CN104220442B - 烷化剂 - Google Patents

烷化剂 Download PDF

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Publication number
CN104220442B
CN104220442B CN201380016674.4A CN201380016674A CN104220442B CN 104220442 B CN104220442 B CN 104220442B CN 201380016674 A CN201380016674 A CN 201380016674A CN 104220442 B CN104220442 B CN 104220442B
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Prior art keywords
methyl
indol
carbonyl
dihydro
carbamoyl
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CN201380016674.4A
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Chinese (zh)
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CN104220442A (zh
Inventor
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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Nerviano Medical Sciences SRL
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Priority to CN201610942350.9A priority Critical patent/CN107011358B/zh
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    • 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
    • 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
    • C07D495/10—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)
  • Immunology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (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)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
CN201380016674.4A 2012-04-05 2013-03-28 烷化剂 Active CN104220442B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201610942350.9A CN107011358B (zh) 2012-04-05 2013-03-28 新的烷化剂

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
PCT/EP2013/056743 WO2013149948A1 (en) 2012-04-05 2013-03-28 New alkylating agents

Related Child Applications (1)

Application Number Title Priority Date Filing Date
CN201610942350.9A Division CN107011358B (zh) 2012-04-05 2013-03-28 新的烷化剂

Publications (2)

Publication Number Publication Date
CN104220442A CN104220442A (zh) 2014-12-17
CN104220442B true CN104220442B (zh) 2016-11-23

Family

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CN201380016674.4A Active CN104220442B (zh) 2012-04-05 2013-03-28 烷化剂
CN201610942350.9A Active CN107011358B (zh) 2012-04-05 2013-03-28 新的烷化剂

Family Applications After (1)

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Country Status (10)

Country Link
US (2) US9527863B2 (https=)
EP (2) EP2836494B1 (https=)
JP (2) JP6314128B2 (https=)
CN (2) CN104220442B (https=)
DK (1) DK2836494T3 (https=)
ES (2) ES2929759T3 (https=)
HR (1) HRP20221356T1 (https=)
HU (1) HUE060655T2 (https=)
RU (1) RU2632206C2 (https=)
WO (1) WO2013149948A1 (https=)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP6251236B2 (ja) * 2012-04-05 2017-12-20 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 癌を治療するための官能性チエノ−インドール誘導体
WO2013149948A1 (en) 2012-04-05 2013-10-10 Nerviano Medical Sciences S.R.L. New alkylating agents
JP6487422B2 (ja) * 2013-09-25 2019-03-20 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 新しい抗腫瘍剤としてのチエノ［２，３−ｅ］インドール誘導体
US10870706B2 (en) 2015-03-20 2020-12-22 Pfizer Inc. Bifunctional cytotoxic agents containing the CTI pharmacophore
WO2017012924A1 (en) * 2015-07-21 2017-01-26 Nerviano Medical Sciences S.R.L. Asymmetric process for the preparation of thieno-indoles derivatives
JP6486316B2 (ja) 2015-11-03 2019-03-20 財團法人工業技術研究院Ｉｎｄｕｓｔｒｉａｌ Ｔｅｃｈｎｏｌｏｇｙ Ｒｅｓｅａｒｃｈ Ｉｎｓｔｉｔｕｔｅ 抗体−薬物複合体（ａｄｃ）およびそれを形成するための方法
CN109641911B (zh) * 2016-08-19 2023-02-21 百时美施贵宝公司 seco-环丙吡咯并吲哚化合物和其抗体-药物缀合物以及制备和使用方法
EP4221705A1 (en) * 2020-09-09 2023-08-09 Clinuvel (UK) Ltd. Pyrrolidine compounds to treat xeroderma pigmentosum

Citations (4)

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GB2344818A (en) * 1998-12-16 2000-06-21 Pharmacia & Upjohn Spa Anti-tumour thieno-indole derivatives
WO2003026577A2 (en) * 2001-09-24 2003-04-03 Seattle Genetics, Inc. P-amidobenzylethers in drug delivery agents
WO2005112919A2 (en) * 2004-05-19 2005-12-01 Medarex, Inc. Self-immolative linkers and drug conjugates
CN101594862A (zh) * 2006-12-20 2009-12-02 内尔维阿诺医学科学有限公司 作为激酶抑制剂的取代吲唑衍生物

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JP3045706B1 (ja) 1998-09-14 2000-05-29 科学技術振興事業団 Ｄｎａの特定塩基配列をアルキル化する化合物及びその合成法
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WO2013149948A1 (en) 2012-04-05 2013-10-10 Nerviano Medical Sciences S.R.L. New alkylating agents
JP6251236B2 (ja) * 2012-04-05 2017-12-20 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 癌を治療するための官能性チエノ−インドール誘導体

Patent Citations (4)

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Publication number Priority date Publication date Assignee Title
GB2344818A (en) * 1998-12-16 2000-06-21 Pharmacia & Upjohn Spa Anti-tumour thieno-indole derivatives
WO2003026577A2 (en) * 2001-09-24 2003-04-03 Seattle Genetics, Inc. P-amidobenzylethers in drug delivery agents
WO2005112919A2 (en) * 2004-05-19 2005-12-01 Medarex, Inc. Self-immolative linkers and drug conjugates
CN101594862A (zh) * 2006-12-20 2009-12-02 内尔维阿诺医学科学有限公司 作为激酶抑制剂的取代吲唑衍生物

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Also Published As

Publication number Publication date
US10071074B2 (en) 2018-09-11
EP3587426B1 (en) 2022-08-10
CN107011358A (zh) 2017-08-04
JP6314128B2 (ja) 2018-04-18
ES2929759T3 (es) 2022-12-01
US20170071907A1 (en) 2017-03-16
ES2755719T3 (es) 2020-04-23
WO2013149948A1 (en) 2013-10-10
HRP20221356T1 (hr) 2022-12-23
EP2836494B1 (en) 2019-08-21
CN104220442A (zh) 2014-12-17
HUE060655T2 (hu) 2023-04-28
JP2018070599A (ja) 2018-05-10
HK1203957A1 (en) 2015-11-06
DK2836494T3 (da) 2019-11-11
RU2632206C2 (ru) 2017-10-03
JP2015514101A (ja) 2015-05-18
US20150051154A1 (en) 2015-02-19
EP3587426A1 (en) 2020-01-01
EP2836494A1 (en) 2015-02-18
CN107011358B (zh) 2020-05-05
US9527863B2 (en) 2016-12-27
RU2014143994A (ru) 2016-05-27

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