title: Discovery of (2S)-N-[(1R)-2-[4-cyclohexyl-4-[[(1,1-dimethylethyl)amino]carbonyl]-1-piperidinyl]-1-[(4-fluorophenyl)methyl]-2-oxoethyl]-4-methyl-2-piperazinecarboxamide (MB243), a potent and selective melanocortin subtype-4 receptor agonist.
abstract: We report the discovery and optimization of substituted 2-piperazinecarboxamides as potent and selective agonists of the melanocortin subtype-4 receptor. Further in vivo development of lead agonist, MB243, is disclosed.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065-0900, USA. brenda_palucki@merck.com
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Palucki
authors.forename: Min K
authors.initials: MK
authors.lastname: Park
authors.forename: Ravi P
authors.initials: RP
authors.lastname: Nargund
authors.forename: Zhixiong
authors.initials: Z
authors.lastname: Ye
authors.forename: Iyassu K
authors.initials: IK
authors.lastname: Sebhat
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Pollard
authors.forename: Rubana N
authors.initials: RN
authors.lastname: Kalyani
authors.forename: Rui
authors.initials: R
authors.lastname: Tang
authors.forename: Tanya
authors.initials: T
authors.lastname: Macneil
authors.forename: David H
authors.initials: DH
authors.lastname: Weinberg
authors.forename: Aurawan
authors.initials: A
authors.lastname: Vongs
authors.forename: Charles I
authors.initials: CI
authors.lastname: Rosenblum
authors.forename: George A
authors.initials: GA
authors.lastname: Doss
authors.forename: Randall R
authors.initials: RR
authors.lastname: Miller
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Stearns
authors.forename: Qianping
authors.initials: Q
authors.lastname: Peng
authors.forename: Constantin
authors.initials: C
authors.lastname: Tamvakopoulos
authors.forename: Erin
authors.initials: E
authors.lastname: McGowan
authors.forename: William J
authors.initials: WJ
authors.lastname: Martin
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Metzger
authors.forename: Cherrie A
authors.initials: CA
authors.lastname: Shepherd
authors.forename: Alison M
authors.initials: AM
authors.lastname: Strack
authors.forename: D Euan
authors.initials: DE
authors.lastname: Macintyre
authors.forename: Lex H T
authors.initials: LH
authors.lastname: Van der Ploeg
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Patchett
mesh_terms: D000818:Animals; D004285:Dogs; D007172:Erectile Dysfunction / Q000188:drug therapy; D000882:Haplorhini; D008297:Male; D051379:Mice; D009765:Obesity / Q000188:drug therapy; D010879:Piperazines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D010880:Piperidines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists*
chemical_list: C500023:(2S)-N-((1R)-2-(4-cyclohexyl-4-(((1,1-dimethylethyl)amino)carbonyl)-1-piperidinyl)-1-((4-fluorophenyl)methyl)-2-oxoethyl)-4-methyl-2-piperazinecarboxamide; D010879:Piperazines; D010880:Piperidines; D044105:Receptor, Melanocortin, Type 4