20691-92-3

Usage

Chemical Properties

Colourless liquid

InChI:InChI=1/C7H12N2/c1-9-4-2-7(6-8)3-5-9/h7H,2-5H2,1H3

Upstream product

• 62718-28-9 1-methylpiperidine-4-carboxamide 
• 2459-09-8 4-pyridinecarboxylic acid, methyl ester 
• 1690-75-1 1-methyl-piperidine-4-carboxylic acid methyl ester 
• 7630-02-6 4-(methoxycarbonyl)-1-methylpyridinium iodide 
• 4395-98-6 4-cyanopiperidine 
• 50-00-0 formaldehyd 
• 1453-82-3 isonicotinamide 
• 39546-32-2 4-carboxamidopiperidine 

Downstream Products

• 20691-91-2 1-(1-methylpiperidin-4-yl)ethanone 
• 855638-82-3 4-benzyl-1-methyl-piperidine-4-carbonitrile 
• 92040-00-1 (1-methylpiperidin-4-yl)(phenyl)methanone 
• 112864-70-7 4-cyano-1-methyl-quinuclidinium; chloride 
• 7149-42-0 1-(1-methylpiperidin-4-yl)methanamine 
• 1027041-17-3 4-[2-(1,4-dimethyl-piperidin-4-yl)-thiazol-4-yl]-benzoic acid 
• 26458-78-6 4-cyanoquinuclidine 
• 78815-71-1 4-benzyl-4-ethoxycarbonyl-1-methylpiperidine 
• 65345-83-7 4-cyano-1-methyl-quinuclidinium; iodide 
• 55022-88-3 1-azabicyclo[2.2.2]octane-4-carboxylic acid 

Relevant academic research and scientific papers

Protein Modification at Tyrosine with Iminoxyl Radicals

Post-translational modifications (PTMs) of proteins are a biological mechanism for reversibly controlling protein function. Synthetic protein modifications (SPMs) at specific canonical amino acids can mimic PTMs. However, reversible SPMs at hydrophobic amino acid residues in proteins are especially limited. Here, we report a tyrosine (Tyr)-selective SPM utilizing persistent iminoxyl radicals, which are readily generated from sterically hindered oximes via single-electron oxidation. The reactivity of iminoxyl radicals with Tyr was dependent on the steric and electronic demands of oximes; isopropyl methyl piperidinium oxime 1f formed stable adducts, whereas the reaction of tert-butyl methyl piperidinium oxime 1o was reversible. The difference in reversibility between 1f and 1o, differentiated only by one methyl group, is due to the stability of iminoxyl radicals, which is partly dictated by the bond dissociation energy of oxime O-H groups. The Tyr-selective modifications with 1f and 1o proceeded under physiologically relevant, mild conditions. Specifically, the stable Tyr-modification with 1f introduced functional small molecules, including an azobenzene photoswitch, to proteins. Moreover, masking critical Tyr residues by SPM with 1o, and subsequent deconjugation triggered by the treatment with a thiol, enabled on-demand control of protein functions. We applied this reversible Tyr modification with 1o to alter an enzymatic activity and the binding affinity of a monoclonal antibody with an antigen upon modification/deconjugation. The on-demand ON/OFF switch of protein functions through Tyr-selective and reversible covalent-bond formation will provide unique opportunities in biological research and therapeutics.

Design and synthesis of tri-ring P3 benzamide-containing aminonitriles as potent, selective, orally effective inhibitors of cathepsin K

We have prepared a series of achiral aminoacetonitriles, bearing tri-ring benzamide moieties and an aminocyclohexanecarboxylate residue at P2. This combination of binding elements resulted in sub-250 pM, reversible, selective, and orally bioavailable cathepsin K inhibitors. Lead compounds displayed single digit nanomolar inhibition in vitro (of rabbit osteoclast-mediated degradation of bovine bone). The best compound in this series, 39n (CRA-013783/L-006235), was orally bioavailable in rats, with a terminal half-life of over 3 h. 39n was dosed orally in ovariectomized rhesus monkeys once per day for 7 days. Collagen breakdown products were reduced by up to 76% dose-dependently. Plasma concentrations of 39n above the bone resorption IC50 after 24 h indicated a correlation between functional cellular and in vivo assays. Inhibition of collagen breakdown by cathepsin K inhibitors suggests this mechanism of action may be useful in osteoporosis and other indications involving bone resorption.

5-HT3 receptor agonist, novel thiazole derivative and intermediate thereof

A 5-HT3 receptor against containing a thiazole derivative as the effective ingredient is provided and is represented by the Formula (I): STR1 wherein the A ring is substituted or unsubstituted and represents a benzene or a heterocyclic ring with one or two heteroatoms; one of L1 or L2 represents a single bond and the other is non-existent or represents an alkylene or alkenylene group; R represents: STR2