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.
Neurocrine Biosciences, San Diego, CA 92130, USA.
Bin-Feng
BF
Li
Wilna J
WJ
Moree
Jinghua
J
Yu
Timothy
T
Coon
Said
S
Zamani-Kord
Siobhan
S
Malany
Kayvon
K
Jalali
Jianyun
J
Wen
Hua
H
Wang
Chun
C
Yang
Samuel R J
SR
Hoare
Robert E
RE
Petroski
Ajay
A
Madan
Paul D
PD
Crowe
Graham
G
Beaton
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