1228783-99-0

Upstream product

• 1194-16-7 2,2-dimethyltetrahydropyran-4-one 
• 1679-18-1 4-Chlorophenylboronic acid 
• 1228783-97-8 methyl 4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-carboxylate 
• 1228783-96-7 methyl 6,6-dimethyl-4-(trifluoromethylsulfonyloxy)-5,6-dihydro-2H-pyran-3-carboxylate 
• 1228386-26-2 methyl 6,6-dimethyl-4-oxotetrahydro-2H-pyran-3-carboxylate 
• 1228783-98-9 (4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl)methanol 

Downstream Products

• 1228943-34-7 methyl 2-(2-chlorophenoxy)-4-(4-((4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl)methyl)piperazin-1-yl)benzoate 

Relevant academic research and scientific papers

CONDENSED HETEROCYCLES AS BCL-2 INHIBITORS

The disclosure includes compounds of Formula (A) wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11, h, j, m, n, k, v, s, g, V, W, L, Z1 Q1, Q2, Q3, Q4, Q5, Q6, and Q7, are defined herein. Also disclosed is a method for treating a neoplastic disease, an autoimmune disease, or a neorodegenerative disease with these compounds.

HOT MELT EXTRUDED SOLID DISPERSIONS CONTAINING A BCL2 INHIBITOR

A pro-apoptotic solid dispersion comprises, a Bcl -2 family protein inhibitory compound of Formula A as defined herein, dispersed in a solid matrix that comprises (a) a pharmaceutically acceptable water-soluble polymeric carrier, and (b) a pharmaceutically acceptable surfactant. A process for preparing such a solid dispersion comprises subjecting to elevated temperature the compound of Formula A, the water-soluble polymeric carrier, and the surfactant to provide an extrudable semi-solid mixture; extruding the semi-solid mixture; and cooling the resulting extrudate to provide a solid matrix comprising the polymeric carrier, and the surfactant and having the compound dispersed in essentially non-crystalline form therein. The solid dispersion is suitable for oral administration to a subject in need thereof for treatment of a disease characterized by overexpression of one or more anti-apoptotic Bcl -2 family proteins, for example cancer or an immune or autoimmune disease.

Solid dispersions containing an apoptosis-inducing agent

A pro-apoptotic solid dispersion comprises, in essentially non-crystalline form, a Bcl-2 family protein inhibitory compound of Formula I as defined herein, dispersed in a solid matrix that comprises (a) a pharmaceutically acceptable water-soluble polymeric carrier and (b) a pharmaceutically acceptable surfactant. A process for preparing such a solid dispersion comprises dissolving the compound, the polymeric carrier and the surfactant in a suitable solvent, and removing the solvent to provide a solid matrix comprising the polymeric carrier and the surfactant and having the compound dispersed in essentially non-crystalline form therein. The solid dispersion is suitable for oral administration to a subject in need thereof for treatment of a disease characterized by overexpression of one or more anti-apoptotic Bcl-2 family proteins, for example cancer.

APOPTOSIS-INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE AND AUTOIMMUNE DISEASES

Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-2 proteins, compositions containing the compounds and methods of treating diseases during which is expressed anti-apoptotic Bcl-2 protein.