Novel lactam NK1 antagonists with anti-emetic activity.
A series of 4,4-disubstituted cyclohexylamine NK(1) antagonists containing a lactam ring is described. The compounds are brain penetrant and activity is demonstrated in a ferret emesis model.
Hollingworth
Gregory J
GJ
Department of Medicinal Chemistry, Merck Sharp & Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK. greg_hollingworth@merck.com
Carlson
Emma J
EJ
Castro
José L
JL
Chicchi
Gary G
GG
Clark
Natalie
N
Cooper
Laura C
LC
Dirat
Olivier
O
Salvo
Jerry Di
JD
Elliott
Jason M
JM
Kilburn
Ruth
R
Kurtz
Marc M
MM
Rycroft
Wayne
W
Tattersall
F David
FD
Tsao
Kwei-Lan
KL
Swain
Christopher J
CJ
D000577:Amides / Q000737:chemistry; D000818:Animals; D000932:Antiemetics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005849:Gerbillinae; D006801:Humans; D020128:Inhibitory Concentration 50; D007769:Lactams / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008745:Methylation; D015394:Molecular Structure; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D013329:Structure-Activity Relationship; D015320:Tachykinins / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000577:Amides; D000932:Antiemetics; D007769:Lactams; D018040:Receptors, Neurokinin-1; D015320:Tachykinins