Effect of novel N-aryl sulfonamide substituted 3-morpholino arecoline derivatives as muscarinic receptor 1 agonists in Alzheimer's dementia models.
A series of novel, potent, and selective muscarinic receptor 1 agonists (M1 receptor agonists) that employ a key N-substituted morpholine Arecoline moiety has been synthesized as part of research effort for the therapy of Alzheimer's diseases. The ester group of arecoline (which is reported as muscarinic agonist) has been replaced by N-substituted morpholine ring. The structure-activity relationship reveals that the electron donating 4-substituted sulfonyl derivatives (9a, 9b, 9c, and 9e) on the nitrogen atom of the morpholine ring increases the affinity of M1 receptor binding 50- to 80-fold greater than the corresponding arecoline. Other derivatives also showed considerable M1 receptor binding affinity.
Kumar
Y C Sunil
YC
Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570006, India.
Malviya
Manish
M
Chandra
J N Narendra Sharath
JN
Sadashiva
C T
CT
Kumar
C S Ananda
CS
Prasad
S B Benaka
SB
Prasanna
D S
DS
Subhash
M N
MN
Rangappa
K S
KS
D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D001667:Binding, Competitive; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy; D015394:Molecular Structure; D009025:Morpholines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D043643:Receptor, Muscarinic M1 / Q000819:agonists*; D012601:Scopolamine; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry*
D009025:Morpholines; D043643:Receptor, Muscarinic M1; D013449:Sulfonamides; D012601:Scopolamine