191231-58-0Relevant articles and documents
Discovery of substituted 3H-pyrido[2,3-d]pyrimidin-4-ones as potent, biased, and orally bioavailable sst2 agonist
Betz, Stephen F.,Chen, Zhiyong,Kusnetzow, Ana Karin,Nguyen, Julie,Rico-Bautista, Elizabeth,Struthers, R. Scott,Tan, Hannah,Zhao, Jian,Zhu, Yunfei
supporting information, (2020/08/26)
The discovery of a novel 3H-pyrido[2,3-d]pyrimidin-4-one series as potent and biased sst2 agonists is described. This class of molecules exhibits excellent sst2 potency and selectivity against sst1, sst3, and sst5 receptors, and they are significantly more potent at inhibiting cAMP production than inducing internalization. The orally bioavailable 6-(3-chloro-5-methylphenyl)-3-(3-fluoro-5-hydroxyphenyl)-5-({methyl[(2S)-pyrrolidin-2-ylmethyl]amino}methyl)-3H,4H-pyrido[2,3-d]pyrimidin-4-one (36) also suppresses GH secretion in GHRH-challenged rats in a dose-dependent manner.
SOMATOSTATIN MODULATORS AND USES THEREOF
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Paragraph 0315; 0318; 0319, (2017/01/23)
Described herein are compounds that are somatostatin modulators, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in the treatment of conditions, diseases, or disorders that would benefit from modulation of somatostatin activity.
Discovery of imidazo[1,2-b]pyridazines as IKKβ inhibitors. Part 2: Improvement of potency in vitro and in vivo
Shimizu, Hiroki,Yasumatsu, Isao,Hamada, Tomoaki,Yoneda, Yoshiyuki,Yamasaki, Tomonori,Tanaka, Shinji,Toki, Tadashi,Yokoyama, Mika,Morishita, Kaoru,Iimura, Shin
, p. 904 - 908 (2011/03/21)
We have increased the potency of imidazo[1,2-b]pyridazine derivatives as IKKβ inhibitors with two strategies. One is to enhance the activity in cell-based assay by adjusting the polarity of molecules to improve permeability. Another is to increase the affinity for IKKβ by the introduction of additional substituents based on the hypothesis derived from an interaction model study. These improved compounds showed inhibitory activity of TNFα production in mice.