CP 316311
目录号 : GC31043CP316311是一种有效的,选择性的CRF1receptor拮抗剂,IC50值为6.8nM。
Cas No.:175139-41-0
Sample solution is provided at 25 µL, 10mM.
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CP 316311 is a potent and selective CRF1 receptor antagonist with an IC50 value of 6.8 nM.
CP 316311 fully antagonizes CRF-stimulated adenylate cyclase activity in rat cortex and at human CRF1 receptors endogenously expressed in IMR32 cells with apparent Ki values of 7.6 and 8.5 nM, respectively[1].
CP 316311 (3.2 mg/kg) inhibits 125I-oCRF binding by >80% in rats. CP 316311 significantly attenuates activation of the hypothalamic-pituitary-adrenal (HPA) axis, with an MED value of 10 mg/kg, p.o. CP 316311 blocks the effects of both the exogenous and endogenous CRF in the CNS. CP 316311 blocks the effects induced by the exogeneous or endogeneous CRF in the brain in rat models[1].
[1]. Chen YL, et al. Synthesis and SAR of 2-aryloxy-4-alkoxy-pyridines as potent orally active corticotropin-releasing factor 1 receptor antagonists. J Med Chem. 2008 Mar 13;51(5):1377-84.
Cas No. | 175139-41-0 | SDF | |
Canonical SMILES | CCC(CC)OC1=C(C)C(OC2=C(C)C=C(C)C=C2C)=NC(C)=C1 | ||
分子式 | C21H29NO2 | 分子量 | 327.46 |
溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg | |
1 mM | 3.0538 mL | 15.269 mL | 30.5381 mL |
5 mM | 0.6108 mL | 3.0538 mL | 6.1076 mL |
10 mM | 0.3054 mL | 1.5269 mL | 3.0538 mL |
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Behavioral, biological, and chemical perspectives on targeting CRF(1) receptor antagonists to treat alcoholism
Drug Alcohol Depend.2013 Mar 1;128(3):175-86.PMID:23294766DOI: 10.1016/j.drugalcdep.2012.12.017.
Background: Alcohol use disorders are chronic disabling conditions for which existing pharmacotherapies have only modest efficacy. In the present review, derived from the 2012 Behavior, Biology and Chemistry "Translational Research in Addiction" symposium, we summarize the anti-relapse potential of corticotropin-releasing factor type 1 (CRF(1)) receptor antagonists to reduce negative emotional symptoms of acute and protracted alcohol withdrawal and stress-induced relapse to alcohol seeking. Methods: We review the biology of CRF(1) systems, the activity of CRF(1) receptor antagonists in animal models of anxiolytic and antidepressant activity, and experimental findings in alcohol addiction models. We also update the clinical trial status of CRF(1) receptor antagonists, including pexacerfont (BMS-562086), emicerfont (GW876008), verucerfont (GSK561679), CP316311, SSR125543A, R121919/NBI30775, R317573/19567470/CRA5626, and ONO-2333Ms. Finally, we discuss the potential heterogeneity and pharmacogenomics of CRF(1) receptor pharmacotherapy for alcohol dependence. Results: The evidence suggests that brain penetrant-CRF(1) receptor antagonists have therapeutic potential for alcohol dependence. Lead compounds with clinically desirable pharmacokinetic properties now exist, and longer receptor residence rates (i.e., slow dissociation) may predict greater CRF(1) receptor antagonist efficacy. Functional variants in genes that encode CRF system molecules, including polymorphisms in Crhr1 (rs110402, rs1876831, rs242938) and Crhbp genes (rs10055255, rs3811939) may promote alcohol seeking and consumption by altering basal or stress-induced CRF system activation. Conclusions: Ongoing clinical trials with pexacerfont and verucerfont in moderately to highly severe dependent anxious alcoholics may yield insight as to the role of CRF(1) receptor antagonists in a personalized medicine approach to treat drug or alcohol dependence.
Synthesis and SAR of 2-aryloxy-4-alkoxy-pyridines as potent orally active corticotropin-releasing factor 1 receptor antagonists
J Med Chem.2008 Mar 13;51(5):1377-84.PMID:18260619DOI: 10.1021/jm070578k.
A series of 2-aryloxy-4-alkoxy-pyridines ( 1) was identified as novel, selective, and orally active antagonists of the corticotropin-releasing factor 1 (CRF 1) receptor. Among these, compound 2 (CP-316311) is a potent and selective CRF 1 receptor antagonist with an IC 50 value of 6.8 nM in receptor binding and demonstrates oral efficacy in central nervous system (CNS) in vivo models. The regiochemistry of compounds in this series was determined by an X-ray structural analysis. A method to control regioselectivity via pyridine- N-oxides was developed. The synthesis of compounds in series 1 (Figure ) and [ (3)H]- 2 as well as the structure-activity relationship (SAR) are discussed. The in vitro, ex vivo, and in vivo properties of representative compounds are described herein. Compound 2 was advanced to phase II depression trials to test the hypothesis that CRF 1 antagonists could be used clinically as antidepressant drugs.