CN110291065A - 一种新的异二氢吲哚衍生物、其药物组合物及应用 - Google Patents

一种新的异二氢吲哚衍生物、其药物组合物及应用 Download PDF

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CN110291065A
CN110291065A CN201880011566.0A CN201880011566A CN110291065A CN 110291065 A CN110291065 A CN 110291065A CN 201880011566 A CN201880011566 A CN 201880011566A CN 110291065 A CN110291065 A CN 110291065A
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ethyl
base
independently
general formula
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CN110291065B (zh
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李文成
廖柏松
张雷
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Kangpu Biopharmaceuticals Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • 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
    • A61K31/40—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
    • A61K31/403—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 carbocyclic rings, e.g. carbazole
    • A61K31/4035—Isoindoles, e.g. phthalimide
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
    • C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
    • C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
    • C07D209/49—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide and having in the molecule an acyl radical containing a saturated three-membered ring, e.g. chrysanthemumic acid esters
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/56—Ring systems containing three or more rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic 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
    • C07D401/02—Heterocyclic 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 two hetero rings
    • C07D401/06—Heterocyclic 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 two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic 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
    • C07D401/02—Heterocyclic 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 two hetero rings
    • C07D401/08—Heterocyclic 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 two hetero rings linked by a carbon chain containing alicyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

Abstract

本发明公开了一种新的异二氢吲哚衍生物、其药物组合物及应用。本发明公开的通式I所示的化合物，其药学上可接受的盐、溶剂化物、晶型、立体异构体、同位素化合物、代谢物或前药，能够调节PDE4或TNF‑α的产生或活性，从而有效的治疗癌症和炎症性疾病。

Description

PCT国内申请，说明书已公开。

Claims (20)

  1. PCT国内申请，权利要求书已公开。
CN201880011566.0A 2017-02-28 2018-02-27 一种新的异二氢吲哚衍生物、其药物组合物及应用 Active CN110291065B (zh)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
CN201710112364 2017-02-28
CN2017101123642 2017-02-28
CN201710725987 2017-08-22
CN2017107259877 2017-08-22
PCT/CN2018/077324 WO2018157779A1 (zh) 2017-02-28 2018-02-27 一种新的异二氢吲哚衍生物、其药物组合物及应用

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US (2) US11337964B2 (zh)
EP (1) EP3590924B1 (zh)
JP (1) JP6942380B2 (zh)
KR (1) KR102318401B1 (zh)
CN (1) CN110291065B (zh)
AU (1) AU2018228541B2 (zh)
CA (1) CA3052516C (zh)
DK (1) DK3590924T3 (zh)
ES (1) ES2902052T3 (zh)
NZ (1) NZ756231A (zh)
PL (1) PL3590924T3 (zh)
RU (1) RU2728829C1 (zh)
WO (1) WO2018157779A1 (zh)
ZA (1) ZA201905098B (zh)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109280027A (zh) * 2018-12-13 2019-01-29 康化（上海）新药研发有限公司 一种5,6-二甲氧基-2-吡啶甲酸的合成方法
CN111777518A (zh) * 2019-04-03 2020-10-16 上海安谱实验科技股份有限公司 一种稳定同位素标记的苯乙醇胺a的合成制备方法
EP3953332A4 (en) 2019-04-12 2023-06-14 C4 Therapeutics, Inc. TRICYCLIC DEGRADATION PRODUCTS FROM IKAROS AND AIOLOS
WO2020246329A1 (ja) * 2019-06-05 2020-12-10 住友化学株式会社 β－ケトスルホン化合物の製造方法
CN110423213B (zh) * 2019-08-22 2021-06-04 上海英诺富成生物科技有限公司 一种阿普斯特衍生物及其制备方法与应用
CN110627694B (zh) * 2019-10-18 2021-06-15 山东邹平大展新材料有限公司 一种回收3-乙氧基-4-甲氧基-α-[(甲基磺酰基)甲基]-苯甲胺的方法
CN112979442A (zh) * 2019-12-12 2021-06-18 上海安谱实验科技股份有限公司 一种稳定同位素标记的甲基香兰素及其合成方法
CN113121404A (zh) * 2019-12-30 2021-07-16 江苏先声药业有限公司 阿普斯特的合成方法
EP4101848A4 (en) * 2020-02-24 2023-07-26 Suzhou Longbotai Pharmaceuticals Co., Ltd. PDE4 INHIBITOR COMPOUND AND MEDICAL USE
CN113527179B (zh) * 2020-04-13 2023-07-07 苏州璞正医药有限公司 链烃取代异吲哚啉-1,3-二酮类pde4抑制剂及其药物用途
CN112898132B (zh) * 2020-10-23 2023-03-14 上海安谱实验科技股份有限公司 一种稳定同位素氘标记的甲基三氯生的合成方法
CN114790164B (zh) 2021-08-13 2022-12-27 苏州璞正医药有限公司 一种取代的异吲哚啉-1,3-二酮类pde4抑制剂及其药物用途
WO2024035626A1 (en) 2022-08-11 2024-02-15 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Halophthalimide compounds and methods of use against tbi, inflammatory disorder, autoimmune disorder, neurodegenerative disease or viral infection

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000025777A1 (en) * 1998-10-30 2000-05-11 Celgene Corporation SUBSTITUTED PHENETHYLSULFONES AND METHOD OF REDUCING TNFαLEVELS
AU2006200033A1 (en) * 1998-10-30 2006-02-02 Celgene Corporation Substituted phenethylsulfones and methods of reducing TNF-alpha levels
CN1802353A (zh) * 2002-12-30 2006-07-12 细胞基因公司 氟烷氧基取代的1,3－二氢－异吲哚化合物及其药物用途
WO2010147922A1 (en) * 2009-06-18 2010-12-23 Concert Pharmaceuticals, Inc. Deuterated i soindoline- i, 3-dione derivatives as pde4 and tnf-alpha inhibitors
WO2012097116A2 (en) * 2011-01-14 2012-07-19 Celgene Corporation Isotopologues of isoindole derivatives
CN103402980A (zh) * 2011-01-10 2013-11-20 细胞基因公司 作为pde 4 和/或细胞因子抑制剂的苯乙基砜异吲哚啉衍生物

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7034052B2 (en) 2003-03-12 2006-04-25 Celgene Corporation 7-Amido-isoindolyl compounds and their pharmaceutical uses
US20060058311A1 (en) 2004-08-14 2006-03-16 Boehringer Ingelheim International Gmbh Combinations for the treatment of diseases involving cell proliferation
AU2005316593A1 (en) * 2004-12-13 2006-06-22 Celgene Corporation Compositions comprising PDE4 modulators and their use for the treatment or prevention of airway inflammation
PL2276483T3 (pl) * 2008-03-27 2014-09-30 Celgene Corp Stałe postacie zawierające (+)-2-[1-(3-etoksy-4-metoksyfenylo)-2-metylosulfonyloetylo]-4-acetyloaminoizoindolino-1,3-dion, kompozycje je zawierające i ich zastosowania
PE20110547A1 (es) 2008-10-29 2011-08-04 Celgene Corp Compuestos de isoindolina con actividad anticancerigena
US9045453B2 (en) 2008-11-14 2015-06-02 Concert Pharmaceuticals, Inc. Substituted dioxopiperidinyl phthalimide derivatives
WO2012083153A1 (en) * 2010-12-16 2012-06-21 Nektar Therapeutics Oligomer-containing apremilast moiety compounds
EP2730278A1 (en) * 2012-11-08 2014-05-14 Ratiopharm GmbH Composition melt
ES2751773T3 (es) * 2014-05-15 2020-04-01 Amgen Europe Gmbh Uso de inhibidores pde4 y combinaciones de los mismos para el tratamiento de la fibrosis quística
US20170087129A1 (en) * 2014-05-16 2017-03-30 Celgene Corporation Compositions and methods for the treatment of atherosclerotic cardiovascular diseases with pde4 modulators

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000025777A1 (en) * 1998-10-30 2000-05-11 Celgene Corporation SUBSTITUTED PHENETHYLSULFONES AND METHOD OF REDUCING TNFαLEVELS
AU2006200033A1 (en) * 1998-10-30 2006-02-02 Celgene Corporation Substituted phenethylsulfones and methods of reducing TNF-alpha levels
CN1802353A (zh) * 2002-12-30 2006-07-12 细胞基因公司 氟烷氧基取代的1,3－二氢－异吲哚化合物及其药物用途
WO2010147922A1 (en) * 2009-06-18 2010-12-23 Concert Pharmaceuticals, Inc. Deuterated i soindoline- i, 3-dione derivatives as pde4 and tnf-alpha inhibitors
CN103402980A (zh) * 2011-01-10 2013-11-20 细胞基因公司 作为pde 4 和/或细胞因子抑制剂的苯乙基砜异吲哚啉衍生物
WO2012097116A2 (en) * 2011-01-14 2012-07-19 Celgene Corporation Isotopologues of isoindole derivatives

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US20200061033A1 (en) 2020-02-27
KR20190122678A (ko) 2019-10-30
CA3052516C (en) 2022-08-16
PL3590924T3 (pl) 2022-01-24
AU2018228541B2 (en) 2020-07-16
EP3590924A4 (en) 2020-02-19
KR102318401B1 (ko) 2021-10-29
WO2018157779A1 (zh) 2018-09-07
EP3590924B1 (en) 2021-10-27
NZ756231A (en) 2021-12-24
ZA201905098B (en) 2020-12-23
US11628161B2 (en) 2023-04-18
JP6942380B2 (ja) 2021-09-29
CN110291065B (zh) 2022-08-19
US11337964B2 (en) 2022-05-24
CA3052516A1 (en) 2018-09-07
DK3590924T3 (da) 2022-01-03
EP3590924A1 (en) 2020-01-08
AU2018228541A1 (en) 2019-09-05
US20220152002A1 (en) 2022-05-19
RU2728829C1 (ru) 2020-07-31
ES2902052T3 (es) 2022-03-24
JP2020509017A (ja) 2020-03-26

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