TWI543988B - 結合於細胞凋亡抑制蛋白(iap)之桿狀病毒iap重複序列(bir)區域之化合物 - Google Patents

結合於細胞凋亡抑制蛋白(iap)之桿狀病毒iap重複序列(bir)區域之化合物 Download PDF

Info

Publication number
TWI543988B
TWI543988B TW103145747A TW103145747A TWI543988B TW I543988 B TWI543988 B TW I543988B TW 103145747 A TW103145747 A TW 103145747A TW 103145747 A TW103145747 A TW 103145747A TW I543988 B TWI543988 B TW I543988B
Authority
TW
Taiwan
Prior art keywords
alkyl
group
compound
aryl
heteroaryl
Prior art date
Application number
TW103145747A
Other languages
English (en)
Chinese (zh)
Other versions
TW201538520A (zh
Inventor
艾倫 布達爾
派翠克 布瑞爾
詹姆士B 捷昆斯
約翰W 吉拉德
阿萊恩 勞倫特
Original Assignee
科學製藥股份有限公司
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 科學製藥股份有限公司 filed Critical 科學製藥股份有限公司
Publication of TW201538520A publication Critical patent/TW201538520A/zh
Application granted granted Critical
Publication of TWI543988B publication Critical patent/TWI543988B/zh

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K5/00Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08Tripeptides
    • C07K5/0802Tripeptides with the first amino acid being neutral
    • C07K5/0812Tripeptides with the first amino acid being neutral and aromatic or cycloaliphatic
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/4025Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/04Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/08Peptides having 5 to 11 amino acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/1703Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • A61K38/1709Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • A61K38/1761Apoptosis related proteins, e.g. Apoptotic protease-activating factor-1 (APAF-1), Bax, Bax-inhibitory protein(s)(BI; bax-I), Myeloid cell leukemia associated protein (MCL-1), Inhibitor of apoptosis [IAP] or Bcl-2
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/06Immunosuppressants, e.g. drugs for graft rejection
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D207/00Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/14Nitrogen atoms not forming part of a nitro radical
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D207/00Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/16Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K5/00Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08Tripeptides
    • C07K5/0802Tripeptides with the first amino acid being neutral
    • C07K5/0804Tripeptides with the first amino acid being neutral and aliphatic
    • C07K5/0806Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K5/00Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08Tripeptides
    • C07K5/0802Tripeptides with the first amino acid being neutral
    • C07K5/0804Tripeptides with the first amino acid being neutral and aliphatic
    • C07K5/0808Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K5/00Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08Tripeptides
    • C07K5/0802Tripeptides with the first amino acid being neutral
    • C07K5/0804Tripeptides with the first amino acid being neutral and aliphatic
    • C07K5/081Tripeptides with the first amino acid being neutral and aliphatic the side chain containing O or S as heteroatoms, e.g. Cys, Ser
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K7/00Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04Linear peptides containing only normal peptide links
    • C07K7/06Linear peptides containing only normal peptide links having 5 to 11 amino acids

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Immunology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Marine Sciences & Fisheries (AREA)
  • Zoology (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Transplantation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pyrrole Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)
TW103145747A 2006-03-16 2007-03-15 結合於細胞凋亡抑制蛋白(iap)之桿狀病毒iap重複序列(bir)區域之化合物 TWI543988B (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US78252306P 2006-03-16 2006-03-16
US87699406P 2006-12-26 2006-12-26

Publications (2)

Publication Number Publication Date
TW201538520A TW201538520A (zh) 2015-10-16
TWI543988B true TWI543988B (zh) 2016-08-01

Family

ID=38509005

Family Applications (2)

Application Number Title Priority Date Filing Date
TW103145747A TWI543988B (zh) 2006-03-16 2007-03-15 結合於細胞凋亡抑制蛋白(iap)之桿狀病毒iap重複序列(bir)區域之化合物
TW096108935A TWI504597B (zh) 2006-03-16 2007-03-15 結合於細胞凋亡抑制蛋白(iap)之桿狀病毒iap重複序列(bir)區域之化合物

Family Applications After (1)

Application Number Title Priority Date Filing Date
TW096108935A TWI504597B (zh) 2006-03-16 2007-03-15 結合於細胞凋亡抑制蛋白(iap)之桿狀病毒iap重複序列(bir)區域之化合物

Country Status (15)

Country Link
US (5) US7579320B2 (enExample)
EP (1) EP2004600A4 (enExample)
JP (1) JP5419468B2 (enExample)
KR (1) KR101446907B1 (enExample)
AU (1) AU2007224932B2 (enExample)
BR (1) BRPI0709610A2 (enExample)
CA (1) CA2581960C (enExample)
IL (1) IL193951A (enExample)
MX (1) MX2008011837A (enExample)
NO (1) NO20083868L (enExample)
NZ (1) NZ571577A (enExample)
PH (1) PH12014502420B1 (enExample)
SG (1) SG170739A1 (enExample)
TW (2) TWI543988B (enExample)
WO (1) WO2007104162A1 (enExample)

Families Citing this family (46)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2475207T3 (es) * 2004-07-15 2014-07-10 Tetralogic Pharmaceuticals Corporation Compuestos de unión a IAP
ATE477254T1 (de) 2004-12-20 2010-08-15 Genentech Inc Pyrrolidine als inhibitoren von iap
EA012810B1 (ru) 2005-02-25 2009-12-30 Тетралоджик Фармасеутикалс Димерные ингибиторы ингибиторов белков апоптоза (iap)
CA2607940C (en) 2005-05-18 2009-12-15 Aegera Therapeutics Inc. Bir domain binding compounds
US20100256046A1 (en) * 2009-04-03 2010-10-07 Tetralogic Pharmaceuticals Corporation Treatment of proliferative disorders
KR20080067357A (ko) 2005-10-25 2008-07-18 에게라 쎄라퓨틱스 인코포레이티드 Iap bir 도메인 결합 화합물
RU2451025C2 (ru) 2005-12-19 2012-05-20 Дженентек, Инк. Ингибиторы iap
TWI543988B (zh) 2006-03-16 2016-08-01 科學製藥股份有限公司 結合於細胞凋亡抑制蛋白(iap)之桿狀病毒iap重複序列(bir)區域之化合物
US7807699B2 (en) * 2006-03-21 2010-10-05 Joyant Pharmaceuticals, Inc. Dimeric pyrrolidine amide-containing small molecule apoptosis promoters
MY159563A (en) * 2006-05-16 2017-01-13 Pharmascience Inc Iap bir domain binding compounds
WO2008014252A2 (en) * 2006-07-24 2008-01-31 Tetralogic Pharmaceuticals Corporation Iap inhibitors
AU2007276760B2 (en) * 2006-07-24 2012-01-19 Tetralogic Pharmaceuticals Corporation Dimeric IAP antagonists
WO2008014229A2 (en) * 2006-07-24 2008-01-31 Tetralogic Pharmaceuticals Corporation Dimeric iap inhibitors
BRPI0810178A2 (pt) * 2007-04-12 2014-09-23 Joyant Pharmaceuticals Inc Dímeros e trímeros miméticos de smac úteis como agentes anticâncer
BRPI0809867A2 (pt) * 2007-04-30 2014-09-30 Genentech Inc Composto, método de indução da apoptose em uma célula, método de sensibilização de uma célula para um sinal apoptótico, método para inibir a ligação de uma proteína iap a uma proteína caspase e métodos
US20110008802A1 (en) * 2007-05-07 2011-01-13 Tetralogic Pharmaceuticals Corp. TNFalpha GENE EXPRESSION AS A BIOMARKER OF SENSITIVITY TO ANTAGONISTS OF INHIBITOR OF APOPTOSIS PROTEINS
US20100203012A1 (en) * 2007-05-30 2010-08-12 Aegera Therapeutics, Inc. Iap bir domain binding compounds
CN102099357B (zh) 2008-04-23 2014-07-02 里格尔药品股份有限公司 用于治疗代谢障碍的甲酰胺化合物
US20110117081A1 (en) * 2008-05-05 2011-05-19 Aegera Therapeutics, Inc. Functionalized pyrrolidines and use thereof as iap inhibitors
US20110171171A1 (en) * 2008-06-27 2011-07-14 Aegera Therapeutics, Inc. Bridged secondary amines and use thereof as iap bir domain binding compounds
CA2730448A1 (en) 2008-08-02 2010-02-11 Genentech, Inc. Inhibitors of iap
US20120009141A1 (en) * 2008-08-07 2012-01-12 Pharmascience Inc. Functionalized pyrrolidines and use thereof as iap inhibitors
US20110177060A1 (en) * 2008-09-19 2011-07-21 Aegera Therapeutics, Inc. Iap bir domain binding compounds
US20100317593A1 (en) * 2009-06-12 2010-12-16 Astrazeneca Ab 2,3-dihydro-1h-indene compounds
US8283372B2 (en) 2009-07-02 2012-10-09 Tetralogic Pharmaceuticals Corp. 2-(1H-indol-3-ylmethyl)-pyrrolidine dimer as a SMAC mimetic
EP2784076A1 (en) 2009-10-28 2014-10-01 Joyant Pharmaceuticals, Inc. Dimeric SMAC mimetics
KR20120140658A (ko) 2010-02-12 2012-12-31 파마사이언스 인크. Iap bir 도메인 결합 화합물
UY33236A (es) 2010-02-25 2011-09-30 Novartis Ag Inhibidores dimericos de las iap
WO2012052758A1 (en) * 2010-10-22 2012-04-26 Astrazeneca Ab Response biomarkers for iap antagonists in human cancers
UY33794A (es) 2010-12-13 2012-07-31 Novartis Ag Inhibidores diméricos de las iap
US10478498B2 (en) 2014-06-20 2019-11-19 Reform Biologics, Llc Excipient compounds for biopolymer formulations
US11357857B2 (en) 2014-06-20 2022-06-14 Comera Life Sciences, Inc. Excipient compounds for protein processing
US20160074515A1 (en) 2014-06-20 2016-03-17 Reform Biologics, Llc Viscosity-reducing excipient compounds for protein formulations
CA2916970A1 (en) * 2016-01-08 2017-07-08 Pharmascience Inc. A smac mimetic compound for use in the treatment of proliferative diseases
JP2020528902A (ja) * 2017-07-25 2020-10-01 へパジーン セラピューティクス インコーポレイテッド アポトーシスタンパク質の二量体ペプチド阻害剤
CN117130035A (zh) * 2017-08-18 2023-11-28 南京中硼联康医疗科技有限公司 生物剂量计及具有其的中子捕获治疗系统
WO2019180627A1 (en) * 2018-03-21 2019-09-26 Piramal Enterprises Limited AN IMPROVED ASYMMETRIC SYNTHESIS OF alpha-(DIARYLMETHYL) ALKYL AMINES
EP3831811A4 (en) 2018-07-31 2022-04-20 Fimecs, Inc. HETEROCYCLIC COMPOUND
KR20210096633A (ko) * 2018-11-29 2021-08-05 리폼 바이오로직스, 엘엘씨 단백질 처리를 위한 부형제 화합물
JP7455141B2 (ja) * 2019-04-05 2024-03-25 へパジーン セラピューティクス (エイチケイ) リミテッド アポトーシスタンパク質の阻害剤の二価拮抗薬
WO2020223403A1 (en) * 2019-04-29 2020-11-05 The Regents Of The University Of California Anticancer smac derivatives
WO2021020585A1 (ja) 2019-07-31 2021-02-04 ファイメクス株式会社 複素環化合物
MX2022008874A (es) 2020-01-20 2022-08-11 Astrazeneca Ab Inhibidores de la tirosina cinasa del receptor del factor de creciminto epidermico para el tratamiento del cancer.
IL305835A (en) 2021-03-15 2023-11-01 Maze Therapeutics Inc Glycogen synthase 1 (GYS1) inhibitors and methods of using them
WO2023127331A1 (ja) * 2021-12-27 2023-07-06 株式会社トクヤマ ペプチド製造方法、保護基の除去方法、除去剤、及びベンジル化合物
JP7260725B1 (ja) * 2021-12-27 2023-04-18 株式会社トクヤマ ペプチド製造方法、保護基の除去方法、及び除去剤

Family Cites Families (77)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US219140A (en) * 1879-09-02 Improvement in the art of ornamenting metallic foils
US207525A (en) * 1878-08-27 Improvement in car-coupling draw-bars
US32437A (en) * 1861-05-28 Improvement in steam-plows
US93428A (en) * 1869-08-10 Improvement in spurs for excelsior-machines
US194741A (en) * 1877-08-28 Improvement in circular looms
US89896A (en) * 1869-05-11 Improvement in bee-hive
US180828A (en) * 1876-08-08 Improvement in horse-powers
US25347A (en) * 1859-09-06 Improvement
US211627A (en) * 1879-01-28 Improvement in perforating-stamps
US69812A (en) * 1867-10-15 Improved refrigerator
US93429A (en) * 1869-08-10 Improvement in flasks for vulcanizing rubber plates for setting teeth
US258581A (en) * 1882-05-30 husset
JPH0680077B2 (ja) 1985-02-08 1994-10-12 サントリー株式会社 プロリンエンドペプチダ−ゼインヒビタ−活性を有する新規ペプチド化合物
JPH04208299A (ja) 1990-11-30 1992-07-29 Ajinomoto Co Inc プロリルエンドペプチターゼ阻害ペプチド
US5817667A (en) * 1991-04-17 1998-10-06 University Of Georgia Research Foudation Compounds and methods for the treatment of cancer
US5595756A (en) * 1993-12-22 1997-01-21 Inex Pharmaceuticals Corporation Liposomal compositions for enhanced retention of bioactive agents
AUPN727595A0 (en) * 1995-12-22 1996-01-18 Walter And Eliza Hall Institute Of Medical Research, The Therapeutic compositions
JP4208299B2 (ja) 1998-08-19 2009-01-14 東レ株式会社 金属板貼合わせ成形加工用ポリエステルフィルム
US6110691A (en) * 2000-01-06 2000-08-29 Board Of Regents, The University Of Texas System Activators of caspases
US6608026B1 (en) * 2000-08-23 2003-08-19 Board Of Regents, The University Of Texas System Apoptotic compounds
WO2002026775A2 (en) 2000-09-29 2002-04-04 Trustees Of Princeton University Compositions and methods for regulating apoptosis
WO2004007529A2 (en) 2002-07-15 2004-01-22 The Trustees Of Princeton University Iap binding compounds
US6992063B2 (en) * 2000-09-29 2006-01-31 The Trustees Of Princeton University Compositions and method for regulating apoptosis
WO2002030959A2 (en) 2000-10-13 2002-04-18 Abbott Laboratories Peptides derived from smac (diablo) and methods of use therefor
JP2004536079A (ja) * 2001-05-16 2004-12-02 アンテックスファーマ・インコーポレーテッド 置換1−ベンズアゼピンおよびその誘導体
US20050176649A1 (en) 2001-05-31 2005-08-11 Mclendon George Iap binding peptides and assays for identifying compounds that bind iap
CA2450659A1 (en) * 2001-06-19 2002-12-27 Altana Pharma Ag Tryptase inhibitors
US20060258581A1 (en) 2001-11-21 2006-11-16 Reed John C Methods and composition for derepressions of IAP-inhibited caspase
EP1495124A2 (en) 2002-04-17 2005-01-12 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Smac-peptides as therapeutics against cancer and autoimmune diseases
JP4541882B2 (ja) * 2002-07-02 2010-09-08 ノバルティス アーゲー Smacタンパク質のアポトーシスタンパク質阻害物質(iap)との結合に対するペプチド阻害剤
FR2844271A1 (fr) * 2002-09-09 2004-03-12 Oreal Derives bis-paraphenylenediamine a groupement pyrrolidinyle et utilisation de ces derives pour la coloration de fibres keratiniques
MXPA05005726A (es) * 2002-11-27 2005-08-16 Irm Llc Metodos y composiciones para inducir apoptosis en celulas de cancer.
US20040180828A1 (en) 2003-01-30 2004-09-16 Yigong Shi Caspase-9 : BIR domain of XIAP complexes and methods of use
JP2007515158A (ja) * 2003-11-13 2007-06-14 ジェネンテック・インコーポレーテッド アポトーシス促進性化合物のスクリーニングのための組成物と方法
WO2005069888A2 (en) 2004-01-16 2005-08-04 The Regents Of The University Of Michigan Smac peptidomimetics and the uses thereof
EP1713542A2 (en) 2004-02-05 2006-10-25 Novartis AG COMBINATION OF (a) A DNA TOPOISOMERASE INHIBITOR AND (b) AN IAP INHIBITOR
CN1926118A (zh) 2004-03-01 2007-03-07 德克萨斯大学董事会 二聚的小分子细胞凋亡增强剂
JP5122275B2 (ja) 2004-03-23 2013-01-16 ジェネンテック, インコーポレイテッド Iapのアザビシクロ−オクタンインヒビター
ME02125B (me) 2004-04-07 2013-04-30 Novartis Ag Inhibitori protein apoptoze (iap)
WO2006014361A1 (en) * 2004-07-02 2006-02-09 Genentech, Inc. Inhibitors of iap
US7674787B2 (en) 2004-07-09 2010-03-09 The Regents Of The University Of Michigan Conformationally constrained Smac mimetics and the uses thereof
EP2457895A1 (en) 2004-07-12 2012-05-30 Idun Pharmaceuticals, Inc. Tetrapeptide analogs
ES2475207T3 (es) * 2004-07-15 2014-07-10 Tetralogic Pharmaceuticals Corporation Compuestos de unión a IAP
ATE477254T1 (de) 2004-12-20 2010-08-15 Genentech Inc Pyrrolidine als inhibitoren von iap
EA012810B1 (ru) * 2005-02-25 2009-12-30 Тетралоджик Фармасеутикалс Димерные ингибиторы ингибиторов белков апоптоза (iap)
US20070003535A1 (en) 2005-03-17 2007-01-04 Reed John C Methods and compositions for derepression of IAP-inhibited caspase
DE102005017116A1 (de) 2005-04-13 2006-10-26 Novartis Ag Hemmstoffe für Inhibitoren von Apoptose Proteinen (IAP)
CA2607940C (en) 2005-05-18 2009-12-15 Aegera Therapeutics Inc. Bir domain binding compounds
AU2006254538A1 (en) 2005-05-25 2006-12-07 2Curex Aps Compounds modifying apoptosis
BRPI0611922A2 (pt) 2005-06-08 2010-10-05 Novartis Ag compostos orgánicos
AU2006279929A1 (en) * 2005-08-09 2007-02-22 Tetralogic Pharmaceuticals Corporation Treatment of proliferative disorders
KR20080067357A (ko) 2005-10-25 2008-07-18 에게라 쎄라퓨틱스 인코포레이티드 Iap bir 도메인 결합 화합물
RU2451025C2 (ru) 2005-12-19 2012-05-20 Дженентек, Инк. Ингибиторы iap
CA2632256A1 (en) 2005-12-20 2007-07-05 Novartis Ag Combination of an iap-inhibitor and a taxane7
WO2007101347A1 (en) 2006-03-07 2007-09-13 Aegera Therapeutics Inc. Bir domain binding compounds
TWI543988B (zh) 2006-03-16 2016-08-01 科學製藥股份有限公司 結合於細胞凋亡抑制蛋白(iap)之桿狀病毒iap重複序列(bir)區域之化合物
US7807699B2 (en) 2006-03-21 2010-10-05 Joyant Pharmaceuticals, Inc. Dimeric pyrrolidine amide-containing small molecule apoptosis promoters
JP5230610B2 (ja) 2006-05-05 2013-07-10 ザ リージェンツ オブ ザ ユニバーシティ オブ ミシガン 二価smac模倣物およびその使用
MY159563A (en) 2006-05-16 2017-01-13 Pharmascience Inc Iap bir domain binding compounds
US20100056495A1 (en) 2006-07-24 2010-03-04 Tetralogic Pharmaceuticals Corporation Dimeric iap inhibitors
WO2008014238A2 (en) 2006-07-24 2008-01-31 Tetralogic Pharmaceuticals Corporation Dimeric iap inhibitors
AU2007276760B2 (en) 2006-07-24 2012-01-19 Tetralogic Pharmaceuticals Corporation Dimeric IAP antagonists
WO2008014252A2 (en) 2006-07-24 2008-01-31 Tetralogic Pharmaceuticals Corporation Iap inhibitors
US20100113326A1 (en) 2006-07-24 2010-05-06 Tetralogic Pharmaceuticals Corporation Dimeric iap inhibitors
WO2008014229A2 (en) 2006-07-24 2008-01-31 Tetralogic Pharmaceuticals Corporation Dimeric iap inhibitors
PE20110218A1 (es) 2006-08-02 2011-04-01 Novartis Ag DERIVADOS DE 2-OXO-ETIL-AMINO-PROPIONAMIDA-PIRROLIDIN-2-IL-SUSTITUIDOS COMO INHIBIDORES DEL ENLACE DE LA PROTEINA Smac AL INHIBIDOR DE LA PROTEINA DE APOPTOSIS
US8044209B2 (en) 2006-10-12 2011-10-25 Novartis Ag Pyrrolydine derivatives as IAP inhibitors
MX2009004061A (es) 2006-10-19 2009-04-27 Novartis Ag Compuestos organicos.
CN101541325A (zh) 2006-11-28 2009-09-23 诺瓦提斯公司 Iap抑制剂用于治疗急性髓性白血病的用途
RU2456983C2 (ru) 2006-11-28 2012-07-27 Новартис Аг Комбинация ингибиторов iap и flt3
KR20090086582A (ko) 2006-12-07 2009-08-13 노파르티스 아게 유기 화합물
KR20090094461A (ko) 2006-12-19 2009-09-07 제넨테크, 인크. Iap의 이미다조피리딘 억제제
BRPI0810178A2 (pt) 2007-04-12 2014-09-23 Joyant Pharmaceuticals Inc Dímeros e trímeros miméticos de smac úteis como agentes anticâncer
EP2139490B1 (en) 2007-04-13 2014-07-02 The Regents of the University of Michigan Diazo bicyclic smac mimetics and the uses thereof
BRPI0809867A2 (pt) 2007-04-30 2014-09-30 Genentech Inc Composto, método de indução da apoptose em uma célula, método de sensibilização de uma célula para um sinal apoptótico, método para inibir a ligação de uma proteína iap a uma proteína caspase e métodos
US20100203012A1 (en) 2007-05-30 2010-08-12 Aegera Therapeutics, Inc. Iap bir domain binding compounds
EP2058312A1 (en) 2007-11-09 2009-05-13 Universita' degli Studi di Milano SMAC mimetic compounds as apoptosis inducers

Also Published As

Publication number Publication date
TW200800961A (en) 2008-01-01
KR20080112304A (ko) 2008-12-24
MX2008011837A (es) 2009-02-10
RU2008140935A (ru) 2010-04-27
PH12014502420B1 (en) 2017-11-08
KR101446907B1 (ko) 2014-10-06
TW201538520A (zh) 2015-10-16
US20130071411A1 (en) 2013-03-21
EP2004600A4 (en) 2012-05-02
PH12014502420A1 (en) 2015-11-16
NO20083868L (no) 2008-11-06
SG170739A1 (en) 2011-05-30
JP5419468B2 (ja) 2014-02-19
TWI504597B (zh) 2015-10-21
BRPI0709610A2 (pt) 2011-07-19
US8765681B2 (en) 2014-07-01
CA2581960C (en) 2015-11-24
US20080069812A1 (en) 2008-03-20
US7645741B2 (en) 2010-01-12
EP2004600A1 (en) 2008-12-24
CA2581960A1 (en) 2007-09-16
IL193951A (en) 2015-09-24
US20100221261A1 (en) 2010-09-02
JP2009529544A (ja) 2009-08-20
AU2007224932A1 (en) 2007-09-20
AU2007224932B2 (en) 2013-05-23
NZ571577A (en) 2011-09-30
US20140336134A1 (en) 2014-11-13
US7579320B2 (en) 2009-08-25
US9365614B2 (en) 2016-06-14
WO2007104162A1 (en) 2007-09-20
US20080207525A1 (en) 2008-08-28

Similar Documents

Publication Publication Date Title
TWI543988B (zh) 結合於細胞凋亡抑制蛋白(iap)之桿狀病毒iap重複序列(bir)區域之化合物
JP5419685B2 (ja) Iapbirドメイン結合タンパク質
JP4954983B2 (ja) Birドメイン結合化合物
CN102985439B9 (zh) Iap bir结构域结合化合物
JP2009512719A (ja) Iapbirドメイン結合化合物
US20020123468A1 (en) Alpha-ketoamide inhibitors of hepatitis C virus NS3 protease
JP4416501B2 (ja) 2−{[n−(2−アミノ−3−(ヘテロアリールまたはアリール)プロピオニル)−アミノアシル]−アミノ}−アルキルボロン酸誘導体
EP2058312A1 (en) SMAC mimetic compounds as apoptosis inducers
JP2008505976A (ja) テトラペプチド類似体
KR20110028665A (ko) 세린 프로테아제, 특히 c형 간염 바이러스 ns3-ns4 프로테아제의 억제제
WO2009136290A1 (en) Functionalized pyrrolidines and use thereof as iap inhibitors
US7217688B2 (en) Methods and compositions for derepression of IAP-inhibited caspase
EP3127912A1 (en) Tripeptide epoxyketone compound constructed by heterocycle and preparation method and use thereof
TW201141846A (en) Dimeric IAP inhibitors
KR20150042792A (ko) Bir2 및/또는 bir3 억제제로서 아자헤테로사이클
US20240083846A1 (en) Smac mimetics for treatment of cancer, process for preparation and pharmaceutical composition thereof
CN101443309B (zh) Iap bir域结合化合物
EP1864994B1 (en) Par-2 agonist
RU2446170C2 (ru) Соединения, связывающиеся с bir доменом iap
RU2472780C2 (ru) Соединения, связывающие домен bir белков iap
MX2008005477A (en) Iap bir domain binding compounds
WO2011090316A2 (ko) 세포사멸 유도 활성을 갖는 신규 피라지논 유도체 및 이를 포함하는 약학 조성물
HK1112899A (en) Tetrapeptide analogs

Legal Events

Date Code Title Description
MM4A Annulment or lapse of patent due to non-payment of fees