ChemInform Abstract: 1,3-Asymmetric Induction in Enolate Alkylation Reactions of N- Protected γ-Amino Acid Derivatives.

ChemInform ◽  
2010 ◽  
Vol 28 (18) ◽  
pp. no-no
Author(s):  
S. HANESSIAN ◽  
R. SCHAUM
Keyword(s):  
Amino Acid ◽  
Asymmetric Induction ◽  
Amino Acid Derivatives ◽  
Enolate Alkylation ◽  
Alkylation Reactions

1,2-Asymmetric induction in radical reactions of β-amino acid derivatives

1995 ◽  
Vol 36 (23) ◽  
pp. 4047-4050 ◽  
Author(s):  
E. Peter Kündig ◽  
Long-He Xu ◽  
Patrick Romanens
Keyword(s):  
Amino Acid ◽  
Asymmetric Induction ◽  
Radical Reactions ◽  
Amino Acid Derivatives

An Anthrone-Based Kv7.2/7.3 Channel Blocker with Improved Properties for the Investigation of Psychiatric and Neurodegenerative Disorders

2019 ◽  
Author(s):  
Jacob Porter ◽  
Oscar Vivas-Rodriguez ◽  
C. David Weaver ◽  
Eamonn Dickson ◽  
Abdulmohsen Alsafran ◽  
...  
Keyword(s):  
Patch Clamp ◽  
Neurodegenerative Disorders ◽  
Channel Blocker ◽  
Optimal Combination ◽  
Channel Blockers ◽  
Enolate Alkylation ◽  
Cyp Inhibition ◽  
Alkylation Reactions ◽  
Metabolic Instability

A set of novel Kv7.2/7.3 (KCNQ2/3) channel blockers was synthesized to address several liabilities of the known compounds XE991 (metabolic instability and CYP inhibition) and the clinical compound DMP 543 (acid instability, insolubility, and lipophilicity). Using the anthrone scaffold of the prior channel blockers, alternative heteroarylmethyl substituents were installed via enolate alkylation reactions. Incorporation of a pyridazine and a fluorinated pyridine gave an analog (JDP-107) with an optimal combination of potency (IC<sub>50</sub>= 0.16 𝜇M in a Kv7.2 thallium flux assay), efficacy in a Kv7.2/7.3 patch clamp assay, and drug-like properties.

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