CN107011358B - 新的烷化剂 - Google Patents

新的烷化剂 Download PDF

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Publication number
CN107011358B
CN107011358B CN201610942350.9A CN201610942350A CN107011358B CN 107011358 B CN107011358 B CN 107011358B CN 201610942350 A CN201610942350 A CN 201610942350A CN 107011358 B CN107011358 B CN 107011358B
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methyl
indol
compound
carbonyl
formula
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CN107011358A (zh
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I·伯利亚
M·卡鲁索
V·卢皮
P·奥西尼
M·萨尔萨
A·潘泽利
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Nerviano Medical Sciences SRL
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic 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
    • A61K31/407—Heterocyclic 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 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic 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
    • A61K31/4353—Heterocyclic 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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—Heterocyclic 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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/05—Dipeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/06—Tripeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/545—Heterocyclic compounds
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
    • 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
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • 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
    • C07K5/08—Tripeptides
    • C07K5/0802—Tripeptides with the first amino acid being neutral
    • C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
CN201610942350.9A 2012-04-05 2013-03-28 新的烷化剂 Active CN107011358B (zh)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
EP12163459 2012-04-05
EP12163459.6 2012-04-05
EP12176162 2012-07-12
EP12176162.1 2012-07-12
CN201380016674.4A CN104220442B (zh) 2012-04-05 2013-03-28 烷化剂

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CN107011358A CN107011358A (zh) 2017-08-04
CN107011358B true CN107011358B (zh) 2020-05-05

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US (2) US9527863B2 (enExample)
EP (2) EP3587426B1 (enExample)
JP (2) JP6314128B2 (enExample)
CN (2) CN107011358B (enExample)
DK (1) DK2836494T3 (enExample)
ES (2) ES2755719T3 (enExample)
HR (1) HRP20221356T1 (enExample)
HU (1) HUE060655T2 (enExample)
RU (1) RU2632206C2 (enExample)
WO (1) WO2013149948A1 (enExample)

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Publication number Priority date Publication date Assignee Title
JP6314128B2 (ja) 2012-04-05 2018-04-18 ネルビアーノ・メデイカル・サイエンシーズ・エツセ・エルレ・エルレ 新たなアルキル化剤
CN104203956B (zh) * 2012-04-05 2017-03-29 内尔维阿诺医学科学有限公司 用于治疗癌症的功能化的噻吩并吲哚衍生物
EP3049420B1 (en) * 2013-09-25 2019-05-15 Nerviano Medical Sciences S.r.l. Thieno[2,3-e]indole derivatives as new antitumor agents
TWI712605B (zh) 2015-03-20 2020-12-11 美商輝瑞股份有限公司 含有ｃｔｉ藥效基團之雙功能性細胞毒性劑
US10174048B2 (en) * 2015-07-21 2019-01-08 Nerviano Medical Sciences S.R.L. Asymmetric process for the preparation of thieno-indoles derivatives
EP3165237B1 (en) 2015-11-03 2018-12-19 Industrial Technology Research Institute Antibody-drug conjugate (adc) and method for forming the same
JP7023933B2 (ja) * 2016-08-19 2022-02-22 ブリストル－マイヤーズ スクイブ カンパニー セコ－シクロプロパピロロインドール化合物、その抗体－薬物コンジュゲート、ならびに製造および使用方法
US20230355598A1 (en) * 2020-09-09 2023-11-09 Clinuvel (UK) Ltd. Pyrrolidine compounds to treat xeroderma pigmentosum

Citations (4)

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US4443465A (en) * 1981-05-12 1984-04-17 Imperial Chemical Industries Plc Aldose reductase inhibitory pyrrole derivatives
GB2344818A (en) * 1998-12-16 2000-06-21 Pharmacia & Upjohn Spa Anti-tumour thieno-indole derivatives
CN1437485A (zh) * 2000-06-23 2003-08-20 法玛西雅意大利公司 包含取代的丙烯酰基偏端霉素衍生物和烷基化剂的抗肿瘤联合疗法
CN1946395A (zh) * 2004-02-03 2007-04-11 辉瑞意大利有限公司 用作激酶抑制剂的1H－噻吩并[2,3－c]吡唑衍生物

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US5659022A (en) * 1996-01-05 1997-08-19 Epoch Pharmaceuticals, Inc. Oligonucleotide-cyclopropapyrroloindole conjugates as sequence specific hybridization and crosslinking agents for nucleic acids
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CN104203956B (zh) * 2012-04-05 2017-03-29 内尔维阿诺医学科学有限公司 用于治疗癌症的功能化的噻吩并吲哚衍生物

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Publication number Priority date Publication date Assignee Title
US4443465A (en) * 1981-05-12 1984-04-17 Imperial Chemical Industries Plc Aldose reductase inhibitory pyrrole derivatives
GB2344818A (en) * 1998-12-16 2000-06-21 Pharmacia & Upjohn Spa Anti-tumour thieno-indole derivatives
CN1437485A (zh) * 2000-06-23 2003-08-20 法玛西雅意大利公司 包含取代的丙烯酰基偏端霉素衍生物和烷基化剂的抗肿瘤联合疗法
CN1946395A (zh) * 2004-02-03 2007-04-11 辉瑞意大利有限公司 用作激酶抑制剂的1H－噻吩并[2,3－c]吡唑衍生物

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US10071074B2 (en) 2018-09-11
US20150051154A1 (en) 2015-02-19
EP3587426A1 (en) 2020-01-01
JP2018070599A (ja) 2018-05-10
RU2014143994A (ru) 2016-05-27
HUE060655T2 (hu) 2023-04-28
ES2929759T3 (es) 2022-12-01
HK1203957A1 (en) 2015-11-06
CN107011358A (zh) 2017-08-04
DK2836494T3 (da) 2019-11-11
ES2755719T3 (es) 2020-04-23
EP3587426B1 (en) 2022-08-10
WO2013149948A1 (en) 2013-10-10
HRP20221356T1 (hr) 2022-12-23
RU2632206C2 (ru) 2017-10-03
CN104220442B (zh) 2016-11-23
CN104220442A (zh) 2014-12-17
JP2015514101A (ja) 2015-05-18
US20170071907A1 (en) 2017-03-16
US9527863B2 (en) 2016-12-27
EP2836494A1 (en) 2015-02-18
JP6314128B2 (ja) 2018-04-18
EP2836494B1 (en) 2019-08-21

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