Vitronectin-reseptor-antagonister

• Main Authors: BONDINELL, WILLIAM E, SAMANEN, JAMES, ALI, FADIA E, KU, THOMAS W, KEENAN, RICHARD M, MILLER, WILLIAM H
• Format: Patent
• Language: Norwegian
• Published: 26.08.1998
• Edition: 6
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

Forbindelser med formel (I) er beskrevet hvori: A er en fibrinogen-antagonistsjablon;W er en bindingsgruppe med formen -(CHR9)-U-(CHR9)-V-; Q, Qog Qer uavhengig N eller C-RY, forutsatt at ikke mer enn én av Q, Q, Q3 og Qer N; R' er H eller C-i-alkyl, C-cykloalkyl-C-alkyl eller Ar-Co-ealkyl R9 erH eller C-i-alkyl, Het-Co-alkyl, C-cykloalkyl-Co-alkyl eller Ar-Co-alkyl; Rer R9, -C(0)R9 eller-C(0)OR9; R' er H, Ci-alkyl, Het-C-alkyl, C-cykloalkyl-Co-alkyl, Ar-Co-alkyl, Het-Co-ealkyl-U-Cialkyl, C-cykloalkyl-Co-alkyl-U'-Calkyl eller Ar-C-alkyl-U,-C_alkyl; Ry er H, halogen, -OR9, -SR9, -CN, -NR9R, -N0, -CF, CFS(0), -C0R9, -COR9 eller -CONR9eller d-ealkyl eventuelt substituert med halogen, -OR9, -SR9, -CN, -NR9R", -N0, -CF, R'S(0)-, -COR9, -COR9 eller -CONR9; U og V er fraværende eller CO, CR9, C(=CR9), S(0), O, NR9, CR90R9, CR9(OR)CR9, CR9CR9(OR), C(0)CR9, CR9C(0), CONR, NR'CO, OC(O), C(0)0, C(S)0, OC(S), C(S)NR9, NR9C(S), S(0)NR9, NR9S(0)N=N, NR9NR9, NR9CR9, NR9CR9CR90, OCR9, CR9=CR, c= C, Ar eller Het;a er 0, 1, 2 eller 3; b er 0, 1 eller 2; c er 0, 1 eller 2; u er 0 eller 1; eller farmasøytisk godtagbare salter derav som er vitronectin-reseptor-antagonister anvendelige ved behandling av osteoporose. PCT No. PCT/US96/20327 Sec. 371 Date Jul. 27, 1999 Sec. 102(e) Date Jul. 27, 1999 PCT Filed Dec. 20, 1996 PCT Pub. No. WO97/24124 PCT Pub. Date Jul. 10, 1999Compounds of formula (I) are disclosed, wherein: A is a fibrinogen antagonist template; W is a linking moiety of the form -(CHRg)a-U-(CHRg)b-V-; Q1, Q2, Q3 and Q4 are independently N or C-Ry, provided that no more than one Q1, Q2, Q3 and Q4 is N; R' is H or C1-6alkyl, C3-7cycloalkyl-C0-6-alkyl or Ar-C0-6alkyl; Rg is H or C1-6alkyl, Het-C0-6alkyl, C3-7cycloalkyl-C0-6alkyl or Ar-C0-6alkyl; Rk is Rg, -C(O)Rg or -C(O)ORg Ri is H, C1-6alkyl, Het-C0-6alkyl, C3-7cycloalkyl-C0-6alkyl, Ar-C0-6alkyl, Het-C0-6alkyl-U'-C1-6alkyl, C3-7cycloalkyl-C0-6alkyl-U'-C1-6alkyl or Ar-C0-6alkyl-U'-C1-6alkyl; Ry is H, halo, -ORg, -SRg, -CN, -NRgRk, -NO2, -CF3, CF3S(O)r, -CO2Rg, -CORg or -CONRg2, or C1-6alkyl optionally substituted by halo, -ORg, -SRg, -CN, -NR8R'', -NO2, -CF3, R'S(O)3-, -CO2Rg, -CORg or -CONRg2; U and V are absent or CO, CRg2, C(=CRg2), S(O)c, O, NRg, CRgORg, CRg(ORk)CRg2, CRg7CRg(ORk), C(O)CRg2, CRg2C(O), CONRi, NRiCO, OC(O), C(O)O, OC(S), C(S)NRg, NR8C(S), S(O2NRg, NRgS(O)2N=N, NRgNRg, NRgCRg2, NRgCRg2, CRg2O, OCRg2, CRg=CRg, C=C, Ar or Het; a is 0, 1 or 2; c is 0, 1 or 2; r is 0, 1 or 2; and u is 0 or 1; or pharmaceutically acceptable salts thereof, which are vitronectin receptor antagonists useful in the treatment of osteoporosis.