Literature DB >> 19143533

Discovery and structure-activity relationships of trisubstituted pyrimidines/pyridines as novel calcium-sensing receptor antagonists.

Wu Yang1, Zheming Ruan, Yufeng Wang, Katy Van Kirk, Zhengping Ma, Brian J Arey, Christopher B Cooper, Ramakrishna Seethala, Jean H M Feyen, John K Dickson.   

Abstract

The trisubstituted pyrimidine 1 was identified through high-throughput screening as a novel calcium-sensing receptor (CaSR) antagonist. Small molecule CaSR antagonists and/or negative allosteric modulators have the potential to act as an anabolic agent for the treatment of osteoporosis. The investigation of structure-activity relationships around 1 resulted in the identification of 18c and 18d, which showed efficacy at promoting PTH release in vivo and exhibited improved potency and solubility over the original lead 1.

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Year:  2009        PMID： 19143533     DOI： 10.1021/jm801178c

Source DB:  PubMed          Journal:  J Med Chem        ISSN： 0022-2623            Impact factor:   7.446


  4 in total

1.  Efficient assembly of 2,5,6-substituted pyrimidines via MgI(2)-mediated Morita-Baylis-Hillman reaction.

Authors:  Vasudha Sharma; Mark L McLaughlin
Journal:  J Comb Chem       Date:  2010-05-10

2.  Discovery of a potent and short-acting oral calcilytic with a pulsatile secretion of parathyroid hormone.

Authors:  Yuko Shinagawa; Teruhiko Inoue; Takeo Katsushima; Toshihiro Kiguchi; Taku Ikenogami; Naoki Ogawa; Kenji Fukuda; Kazuyuki Hirata; Kazuhito Harada; Masaki Takagi; Takashi Nakagawa; Shuichi Kimura; Yushi Matsuo; Mariko Maekawa; Mikio Hayashi; Yuki Soejima; Mitsuru Takahashi; Masanori Shindo; Hiromasa Hashimoto
Journal:  ACS Med Chem Lett       Date:  2010-12-29       Impact factor: 4.345

3.  Negative allosteric modulators of the human calcium-sensing receptor bind to overlapping and distinct sites within the 7-transmembrane domain.

Authors:  Tracy M Josephs; Andrew N Keller; Elham Khajehali; Aaron DeBono; Christopher J Langmead; Arthur D Conigrave; Ben Capuano; Irina Kufareva; Karen J Gregory; Katie Leach
Journal:  Br J Pharmacol       Date:  2020-02-12       Impact factor: 8.739

Review 4.  Pd-Catalyzed Cross-Couplings: On the Importance of the Catalyst Quantity Descriptors, mol % and ppm.

Authors:  Christopher S Horbaczewskyj; Ian J S Fairlamb
Journal:  Org Process Res Dev       Date:  2022-07-11       Impact factor: 3.858
  4 in total

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