811867-40-0

Basic information

• Product Name: C₂₉H₄₀FNO₆Si
• Synonyms: C₂₉H₄₀FNO₆Si
• CAS NO: 811867-40-0
• Molecular Weight: 545.724
• Mol File: 811867-40-0.mol
• Article Data: 3

Chemical Properties

• CAS DataBase Reference: C₂₉H₄₀FNO₆Si(CAS DataBase Reference)
• NIST Chemistry Reference: C₂₉H₄₀FNO₆Si(811867-40-0)
• EPA Substance Registry System: C₂₉H₄₀FNO₆Si(811867-40-0)

Safety Data

• Hazardous Substances Data: 811867-40-0(Hazardous Substances Data)

Upstream product

• 39508-01-5 (3’,5’-dimethoxy-1,1-dimethylbenzyloxy)carbonyl azide 
• 496-69-5 2-bromo-4-fluoro-phenol 
• 86864-60-0 2-(tert-butyldimethylsilyloxy)ethyl bromide 
• 811867-16-0 Ddz-propargylamine 
• 811867-39-7 C₁₄H₂₂BrFO₂Si 

Downstream Products

• 811867-41-1 C₂₃H₃₀FNO₆ 
• 874335-98-5 C₂₉H₄₄FNO₆Si 

Relevant articles and documents

Macrocyclic Modulators of the Ghrelin Receptor

The present invention provides novel conformationally-defined macrocyclic compounds that have been demonstrated to be selective modulators of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R1a and subtypes, isoforms and variants thereof). Methods of synthesizing the novel compounds are also described herein. These compounds are useful as agonists of the ghrelin receptor and as medicaments for treatment and prevention of a range of medical conditions including, but not limited to, metabolic and/or endocrine disorders, gastrointestinal disorders, cardiovascular disorders, obesity and obesity-associated disorders, central nervous system disorders, genetic disorders, hyperproliferative disorders and inflammatory disorders.

Optimization of the potency and pharmacokinetic properties of a macrocyclic ghrelin receptor agonist (Part I): Development of ulimorelin (TZP-101) from Hit to Clinic

High-throughput screening of Tranzyme Phar-ma's proprietary macrocycle library using the aequorin Ca2+-bioluminescence assay against the human ghrelin receptor (GRLN) led to the discovery of novel agonists against this G-protein coupled receptor. Early hits such as 1 (Ki = 86 nM, EC50 = 134 nM) though potent in vitro displayed poor pharmacokinetic properties that required optimization. While such macrocycles are not fully rule-of-five compliant, principally due to their molecular weight and clogP, optimization of their pharmacokinetic properties proved feasible largely through conformational rigidification. Extensive SAR led to the identification of 2 (Ki = 16 nM, EC50 = 29 nM), also known as ulimorelin or TZP-101, which has progressed to phase III human clinical trials for the treatment of postoperative ileus. X-ray structure and detailed NMR studies indicated a rigid peptidomimetic portion in 2 that is best defined as a nonideal type-I′ β-turn. Compound 2 is 24% orally bioavailable in both rats and monkeys. Despite its potency, in vitro and in gastric emptying studies, 2 did not induce growth hormone (GH) release in rats, thus demarcating the GH versus GI pharmacology of GRLN. (Figure presented)