A series of pyridine derivatives in the C-region of N-((6-trifluoromethyl-pyridin-3-yl)methyl) 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides were investigated as hTRPV1 antagonists. The SAR analysis indicated that 6-difluorochloromethyl pyridine derivatives were the best surrogates of the C-region for previous leads. Among them, compound 31 showed excellent antagonism to capsaicin as well as to multiple hTRPV1 activators. It demonstrated strong analgesic activity in the formalin test in mice with full efficacy and it blocked capsaicin-induced hypothermia in vivo.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959515 | PMC |
| http://dx.doi.org/10.1016/j.ejmech.2015.02.001 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
N6-methyladenosine-modified long non-coding RNA promotes stemness and sorafenib resistance in hepatocellular carcinoma by upregulating SHOX2 expression.
World J Gastroenterol
December 2024
Department of Gastroenterology and Hepatology, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
Background: Hepatocellular carcinoma (HCC) is a prevalent and aggressive tumor. Sorafenib is the first-line treatment for patients with advanced HCC, but resistance to sorafenib has become a significant challenge in this therapy. Cancer stem cells play a crucial role in sorafenib resistance in HCC.
View Article and Find Full Text PDFEfficacy of glutathione inhibitor eprenetapopt against the vulnerability of glutathione metabolism in SMARCA4-, SMARCB1- and PBRM1-deficient cancer cells.
Sci Rep
December 2024
Division of Cancer Therapeutics, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Mutation of genes related to the SWI/SNF chromatin remodeling complex is detected in 20% of all cancers. The SWI/SNF chromatin remodeling complex comprises about 15 subunits and is classified into three subcomplexes: cBAF, PBAF, and ncBAF. Previously, we showed that ovarian clear cell carcinoma cells deficient in ARID1A, a subunit of the cBAF complex, are synthetic lethal with several genes required for glutathione (GSH) synthesis and are therefore sensitive to the GSH inhibitor eprenetapopt (APR-246).
View Article and Find Full Text PDFPhytotoxicity Study of (Amino)imidazo[1,2-]pyridine Derivatives Toward the Control of , , and Weeds.
J Agric Food Chem
December 2024
Instituto de Química, Laboratório de Química Metodológica e Orgânica Sintética (LaQMOS), Universidade de Brasília, 70904-970 Brasília, DF, Brazil.
In this work, several imidazo[1,2-]pyridines were synthesized through the Groebke-Blackburn-Bienaymé three-component reaction (GBB-3CR), and their phytotoxicity was evaluated by the influence on the growth of wheat coleoptiles and three important agricultural seeds (, , and ) at test concentrations of 1000, 300, 100, 30, and 10 μM. A structure-activity relationship was established, showing the importance of halogen groups at the position of the attached aromatic ring and the presence of a cyclohexylamine group for greater activity. Post-modification of some GBB-3CR adducts was carried out, leading to imidazo[1,2-]pyridine-tetrazole hybrids, which were also evaluated in these bioassays.
View Article and Find Full Text PDF[Evaluation of the efficacy of antifibrotic drugs on cell cultures in Salzmann's nodular degeneration].
Vestn Oftalmol
December 2024
Krasnov Research Institute of Eye Diseases, Moscow, Russia.
Unlabelled: Excessive production of extracellular matrix is a key component in the pathogenesis of Salzmann's nodular degeneration (SND). studies of drugs that suppress excessive fibroblast activity may become crucial in developing pathogenetically oriented treatments for SND.
Purpose: This study evaluates the antifibrotic properties of pirfenidone and cyclosporine A (CsA) on cell cultures obtained from patients with SND.
Photoinduced Reductive C-O Couplings from Unsymmetrical Bis-Cyclometalated Pt(IV) Dicarboxylato Complexes.
Inorg Chem
December 2024
Departamento de Química Inorgánica, Facultad de Química, Universidad de Murcia, Campus de Espinardo 19, Murcia 30100, Spain.
Unsymmetrical bis-cyclometalated dicarboxylato complexes (-6-32)-[Pt(tpy)(OCR)] [tpy = cyclometalated 2-(-tolyl)pyridine, R = -Bu (), Me (), Ph (), CF ()], are obtained from the reaction of -[Pt(tpy)] with the appropriate PhI(OCR) reagent. Treatment of complexes of this type with different carboxylates (R'CO) results in the formation of mixed-carboxylato derivatives, namely (-6-43)-[Pt(tpy)(OCMe)(OCR')] [R' = -Bu (), CF (), Ph ()], (-6-34)-[Pt(tpy)(OCCF)(OCR')] [R' = -Bu (), Me (), Ph ()], and (-6-34)-[Pt(tpy)(OC--Bu)(OCMe)] (). Irradiation of - and - with UV light (365 nm) in MeCN gives 5-methyl-2-(2-pyridyl)phenyl pivalate (), 5-methyl-2-(2-pyridyl)phenyl acetate () or 5-methyl-2-(2-pyridyl)phenyl benzoate () as the major photoproduct from most complexes, resulting from a reductive C-O coupling between a tpy ligand and a carboxylato ligand.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!