin receptor antagonists

Abstract

A compound represented by the structural formula and pharmaceutically acceptable salts and solvents thereof are disclosed, wherein: the single-dashed line between the ring carbons to which R<10> and R<34> are attached represents either a single bond or a double bond; the double-dashed line between X and the carbon to which Y is attached represents either a single bond or an absent bond; X is -O- or -NR<6>- when the double-dashed line represents a single bond; X is H, -OH or -NHR<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.

Description

Background technique Various himbacine derivatives and pharmaceutical compositions containing these compounds have been disclosed in US Patent Nos. 6,063,847, 6,645,987 and 6,326,380 and US Application Nos. 10 / 271,715, 10 / 671,216 and 10 / 412,982. In the treatment of diseases related to thrombosis, arteriosclerosis, restenosis, hypertension, angina pectoris, arrhythmia, heart failure, cerebral ischemia, stroke, neurodegenerative diseases and cancer, these hibacin derivatives can be used as Thrombin receptor antagonist. Thrombin receptor antagonists are also known as protease-activated receptor-1 (PAR-1) antagonists. Many hebacin derivatives can also bind to cannabinoid receptors, and can be used to treat rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, diabetes, osteoporosis, renal ischemia, stroke, cerebral Ischemia, nephritis, inflammatory conditions of the lung and gastrointestinal tract, and respiratory diseases (such as reversible airway obstruction...

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