59189-98-9

Upstream product

• 452-79-9 2‐fluoro‐1‐iodo‐4‐methylbenzene 
• 141-75-3 butyryl chloride 
• 452-74-4 4-bromo-3-fluorotoluene 
• 7697-23-6 2-fluoro-4-methylbenzoic Acid 

Downstream Products

• 74733-29-2 2-methyl-3-hydroxybenzoic acid methyl ester 
• 37135-22-1 2'-hydroxy-2-fluoro-p-toluanilide 
• 1443144-17-9 2-fluoro-N-(quinolin-8-yl)-4-methylbenzamide 
• 32701-16-9 3-methylbenzo[4,5]imidazo[2,1-b]quinazolin-12-one 
• 1160822-99-0 {3-[[1-(3-benzyl-8-chloro-7-methoxy-4-oxo-3,4-dihydro-pyrazolo[1,5-a][1,3,5]triazin-2-yl)-2-methyl-n-propyl]-(2-fluoro-4-methyl-benzoyl)-amino]-n-propyl}-carbamic acid tert-butyl ester 
• 960292-34-6 (3-{[(RS)-1-(6-benzyl-3-chloro-2-methyl-7-oxo-6,7-dihydro-pyrazolo[1,5-c]pyrimidin-5-yl)-2-methyl-propyl]-[(2-fluoro-4-methyl-phenyl)-carbonyl]-amino}-propyl)-carbamic acid tert-butyl ester 

Relevant academic research and scientific papers

Structure-Based Design of ASK1 Inhibitors as Potential Agents for Heart Failure

Apoptosis signal-regulating kinase 1 (ASK1/MAP3K) is a mitogen-activated protein kinase family member shown to contribute to acute ischemia/reperfusion injury. Using structure-based drug design, deconstruction, and reoptimization of a known ASK1 inhibitor

PIPERAZINE SUBSTITUTED AZAPINE DERIVATIVES AND USES THEREOF

The present disclosure relates to compounds of Formula (I) and (II): and to their prodrugs, pharmaceutically acceptable salts, pharmaceutical compositions, methods of use, and methods for their preparation. The compounds disclosed herein are useful for modulating H1 and 5-HT2A receptors and are to be used in the treatment of sleep disorders, such as sleep fragmentation, disturbed sleep/arousals, and arousal threshold.

Palladium-Catalyzed Chlorocarbonylation of Aryl (Pseudo)Halides Through In Situ Generation of Carbon Monoxide

An efficient palladium-catalyzed chlorocarbonylation of aryl (pseudo)halides that gives access to a wide range of carboxylic acid derivatives has been developed. The use of butyryl chloride as a combined CO and Cl source eludes the need for toxic, gaseous carbon monoxide, thus facilitating the synthesis of high-value products from readily available aryl (pseudo)halides. The combination of palladium(0), Xantphos, and an amine base is essential to promote this broadly applicable catalytic reaction. Overall, this reaction provides access to a great variety of carbonyl-containing products through in situ transformation of the generated aroyl chloride. Combined experimental and computational studies support a reaction mechanism involving in situ generation of CO.

Site-Selective Silylation of Aliphatic C-H Bonds Mediated by [1,5]-Hydrogen Transfer: Synthesis of α-Sila Benzamides

The first example of site-selective silylation of C(sp3)-H bonds mediated by a [1,5]-hydrogen transfer is reported. This reaction occurs selectively at the α-position of benzamides with a combination of tert-butylmagnesium chloride and a catalytic amount of 4,4′-di-tert-butylbipyridine (dtbpy) ligand and provides a facile route for the creation of biologically interesting α-sila benzamides. Late-stage functionalization of the incorporated silyl moieties facilitates the synthesis of N-formyl, cis-enamine, β-hydroxyl, amino, and pyrrole-containing derivatives.

New benzylureas as a novel series of potent, nonpeptidic vasopressin V2 receptor agonists

Vasopressin (AVP) is a hormone that stimulates an increase in water permeability through activation of V2 receptors in the kidney. The analogue of AVP, desmopressin, has proven an effective drug for diseases where a reduction of urine output is desired. However, its peptidic nature limits its bioavailability. We report herein the discovery of potent, nonpeptidic, benzylurea derived agonists of the vasopressin V2 receptor. We describe substitutions on the benzyl group to give improvements in potency and subsequent modifications to the urea end group to provide improvements in solubility and increased oral efficacy in a rat model of diuresis. The lead compound 20e (VA106483) is reported for the first time and has been selected for clinical development.

HETEROCYCLIC CONDENSED COMPOUNDS USEFUL AS ANTIDIURETIC AGENTS

The invention concerns compounds according to general formulae 1, wherein G1 is an amine. Compounds according to the invention are vasopressin V2 receptor agonists. Pharmaceutical compositions of the compounds are useful as antidiuretic agents.