Conformationally restricted analogues of nicotine and anabasine.
A series of conformationally restricted analogues of nicotine has been synthesized and evaluated as agonists of neuronal acetylcholine receptors. Compound 2 (SIB-1663), which selectively activated human recombinant alpha 2 beta 4 and alpha 4 beta 4 nAChRs, was shown to be active in animal models of Parkinson's disease and pain.
Vernier
J M
JM
SIBIA Neurosciences Inc., La Jolla, CA 92037, USA.
Holsenback
H
H
Cosford
N D
ND
Whitten
J P
JP
Menzaghi
F
F
Reid
R
R
Rao
T S
TS
Sacaan
A I
AI
Lloyd
G K
GK
Suto
C M
CM
Chavez-Noriega
L E
LE
Washburn
M S
MS
Urrutia
A
A
McDonald
I A
IA
D000691:Anabasine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000978:Antiparkinson Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D018679:Cholinergic Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D046911:Macromolecular Substances; D008968:Molecular Conformation; D009474:Neurons / Q000378:metabolism*; D009538:Nicotine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010302:Parkinson Disease, Secondary / Q000188:drug therapy; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011994:Recombinant Proteins / Q000187:drug effects; D013329:Structure-Activity Relationship; D014162:Transfection
D000978:Antiparkinson Agents; D018679:Cholinergic Agonists; D046911:Macromolecular Substances; D010880:Piperidines; D011725:Pyridines; D011994:Recombinant Proteins; D009538:Nicotine; D000691:Anabasine; D002118:Calcium