WO1995012612A1 - Inhibiteurs di- et tripeptidiques substitues de l'enzyme proteine:la farnesyle transferase - Google Patents

Inhibiteurs di- et tripeptidiques substitues de l'enzyme proteine:la farnesyle transferase Download PDF

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Publication number
WO1995012612A1
WO1995012612A1 PCT/US1994/011553 US9411553W WO9512612A1 WO 1995012612 A1 WO1995012612 A1 WO 1995012612A1 US 9411553 W US9411553 W US 9411553W WO 9512612 A1 WO9512612 A1 WO 9512612A1
Authority
WO
WIPO (PCT)
Prior art keywords
obn
tyr
cbz
ser
conh
Prior art date
Application number
PCT/US1994/011553
Other languages
English (en)
Inventor
Gary Louis Bolton
Mark Wallace Creswell
John Cooke Hodges
Michael William Wilson
Original Assignee
Warner-Lambert Company
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Warner-Lambert Company filed Critical Warner-Lambert Company
Priority to NZ275691A priority Critical patent/NZ275691A/en
Priority to AU79760/94A priority patent/AU681454B2/en
Priority to JP51322495A priority patent/JP3597863B2/ja
Priority to EP94930725A priority patent/EP0730605A1/fr
Publication of WO1995012612A1 publication Critical patent/WO1995012612A1/fr
Priority to FI961819A priority patent/FI961819A/fi
Priority to NO961814A priority patent/NO961814L/no

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06139—Dipeptides with the first amino acid being heterocyclic
    • C07K5/06147—Dipeptides with the first amino acid being heterocyclic and His-amino acid; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • the compounds of Formula I may be prepared by solid phase peptide synthesis on a peptide synthesizer, for example, an Applied Biosystems 431A peptide synthesizer using activated esters or anhydrides of Boc or Fmoc protected amino acids, acid chlorides, isocyanates, isothiocyanates, etc., on PAM, MBHA, or NH 2 -Rink resins with solution phase modifications to the carboxyl terminus as appropriate.
  • Methodology for the solid phase synthesis of peptides is widely known to those skilled in the art thereof (see, for example: J.M. Stewart and J.D. Young in Solid Phase Peptide Synthesis: Pierce Chemical Co.; Rockford, IL (1984); Fields G.B. and Noble R.L.
  • the compounds of Formula I may be prepared by simultaneous multiple solid phase syntheses using an apparatus described by S. H. DeWitt, et al. , Proc. Natl. Acad. Sci. USA. 9 . 0:6909 (1993), and referred to by the trademark, DiversomerTM, both trademark and apparatus being owned in whole by the Warner-Lambert Company.
  • the multiple solid phase synthesis apparatus is currently the subject of now abandoned US Serial 07/958,383 filed October 8, 1992 and pending continuation-in-part US Serial 08/012,557 filed February 2, 1993.
  • the pharmaceutical preparation is preferably in unit dosage form.
  • the preparation is subdivided into unit doses containing appropriate quantities of the active component.
  • the unit dosage form can be a packaged preparation, the package containing discrete quantities of preparation, such as packeted tablets, capsules, and powders in vials or ampoules.
  • the unit dosage form can be a capsules, tablet, cachet, or lozenge itself, or it can be the appropriate number of any of these in packaged form.
  • Step 3 BnNHCO-His (Tr) -Tyr(OBn) -Ser(OBn) -CQ 2 Me
  • Example 20 by substituting Boc- ( ⁇ !-Me)Tyr(OBn) for Boc-Tyr(OBn) , the title compound was obtained, mp 66-78°C; ES-MS 690 (m+1) .
  • EXAMPLE 23 N- (2-Phenylethyl) -N a - fN- f (phenylmethoxy) carbonyl! - L-histidyl! -0- (phenylmethyl) -L-tyrosinamide ⁇ Cbz-His-Tyr(OBn) -C0NHCH CH 2 Ph) According to Example 19, Step 3, by substituting

Abstract

L'invention concerne de nouveaux inhibiteurs de l'enzyme protéine:farnésyle transférase, de même que des procédés de préparation de ceux-ci ainsi que des compositions pharmaceutiques contenant lesdits inhibiteurs, lesquels sont utiles dans la maîtrise des maladies à prolifération tissulaire, notamment le cancer et la resténose.
PCT/US1994/011553 1993-11-05 1994-10-12 Inhibiteurs di- et tripeptidiques substitues de l'enzyme proteine:la farnesyle transferase WO1995012612A1 (fr)

Priority Applications (6)

Application Number Priority Date Filing Date Title
NZ275691A NZ275691A (en) 1993-11-05 1994-10-12 Di and tripeptides and compositions thereof which inhibit farnesyl transferase
AU79760/94A AU681454B2 (en) 1993-11-05 1994-10-12 Substituted DI- and tripeptide inhibitors of protein:farnesyl transferase
JP51322495A JP3597863B2 (ja) 1993-11-05 1994-10-12 タンパク質：ファルネシルトランスフェラーゼの置換されたジ‐およびトリペプチド阻害剤
EP94930725A EP0730605A1 (fr) 1993-11-05 1994-10-12 Inhibiteurs di- et tripeptidiques substitues de l'enzyme proteine:la farnesyle transferase
FI961819A FI961819A (fi) 1993-11-05 1996-04-29 Proteiini:farnesyylitransferaasin substituoidut di- ja tripeptidi-inhibiittorit
NO961814A NO961814L (no) 1993-11-05 1996-05-03 Substituerte di- og tripetidinhibitorer for protein:farnesyl-transferase

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US14873593A 1993-11-05 1993-11-05
US30330194A 1994-09-13 1994-09-13
US08/303,301 1994-09-13
US08/148,735 1994-09-13

Publications (1)

Publication Number Publication Date
WO1995012612A1 true WO1995012612A1 (fr) 1995-05-11

Family

ID=26846110

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1994/011553 WO1995012612A1 (fr) 1993-11-05 1994-10-12 Inhibiteurs di- et tripeptidiques substitues de l'enzyme proteine:la farnesyle transferase

Country Status (10)

Country Link
EP (1) EP0730605A1 (fr)
JP (1) JP3597863B2 (fr)
KR (1) KR100362338B1 (fr)
AU (1) AU681454B2 (fr)
CA (1) CA2170766A1 (fr)
FI (1) FI961819A (fr)
HU (1) HUT75308A (fr)
NO (1) NO961814L (fr)
NZ (1) NZ275691A (fr)
WO (1) WO1995012612A1 (fr)

Cited By (75)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0675112A1 (fr) * 1994-03-31 1995-10-04 Bristol-Myers Squibb Company Inhibiteurs de farnésyl-protéine-transférase contenant l'imidazole
WO1996010034A2 (fr) * 1994-09-29 1996-04-04 Merck & Co., Inc. Inhibiteurs de la transferase de proteines farnesylees exempts de thiol
FR2736641A1 (fr) * 1995-07-10 1997-01-17 Rhone Poulenc Rorer Sa Nouveaux inhibiteurs de farnesyl transferase, leur preparation et les compositions pharmaceutiques qui les contiennent
EP0783318A1 (fr) * 1994-09-29 1997-07-16 Merck & Co. Inc. Inhibiteurs de farnesyle-proteine transferase
US5652257A (en) * 1994-09-29 1997-07-29 Merck & Co., Inc. Heterocycle-containing inhibitors of farnesyl-protein transferase
EP0787123A1 (fr) * 1994-09-29 1997-08-06 Merck & Co. Inc. Inhibiteurs de farnesyle-proteine transferase
WO1997044350A1 (fr) * 1996-05-22 1997-11-27 Warner-Lambert Company Inhibiteurs de farnesyltransferase de proteines
US5756528A (en) * 1995-06-06 1998-05-26 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
WO1998027109A1 (fr) * 1996-12-17 1998-06-25 Warner-Lambert Company Inhibiteurs cycloalkyle de proteine farnesyltransferase
FR2757855A1 (fr) * 1996-12-30 1998-07-03 Rhone Poulenc Rorer Sa Nouveaux inhibiteurs de farnesyl transferase, leur preparation et les compositions pharmaceutiques qui les contiennent
EP0892797A1 (fr) * 1996-02-26 1999-01-27 Bristol-Myers Squibb Company Inhibiteurs de la farnesyl-transferase
US5968965A (en) * 1996-01-30 1999-10-19 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5972984A (en) * 1995-06-06 1999-10-26 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
WO1999055725A1 (fr) * 1998-04-27 1999-11-04 Warner-Lambert Company Derives fonctionnalises de glycinamides, a chaine laterale alkyle et alcenyle, utilises comme inhibiteurs de la farnesyl-transferase
US5981562A (en) * 1996-01-30 1999-11-09 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US6013662A (en) * 1996-12-30 2000-01-11 Rhone-Poulenc Rorer S.A. Farnesyl transferase inhibitors, their preparation, the pharmaceutical compositions which contain them and their use in the preparation of medicaments
WO2000034313A1 (fr) * 1998-12-10 2000-06-15 F. Hoffmann-La Roche Ag Inhibiteurs de la c-proteinase de procollagene
US6124465A (en) * 1997-11-25 2000-09-26 Rhone-Poulenc S.A. Farnesyl transferase inhibitors, their preparation, the pharmaceutical compositions which contain them and their use in the preparation of medicaments
US6166052A (en) * 1998-03-11 2000-12-26 Warner-Lambert Company Heteroaryl alkyl alpha substituted peptidylamine calcium channel blockers
US6251919B1 (en) 1998-02-27 2001-06-26 Warner-Lambert Heterocyclic substituted aniline calcium channel blockers
US6291679B1 (en) 1999-07-22 2001-09-18 Rhone-Poulenc Rorer S.A. Process for preparing benzoperhydroisoindole compounds
US6300501B1 (en) 1996-05-22 2001-10-09 Warner-Lambert Company Histidine-(N-benzyl glycinamide) inhibitors of protein farnesyl transferase
US6423689B1 (en) 1997-12-22 2002-07-23 Warner-Lambert Company Peptidyl calcium channel blockers
US6441006B2 (en) 1998-04-02 2002-08-27 Targacept, Inc. Pharmaceutical compositions and methods for use
US6627648B1 (en) 1999-05-24 2003-09-30 Targacept, Inc. Pharmaceutical compositions and methods for use
WO2006123182A2 (fr) 2005-05-17 2006-11-23 Merck Sharp & Dohme Limited Sulfones de cyclohexyle pour le traitement du cancer
WO2007093827A1 (fr) 2006-02-15 2007-08-23 Istituto Di Ricerche Di Biologia Molecolare P. Angeletti Spa Dérivés de trifluoroéthanone substitués par thiophène et thiazole en tant qu'inhibiteurs d'histone désacétylase (hdac)
WO2008106692A1 (fr) 2007-03-01 2008-09-04 Novartis Vaccines And Diagnostics, Inc. Inhibiteurs de pim kinase et procédés de leur utilisation
WO2008144062A1 (fr) 2007-05-21 2008-11-27 Novartis Ag Inhibiteurs du csf-1r, compositions et procédés d'utilisation
WO2009002495A1 (fr) 2007-06-27 2008-12-31 Merck & Co., Inc. Dérivés de 4-carboxybenzylamino utilisés en tant qu'inhibiteurs de l'histone désacétylase
US7553854B2 (en) 2006-04-19 2009-06-30 Novartis Vaccines And Diagnostics, Inc. 6-O-substituted benzoxazole and benzothiazole compounds and methods of inhibiting CSF-1R signaling
WO2010114780A1 (fr) 2009-04-01 2010-10-07 Merck Sharp & Dohme Corp. Inhibiteurs de l'activité akt
WO2011046771A1 (fr) 2009-10-14 2011-04-21 Schering Corporation Pipéridines substituées qui accroissent l'activité de p53, et utilisations de ces composés
EP2336120A1 (fr) 2007-01-10 2011-06-22 Istituto di ricerche di Biologia Molecolare P. Angeletti S.R.L. Combinaisons contenant indazoles à substitution amide utilisés comme inhibiteurs de la poly(ADP-ribose)polymérase (PARP)
WO2011115725A2 (fr) 2010-03-16 2011-09-22 Dana-Farber Cancer Institute, Inc. Composés d'indazole et leurs utilisations
WO2011163330A1 (fr) 2010-06-24 2011-12-29 Merck Sharp & Dohme Corp. Nouveaux composés hétérocycliques utilisés comme inhibiteurs de erk
WO2012018754A2 (fr) 2010-08-02 2012-02-09 Merck Sharp & Dohme Corp. Inhibition à médiation par interférence arn de caténine (protéine associée à cadhérine), expression du gène bêta 1 (ctnnb1) à l'aide de petit acide nucléique interférent (sian)
WO2012024170A2 (fr) 2010-08-17 2012-02-23 Merck Sharp & Dohme Corp. Inhibition médiée par des arn interférents de l'expression génique du virus de l'hépatite b (vhb) à l'aide de petits acides nucléiques interférents (pani)
WO2012027236A1 (fr) 2010-08-23 2012-03-01 Schering Corporation Nouveaux dérivés de pyrazolo[1,5-a]pyrimidine utilisés comme inhibiteurs de mtor
WO2012030685A2 (fr) 2010-09-01 2012-03-08 Schering Corporation Dérivés d'indazole utilisables en tant qu'inhibiteurs de la voie erk
WO2012036997A1 (fr) 2010-09-16 2012-03-22 Schering Corporation Dérivés condensés de pyrazole utilisés comme nouveaux inhibiteurs erk
WO2012058210A1 (fr) 2010-10-29 2012-05-03 Merck Sharp & Dohme Corp. INHIBITION FACILITÉE PAR L'INTERFÉRENCE D'ARN DE L'EXPRESSION D'UN GÈNE AU MOYEN D'ACIDES NUCLÉIQUES INTERFÉRENTS COURTS (siNA)
WO2012087772A1 (fr) 2010-12-21 2012-06-28 Schering Corporation Dérivés d'indazole utiles en tant qu'inhibiteurs de erk
WO2012145471A1 (fr) 2011-04-21 2012-10-26 Merck Sharp & Dohme Corp. Inhibiteurs du récepteur du facteur de croissance 1 analogue à l'insuline
WO2013063214A1 (fr) 2011-10-27 2013-05-02 Merck Sharp & Dohme Corp. Nouveaux composés qui sont des inhibiteurs d'erk
WO2013165816A2 (fr) 2012-05-02 2013-11-07 Merck Sharp & Dohme Corp. Compositions de petit acide nucléique interférent (sina)
EP2698157A1 (fr) 2006-09-22 2014-02-19 Merck Sharp & Dohme Corp. Procédé de traitement utilisant des inhibiteurs de synthèse d'acide gras
US20140094614A1 (en) * 2011-10-26 2014-04-03 Allergan, Inc. Amide derivatives of n-urea substituted amino acids as formyl peptide receptor like-1 (fprl-1) receptor modulators
WO2014052563A2 (fr) 2012-09-28 2014-04-03 Merck Sharp & Dohme Corp. Nouveaux composés inhibiteurs de erk
WO2014085216A1 (fr) 2012-11-28 2014-06-05 Merck Sharp & Dohme Corp. Compositions et procédés pour traiter le cancer
WO2014100065A1 (fr) 2012-12-20 2014-06-26 Merck Sharp & Dohme Corp. Imidazopyridines substituées en tant qu'inhibiteurs de hdm2
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WO2014120748A1 (fr) 2013-01-30 2014-08-07 Merck Sharp & Dohme Corp. Purines 2,6,7,8-substituées utilisées en tant qu'inhibiteurs de hdm2
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Cited By (116)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0675112A1 (fr) * 1994-03-31 1995-10-04 Bristol-Myers Squibb Company Inhibiteurs de farnésyl-protéine-transférase contenant l'imidazole
EP0787123A4 (fr) * 1994-09-29 1999-10-13 Merck & Co Inc Inhibiteurs de farnesyle-proteine transferase
WO1996010034A2 (fr) * 1994-09-29 1996-04-04 Merck & Co., Inc. Inhibiteurs de la transferase de proteines farnesylees exempts de thiol
EP0783318A4 (fr) * 1994-09-29 1999-10-20 Merck & Co Inc Inhibiteurs de farnesyle-proteine transferase
WO1996010034A3 (fr) * 1994-09-29 1996-05-09 Merck & Co Inc Inhibiteurs de la transferase de proteines farnesylees exempts de thiol
EP0783318A1 (fr) * 1994-09-29 1997-07-16 Merck & Co. Inc. Inhibiteurs de farnesyle-proteine transferase
US5652257A (en) * 1994-09-29 1997-07-29 Merck & Co., Inc. Heterocycle-containing inhibitors of farnesyl-protein transferase
EP0787123A1 (fr) * 1994-09-29 1997-08-06 Merck & Co. Inc. Inhibiteurs de farnesyle-proteine transferase
US5756528A (en) * 1995-06-06 1998-05-26 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5972984A (en) * 1995-06-06 1999-10-26 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
CN1096448C (zh) * 1995-07-10 2002-12-18 罗纳-布朗克·罗莱尔股份有限公司 新的法呢基转移酶的抑制剂,其制备方法及其药物组合物
FR2736641A1 (fr) * 1995-07-10 1997-01-17 Rhone Poulenc Rorer Sa Nouveaux inhibiteurs de farnesyl transferase, leur preparation et les compositions pharmaceutiques qui les contiennent
WO1997003050A1 (fr) * 1995-07-10 1997-01-30 Rhone-Poulenc Rorer S.A. DERIVES DE 4,9-ETHANO-BANZO(f)ISOINDOLE COMME INHIBITEURS DE FARNESYL TRANSFERASE
EA000797B1 (ru) * 1995-07-10 2000-04-24 Рон-Пуленк Роре С.А. Новые ингибиторы фарнезилтрансферазы, способы их получения и содержащая их фармацевтическая композиция
US5936097A (en) * 1995-07-10 1999-08-10 Rhone-Poulenc Rorer, S.A. 4,9-ethano-benzo(F)isoindole derivatives as farnesyl transferase inhibitors
US5981562A (en) * 1996-01-30 1999-11-09 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5968965A (en) * 1996-01-30 1999-10-19 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
EP1481975A1 (fr) * 1996-02-26 2004-12-01 Bristol-Myers Squibb Company Inhibiteurs de la farnésyl protéine transférase
EP0892797A1 (fr) * 1996-02-26 1999-01-27 Bristol-Myers Squibb Company Inhibiteurs de la farnesyl-transferase
EP0892797A4 (fr) * 1996-02-26 2004-10-20 Bristol Myers Squibb Co Inhibiteurs de la farnesyl-transferase
WO1997044350A1 (fr) * 1996-05-22 1997-11-27 Warner-Lambert Company Inhibiteurs de farnesyltransferase de proteines
US6300501B1 (en) 1996-05-22 2001-10-09 Warner-Lambert Company Histidine-(N-benzyl glycinamide) inhibitors of protein farnesyl transferase
US6281194B1 (en) 1996-12-17 2001-08-28 Warner-Lambert Company Cycloalkyl inhibitors of protein farnesyltransferase
WO1998027109A1 (fr) * 1996-12-17 1998-06-25 Warner-Lambert Company Inhibiteurs cycloalkyle de proteine farnesyltransferase
WO1998029390A1 (fr) * 1996-12-30 1998-07-09 Rhone-Poulenc Rorer S.A. Inhibiteurs de farnesyle transferase
US6013662A (en) * 1996-12-30 2000-01-11 Rhone-Poulenc Rorer S.A. Farnesyl transferase inhibitors, their preparation, the pharmaceutical compositions which contain them and their use in the preparation of medicaments
US6218406B1 (en) 1996-12-30 2001-04-17 Aventis Pharma S.A. Farnesyl transferase inhibitors, their preparation, the pharmaceutical compositions which contain them and their use in the preparation of medicaments
FR2757855A1 (fr) * 1996-12-30 1998-07-03 Rhone Poulenc Rorer Sa Nouveaux inhibiteurs de farnesyl transferase, leur preparation et les compositions pharmaceutiques qui les contiennent
US6124465A (en) * 1997-11-25 2000-09-26 Rhone-Poulenc S.A. Farnesyl transferase inhibitors, their preparation, the pharmaceutical compositions which contain them and their use in the preparation of medicaments
US6423689B1 (en) 1997-12-22 2002-07-23 Warner-Lambert Company Peptidyl calcium channel blockers
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FI961819A (fi) 1996-04-29
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NO961814D0 (no) 1996-05-03
HUT75308A (en) 1997-05-28
CA2170766A1 (fr) 1995-05-11
HU9601193D0 (en) 1996-07-29
AU7976094A (en) 1995-05-23
JPH09504547A (ja) 1997-05-06
EP0730605A1 (fr) 1996-09-11

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