65141-19-7

Upstream product

• 1885-14-9 phenyl chloroformate 
• 328-74-5 3,5-Bis-(trifluoromethyl)aniline 
• 622-46-8 carbamic acid phenyl ester 
• 98550-05-1 nitrophenyl carbamate 
• 144-55-8 sodium hydrogencarbonate 

Downstream Products

• 307989-30-6 3-{4-[3-(3,5-bis-trifluoromethylphenyl)-1-(4-trans-tert-butylcyclohexyl)ureidomethyl]benzoylamino}propionic acid methyl ester 

Relevant academic research and scientific papers

3-(dimethylaminomethyl) piperidine-4-alcohol derivative as well as preparation method and pharmaceutical application thereof

The present invention provides compounds of formula (FWBF) or pharmaceutically acceptable salts thereof, in which the substituents are as defined in the specification, as well as a preparation method and pharmaceutical use thereof.

Discovery of 3-((dimethylamino)methyl)-4-hydroxy-4-(3-methoxyphenyl)-N-phenylpiperidine-1-carboxamide as novel potent analgesic

Management of moderate to severe pain by clinically used opioid analgesics is associated with a plethora of side effects. Despite many efforts have been dedicated to reduce undesirable side effects, moderate progress has been made. In this work, starting from Tramadol, a series of 3-((dimethylamino)methyl)-4-hydroxy-4-(3-methoxyphenyl)piperidine-1-carboxamide derivatives were designed and synthesized, and their in vitro and in vivo activities were evaluated. Our campaign afforded selective μ opioid receptor (MOR) ligand 2a (KiMOR: 7.3 ± 0.5 nM; KiDOR: 849.4 ± 96.6 nM; KiKOR: 49.1 ± 6.9 nM) as potent analgesic with ED50 of 3.1 mg/kg in 55 °C hot plate model. Its antinociception effect was blocked by opioid antagonist naloxone. High binding affinity toward MOR of compound 2a was associated with water bridge, salt bridge, hydrogen bond and hydrophobic interaction with MOR. The high selectivity of compound 2a for MOR over δ opioid receptor (DOR) and κ opioid receptor (KOR) was due to steric hindrance of compound 2a with DOR and KOR. 2a, a compound with novel scaffold, could serve as a lead for the development of novel opioid ligands.

Arylureas derived from colchicine: Enhancement of colchicine oncogene downregulation activity

Our efforts to get therapeutically useful colchicine derivatives for the treatment of cancer have led us to synthetize and biologically evaluate twenty-seven N,N′-disubstituted ureas containing a colchicine moiety and an aryl fragment. The cytotoxicity of

New β-alanine derivatives are orally available glucagon receptor antagonists

A weak human glucagon receptor antagonist with an IC50 of 7 μM was initially found by screening of libraries originally targeted to mimic the binding of the glucagon-like peptide (GLP-1) hormone to its receptor. Optimization of this hit for binding affinity for the glucagon receptor led to ligands with affinity in the nanomolar range. In addition to receptor binding, optimization efforts were made to stabilize the molecules against fast metabolic turnover. A potent antagonist of the human human glucagon receptor was obtained that had 17% oral availability in rats with a plasma half-life of 90 min. The major metabolites of this lead were identified and used to further optimize this series with respect to pharmacokinetic properties. This final optimization led to a potent glucagon antagonist that was orally available in rats and dogs and was efficacious in lowering blood glucose levels in a diabetic animal model.

GLUCAGON ANTAGONISTS/INVERSE AGONISTS

A novel class of compounds, which act to antagonize the action of the glucagon hormone on the glucagon receptor. Owing to their antagonizing effect of the glucagon receptor the compounds may be suitable for the treatment and/or prevention of any glucagon-

Glucagon antagonists/inverse agonists

Disclosed is a novel class of compounds of formula (I) wherein V, A, Y, Z, R1, E, X and D are as defined in the specification. These compounds act to antagonize the action of the glucagon hormone on the glucagon receptor. Owing to their antagonizing effect of the glucagon receptor, the compounds are suitable for treating or preventing glucagon-mediated conditions and diseases such as hyperglycemia, Type 1 diabetes, Type 2 diabetes and obesity.