Category Ranking

98%

Total Visits

921

Avg Visit Duration

2 minutes

Citations

20

Article Abstract

As part of our efforts to develop agents for cognitive enhancement, we have been focused on the 5-HT(6) receptor in order to identify potent and selective ligands for this purpose. Herein we report the identification of a novel series of 3-sulfonylindazole derivatives with acyclic amino side chains as potent and selective 5-HT(6) antagonists. The synthesis and detailed SAR of this class of compounds are reported.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmc.2010.10.033DOI Listing

Publication Analysis

Top Keywords

potent selective
12
3-sulfonylindazole derivatives
8
selective 5-ht6
8
5-ht6 antagonists
8
identification 3-sulfonylindazole
4
derivatives potent
4
antagonists efforts
4
efforts develop
4
develop agents
4
agents cognitive
4

Similar Publications

Discovery of APS03118, a Potent and Selective Next-Generation RET Inhibitor with a Novel Kinase Hinge Scaffold.

J Med Chem

September 2025

Applied Pharmaceutical Science, Inc., Building 10-1, No.2, Jingyuan North Street, BDA, Beijing 100176, China.

This study reports the discovery and preclinical activity of APS03118, a novel selective RET inhibitor featuring a novel tricyclic pyrazolo[3',4':3,4]pyrazolo[1,5-]pyridine hinge-binding scaffold designed to overcome acquired resistance to first-generation selective RET inhibitors (SRIs). By enhancing hydrogen bonding with conserved hinge residues (Glu805, Ala807), APS03118 potently inhibits wild-type RET and diverse resistance mutations, including solvent-front (G810R/S/C), gatekeeper (V804M/L/E), roof (L730I/M), and hinge (Y806C/N/H) variants. In preclinical models, APS03118 induced complete tumor regression in KIF5B-RET and CCDC6-RET V804 M patient-derived xenografts (PDXs) and significantly prolonged survival in an intracranial CCDC6-RET metastasis model.

View Article and Find Full Text PDF

The Discovery of RP-2119: A Potent, Selective, and Orally Bioavailable Polθ ATPase Inhibitor.

J Med Chem

September 2025

Repare Therapeutics, 7171 Frederick-Banting, Building 2, H4S 1Z9 Montréal, Québec, Canada.

DNA polymerase theta (Polθ) plays a critical role in repairing DNA double-strand breaks through microhomology-mediated end joining (MMEJ) and has emerged as a key synthetic lethal drug target in cancers with homologous recombination (HR) deficiencies. Its inhibition has shown a strong potential to synergize with PARP inhibitors, particularly in tumors with deleterious or mutations. Here, we describe the discovery and preclinical development of RP-2119, a selective, potent, and bioavailable Polθ ATPase inhibitor.

View Article and Find Full Text PDF

Innovative, sustainable therapies are urgently needed for neglected vector-borne parasitic diseases. In this study, we leveraged cashew nutshell liquid (CNSL), an agro-industrial byproduct, to develop biobased phosphonium and ammonium salts (-) targeting parasite mitochondria. By combining CNSL-derived C8 alkyl chains with lipophilic cations, we synthesized novel compounds exhibiting highly potent and activity against and spp.

View Article and Find Full Text PDF

The utility of bio-reductive prodrugs in cancer research has emerged as an attractive strategy. We synthesized and characterized a couple of cobalt(iii)-Schiff base complexes of general molecular formula Co(L)(L) and Co(L)(dox) , where L and L are ,-(ethane-1,2-diyl)bis(1-(pyridine-2-yl)methanimine) and 1-phenyl-1,3-butanedione, and dox = doxorubicin, as bio-reductive prodrugs. UV-vis and fluorescence spectroscopic assays confirmed the reductive release of doxorubicin from the complex in a GSH-dependent manner under physiological conditions, showing its potential for drug release.

View Article and Find Full Text PDF

Challenges in cancer treatment lie in the identification and development of novel agents with potent anti-tumor activity. A series of novel dehydroabietylamine-pyrimidine derivatives 3a-3s were designed and synthesized based on the principles of molecular hybridization. The inhibitory activities of the target compounds against the proliferation of four different human cancer cell lines (HepG2, A549, HCT116 and MCF-7) were evaluated.

View Article and Find Full Text PDF