1448039-58-4

Basic information

• Product Name: N-(2-chlorobenzyl)-2-cyclopropyl-1-[(4-fluorophenyl)sulfonyl]-1,2,2',3',5',6'-hexahydrospiro[indole-3,4'-thiopyran]-5-carboxamide
• Synonyms: N-(2-chlorobenzyl)-2-cyclopropyl-1-[(4-fluorophenyl)sulfonyl]-1,2,2',3',5',6'-hexahydrospiro[indole-3,4'-thiopyran]-5-carboxamide
• CAS NO: 1448039-58-4
• Molecular Weight: 571.136
• Mol File: 1448039-58-4.mol
• Article Data: 2

Chemical Properties

• CAS DataBase Reference: N-(2-chlorobenzyl)-2-cyclopropyl-1-[(4-fluorophenyl)sulfonyl]-1,2,2',3',5',6'-hexahydrospiro[indole-3,4'-thiopyran]-5-carboxamide(CAS DataBase Reference)
• NIST Chemistry Reference: N-(2-chlorobenzyl)-2-cyclopropyl-1-[(4-fluorophenyl)sulfonyl]-1,2,2',3',5',6'-hexahydrospiro[indole-3,4'-thiopyran]-5-carboxamide(1448039-58-4)
• EPA Substance Registry System: N-(2-chlorobenzyl)-2-cyclopropyl-1-[(4-fluorophenyl)sulfonyl]-1,2,2',3',5',6'-hexahydrospiro[indole-3,4'-thiopyran]-5-carboxamide(1448039-58-4)

Safety Data

• Hazardous Substances Data: 1448039-58-4(Hazardous Substances Data)

Upstream product

• 1448038-91-2 5-bromo-2-cyclopropyl-1-[(4-fluorophenyl)sulfonyl]-1,2,2',3',5',6'-hexahydrospiro[indole-3,4'-thiopyran] 
• 89-97-4 2-CHLOROBENZYLAMINE 
• 13939-06-5 molybdenum hexacarbonyl 
• 131992-30-8 4-(methoxymethylene)-3,4,5,6-tetrahydro-2H-thiopyran 
• 100277-27-8 (tetrahydro-2H-thiopyran-4-yl)methanol 
• 50675-19-9 4-thianylcarbaldehyde 
• 1072-72-6 Tetrahydrothiopyran-4-one 

Downstream Products

• 1448039-59-5 (R)-N-(2-chlorobenzyl)-2-cyclopropyl-1-[(4-fluorophenyl)sulfonyl]-1,2,2',3',5',6'-hexahydrospiro[indole-3,4'-thiopyran]-5-carboxamide 
• 1448039-60-8 (S)-N-(2-chlorobenzyl)-2-cyclopropyl-1-[(4-fluorophenyl)sulfonyl]-1,2,2',3',5',6'-hexahydrospiro[indole-3,4'-thiopyran]-5-carboxamide 
• 1448041-28-8 N-(2-chlorobenzyl)-2-cyclopropyl-1-[(4-fluorophenyl)sulfonyl]-1,2,2',3',5',6'-hexahydrospiro[indole-3,4'-thiopyran]-5-carboxamide 1'-oxide 

Relevant articles and documents

Discovery and Characterization of BAY 1214784, an Orally Available Spiroindoline Derivative Acting as a Potent and Selective Antagonist of the Human Gonadotropin-Releasing Hormone Receptor as Proven in a First-In-Human Study in Postmenopausal Women

The growth of uterine fibroids is sex hormone-dependent and commonly associated with highly incapacitating symptoms. Most treatment options consist of the control of these hormonal effects, ultimately blocking proliferative estrogen signaling (i.e., oral contraceptives/antagonization of human gonadotropin-releasing hormone receptor [hGnRH-R] activity). Full hGnRH-R blockade, however, results in menopausal symptoms and affects bone mineralization, thus limiting treatment duration or demanding estrogen add-back approaches. To overcome such issues, we aimed to identify novel, small-molecule hGnRH-R antagonists. This led to the discovery of compound BAY 1214784, an orally available, potent, and selective hGnRH-R antagonist. Altering the geminal dimethylindoline core of the initial hit compound to a spiroindoline system significantly improved GnRH-R antagonist potencies across several species, mandatory for a successful compound optimization in vivo. In a first-in-human study in postmenopausal women, once daily treatment with BAY 1214784 effectively lowered plasma luteinizing hormone levels by up to 49%, at the same time being associated with low pharmacokinetic variability and good tolerability.