Invention of novel 3-aminopiperidin-2-ones as calcitonin gene-related peptide receptor antagonists.

Autor: Staas DD; Department of Discovery Chemistry, Merck & Co., Inc., West Point, PA 19486, USA., Bell IM; Department of Discovery Chemistry, Merck & Co., Inc., West Point, PA 19486, USA. Electronic address: ian_bell@merck.com., Burgey CS; Department of Discovery Chemistry, Merck & Co., Inc., West Point, PA 19486, USA., Deng JZ; Department of Discovery Chemistry, Merck & Co., Inc., West Point, PA 19486, USA., Gallicchio SN; Department of Discovery Chemistry, Merck & Co., Inc., West Point, PA 19486, USA., Lim JJ; Department of Discovery Chemistry, Merck & Co., Inc., West Point, PA 19486, USA., Paone DV; Department of Discovery Chemistry, Merck & Co., Inc., West Point, PA 19486, USA., Potteiger CM; Department of Discovery Chemistry, Merck & Co., Inc., West Point, PA 19486, USA., Shaw AW; Department of Discovery Chemistry, Merck & Co., Inc., West Point, PA 19486, USA., Stevenson H; Department of Discovery Chemistry, Merck & Co., Inc., West Point, PA 19486, USA., Stump CA; Department of Discovery Chemistry, Merck & Co., Inc., West Point, PA 19486, USA., Blair Zartman C; Department of Discovery Chemistry, Merck & Co., Inc., West Point, PA 19486, USA., Moore EL; Department of Neuroscience, Merck & Co., Inc., West Point, PA 19486, USA., Bruno JG; Department of In Vitro Pharmacology, Merck & Co., Inc., West Point, PA 19486, USA., Mosser SD; Department of In Vitro Pharmacology, Merck & Co., Inc., West Point, PA 19486, USA., White RB; Department of Drug Metabolism & Pharmacokinetics, Merck & Co., Inc., West Point, PA 19486, USA., Kane SA; Department of Neuroscience, Merck & Co., Inc., West Point, PA 19486, USA., Salvatore CA; Department of Neuroscience, Merck & Co., Inc., West Point, PA 19486, USA., Graham SL; Department of Discovery Chemistry, Merck & Co., Inc., West Point, PA 19486, USA., Williams TM; Department of Discovery Chemistry, Merck & Co., Inc., West Point, PA 19486, USA., Selnick HG; Department of Discovery Chemistry, Merck & Co., Inc., West Point, PA 19486, USA., Fraley ME; Department of Discovery Chemistry, Merck & Co., Inc., West Point, PA 19486, USA.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2024 Nov 01; Vol. 112, pp. 129944. Date of Electronic Publication: 2024 Sep 02.
DOI: 10.1016/j.bmcl.2024.129944
Abstrakt: A novel series of 3-amino-piperidin-2-one-based calcitonin gene-related peptide (CGRP) receptor antagonists was invented based upon the discovery of unexpected structure-activity observations. Initial exploration of the structure-activity relationships enabled the generation of a moderately potent lead structure (4). A series of modifications, including ring contraction and inversion of stereocenters, led to surprising improvements in CGRP receptor affinity. These studies identified compound 23, a structurally novel potent, orally bioavailable CGRP receptor antagonist.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ian M. Bell reports a relationship with Merck & Co Inc that includes: employment and equity or stocks. Donnette D. Staas reports a relationship with Merck & Co Inc that includes: employment and equity or stocks. Christopher S. Burgey reports a relationship with Merck & Co Inc that includes: employment and equity or stocks. James Z. Deng reports a relationship with Merck & Co Inc that includes: employment and equity or stocks. Anthony W. Shaw reports a relationship with Merck & Co Inc that includes: employment and equity or stocks. Heather Stevenson reports a relationship with Merck & Co Inc that includes: employment and equity or stocks. Craig A. Stump reports a relationship with Merck & Co Inc that includes: employment and equity or stocks. C. Blair Zartman reports a relationship with Merck & Co Inc that includes: employment and equity or stocks. Eric L. Moore reports a relationship with Merck & Co Inc that includes: employment and equity or stocks. Scott D. Mosser reports a relationship with Merck & Co Inc that includes: employment and equity or stocks. Rebecca B. White reports a relationship with Merck & Co Inc that includes: employment and equity or stocks. Christopher A. Salvatore reports a relationship with Merck & Co Inc that includes: employment and equity or stocks. Mark E. Fraley reports a relationship with Merck & Co Inc that includes: employment and equity or stocks. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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