oai-hal-hal-00091553v1
type: Dataset
title: N1-Benzoyl-N2-[1-(1-naphthyl)ethyl]-trans-1,2-diaminocyclohexanes: Development of 4-chlorophenylcarboxamide (calhex 231) as a new calcium sensing receptor ligand demonstrating potent calcilytic activity.
description: A structure-activity relationship (SAR) study was performed principally at the N1 position of N1-arylsulfonyl-N2-[1-(1-naphthyl)ethyl]-trans-1,2-diaminocyclohexanes, a new family of calcilytics acting at the calcium sensing receptor (CaSR). The most active compound in this series was the 4-(trifluoromethoxy)benzenesulfonyl derivative 7e, which displayed an IC50 of 5.4 +/- 0.5 microM with respect to the inhibition of calcium-induced tritiated inositol phosphate ([3H]IP) accumulation in Chinese hamster ovarian (CHO) cells expressing the CaSR. Replacement of the sulfonamide linkage of this compound by a carboxamide led to a 6-fold increase in activity (7m, IC50 = 0.9 +/- 0.2 microM). Among the carboxamides synthesized, one of the most active compounds was the 4-chlorophenylcarboxamide (1S,2S,1'R)-7n (Calhex 231, IC50 = 0.33 +/- 0.02 microM). The absolute configuration of (1S,2S,1'R)-7n was deduced from an X-ray crystallographic study of one of the diastereomers of compound 7d. The stereochemical preference for the (1S,2S,1'R)-isomers can be rationalized on the basis of a three-dimensional model of the calcilytic binding pocket of the CaSR. Removal of the C-1' methyl group or replacement of the 1-naphthyl group by a 2-naphthyl or biphenyl moiety led to appreciable loss of calcilytic activity. Compounds 7e, 7m, and Calhex 231 did not stimulate [3H]IP accumulation in CHO cells expressing or not expressing the CaSR.
landing page: 0022-2623
keyword: chimorgachemical-sciencesorganic-chemistry
keyword: infoeu-reposemanticsarticle
keyword: journal-articles
keyword: mesh-animals
keyword: mesh-benzamides
keyword: mesh-cho-cells
keyword: mesh-cricetinae
keyword: mesh-crystallography-x-ray
keyword: mesh-cyclohexylamines
keyword: mesh-inositol-phosphates
keyword: mesh-ligands
keyword: mesh-models-molecular
keyword: mesh-molecular-structure
keyword: mesh-protein-conformation
keyword: mesh-rats
keyword: mesh-receptors-calcium-sensing
keyword: mesh-stereoisomerism
keyword: mesh-structure-activity-relationship
keyword: sdvneulife-sciences-q-bioneurons-and-cognition-q-bionc
issued: 2026-05-07T21:58:24.194363
modified: 2026-05-07T21:58:24.194367
language: en
contact point: Organization
  fn: CCSD

test_moissonnage_selune
type: Agent

https://rec.harvest-normandie.data4citizen.com/dataset/oai-hal-hal-00091553v1/resource/a3aad29d-57d3-410c-8f22-5e2583e6f870
type: Distribution
title: N1-Benzoyl-N2-[1-(1-naphthyl)ethyl]-trans-1,2-diaminocyclohexanes: Development of 4-chlorophenylcarboxamide (calhex 231) as a new calcium sensing receptor ligand demonstrating potent calcilytic activity.
format: HTML
access URL: https://hal.science/hal-00091553
issued: 2026-05-07T21:58:24.217508
modified: 2026-05-07T21:58:24.173685