1057343-95-9Relevant articles and documents
A convergent process for the preparation of adamantane 11-β-HSD-1 inhibitors
Becker, Calvin L.,Engstrom, Kenneth M.,Kerdesky, Francis A.,Tolle, John C.,Wagaw, Seble H.,Wang, Weifeng
, p. 1114 - 1118 (2008)
A convergent, scalable process was developed for the synthesis of adamantane 11-β-hydroxysteroid dehydrogenase-1 inhibitors E-4-(2-methyl-2-(4-(5-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl) propionylamino)adamantane-1-carboxylic acid (1) and E-4-(2-methyl-2-(4-(5- (trifluoromethyl)pyridin-2-yl)piperazin-1-yl)propionylamino)-adamantane-1- carboxamide (2) to rapidly deliver material for development. The process was high yielding and provided 1 in 52% overall yield over six total steps with a five-step longest linear sequence and 2 in 45% overall yield over seven total steps with a six-step longest linear sequence. A process to prepare active pharmaceutical ingredient (API) of >99% purity at the kilogram scale has been developed under tight delivery timelines.
Design of pyrazolo-pyrimidines as 11β-HSD1 inhibitors through optimisation of molecular electrostatic potential
Robb, Graeme R.,Boyd, Scott,Davies, Christopher D.,Dossetter, Alexander G.,Goldberg, Frederick W.,Kemmitt, Paul D.,Scott, James S.,Swales, John G.
supporting information, p. 926 - 934 (2015/05/27)
The inhibition of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a potentially attractive mechanism for the treatment of obesity and other elements of the metabolic syndrome. A series of pyrazolo-pyrimidine inhibitors of this enzyme were identified from directed library synthesis. Knowledge of how these compounds bind to the enzyme and the key hydrogen-bonding interactions was used to design further compounds. The hydrogen-bond acceptor strength was calculated from the molecular electrostatic potential using quantum mechanical theory. Compounds were designed to modulate the acceptor strength, thus optimising the potency and other drug-like properties. Compounds with enhanced CNS penetration were designed through further modification of the electrostatic potential and the hydrogen-bond properties.
A COMPOUND FOR INHIBITING 11BETA-HYDROXY STEROID DEHYDROGENASE 1, AND A PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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Paragraph 405-407, (2013/03/26)
Disclosed are a novel compound or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition including the same for inhibiting human 11-beta-hydroxy steroid dehydrogenase type 1 (11beta-HSD1). The disclosed compound and the pharmaceutical composition including the same for inhibiting human 11-beta-hydroxy steroid dehydrogenase type 1 (11beta-HSD1) are excellent in activity and solubility, and is more efficient in formulation and transfer.
