41598-57-6

Upstream product

• 1039037-16-5 5-ethyl 1-methyl 4-(1-amino-ethylidene)-pent-2-enedioate 
• 3424-43-9 ethyl 6-hydroxy-2-methylnicotinate 
• 3424-43-9 ethyl 2-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate 
• 53256-25-0 (2E,4Z)-5-ethyl 1-methyl 4-(1-aminoethylidene)pent-2-enedioate 
• 31163-12-9 ethyl 6-chloro-2-methylnicotinate 
• 31163-13-0 ethyl 2-(bromomethyl)-6-chloronicotinate 
• 31163-14-1 diethyl 2-((6-chloro-3-(ethoxycarbonyl)pyridin-2-yl)methyl)-malonate 

Downstream Products

• 1359669-60-5 C₂₃H₂₁NO₂ 
• 1359669-62-7 diethyl {2-[(2',6'-dimethylbiphenyl-3-yl)methoxy]-6,7-dihydro-5H-cyclopenta[b]pyridin-5-yl}malonate 
• 1359668-78-2 2-[(2',6'-dimethylbiphenyl-3-yl)methoxy]-6,7-dihydro-5H-cyclopenta[b]pyridin-5-ol 
• 1359668-80-6 {2-[(2',6'-dimethylbiphenyl-3-yl)methoxy]-6,7-dihydro-5H-cyclopenta[b]pyridin-5-yl}acetic acid 

Relevant academic research and scientific papers

HISTONE ACETYLTRANSFERASE (HAT) INHIBITOR AND USE THEREOF

The present invention relates to a histone acetyltransferase (HAT) inhibitor. Provided are a compound represented by general formula I, a pharmaceutically acceptable salt, a stereoisomer, an enantiomer, a diastereomer, an atropisomer, a racemate, a polymorph, a solvate or an isotope-labeled compound (including deuterium substitution) thereof, a preparation method therefor, a pharmaceutical composition comprising the same, and use thereof in the treatment of various HAT-related diseases or conditions.

Discovery of Highly Potent, Selective, and Orally Efficacious p300/CBP Histone Acetyltransferases Inhibitors

p300 and CREB-binding protein (CBP) are ubiquitously expressed pleiotropic lysine acetyltransferases and play a key role as transcriptional co-Activators that are essential for a multitude of cellular processes. Despite great importance, there is a lack of highly selective, potent, druglike p300/CBP inhibitors. Through the artificial-intelligence-Assisted drug discovery pipeline and further optimization, we reported the discovery of novel, highly selective, potent small-molecule inhibitors of p300/CBP histone acetyltransferases (HAT) with desired druglike properties, exemplified by B026. Our data demonstrated that B026, with half maximal inhibitory concentration (IC50) values of 1.8 nM to p300 and 9.5 nM to CBP enzyme inhibitory activity, is the most potent, selective p300/CBP HAT inhibitor. Moreover, B026 achieves significant and dose-dependent tumor growth inhibition in an animal model of human cancer, suggesting that B026 is a highly promising p300/CBP HAT inhibitor and warrants extensive preclinical investigation as a potential clinical development candidate.

Preparation method of 2-methoxy-6, 7-dihydro-5H-cyclopenta [b] pyridine-5-one

The invention relates to a preparation method of 2-methoxy-6,7-dihydro-5H-cyclopenta[b]pyridine-5-one. According to the preparation method, ethyl acetoacetate is used as a starting raw material, and anovel target product 2-methoxy-6, 7-dihydro-5H-cyclopenta[b]pyridine-5-one is prepared through nine steps of reactions including dehydration, addition, cyclization, chlorination, bromination, substitution, cyclization again, decarboxylation and etherification. The preparation method of the novel target product is simple and efficient. The purity of the novel target product prepared by the methoddisclosed by the invention reaches over 99.0%.

SPIROCYCLIC HAT INHIBITORS AND METHODS FOR THEIR USE

Compounds having a structure of Formula (IX) or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof, wherein R1, R2a, R2b, R3a, R3b, R4a, R4b, Q1----Q2, R6, R7, A, B, W, x, and y are as defined herein and are provided. Pharmaceutical compositions comprising such compounds and methods for treating various HAT-related conditions or diseases, including cancer, by administration of such compounds are also provided.

Identification of fused-ring alkanoic acids with improved pharmacokinetic profiles that Act as G protein-coupled receptor 40/free fatty acid receptor 1 agonists

The G protein-coupled receptor 40 (GPR40)/free fatty acid receptor 1 (FFA1) has emerged as an attractive target for a novel insulin secretagogue with glucose dependency. We previously identified phenylpropanoic acid derivative 1 (3-{4-[(2′,6′-dimethylbiphenyl-3-yl)methoxy]-2-fluorophenyl} propanoic acid) as a potent and orally available GPR40/FFA1 agonist; however, 1 exhibited high clearance and low oral bioavailability, which was likely due to its susceptibility to β-oxidation at the phenylpropanoic acid moiety. To identify long-acting compounds, we attempted to block the metabolically labile sites at the phenylpropanoic acid moiety by introducing a fused-ring structure. Various fused-ring alkanoic acids with potent GPR40/FFA1 activities and good PK profiles were produced. Further optimizations of the lipophilic portion and the acidic moiety led to the discovery of dihydrobenzofuran derivative 53 ((6-{[4′-(2-ethoxyethoxy)-2′,6′-dimethylbiphenyl-3-yl]methoxy} -2,3-dihydro-1-benzofuran-3-yl)acetic acid), which acted as a GPR40/FFA1 agonist with in vivo efficacy during an oral glucose tolerance test (OGTT) in rats with impaired glucose tolerance.