FI961621L - Proteiini:farnesyylitranseraasin substituoidut tetra- ja pentapeptidi-inhibiittorit - Google Patents

Proteiini:farnesyylitranseraasin substituoidut tetra- ja pentapeptidi-inhibiittorit Download PDF

Info

Publication number
FI961621L
FI961621L FI961621A FI961621A FI961621L FI 961621 L FI961621 L FI 961621L FI 961621 A FI961621 A FI 961621A FI 961621 A FI961621 A FI 961621A FI 961621 L FI961621 L FI 961621L
Authority
FI
Finland
Prior art keywords
protein
farnesyl transferase
substituted tetra
pentapeptide inhibitors
pentapeptide
Prior art date
Application number
FI961621A
Other languages
English (en)
Finnish (fi)
Swedish (sv)
Other versions
FI961621A7 (fi
FI961621A0 (fi
Inventor
Gary Louis Bolton
Alfred Campbell
Richard Gowan
John Cooke Hodges
Donald Hupe
Daniele Leonard
Tomi Sawyer
Judith Sebolt-Leopold
Francis J Tinney
Original Assignee
Parke Davis & Co
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 Parke Davis & Co filed Critical Parke Davis & Co
Publication of FI961621A7 publication Critical patent/FI961621A7/fi
Publication of FI961621A0 publication Critical patent/FI961621A0/fi
Publication of FI961621L publication Critical patent/FI961621L/fi

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/82—Translation products from oncogenes
    • 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
    • C07K5/10—Tetrapeptides
    • C07K5/1002—Tetrapeptides with the first amino acid being neutral
    • C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
    • C07K5/1013—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing O or S as heteroatoms, e.g. Cys, Ser
    • 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
    • C07K5/10—Tetrapeptides
    • C07K5/1024—Tetrapeptides with the first amino acid being heterocyclic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Oncology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Peptides Or Proteins (AREA)
FI961621A 1993-10-25 1994-10-21 Proteiini:farnesyylitranseraasin substituoidut tetra- ja pentapeptidi-inhibiittorit FI961621L (fi)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US14275693A 1993-10-25 1993-10-25
US30963594A 1994-09-23 1994-09-23
PCT/US1994/012060 WO1995011917A1 (en) 1993-10-25 1994-10-21 Substituted tetra- and pentapeptide inhibitors of protein:farnesyl transferase

Publications (3)

Publication Number Publication Date
FI961621A7 FI961621A7 (fi) 1996-04-12
FI961621A0 FI961621A0 (fi) 1996-04-12
FI961621L true FI961621L (fi) 1996-04-12

Family

ID=26840404

Family Applications (1)

Application Number Title Priority Date Filing Date
FI961621A FI961621L (fi) 1993-10-25 1994-10-21 Proteiini:farnesyylitranseraasin substituoidut tetra- ja pentapeptidi-inhibiittorit

Country Status (15)

Country Link
EP (1) EP0725790B1 (de)
JP (1) JPH09504295A (de)
KR (1) KR100378615B1 (de)
AT (1) ATE200677T1 (de)
AU (1) AU682906B2 (de)
CA (1) CA2173590A1 (de)
DE (1) DE69427127T2 (de)
DK (1) DK0725790T3 (de)
ES (1) ES2157994T3 (de)
FI (1) FI961621L (de)
GR (1) GR3036188T3 (de)
LV (1) LV12771B (de)
NZ (1) NZ275037A (de)
PT (1) PT725790E (de)
WO (1) WO1995011917A1 (de)

Families Citing this family (88)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU1615895A (en) * 1994-03-31 1995-10-12 Bristol-Myers Squibb Company Imidazole-containing inhibitors of farnesyl protein transferase
IT1273986B (it) * 1994-09-28 1997-07-14 Merck & Co Inc Inibitori peptidici di farnesil proteina transferasi
US5652257A (en) * 1994-09-29 1997-07-29 Merck & Co., Inc. Heterocycle-containing inhibitors of farnesyl-protein transferase
US5661161A (en) * 1994-09-29 1997-08-26 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
JPH10510261A (ja) * 1994-12-09 1998-10-06 ワーナー−ランバート・カンパニー タンパク質:ファルネシルトランスフェラーゼの置換テトラーおよびペンタペプチド阻害剤
US5856326A (en) * 1995-03-29 1999-01-05 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5578629A (en) * 1995-03-29 1996-11-26 Merck & Co., Inc. Benzamide-containing inhibitors of farnesyl-protein transferase
US5631280A (en) * 1995-03-29 1997-05-20 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5627202A (en) * 1995-03-29 1997-05-06 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5534537A (en) * 1995-03-29 1996-07-09 Merck & Co., Inc. Prodrugs of inhibitors of farnesyl-protein transferase
US5624936A (en) * 1995-03-29 1997-04-29 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5710171A (en) * 1995-05-24 1998-01-20 Merck & Co., Inc. Bisphenyl inhibitors of farnesyl-protein transferase
US5972984A (en) * 1995-06-06 1999-10-26 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US5756528A (en) * 1995-06-06 1998-05-26 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
GB9517060D0 (en) * 1995-08-17 1995-10-25 Ciba Geigy Ag Acylated oligopeptide derivatives
US5703241A (en) * 1995-10-16 1997-12-30 Merck & Co., Inc. Inhibitor of farnesyl-protein transferase
US6117641A (en) 1996-04-11 2000-09-12 Mitotix, Inc. Assays and reagents for identifying anti-fungal agents and uses related thereto
JP2001513622A (ja) 1996-04-11 2001-09-04 マイトティックス インコーポレーテッド 抗菌剤の同定のためのアッセイおよび試薬、並びにそれらに関連する利用
US6727082B1 (en) 1996-04-11 2004-04-27 Gpc Biotech Inc. Assays and reagents for identifying anti-fungal agents, and uses related thereto
US6307090B1 (en) 1999-01-22 2001-10-23 The United States Of America As Represented By The Department Of Health And Human Services Acylated oligopeptide derivatives having cell signal inhibiting activity
WO2000056760A1 (en) 1999-03-23 2000-09-28 The United States Of America, Represented By Secretary, Department Of Health And Human Services Phenylalanine derivatives
US7226991B1 (en) 1999-03-23 2007-06-05 United States Of America, Represented By The Secretary, Department Of Health And Human Services Phenylalanine derivatives
US7871981B2 (en) 1999-10-22 2011-01-18 The United States Of America As Represented By The Department Of Health And Human Services Inhibition of cell motility, angiogenesis, and metastasis
AU780697B2 (en) 1999-10-22 2005-04-14 Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The Inhibition of cell motility and angiogenesis by inhibitors of the GRB2 SH2-domain
US7425537B2 (en) 2000-08-22 2008-09-16 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services SH2 domain binding inhibitors
WO2002016407A2 (en) 2000-08-22 2002-02-28 The Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services Sh2 domain binding inhibitors
US20050119163A1 (en) 2003-09-18 2005-06-02 The Government Of The United States Of America, As Represented By The Secretary, SH2 domain binding inhibitors
US8362075B2 (en) 2005-05-17 2013-01-29 Merck Sharp & Dohme Corp. Cyclohexyl sulphones for treatment of cancer
TW200804345A (en) 2005-08-30 2008-01-16 Novartis Ag Substituted benzimidazoles and methods of preparation
GB0603041D0 (en) 2006-02-15 2006-03-29 Angeletti P Ist Richerche Bio Therapeutic compounds
DK2010528T3 (en) 2006-04-19 2018-01-15 Novartis Ag 6-O-Substituted Benzoxazole and Benzothiazole Compounds and Methods for Inhibiting CSF-1R Signaling
US8173629B2 (en) 2006-09-22 2012-05-08 Merck Sharp & Dohme Corp. Method of treatment using fatty acid synthesis inhibitors
US20110218176A1 (en) 2006-11-01 2011-09-08 Barbara Brooke Jennings-Spring Compounds, methods, and treatments for abnormal signaling pathways for prenatal and postnatal development
EA016079B1 (ru) 2007-01-10 2012-01-30 Институто Ди Ричерке Ди Биолоджиа Молеколаре П. Анджелетти Спа Амидзамещенные индазолы в качестве ингибиторов поли(adp-рибоза)полимеразы (parp)
ES2431163T3 (es) 2007-03-01 2013-11-25 Novartis Ag Inhibidores de PIM quinasa y métodos para su uso
BRPI0812159A2 (pt) 2007-05-21 2017-05-02 Novartis Ag inibidores de csf-1r, composições e métodos de uso
AU2008269154B2 (en) 2007-06-27 2014-06-12 Merck Sharp & Dohme Llc 4-carboxybenzylamino derivatives as histone deacetylase inhibitors
WO2010114780A1 (en) 2009-04-01 2010-10-07 Merck Sharp & Dohme Corp. Inhibitors of akt activity
EP2440058A4 (de) 2009-06-12 2012-11-21 Dana Farber Cancer Inst Inc Verschmolzene heterozyklische verbindungen und anwendungen davon
JP5099731B1 (ja) 2009-10-14 2012-12-19 メルク・シャープ・アンド・ドーム・コーポレーション p53活性を増大する置換ピペリジン及びその使用
EP2937345B1 (de) 2009-12-29 2018-03-21 Dana-Farber Cancer Institute, Inc. Typ-ii-raf-kinase-hemmer
BR112012023021A2 (pt) 2010-03-16 2016-05-31 Dana Farber Cancer Inst Inc compostos de indazol e seus usos
EP2584903B1 (de) 2010-06-24 2018-10-24 Merck Sharp & Dohme Corp. Neue heterozyklische verbindungen als erk-hemmer
AU2011285909B2 (en) 2010-08-02 2016-11-10 Sirna Therapeutics, Inc. RNA interference mediated inhibition of catenin (cadherin-associated protein), beta 1 (CTNNB1) gene expression using short interfering nucleic acid (siNA)
EP2606134B1 (de) 2010-08-17 2019-04-10 Sirna Therapeutics, Inc. Rna-interferenz-vermittelte hemmung der hepatitis b-virus (hbv)-genexpression mittels kurzer interferierender nukleinsäure (sina)
US8883801B2 (en) 2010-08-23 2014-11-11 Merck Sharp & Dohme Corp. Substituted pyrazolo[1,5-a]pyrimidines as mTOR inhibitors
EP2613782B1 (de) 2010-09-01 2016-11-02 Merck Sharp & Dohme Corp. Indazolderivate als erk-hemmer
US9242981B2 (en) 2010-09-16 2016-01-26 Merck Sharp & Dohme Corp. Fused pyrazole derivatives as novel ERK inhibitors
EP3766975A1 (de) 2010-10-29 2021-01-20 Sirna Therapeutics, Inc. Rna-interferenz-vermittelte inhibition von genexpression unter verwendung kurzer interferierender nukleinsäure (sina)
EP2654748B1 (de) 2010-12-21 2016-07-27 Merck Sharp & Dohme Corp. Indazolderivate als erk-hemmer
EP2699567A1 (de) 2011-04-21 2014-02-26 Merck Sharp & Dohme Corp. Hemmer des insulinähnlichen wachstumsfaktor-1-rezeptors
WO2013063214A1 (en) 2011-10-27 2013-05-02 Merck Sharp & Dohme Corp. Novel compounds that are erk inhibitors
WO2013074986A1 (en) 2011-11-17 2013-05-23 Dana-Farber Cancer Institute, Inc. Inhibitors of c-jun-n-terminal kinase (jnk)
EP3358013B1 (de) 2012-05-02 2020-06-24 Sirna Therapeutics, Inc. Sina-zusammensetzungen
KR20150060724A (ko) 2012-09-28 2015-06-03 머크 샤프 앤드 돔 코포레이션 Erk 억제제인 신규 화합물
US10112927B2 (en) 2012-10-18 2018-10-30 Dana-Farber Cancer Institute, Inc. Inhibitors of cyclin-dependent kinase 7 (CDK7)
US10000483B2 (en) 2012-10-19 2018-06-19 Dana-Farber Cancer Institute, Inc. Bone marrow on X chromosome kinase (BMX) inhibitors and uses thereof
US9758522B2 (en) 2012-10-19 2017-09-12 Dana-Farber Cancer Institute, Inc. Hydrophobically tagged small molecules as inducers of protein degradation
DK2925888T3 (en) 2012-11-28 2017-12-18 Merck Sharp & Dohme COMPOSITIONS AND METHODS OF CANCER TREATMENT
EP2935263B1 (de) 2012-12-20 2018-12-05 Merck Sharp & Dohme Corp. Substituierte imidazopyridine als hdm2 inhibitoren
US9540377B2 (en) 2013-01-30 2017-01-10 Merck Sharp & Dohme Corp. 2,6,7,8 substituted purines as HDM2 inhibitors
WO2015034925A1 (en) 2013-09-03 2015-03-12 Moderna Therapeutics, Inc. Circular polynucleotides
WO2015058140A1 (en) 2013-10-18 2015-04-23 Dana-Farber Cancer Institute, Inc. Polycyclic inhibitors of cyclin-dependent kinase 7 (cdk7)
WO2015058126A1 (en) 2013-10-18 2015-04-23 Syros Pharmaceuticals, Inc. Heteroaromatic compounds useful for the treatment of prolferative diseases
WO2015164604A1 (en) 2014-04-23 2015-10-29 Dana-Farber Cancer Institute, Inc. Hydrophobically tagged janus kinase inhibitors and uses thereof
US10017477B2 (en) 2014-04-23 2018-07-10 Dana-Farber Cancer Institute, Inc. Janus kinase inhibitors and uses thereof
JO3589B1 (ar) 2014-08-06 2020-07-05 Novartis Ag مثبطات كيناز البروتين c وطرق استخداماتها
AU2015371251B2 (en) 2014-12-23 2020-06-11 Dana-Farber Cancer Institute, Inc. Inhibitors of cyclin-dependent kinase 7 (CDK7)
CN107427521B (zh) 2015-03-27 2021-08-03 达纳-法伯癌症研究所股份有限公司 细胞周期蛋白依赖性激酶的抑制剂
EP3307728A4 (de) 2015-06-12 2019-07-17 Dana Farber Cancer Institute, Inc. Kombinationstherapie von transkriptionshemmern und kinasehemmern
JP7028766B2 (ja) 2015-09-09 2022-03-02 ダナ-ファーバー キャンサー インスティテュート, インコーポレイテッド サイクリン依存性キナーゼの阻害剤
JOP20190055A1 (ar) 2016-09-26 2019-03-24 Merck Sharp & Dohme أجسام مضادة ضد cd27
WO2018071283A1 (en) 2016-10-12 2018-04-19 Merck Sharp & Dohme Corp. Kdm5 inhibitors
WO2018190719A2 (en) 2017-04-13 2018-10-18 Aduro Biotech Holdings, Europe B.V. Anti-sirp alpha antibodies
US11098059B2 (en) 2017-11-08 2021-08-24 Merck Sharp & Dohme Corp. PRMT5 inhibitors
WO2019094311A1 (en) 2017-11-08 2019-05-16 Merck Sharp & Dohme Corp. Prmt5 inhibitors
US10311444B1 (en) 2017-12-02 2019-06-04 M-Fire Suppression, Inc. Method of providing class-A fire-protection to wood-framed buildings using on-site spraying of clean fire inhibiting chemical liquid on exposed interior wood surfaces of the wood-framed buildings, and mobile computing systems for uploading fire-protection certifications and status information to a central database and remote access thereof by firefighters on job site locations during fire outbreaks on construction sites
WO2019148412A1 (en) 2018-02-01 2019-08-08 Merck Sharp & Dohme Corp. Anti-pd-1/lag3 bispecific antibodies
JP7590185B2 (ja) 2018-06-25 2024-11-26 ダナ-ファーバー キャンサー インスティテュート, インコーポレイテッド Taireファミリーキナーゼインヒビターおよびそれらの使用
WO2020033285A1 (en) 2018-08-07 2020-02-13 Merck Sharp & Dohme Corp. Prmt5 inhibitors
EP3833668B1 (de) 2018-08-07 2025-03-19 Merck Sharp & Dohme LLC Prmt5-inhibitoren
EP3833667B1 (de) 2018-08-07 2024-03-13 Merck Sharp & Dohme LLC Prmt5-inhibitoren
BR112021002267A8 (pt) 2018-08-07 2023-02-07 Merck Sharp & Dohme Inibidores de prmt5
WO2020140098A1 (en) 2018-12-28 2020-07-02 Dana-Farber Cancer Institute, Inc. Inhibitors of cyclin-dependent kinase 7 and uses thereof
EP4076460B1 (de) 2019-12-17 2026-01-21 Merck Sharp & Dohme LLC 1,4-dihydro-2h-spiro[isoquinoline-3,4'-piperidin]-derivate als prmt5 inhibitoren zur behandlung von krebs
BR112022012015A2 (pt) 2019-12-17 2022-08-30 Merck Sharp & Dohme Llc Inibidores de prmt5
JP2026509792A (ja) 2023-03-02 2026-03-25 カルツィムン ビオテック ゲゼルシャフト ミット ベシュレンクテル ハフツング がん及び/又は急性炎症性疾患を診断するための手段及び方法
WO2026027944A1 (en) 2024-07-30 2026-02-05 Sairopa B.V. Anti-sirp alpha antibody formulations and uses thereof

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0528486A2 (de) * 1991-08-16 1993-02-24 Merck & Co. Inc. Nicht-Substrat Inhibitor des Farnesyl-Protein-Transferases

Also Published As

Publication number Publication date
ATE200677T1 (de) 2001-05-15
LV12771A (lv) 2001-12-20
CA2173590A1 (en) 1995-05-04
NZ275037A (en) 1998-01-26
DK0725790T3 (da) 2001-06-11
AU8051394A (en) 1995-05-22
EP0725790B1 (de) 2001-04-18
AU682906B2 (en) 1997-10-23
FI961621A7 (fi) 1996-04-12
JPH09504295A (ja) 1997-04-28
WO1995011917A1 (en) 1995-05-04
DE69427127T2 (de) 2001-10-04
EP0725790A1 (de) 1996-08-14
KR100378615B1 (ko) 2003-10-10
PT725790E (pt) 2001-08-30
FI961621A0 (fi) 1996-04-12
LV12771B (en) 2002-03-20
DE69427127D1 (de) 2001-05-23
GR3036188T3 (en) 2001-10-31
ES2157994T3 (es) 2001-09-01

Similar Documents

Publication Publication Date Title
FI961621A7 (fi) Proteiini:farnesyylitranseraasin substituoidut tetra- ja pentapeptidi- inhibiittorit
FI941519L (fi) Farnesyyliproteiinitransferaasin heterosyklisiä inhibiittoreita
FI961819A7 (fi) Proteiini:farnesyylitransferaasin substituoidut di- ja tripeptidi-inhi biittorit
EE9700314A (et) Farnesüül-proteiini transferaasi inhibiitorid
FI952010L (fi) Farnesyyliproteiinitransferaasin estäjät
FI952011A7 (fi) Farnesyyliproteiinitransferaasin estäjät
NO983892D0 (no) Inhibitorer for farnesyl-proteintransferase
EE9800146A (et) Farnesüülproteiintransferaasi inhibeerivad (5-imidasolüül)metüül-2-kinolinooni derivaadid
EE9800408A (et) Proteiinfarnesüültransferaasi inhibiitorid
EP0944388A4 (de) Hemmern von farnesyl protein transferase
EP1011669A4 (de) Farnesyl-protein transferase inhibitoren
NO951266D0 (no) Imidazol-holdige inhibitorer for farnesyl-protein-transferase
EP0696593A3 (de) Inhibitoren der farnesyl protein Transferase
EP0783318A4 (de) Inhibitoren der farnesyl-protein-transferase
NO996571L (no) Inhibitorer for farnesyl-protein-transferase
EP0664789A4 (en) Inhibitors of farnesyl protein transferase.
EP0841919A4 (de) Inhibitoren der farnesyl-protein transferase
EP0891360A4 (de) Inhibitoren der farnesyl-protein transferase
EP0891352A4 (de) Inhibitoren der farnesyl-protein transferase
EP1035850A4 (de) Inhibitoren der farnesyl-protein transferase
NO20012961D0 (no) Trisykliske farnesylproteintransferase-inhibitorer
EP1035849A4 (de) Farnesyl-protein transferase inhibitoren
SI0725790T1 (en) Substituted tetra- and pentapeptide inhibitors of protein:farnesyl transferase
ITRM940620A0 (it) "inibitori peptidici di farnesil proteina transferasi"
ZA941902B (en) Heterocyclic inhibitors of farnesyl protein transferase