Title:
【発明の名称】ギャップ結合連絡の阻害剤
Document Type and Number:
Japanese Patent JP2001523695
Kind Code:
A
Abstract:
Oleamide is an endogenous fatty acid primary amide that possesses sleep-inducing properties in animals and has been shown to effect seratonergic systems and block gap junction communication in a structurally specific manner. Certain agents can serve both as an oleamide agonist and as an inhibitor of fatty acid amide hydrolase. Fatty acid amide hydrolase is responsible for the rapid inactivation of oleamide in vivo. The structural features of oleamide required for inhibition of gap junction-mediated chemical and electrical transmission in rat glial cells are defined. Effective inhibitors fall into two classes of fatty acid primary amides of which oleamide and arachidonamide are the prototypical members. Of these two, oleamide constitutes the most effective and its structural requirements for inhibition of the gap junction are well defined. It requires a chain length of 16-24 carbons of which 16-18 carbons appears optimal, a polarized terminal carbonyl group capable of accepting but not necessarily donating a hydrogen bond, a DELTA 9 cis double bond, and a hydrophobic methyl terminus. Within these constraints, a range of modifications are possible, many of which may with enhanced in vivo properties.
Inventors:
Bogger Dale El
Giller norton bee
Learner Richard A
Clavat Benjamin F
Giller norton bee
Learner Richard A
Clavat Benjamin F
Application Number:
JP2000521789A
Publication Date:
November 27, 2001
Filing Date:
November 24, 1998
Export Citation:
Assignee:
THE SCRIPPS RESEARCH INSTITUTE
International Classes:
C07D295/18; A61K31/16; A61K31/201; A61K31/231; A61K31/27; A61K31/40; C07C47/21; C07C49/227; C07C57/12; C07C69/58; C07C233/09; C07C233/10; C07C233/11; C07C233/20; C07C233/49; C07C235/06; C07C235/28; C07C235/76; C07C237/22; C07C243/30; C07C245/14; C07C259/06; C07C271/10; C07C275/20; C07C323/60; C07C327/32; C07D207/00; (IPC1-7): C07C47/21; A61K31/16; A61K31/201; A61K31/231; A61K31/27; A61K31/40; C07C49/227; C07C57/12; C07C69/58; C07C233/09; C07C233/10; C07C233/11; C07C233/20; C07C233/49; C07C235/06; C07C235/28; C07C235/76; C07C237/22; C07C243/30; C07C245/14; C07C259/06; C07C271/10; C07C275/20; C07C323/60; C07C327/32; C07D207/00; C07D295/18
Attorney, Agent or Firm:
Minoru Nakamura (9 outside)