Selectivity profiling of novel indene H(1)-antihistamines for the treatment of insomnia.
A series of indene analogs of the H(1)-antihistamine (-)-R-dimethindene was evaluated for selectivity in the search for potentially improved sedative-hypnotics. Variation of the 6-substitutent in the indene core in combination with a pendant electron rich heterocycle led to the identification of several potent H(1)-antihistamines with desirable selectivity over CYP enzymes, the M(1) muscarinic receptor and the hERG channel. These compounds were candidates for further ADME profiling and in vivo evaluation.
Li
Bin-Feng
BF
Neurocrine Biosciences, San Diego, CA 92130, USA.
Moree
Wilna J
WJ
Yu
Jinghua
J
Coon
Timothy
T
Zamani-Kord
Said
S
Malany
Siobhan
S
Jalali
Kayvon
K
Wen
Jianyun
J
Wang
Hua
H
Yang
Chun
C
Hoare
Samuel R J
SR
Petroski
Robert E
RE
Madan
Ajay
A
Crowe
Paul D
PD
Beaton
Graham
G
D006633:Histamine Antagonists / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007192:Indenes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy*
D006633:Histamine Antagonists; D007192:Indenes