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Literature DB >> 18288792

2-aryloxy-4-alkylaminopyridines: discovery of novel corticotropin-releasing factor 1 antagonists.

Yuhpyng L Chen¹, R Scott Obach, John Braselton, Michael L Corman, James Forman, Jody Freeman, Randall J Gallaschun, Robert Mansbach, Anne W Schmidt, Jeffrey S Sprouse, F David Tingley Iii, Elizabeth Winston, David W Schulz.

Abstract

An orally active clinical candidate of corticotropin-releasing factor 1 (CRF 1) antagonist 1 showed a significant positive food effect in dog and human after oral administration. Efforts to address the food effect issue led us to explore and discover compounds in series 2 as orally active CRF 1 receptor antagonists, in which some compounds showed improved physicochemical properties while retaining desired pharmacological properties. Compound 3a (CP-376395) was selected for further development, due not only to its reduced food effects but also its greater efficacy in CNS models. Compound 3a was advanced to the clinic. The synthesis of representative potential candidates and their in vitro, ex vivo, and in vivo data are described.

Entities: Chemical Species

Mesh：

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Year: 2008 PMID： 18288792 DOI： 10.1021/jm070579c

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

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Cited

14 in total

1. Dissociation of corticotropin-releasing factor receptor subtype involvement in sensitivity to locomotor effects of methamphetamine and cocaine.

Authors: William J Giardino; Gregory P Mark; Mary P Stenzel-Poore; Andrey E Ryabinin
Journal: Psychopharmacology (Berl) Date: 2011-08-11 Impact factor: 4.530

2. Structure of class B GPCR corticotropin-releasing factor receptor 1.

Authors: Kaspar Hollenstein; James Kean; Andrea Bortolato; Robert K Y Cheng; Andrew S Doré; Ali Jazayeri; Robert M Cooke; Malcolm Weir; Fiona H Marshall
Journal: Nature Date: 2013-07-17 Impact factor: 49.962

3. Augmented cocaine seeking in response to stress or CRF delivered into the ventral tegmental area following long-access self-administration is mediated by CRF receptor type 1 but not CRF receptor type 2.

Authors: Jordan M Blacktop; Chad Seubert; David A Baker; Nathan Ferda; Geng Lee; Evan N Graf; John R Mantsch
Journal: J Neurosci Date: 2011-08-03 Impact factor: 6.167

4. Dissociation of μ-opioid receptor and CRF-R1 antagonist effects on escalated ethanol consumption and mPFC serotonin in C57BL/6J mice.

Authors: Lara S Hwa; Akiko Shimamoto; Tala Kayyali; Kevin J Norman; Rita J Valentino; Joseph F DeBold; Klaus A Miczek
Journal: Addict Biol Date: 2014-09-28 Impact factor: 4.280

10. CRF type 1 receptor antagonism in ventral tegmental area of adolescent rats during social defeat: prevention of escalated cocaine self-administration in adulthood and behavioral adaptations during adolescence.

Authors: Andrew R Burke; Joseph F DeBold; Klaus A Miczek
Journal: Psychopharmacology (Berl) Date: 2016-06-01 Impact factor: 4.530

2-aryloxy-4-alkylaminopyridines: discovery of novel corticotropin-releasing factor 1 antagonists.

1. Dissociation of corticotropin-releasing factor receptor subtype involvement in sensitivity to locomotor effects of methamphetamine and cocaine.

2. Structure of class B GPCR corticotropin-releasing factor receptor 1.

3. Augmented cocaine seeking in response to stress or CRF delivered into the ventral tegmental area following long-access self-administration is mediated by CRF receptor type 1 but not CRF receptor type 2.

4. Dissociation of μ-opioid receptor and CRF-R1 antagonist effects on escalated ethanol consumption and mPFC serotonin in C57BL/6J mice.

5. Differential sensitivity of alcohol drinking and partner preference to a CRFR1 antagonist in prairie voles and mice.

6. The Concise Guide to PHARMACOLOGY 2013/14: G protein-coupled receptors.

Review 7. Insights into the structure of class B GPCRs.

Review 8. Progress in corticotropin-releasing factor-1 antagonist development.

9. Noradrenergic tone mediates marble burying behavior after chronic stress and ethanol.

10. CRF type 1 receptor antagonism in ventral tegmental area of adolescent rats during social defeat: prevention of escalated cocaine self-administration in adulthood and behavioral adaptations during adolescence.