1437778-93-2

Upstream product

• 91361-59-0 methyl 2-(2-fluoro-4-hydroxyphenyl)acetate 
• 1416366-34-1 2-chloro-5-(methoxymethyl)pyrimidine 
• 1266335-37-8 tert-butyl 4-[(1R,2S)-2-(2-hydroxyethyl)cyclopropyl]piperidine-1-carboxylate 
• 1192063-72-1 racemic tert-butyl 4-[(1Z)-4-(benzyloxy)but-1-en-1-yl]piperidine-1-carboxylate 
• 137076-22-3 tert butyl 4-formylpiperidine-1-carboxylate 
• 1046816-75-4 2-chloro-5-hydroxymethyl-pyrimidine 
• 1402554-67-9 benzyl 4-[(1R,2S)-2-(2-hydroxyethyl)cyclopropyl]piperidine-1-carboxylate 
• 1192063-81-2 tert-butyl 4-[(1Z,4R)-5-(benzyloxy)-4-hydroxypent-1-en-1-yl]piperidine-1-carboxylate 
• 1192063-78-7 tert-butyl 4-[(4R)-5-(benzyloxy)-4-hydroxypent-1-yn-1-yl]piperidine-1-carboxylate 
• 287192-97-6 4-ethynyl-piperidine-1-carboxylic acid tert-butyl ester 
• 1437778-81-8 2-[(1S,2R)-2-{1-[5-(methoxymethyl)pyrimidin-2-yl]piperidin-4-yl}cyclopropyl]ethanol 
• 68886-07-7 (2-fluoro-4-hydroxylphenyl)acetic acid 

Downstream Products

• 1437778-94-3 {2-fluoro-4-[2-((1S,2R)-2-{1-[5-(methoxymethyl)pyrimidin-2-yl]piperidin-4-yl}cyclopropyl)ethoxy]phenyl}acetic acid 
• 1437776-63-0 1-(azetidin-1-yl)-2-(2-fluoro-4-{2-[(1S,2R)-2-{1-[5-(methoxylmethyl)pyrimidin-2-yl]piperidin-4-yl}cyclopropyl]ethoxyl}phenyl)ethanone 
• 1437779-20-8 2-[2-fluoro-4-(2-{(1S,2R)-2-[1-[5-(methoxymethyl)pyrimidine-2-yl]piperidin-4-yl]cyclopropyl}ethoxy)phenyl]acetohydrazide 
• 1437778-75-0 2-[4-((1R,2S)-2-{2-[3-fluoro-4-(1,3,4-thiadiazol-2-ylmethyl)phenoxy]ethyl}cyclopropyl)piperidin-1-yl]-5-(methoxymethyl)pyrimidine 

Relevant academic research and scientific papers

GPR119 AGONISTS

This disclosure is directed, at least in part, to GPR119 agonists useful for the treatment of conditions or disorders involving the gut-brain axis. In some embodiments, the GPR119 agonists are gut-restricted compounds. In some embodiments, the condition or disorder is a metabolic disorder, such as diabetes, obesity, nonalcoholic steatohepatitis (NASH), or a nutritional disorder such as short bowel syndrome.

Discovery of phenyl acetamides as potent and selective GPR119 agonists

The paper describes the SAR/SPR studies that led to the discovery of phenoxy cyclopropyl phenyl acetamide derivatives as potent and selective GPR119 agonists. Based on a cis cyclopropane scaffold discovered previously, phenyl acetamides such as compound 17 were found to have excellent GPR119 potency and improved physicochemical properties. Pharmacokinetic data of compound 17 in rat, dog and rhesus will be described. Compound 17 was suitable for QD dosing based on its predicted human half-life, and its projected human dose was much lower than that of the recently reported structurally-related benzyloxy compound 2. Compound 17 was selected as a tool compound candidate for NHP (Non-Human Primate) efficacy studies.

SUBSTITUTED CYCLOPROPYL COMPOUNDS USEFUL AS GPR119 AGONISTS

Substituted cyclopropyl compounds of the formula (I): and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing type 2 diabetes and similar conditions. The compounds are useful as agonists of the G-protein coupled receptor GPR-119. Pharmaceutical compositions and methods of treatment are also included