title: Marcfortine and paraherquamide class of anthelmintics: discovery of PNU-141962.
abstract: Three distinct chemical classes for the control of gastrointestinal nematodes are available: benzimidazoles, imidazothiazoles, and macrocyclic lactones. The relentless development of drug resistance has severely limited the usefulness of such drugs and the search for a new class of compounds   preferably with a different mode of action   is an important endeavor. Marcfortine A (1), a metabolite of Penicillium roqueforti, is structurally related to paraherquamide A (2), originally isolated from Penicillium paraherquei. Chemically the two compounds differ only in one ring; in marcfortine A, ring G is six-membered and carries no substituents, while in paraherquamide A, ring G is five-membered with methyl and hydroxyl substituents at C14. Paraherquamide A (2) is superior to marcfortine A as a nematocide. 2-Desoxoparaherquamide A (PNU-141962, 53) has excellent nematocidal activity, a superior safely profile, and is the first semi-synthetic member of this totally new class of nematocides that is a legitimate candidate for development. This review describes the chemistry, efficacy and mode of action of PNU-141962.
authors.affiliation: Animal Health Discovery Research, Kalamazoo, MI 49001, USA. byung.h.lee@pharmacia.com
authors.forename: Byung H
authors.initials: BH
authors.lastname: Lee
authors.forename: Michael F
authors.initials: MF
authors.lastname: Clothier
authors.forename: Fred E
authors.initials: FE
authors.lastname: Dutton
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Nelson
authors.forename: Sandra S
authors.initials: SS
authors.lastname: Johnson
authors.forename: David P
authors.initials: DP
authors.lastname: Thompson
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Geary
authors.forename: Howard D
authors.initials: HD
authors.lastname: Whaley
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Haber
authors.forename: Vincent P
authors.initials: VP
authors.lastname: Marshall
authors.forename: Gabe I
authors.initials: GI
authors.lastname: Kornis
authors.forename: Patty L
authors.initials: PL
authors.lastname: McNally
authors.forename: Joyce I
authors.initials: JI
authors.lastname: Ciadella
authors.forename: David G
authors.initials: DG
authors.lastname: Martin
authors.forename: Jerry W
authors.initials: JW
authors.lastname: Bowman
authors.forename: Carol A
authors.initials: CA
authors.lastname: Baker
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Coscarelli
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Alexander-Bowman
authors.forename: John P
authors.initials: JP
authors.lastname: Davis
authors.forename: Erich W
authors.initials: EW
authors.lastname: Zinser
authors.forename: Veronica
authors.initials: V
authors.lastname: Wiley
authors.forename: Michael F
authors.initials: MF
authors.lastname: Lipton
authors.forename: Michael A
authors.initials: MA
authors.lastname: Mauragis
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D007212:Indolizines / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D015394:Molecular Structure; D009349:Nematode Infections / Q000188:drug therapy / Q000517:prevention & control / Q000662:veterinary; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D013329:Structure-Activity Relationship
chemical_list: C476163:2-desoxoparaherquamide A; D000871:Anthelmintics; D007212:Indolizines; D013141:Spiro Compounds; C103037:marcfortine A; C063985:paraherquamide