26413-58-1

Usage

Chemical Properties

Colorless to light yellow liquid

InChI:InChI=1/C7H5Cl2NO/c1-4-2-5(7(9)11)3-6(8)10-4/h2-3H,1H3

Upstream product

• 86454-13-9 1,2-dihydro-6-methyl-2-oxo-4-pyridinecarboxylic acid 
• 25462-85-5 2-chloro-6-methylpyridine-4-carboxylic acid 

Downstream Products

• 896739-39-2 2-chloro-N-{4-[2-(4-fluoro-3-methylphenyl)imidazo[1,2-b]pyridazin-3-yl]pyridin-2-yl}-6-methylpyridin-4-carboxamide 
• 3998-90-1 2-chloro-6-methyl-isonicotinic acid methyl ester 
• 1112174-77-2 N-(4-fluoro-3-methoxybenzyl)-4-(2-(((trans)-4-(hydroxymethyl)cyclohexyl)methyl)-2H-tetrazol-5-yl)-6-methylpicolinamide 
• 1112174-59-0 N-(4-fluoro-3-(trifluoromethyl)benzyl)-4-(2-(((trans)-4-(hydroxymethyl)cyclohexyl)methyl)-2H-tetrazol-5-yl)-6-methylpicolinamide 
• 1112174-56-7 N-(4-fluoro-3-methylbenzyl)-4-(2-(((trans)-4-(hydroxymethyl)cyclohexyl)methyl)-2H-tetrazol-5-yl)-6-methylpicolinamide 
• 1112174-53-4 N-(3,4-difluorobenzyl)-4-(2-(((trans)-4-(hydroxymethyl)cyclohexyl)methyl)-2H-tetrazol-5-yl)-6-methylpicolinamide 
• 1112174-31-8 N-(3-(trifluoromethyl)benzyl)-4-(2-(((trans)-4-(hydroxymethyl)cyclohexyl)methyl)-2H-tetrazol-5-yl)-6-methylpicolinamide 
• 1112174-40-9 N-(3-methylbenzyl)-4-(2-(((trans)-4-(hydroxymethyl)cyclohexyl)methyl)-2H-tetrazol-5-yl)-6-methylpicolinamide 
• 1112174-37-4 N-(3-chlorobenzyl)-4-(2-(((trans)-4-(hydroxymethyl)cyclohexyl)methyl)-2H-tetrazol-5-yl)-6-methylpicolinamide 
• 1112174-95-4 N-(4-fluorobenzyl)-4-(2-(((trans)-4-(hydroxymethyl)cyclohexyl)-methyl)-2H-tetrazol-5-yl)-6-methylpicolinamide 
• 1112182-62-3 4-(2-(((trans)-4-(hydroxymethyl)cyclohexyl)methyl)-2H-tetrazol-5-yl)-6-methylpicolinic acid 
• 1112173-02-0 trans-4-((5-(2-((3-methoxybenzyl)carbamoyl)-6-methyl-pyridin-4-yl)-2H-tetrazol-2-yl)methyl)cyclohexanecarboxylic acid 
• 1112171-88-6 N-(3-methoxybenzyl)-4-(2-(((cis)-4-aminocyclohexyl)methyl)-2H-tetrazol-5-yl)-6-methylpicolinamide 
• 1112182-36-1 tert-butyl (cis)-4-((5-(2-((3-methoxybenzyl)carbamoyl)-6-methylpyridin-4-yl)-2H-tetrazol-2-yl)methyl)cyclohexylcarbamate 

Relevant academic research and scientific papers

HETEROCYCLIC AZOLES FOR THE TREATMENT OF DEMYELINATING DISEASES

The invention relates to heterocyclic compounds of formula (I) and (IV) or pharmaceutically acceptable salts thereof, useful as modulators of demyelinating diseases. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention, methods of using the compositions and kits thereof in the treatment of various demyelinating and neurodegenerative diseases, including multiple sclerosis.

Discovery of N-(4-Fluoro-3-methoxybenzyl)-6-(2-(((2S,5R)-5-(hydroxymethyl)-1,4-dioxan-2-yl)methyl)-2H-tetrazol-5-yl)-2-methylpyrimidine-4-carboxamide. A Highly Selective and Orally Bioavailable Matrix Metalloproteinase-13 Inhibitor for the Potential Treatment of Osteoarthritis

Matrix metalloproteinase-13 (MMP-13) is a zinc-dependent protease responsible for the cleavage of type II collagen, the major structural protein of articular cartilage. Degradation of this cartilage matrix leads to the development of osteoarthritis. We previously have described highly potent and selective carboxylic acid containing MMP-13 inhibitors; however, nephrotoxicity in preclinical toxicology species precluded development. The accumulation of compound in the kidneys mediated by human organic anion transporter 3 (hOAT3) was hypothesized as a contributing factor for the finding. Herein we report our efforts to optimize the MMP-13 potency and pharmacokinetic properties of non-carboxylic acid leads resulting in the identification of compound 43a lacking the previously observed preclinical toxicology at comparable exposures.

NOVEL SPIROINDOLINE COMPOUNDS

This invention relates to novel spiroindoline compounds of formula (I) that are generally useful as medicaments, more specifically as medicaments for animals. The medicament can preferably be used for the treatment of helminth infections and the treatment of parasitosis, such as caused by helminth infections. This invention also relates to uses of the compounds to make medicaments and treatments comprising the administration of the compounds to animals in need of the treatments. This invention also relates to the preparation of said compounds. Moreover this invention relates to pharmaceutical compositions and kits comprising the compounds.

Discovery of (pyridin-4-yl)-2H-tetrazole as a novel scaffold to identify highly selective matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis

Potent, highly selective and orally-bioavailable MMP-13 inhibitors have been identified based upon a (pyridin-4-yl)-2H-tetrazole scaffold. Co-crystal structure analysis revealed that the inhibitors bind at the S1′ active site pocket

6,6′-Dimethyl-2,2′-bipyridine-4-ester: A pivotal synthon for building tethered bipyridine ligands

We describe an efficient and scalable synthesis of 4-carbomethoxy-6,6′-dimethyl-2,2′-bipyridine starting from easily available substituted 2-halopyridines and based on the application of modified Negishi cross-coupling conditions. This compound is a versatile starting material for the synthesis of 4-functionalized 2,2′-bipyridines bearing halide, alcohol, amine, and other functionalities, suitable for conjugation to biological material (2a-c, 3a-g). The utility of this compound in the construction of more complex architectures was further demonstrated by the synthesis of two bifunctional lanthanide chelators; an open chain ligand based on one 2,2′-bipyridine unit and a cryptand based on three 2,2′-bipyridine units [N2(bpy)3COOMe]. In the field of luminophoric biolabels, the photophysical properties of the corresponding Eu(III) cryptate are reported.

AMIDE-SUBSTITUTED ARYL PIPERIDINES

Amide-substituted aryl piperidines derivatives of the following Formulas are provided:(Formulas), in which the variables are as described herein. Such compounds may be used to modulate calcitonin gene-related peptide (CGRP) receptor activity in vivo or in vitro, and are particularly useful in the treatment of conditions responsive to CGRP modulation in humans, domesticated companion animals and livestock animals, including headache, such as migraine. Pharmaceutical compositions and methods for using them to treat such disorders are provided, as are methods for using such compounds for receptor localization studies and various in vitro assays.

BIARYL KETONE-SUBSTITUTED PIPERIDINES

Biaryl ketone-substituted piperidines of the following Formulas are provided:, and in which the variables are as described herein. Such compounds may be used to modulate calcitonin gene-related peptide (CGRP) receptor activity in vivo or in vitro, and are particularly useful in the treatment of conditions responsive to CGRP modulation in humans, domesticated companion animals and livestock animals, including headache such as migraine. Pharmaceutical compositions and methods for using them to treat such disorders are provided, as are methods for using such compounds for receptor localization studies and various in vitro assays.

CONDENSED IMIDAZOLE COMPOUND AND USE THEREOF

The present invention relates to a compound represented by the formula [I] wherein X1, X2 and X3 are each an optionally substituted CH or a nitrogen atom, and any one of X1, X2 and X3 is a nitrogen atom, X4 is an optionally substituted CH, R1 is an optionally substituted phenyl group or an optionally substituted heterocyclic group, and R2 is an optionally substituted pyridin-4-yl group, an optionally substituted pyridine-N-oxide-4-yl group or an optionally substituted pyrimidin-4-yl group, or a salt thereof. The compound has superior p38 MAP kinase inhibitory activity and MMP-13 production inhibitory activity, and is useful as an agent for the prophylaxis or treatment and the like of an inflammatory disease, an autoimmune disease, a debilitating disease, an osteoarticular degenerative disease, a neurodegenerative disease, a vascular disease, a neoplastic disease or an infectious disease.

MACROCYCLIC LACTAMS AND PHARMACEUTICAL USE THEREOF

The present invention relates to novel macrocyclic compounds of the formula (I) wherein R1, R2, R3, U, V, W, X, Y, Z and n are as defined in the specification, the number of ring atoms included in the macrocyclic ring being 14, 15, 16 or 17, in free base form or in acid addition salt form, to their preparation, to their use as pharmaceuticals and to pharma-ceutical compositions comprising them.