Conformationally constrained LH-RH analogues, their uses and pharmaceutical compositions containing them

US6153587A · kind A · utility

Assignee

• LABORATOIRE THERAMEX · FR

Inventors

• Remi Delansorne · Paris, FR
• Jacques Paris · St-Estève, FR

Key dates

• Filing date: May 24, 1999
• Grant date: Nov 28, 2000
• Expiry date: May 24, 2019

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y10S930/13
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

LH-RH analogues with excellent affinity for LH-RH receptors, of the formula A.sub.1 -A.sub.2 -W-A.sub.3 -A.sub.4 -SPL-A.sub.5 -A.sub.6 -Pro-Z(I) in which: PA1 -A.sub.1 is pGlu, AcSar or an aromatic D-amino acid; PA1 -A.sub.2 is a direct bond, His, DPhe, DpFPhe or DpClPhe; PA1 *W is an aromatic L- or D-amino acid; PA1 -A.sub.3 is Ala, Thr, Ser, DSer, Ser(OBzl) or MeSer; PA1 -A.sub.4 is Tyr, Phe, cPzACAla, L- or D-PicLys, L- or D-NicLys or L- or D-IprLys; PA1 *SPL is the spirolactam of formula: ##STR1## -A.sub.5 is an amino acid with a (C.sub.1 -C.sub.8)alkyl or (C.sub.3-C.sub.6)cycloalkyl side chain; PA1 -A.sub.6 is L- or D-(Arg, HArg, Lys, HLys, Orn, Cit, HCit or Aph), where L- or D-(Arg and HArg) can be substituted by one or two (C.sub.1 -C.sub.4)alkyl groups and L- or D-(Lys, HLys, Orn and Aph) can be substituted by an isopropyl, nicotinoyl or picolinoyl group; and PA1 *Z is GlyNH.sub.2, DAlaNH.sub.2, AzaGlyNH.sub.2 or --NHR.sub.1 where R.sub.1 is a (C.sub.1 -C.sub.4)alkyl optionally substituted by a hydroxy or one or several fluorine atoms, a (C.sub.3 -C.sub.6)cycloalkyl or a heterocyclic radical selected from the group consisting of morpholinyl, pyrrolidinyl and piperidyl; PA1 …