Abstract: Multiple stereoisomers of the heterocyclic-substituted tricyclics of the formula: or a pharmaceutically acceptable salt, solvate, or ester of said compound wherein R and the stereochemistry are illustrated in the structural formulas herein 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.

Abstract: This application discloses provides a process for the introduction of nitro-group functionality into a compound which contains also a site of unsaturation and/or oxygen functionality by direct (one step) oxidation of an oxime functional group mediated by a molybdenum VI/VII peroxo complex, the process comprising: (a) providing a substrate of Formula I containing an oxime functional group; ?wherein R1 and R2 are selected independently from linear, branched or cyclic alkyl and linear, branched or cyclic alkenyl groups, optionally substituted, with the proviso that at least one of R1 or R2 contains a carbon/carbon double bond; and (b) contacting said substrate of Formula I with a molybdenum oxidation complex, thereby oxidizing said oxime functional group to a nitro functional group to yield the structure of Formula III. Where R1 and R2 are as defined above.

Abstract: This application discloses a novel process for the preparation of phosphonate esters useful as intermediates in the preparation of himbacine analogs, themselves useful as thrombin receptor antagonists. The chemistry taught herein can be exemplified by the following scheme: wherein R9 is selected from alkyl, aryl heteroaryl and arylalkyl groups having 1 to 10 carbon atoms, and R11 is selected independently for each occurrence from alkyl, aryl heteroaryl and arylalkyl groups having 1 to 10 carbon atoms and hydrogen, X2 is Cl, Br, or I; X3 is selected from Cl and Br; and PdLn is a supported palladium metal catalyst or a soluble heterogeneous palladium catalyst. The L-derivatizing reagent is a moiety which converts the alcohol functional group of compound 137D to any leaving group which can be displaced by a triorgano-phosphite phosphonating agent.

Abstract: A crystalline polymorph of a bislulfate salt of a thrombin receptor antagonist compound, which exhibits a powder x-ray diffraction profile substantially the same as that shown in FIG. 1, or which exhibits a differential scanning calorimtery profile substantially the same as that shown in FIG. 3, and is represented by the formula for Compound 2: and processes for preparing Compound 2 are disclosed. Pharmaceutical compositions comprising the polymorph of the bisulfate salt and at least one excipient or carrier, and methods of using the polymorph of Compound 2 to treat a variety of physiological disorders, such as thrombosis, are also disclosed.

Abstract: This application discloses a novel process for the preparation of himbacine analogs useful as thrombin receptor antagonists. The process is based in part on the use of a base-promoted dynamic epimerization of a chiral nitro center.

Abstract: This application discloses a novel process for the synthesis of himbacine analogs, as well as the compounds produced thereby. The synthesis proceeds by alternative routes including the cyclic ketal amide route, the chiral carbamate amide route, and the chiral carbamate ester route. The compounds produced thereby are useful as thrombin receptor antagonists.

Abstract: 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.

Abstract: A process is provided for preparing azetidinones useful as intermediates in the synthesis of penems and as hypocholesterolemic agents, comprising reacting a ?-(substituted-amino)amide, a ?-(substituted-amino)acid ester, or a ?-(substituted-amino)thiolcarbonic acid ester with a silylating agent and a cyclizing agent selected from the group consisting of alkali metal carboxylates, quaternary ammonium carboxylates, quaternary ammonium hydroxides, quaternary ammonium alkoxides, quaternary ammonium aryloxides and hydrates thereof, or the reaction product of: (i) at least one quaternary ammonium halide and at least one alkali metal carboxylate; or (ii) at least one quaternary ammonium chloride, quaternary ammonium bromide, or quaternary ammonium iodide and at least one alkali metal fluoride, wherein a quaternary ammonium moiety of the cyclizing agent is unsubstituted or substituted by one to four groups independently selected from the group consisting of alkyl, arylalkyl and arylalkyl-alkyl.

Abstract: In an illustrative embodiment, the present invention describes the synthesis of the following compound and similar compounds, in high stereochemical purity by a novel stereoselective alkylation process: