title: The discovery and synthesis of JNJ 31020028, a small molecule antagonist of the Neuropeptide Y Y₂ receptor.
abstract: A series of small molecules based on a chemotype identified from our compound collection were synthesized and tested for binding affinity (IC(50)) at the human Neuropeptide Y Y(2) receptor (NPY Y(2)). Six of the 23 analogs tested possessed an NPY Y(2) IC(50) ≤ 15 nM. One member of this series, JNJ 31020028, is a selective, high affinity, receptor antagonist existing as a racemic mixture. As such a synthetic route to the desired enantiomer was designed starting from commercially available (S)-(+)-mandelic acid.
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C., 3210 Merryfield Row, San Diego, CA 92121, USA. dswanso1@its.jnj.com
authors.forename: Devin M
authors.initials: DM
authors.lastname: Swanson
authors.forename: Victoria D
authors.initials: VD
authors.lastname: Wong
authors.forename: Jill A
authors.initials: JA
authors.lastname: Jablonowski
authors.forename: Chandra
authors.initials: C
authors.lastname: Shah
authors.forename: Dale A
authors.initials: DA
authors.lastname: Rudolph
authors.forename: Curt A
authors.initials: CA
authors.lastname: Dvorak
authors.forename: Mark
authors.initials: M
authors.lastname: Seierstad
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Dvorak
authors.forename: Kirsten
authors.initials: K
authors.lastname: Morton
authors.forename: Diane
authors.initials: D
authors.lastname: Nepomuceno
authors.forename: John R
authors.initials: JR
authors.lastname: Atack
authors.forename: Pascal
authors.initials: P
authors.lastname: Bonaventure
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Lovenberg
authors.forename: Nicholas I
authors.initials: NI
authors.lastname: Carruthers
mesh_terms: D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D006801:Humans; D015394:Molecular Structure; D008970:Molecular Weight; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D001549:Benzamides; C547250:JNJ-31020028; D010879:Piperazines; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor