148065-10-5

Upstream product

• 64-17-5 ethanol 
• 59782-85-3 2,5-dichloronicotinic acid 
• 38076-80-1 5-chloro-2-hydroxypyridine-3-carboxylic acid 
• 13103-07-6 ethyl 2,2-dichlorocyanoacetate 
• 107-02-8 acrolein 

Downstream Products

• 868636-76-4 ethyl 5-chloro-2-methylnicotinate 

Relevant academic research and scientific papers

Hinge Binder Scaffold Hopping Identifies Potent Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CAMKK2) Inhibitor Chemotypes

CAMKK2 is a serine/threonine kinase and an activator of AMPK whose dysregulation is linked with multiple diseases. Unfortunately, STO-609, the tool inhibitor commonly used to probe CAMKK2 signaling, has limitations. To identify promising scaffolds as starting points for the development of high-quality CAMKK2 chemical probes, we utilized a hinge-binding scaffold hopping strategy to design new CAMKK2 inhibitors. Starting from the potent but promiscuous disubstituted 7-azaindole GSK650934, a total of 32 compounds, composed of single-ring, 5,6-, and 6,6-fused heteroaromatic cores, were synthesized. The compound set was specifically designed to probe interactions with the kinase hinge-binding residues. Compared to GSK650394 and STO-609, 13 compounds displayed similar or better CAMKK2 inhibitory potency in vitro, while compounds 13g and 45 had improved selectivity for CAMKK2 across the kinome. Our systematic survey of hinge-binding chemotypes identified several potent and selective inhibitors of CAMKK2 to serve as starting points for medicinal chemistry programs.

Concise, gram-scale synthesis of furo[2,3-b]pyridines with functional handles for chemoselective cross-coupling

A concise 4-step synthesis of furo[2,3-b]pyridines, with handles in the 3- and 5-positions for palladium mediated cross-coupling reactions, is described. The synthetic route has been optimized, with only one step requiring purification by column chromatography. The route is amenable to scale-up, and was successfully executed on a multi-gram scale. Furopyridines are of growing interest in medicinal chemistry, and this route should enable easy access to the core for structure-activity relationship (SAR) studies.

A modified approach to C-14-labeled 2-(3,4-difluorophenoxy)-5- fluoronicotinic acid and other halogen-substituted analogs

A modified approach to a carbon-14-labeled pyridine ring system was developed based on the electrocyclic ring-closure of 1,4,4-trisubstituted butadiene. The new method was applied to prepare 2-(3,4-difluorophenoxy)-5- fluoro-[2-14C] nicotinic a

SUBSTITUTED METHYL ARYL OR HETEROARYL AMIDE COMPOUNDS

This invention provides a compound of the formula (I), wherein X represents a carbon atom or the like: Y represents imino, or the like: R1 represents an alkyl group having from 1 to 6 carbon atoms or the like: R2 and R3 in

COMBINATIONS COMPRISING ALPHA-2-DELTA LIGANDS

The instant invention relates to a combination of an EP4-receptor antagonist and an alpha-2-delta ligand, and pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof and their use in the treatment of pain, particularly inflammatory,

Nicotinamide derivatives and their mimetics as inhibitors of PDE4 isozymes

Compounds useful as inhibitors of PDE4 in the treatment of diseases regulated by the activation and degranulation of eosinophils, especially asthma, chronic bronchitis, and chronic obstructive pulmonary disease, of the formula: wherein j is 0 or 1, k is 0 or 1, m is 0, 1, or 2;n is 1 or 2; A is is selected from the partial Formulas: where q is 1, 2, or 3, W3 is -O-; -N(R9)-; or -OC(=O)-; R7 is selected from -H; -(C1-C6)alkyl, -(C2-C6)alkenyl, or -(C2-C6)alkynyl substituted by 0 to 3 substituents R10; -(CH2)u-(C3-C7) cycloalkyl where u is 0, 1 or 2, substituted by 0 to 3 R10; and phenyl or benzyl substituted by 0 to 3 R14; R8 is tetrazol-5-yl; 1,2,4-triazol-3-yl; 1,2,4-triazol-3-on-5-yl; 1,2,3-triazol-5-yl; imidazol-2-yl; imidazol-4-yl; imidazolidin-2-on-4-yl; 1,3,4-oxadiazolyl; 1,3,4-oxadiazol-2-on-5-yl; 1,2,4-oxadiazol-3-yl; 1,2,4-oxadiazol-5-on-3-yl; 1,2,4-oxadiazol-5-yl; 1,2,4-oxadiazol-3-on-5-yl; 1,2,5-thiadiazolyl; 1,3,4-thiadiazolyl; morpholinyl; parathiazinyl; oxazolyl; isoxazolyl; thiazolyl; isothiazolyl; pyrrolyl; pyrazolyl; succinimidyl; glutarimidyl; pyrrolidonyl; 2-piperidonyl; 2-pyridonyl; 4-pyridonyl; pyridazin-3-onyl; pyridyl; pyrimidinyl; pyrazinyl; pyridazinyl; indolyl; indolinyl; isoindolinyl; benzo[b]furanyl; 2,3-dihydrobenzofuranyl; 1,3-dihydroisobenzofuranyl; 2H-1-benzopyranyl; 2-H-chromenyl; chromanyl; benzothienyl; 1H-indazolyl; benzimidazolyl; benzoxazolyl; benzisoxazolyl; benzothiazolyl; benzotriazolyl; benzotriazinyl; phthalazinyl; 1,8-naphthyridinyl; quinolinyl; isoquinolinyl; quinazolinyl; quinoxalinyl; pyrazolo[3,4-d]pyrimidinyl; pyrimido[4,5-d]pyrimidinyl; imidazo[1,2-a]pyridinyl; pyridopyridinyl; pteridinyl; or 1H-purinyl; or A is selected from phosphorous and sulfur acid groups; W is ―O―; ―S(=O)t―, where t is 0, 1, or 2; or -N(R3)―; Y is C(R1a)―, or -[N□(O)k] where k is 0 or 1; R4, R5 and R6 are (1)―H; provided that R5 and R6 are not both -H at the same time, ―F; ―Cl; -(C2-C4) alkynyl; -R16; ―OR16; -S(=O)pR16; ―C(=O)R16, -C(=O)OR16; -OC(=O)R16; -CN; -NO2; -C(=O)NR16R17; -OC(=O)NR16R17; ―NR12aC(=O)NR16R17; -NR12aC(=NR12)NR16R17; -NR12aC(=NCN)NR15R16; -NR12aC(=N-NO2)NR15R16; -C(=NR12a)NR15R16; -CH2C(=NR12a)NR16R17; ―OC(=NR12a)NR16R17; ―OC(=N―NO2)NR16R17; -NR16R17; -CH2NR16R17; -NR12aC(=O)R16; -NR12aC(=O)OR16; =NOR16; ―NR12aS(=O)pR17 -S(=O)pNR16R17; and ―CH2C(=NR12a)NR16R17;(2) -(C1-C4) alkyl including dimethyl and -(C1-C4) alkoxy substituted with 0 to 3 substituents ―F or ―Cl; or 0 or 1 substituent (C1-C2) alkoxycarbonyl―, (C1-C2) alkylcarbonyl―, or (C1-C2) alkylcarbonyloxy―; or (3) an aryl or heterocyclic moiety; or (4) R5 and R6 are taken together to form a moiety of partial Formulas (1.3.1) through (1.3.15):B1 and B2 is a moiety comprising a saturated or unsaturated carbon ring system that is 3- to 7-membered monocyclic, or that is 7- to 12-membered, fused or discontinuous, polycyclic; wherein optionally one carbon atom thereof may be replaced by a heteroatom selected from N, O and S; and where N is selected, optionally a second carbon atom thereof may be replaced by a heteroatom selected from N, O, or S; or a pharmaceutically acceptable salt thereof.

DICHLOROCYANOACETIC ESTERS - NEW REAGENTS FOR ADDITION TO UNSATURATED COMPOUNDS

Methyl and ethyl dichlorocyanoacetates add to functionally substituted terminal alkenes in the presence of copper-containing catalysts with the formation of the corresponding 2,4-dichloro-2-cyanoalkanoic esters. In the reactions with acrolein and methyl vinyl ketone at temperatures above 120 deg C 6-substituted 2,5-dichloronicotinic esters are formed.