133446-40-9

Upstream product

• 7364-20-7 4-ethyl-benzoic acid methyl ester 
• 619-64-7 p-ethylbenzoic acid 
• 113023-73-7 4-(1-bromoethyl)-benzoic acid 
• 3609-53-8 methyl 4-acetylbenzoate 
• 84851-56-9 methyl 4-(1-hydroxy ethyl)benzoate 
• 18107-18-1 diazomethyl-trimethyl-silane 
• 67-56-1 methanol 

Downstream Products

• 32223-88-4 4-(2-Ethoxycarbonyl-1,5-dimethyl-3-oxo-hexyl)-benzoic acid ethyl ester 
• 133446-83-0 4-[1-(2-Methyl-4-oxo-3,4-dihydro-quinazolin-6-ylamino)-ethyl]-benzoic acid methyl ester 
• 212132-39-3 methyl 4-[1'-(2'',2'',6'',6''-tetramethyl-1''-piperidinyloxy)ethyl]benzoate 
• 1076-96-6 methyl 4-vinylbenzoate 
• 1192278-65-1 methyl 4-(1-(thiophen-2-yl)ethyl)benzoate 
• 1192278-64-0 methyl 4-(1-(4-fluorophenyl)ethyl)benzoate 
• 1184924-55-7 methyl 4-{1-[(tert-butoxycarbonyl)({2-chloro-5-[(2-methyl-2,3-dihydro-1H-indol-1-yl)carbamoyl]phenyl}sulphonyl)amino]ethyl}-benzoate 
• 1322084-83-2 4-[1-(3,4-dichloro-phenoxy)-ethyl]-benzoic acid methyl ester 
• 1582754-29-7 methyl 4-{1-[4-(6-amino-4-methylpyridin-2-yl)-1H-1,2,3-triazol-1-yl]ethyl}benzoate 
• 80051-07-6 4-carbomethoxy-α-methylbenzylamine 

Relevant academic research and scientific papers

Tetrahydroquinoline-Capped Histone Deacetylase 6 Inhibitor SW-101 Ameliorates Pathological Phenotypes in a Charcot-Marie-Tooth Type 2A Mouse Model

Histone deacetylase 6 (HDAC6) is a promising therapeutic target for the treatment of neurodegenerative disorders. SW-100 (1a), a phenylhydroxamate-based HDAC6 inhibitor (HDAC6i) bearing a tetrahydroquinoline (THQ) capping group, is a highly potent and sel

SMARCA DEGRADERS AND USES THEREOF

The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same for the modulation of one or more SWI/SNF-related matrix associated actin dependent regulator of chromatin subfamily A (SMARCA) and/or polybromo-1 (PB-1) protein via ubiqitination and/or degradation by compounds. The compounds are bifunctional molecules that link a cereblon-binding moiety to a ligand that binds SMARCA and/or PB1 proteins.

Copper-Catalyzed Late-Stage Benzylic C(sp3)–H Trifluoromethylation

Direct trifluoromethylation of C(sp3)–H bonds, especially in late stages, remains a formidable challenge. Herein, we describe the copper-catalyzed benzylic C(sp3)–H trifluoromethylation. With Cu(I) or Cu(II) as the catalyst, (bpy)Zn(CF3)2 (bpy = 2,2′-bipyridine) as the CF3 source, and NFSI (or Selectfluor) as the oxidant, site-selective benzylic C(sp3)–H trifluoromethylation is successfully implemented in high efficiency under mild conditions. The protocol not only exhibits broad substrate scope and wide functional-group compatibility but also allows efficient late-stage C(sp3)–H trifluoromethylation of natural products or drug derivatives. The introduction of trifluoromethyl groups into organic molecules is of paramount importance in pharmaceuticals and agrochemicals because of their profound effect on properties such as lipophilicity, permeability, and metabolic stability. However, direct C(sp3)–H trifluoromethylation, which is most atom economical, remains a formidable challenge, and only a few examples with limited substrate scope and low to moderate efficiency have been reported to date. In this article, we introduce the copper-catalyzed benzylic C(sp3)–H trifluoromethylation with the easily available (bpy)Zn(CF3)2 complex as the CF3 source. This unprecedented protocol not only exhibits a high efficiency and broad substrate scope but also allows the late-stage trifluoromethylation of bioactive molecules or natural product derivatives. Because the procedure is operationally simple and the conditions are mild, the method should find immediate application in the synthesis of important trifluoromethylated molecules. Trifluoromethylated molecules are of paramount importance in pharmaceuticals and agrochemicals, but methods of making them by direct C(sp3)–H trifluoromethylation are extremely rare. In this issue of Chem, Li and coworkers describe a copper-catalyzed late-stage benzylic C–H trifluoromethylation with broad substrate scope and functional-group tolerance. The reaction may serve the late-stage modification of drug candidates.

BRM TARGETING COMPOUNDS AND ASSOCIATED METHODS OF USE

The present disclosure relates to bifunctional compounds, which find utility as modulators of SMARCA2 or BRM (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a ligand that binds to the Von Hippel-Lindau E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

A Dual Modulator of Farnesoid X Receptor and Soluble Epoxide Hydrolase to Counter Nonalcoholic Steatohepatitis

Nonalcoholic steatohepatitis arising from Western diet and lifestyle is characterized by accumulation of fat in liver causing inflammation and fibrosis. It evolves as serious health burden with alarming incidence, but there is no satisfying pharmacological therapy to date. Considering the disease's multifactorial nature, modulation of multiple targets might provide superior therapeutic efficacy. In particular, farnesoid X receptor (FXR) activation that revealed antisteatotic and antifibrotic effects in clinical trials combined with inhibition of soluble epoxide hydrolase (sEH) as anti-inflammatory strategy promises synergies. To exploit this dual concept, we developed agents exerting partial FXR agonism and sEH inhibitory activity. Merging known pharmacophores and systematic exploration of the structure-activity relationship on both targets produced dual modulators with low nanomolar potency. Extensive in vitro characterization confirmed high dual efficacy in cellular context combined with low toxicity, and pilot in vivo data revealed favorable pharmacokinetics as well as engagement on both targets in vivo.

TETRAHYDROQUINOLINE SUBSTITUTED HYDROXAMIC ACIDS AS SELECTIVE HISTONE DEACETYLASE 6 INHIBITORS

Histone deacetylases inhibitors (HDACIs) and compositions containing the same are disclosed. Methods of treating diseases and conditions wherein inhibition of HDAC provides a benefit, like a cancer, a neurodegenerative disorder, a neurological disease, tr

C-ON bond homolysis in alkoxyamines. Part 12: The effect of the para-substituent in the 1-phenylethyl fragment

The application of alkoxyamines as initiators/controllers in nitroxide mediated polymerization and as agents for theranostics requires the development of switchable (from stable one to labile one) alkoxyamines. One way to achieve this is to tune the polar

Visible-light-mediated benzylic sp3 C-H bond functionalization to C-Br or C-N bond

A visible-light-promoted functionalization of unactivated benzylic sp3 C-H bonds was developed. Ethylbenzene derivatives were converted to the corresponding benzyl bromides or afforded benzylamine derivatives in a one-pot manner under visible light photoredox conditions.

NOVEL COMPOUNDS AS HISTONE DEACETYLASE 6 INHIBITORS AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME

The present invention relates to novel compounds having histone deacetylase 6 (HDAC6) inhibitory activity, isomers thereof, or pharmaceutically acceptable salts thereof, the use thereof for the preparation of therapeutic medicaments, pharmaceutical compositions comprising the same, a method of treating disease using the composition, and methods for preparing the novel compounds. The novel compounds according to the present invention have histone deacetylase 6 (HDAC6) inhibitory activity, and are effective for the prevention or treatment of HDAC6-associated diseases, including cancer, inflammatory diseases, autoimmune diseases, neurological diseases and neurodegenerative disorders.

SPIROLACTAM CGRP RECEPTOR ANTAGONISTS

The present invention is directed to spirolactam analogues which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which CGRP is involved, such as migraine. The invention is also directed to pharmaceutical composit