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Usage

Uses

Used in Pharmaceutical Industry:
(S)-2-((tert-butoxycarbonyl)amino)-2-(3,5-dihydroxyadamantan-1-yl)acetic acid is used as a key reactant in the synthesis of Saxagliptin (S143500), a potent and selective reversible inhibitor of dipeptidyl peptidase-4 (DPP-4). (S)-2-((tert-butoxycarbonyl)amino)-2-(3,5-dihydroxyadamantan-1-yl)acetic acid is being developed for the treatment of type 2 diabetes, as it helps in regulating blood glucose levels by inhibiting the enzyme responsible for breaking down incretin hormones. The rapid absorption after oral administration and its pharmacokinetic profile make it suitable for once-daily dosing, improving patient compliance and treatment outcomes.

Upstream product

• 361441-97-6 (alpha S)-alpha-[[(1,1-dimethylethoxy)carbonyl]amino]tricyclo[3.3.1.1^3,7]decane-1-acetic acid 
• 770-71-8 1-adamantanemethanol 
• 828-51-3 1-Adamantanecarboxylic acid 
• 361442-00-4 (αS)-α-[[(1,1-dimethylethoxy)carbonyl]-amino]-3-hydroxytricyclo[3.3.1.1^3,7]decane-1-acetic acid 
• 95853-35-3 (S)-(+)-β-amino-1-adamantaneacetic acid 
• 711-01-3 methyl adamantane-1-carboxylate 
• 2094-74-8 1-Adamantanecarbaldehyde 
• 361441-95-4 (S)-2-(adamantan-1-yl)-2-(((R)-2-hydroxy-1-phenylethyl)amino)acetonitrile 

Relevant academic research and scientific papers

The synthesis of 14C-labeled, 13CD 2-labeled saxagliptin, and its 13CD2-labeled 5-hydroxy metabolite

14C-labeled saxagliptin, 13CD2-labeled saxagliptin, and its 13CD2-labeled 5-hydroxy metabolite were synthesized to further support development of the compound for biological studies. This paper describes new syntheses leading to the desired compounds. A total of 3.0 mCi of 14C-labeled saxagliptin was obtained with a specific activity of 53.98 μCi/mg (17.13 mCi/mmol). The radiochemical purity determined by HPLC was 99.29%, and the overall radiochemical yield was 3.0% based upon 100 mCi of [14C]CH2I2 starting material. By following similar synthetic routes, 580.0 mg of 13CD2-labeled saxagliptin and 153.1 mg of 13CD2-labeled 5-hydroxysaxagliptin metabolite were prepared. Copyright

Discovery and preclinical profile of saxagliptin (BMS-477118): A highly potent, long-acting, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes

Efforts to further elucidate structure-activity relationships (SAR) within our previously disclosed series of β-quaternary amino acid linked L-cis-4,5-methanoprolinenitrile dipeptidyl peptidase IV (DPP-IV) inhibitors led to the investigation of vinyl substitution at the β-position of α-cycloalkyl-substituted glycines. Despite poor systemic exposure, vinyl-substituted compounds showed extended duration of action in acute rat ex vivo plasma DPP-IV inhibition models. Oxygenated putative metabolites were prepared and were shown to exhibit the potency and extended duration of action of their precursors in efficacy models measuring glucose clearance in Zuckerfa/fa rats. Extension of this approach to adamantylglycine- derived inhibitors led to the discovery of highly potent inhibitors, including hydroxyadamantyl compound BMS-477118 (saxagliptin), a highly efficacious, stable, and long-acting DPP-IV inhibitor, which is currently undergoing clinical trials for treatment of type 2 diabetes.

ADAMANTYGLYCINE-BASED INHIBITORS OF DIPEPTIDYL PEPTIDASE IV AND METHODS

Compounds are provided having the formula (I) [Chemical Structure] wherein: n is 0, 1 or 2; m is 0, 1 or 2; the sum of n + m less then or equal to 2; the dashed bonds forming a cyclopropyl ring can only be present when Y is CH; X is H or CN; Y is CH, CH2, CHF, CF2, O, S, SO, or SO2; and A is adamantyl. Further provided are methods of using such compounds for the treatment of diabetes and related diseases, and to pharmaceutical compositions containing such compounds.