EA201991916A1 - 1,4,6-ТРИЗАМЕЩЕННЫЕ-2-АЛКИЛ-1H-БЕНЗО[d]ИМИДАЗОЛЬНЫЕ ПРОИЗВОДНЫЕ В КАЧЕСТВЕ ДИГИДРООРОТАТНЫХ ОКСИГЕНАЗНЫХ ИНГИБИТОРОВ - Google Patents

1,4,6-ТРИЗАМЕЩЕННЫЕ-2-АЛКИЛ-1H-БЕНЗО[d]ИМИДАЗОЛЬНЫЕ ПРОИЗВОДНЫЕ В КАЧЕСТВЕ ДИГИДРООРОТАТНЫХ ОКСИГЕНАЗНЫХ ИНГИБИТОРОВ

Info

Publication number
EA201991916A1
EA201991916A1 EA201991916A EA201991916A EA201991916A1 EA 201991916 A1 EA201991916 A1 EA 201991916A1 EA 201991916 A EA201991916 A EA 201991916A EA 201991916 A EA201991916 A EA 201991916A EA 201991916 A1 EA201991916 A1 EA 201991916A1
Authority
EA
Eurasian Patent Office
Prior art keywords
benzo
alkyl
imidazole derivatives
dihydro
tri
Prior art date
Application number
EA201991916A
Other languages
English (en)
Inventor
Сива Санджива Рао Тунугунтла
Субраманиа Хосахалли
Сунил Кумар Паниграхи
Маттиас Шварц
Майкл Арлт
Original Assignee
Мерк Патент Гмбх
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 Мерк Патент Гмбх filed Critical Мерк Патент Гмбх
Publication of EA201991916A1 publication Critical patent/EA201991916A1/ru

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C07D235/08—Radicals containing only hydrogen and carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles 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 in position 2
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • 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
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5355—Non-condensed oxazines and containing further heterocyclic rings
    • 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
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/541—Non-condensed thiazines containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • 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
    • 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
    • C07D401/10—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 aromatic 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
    • C07D401/12—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 chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings

Abstract

Настоящее изобретение относится к 1,4,6-тризамещенным-2-алкил-1H-бензо[d]имидазольным производным в качестве ингибиторов соединений дигидрооротата оксигеназы формулы (I), которые могут быть терапевтически применимыми в качестве DHODH ингибиторов.в которой R-Rи m обладают значениями, представленными в описании, и их фармацевтически приемлемым солям или стереоизомерам, которые применимы при лечении и предупреждении заболеваний или нарушений, в частности к их применению при заболеваниях или нарушениях, где существует преимущество в ингибировании DHODH. Настоящее изобретение также относится к способам синтеза 1,4,6-тризамещенных-2-алкил-1H-бензо[d]имидазольных производных формулы (I) и к фармацевтическим составам, содержащим по меньшей мере одно из DHODH ингибиторного соединения формулы (I) вместе с фармацевтически приемлемым носителем, разбавителем или вспомогательным средством.
EA201991916A 2017-02-24 2018-02-23 1,4,6-ТРИЗАМЕЩЕННЫЕ-2-АЛКИЛ-1H-БЕНЗО[d]ИМИДАЗОЛЬНЫЕ ПРОИЗВОДНЫЕ В КАЧЕСТВЕ ДИГИДРООРОТАТНЫХ ОКСИГЕНАЗНЫХ ИНГИБИТОРОВ EA201991916A1 (ru)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN201741006586 2017-02-24
PCT/EP2018/054602 WO2018154088A1 (en) 2017-02-24 2018-02-23 1, 4, 6-trisubstituted-2-alkyl-1h-benzo[d]imidazole derivatives as dihydroorotate oxygenase inhibitors

Publications (1)

Publication Number Publication Date
EA201991916A1 true EA201991916A1 (ru) 2020-01-21

Family

ID=61563366

Family Applications (1)

Application Number Title Priority Date Filing Date
EA201991916A EA201991916A1 (ru) 2017-02-24 2018-02-23 1,4,6-ТРИЗАМЕЩЕННЫЕ-2-АЛКИЛ-1H-БЕНЗО[d]ИМИДАЗОЛЬНЫЕ ПРОИЗВОДНЫЕ В КАЧЕСТВЕ ДИГИДРООРОТАТНЫХ ОКСИГЕНАЗНЫХ ИНГИБИТОРОВ

Country Status (13)

Country Link
US (1) US11028054B2 (ru)
EP (1) EP3585772B1 (ru)
JP (1) JP7146785B2 (ru)
KR (1) KR20190120786A (ru)
CN (1) CN110325514B (ru)
AU (1) AU2018223982B2 (ru)
BR (1) BR112019017567A2 (ru)
CA (1) CA3053068A1 (ru)
EA (1) EA201991916A1 (ru)
IL (1) IL268843B (ru)
MA (1) MA47593A (ru)
MX (1) MX2019010096A (ru)
WO (1) WO2018154088A1 (ru)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TW202104207A (zh) 2019-04-17 2021-02-01 美商健生生物科技公司 二氫乳清酸脫氫酶抑制劑
CN113456817A (zh) * 2020-03-30 2021-10-01 华东理工大学 抗rna病毒药物的dhodh抑制剂及其应用
WO2021209485A1 (en) * 2020-04-16 2021-10-21 F. Hoffmann-La Roche Ag Benzimidazole derivatives
CN115485266A (zh) * 2020-04-16 2022-12-16 豪夫迈·罗氏有限公司 苯并咪唑衍生物
CN115397812A (zh) * 2020-04-16 2022-11-25 豪夫迈·罗氏有限公司 吲唑衍生物
WO2021209473A1 (en) * 2020-04-16 2021-10-21 F. Hoffmann-La Roche Ag Biphenyl derivatives
WO2021209475A1 (en) * 2020-04-16 2021-10-21 F. Hoffmann-La Roche Ag Sulfamoylamide derivatives

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4172896A (en) 1978-06-05 1979-10-30 Dainippon Pharmaceutical Co., Ltd. Methane-sulfonamide derivatives, the preparation thereof and composition comprising the same
CA2083179C (en) 1990-05-18 2001-10-23 Robert Ryder Bartlett Isoxazole-4-carboxamides and hydroxyalkylidenecyanoacetamides, pharmaceuticals containing these compounds and their use
GB9217295D0 (en) 1992-08-14 1992-09-30 Wellcome Found Controlled released tablets
GB9315856D0 (en) 1993-07-30 1993-09-15 Wellcome Found Stabilized pharmaceutical
US5358970A (en) 1993-08-12 1994-10-25 Burroughs Wellcome Co. Pharmaceutical composition containing bupropion hydrochloride and a stabilizer
US5541231A (en) 1993-07-30 1996-07-30 Glaxo Wellcome Inc. Stabilized Pharmaceutical
PT999825E (pt) 1997-07-29 2004-02-27 Alcon Lab Inc Composicoes oftalmicas contendo polimeros de galactomanano e borato
US5904937A (en) 1997-10-03 1999-05-18 Fmc Corporation Taste masked pharmaceutical compositions
US6110973A (en) 1998-01-29 2000-08-29 Sepracor Methods for treating obesity and weight gain using optically pure (-)-bupropion
US8889112B2 (en) 1999-09-16 2014-11-18 Ocularis Pharma, Llc Ophthalmic formulations including selective alpha 1 antagonists
US6841561B1 (en) 1999-10-01 2005-01-11 Institute Of Molecular And Cell Biology Dihydroorotate dehydrogenase inhibitors for the treatment of viral-mediated diseases
AU7622000A (en) * 1999-10-01 2001-05-10 Institute Of Molecular And Cell Biology Compounds for the treatment of viral-mediated diseases
US6933289B2 (en) 2003-07-01 2005-08-23 Allergan, Inc. Inhibition of irritating side effects associated with use of a topical ophthalmic medication
DK1654002T4 (da) 2003-08-07 2014-02-17 Allergan Inc Sammensætninger til fremføring af terapeutiske midler til øjnene
US20050059744A1 (en) 2003-09-12 2005-03-17 Allergan, Inc. Methods and compositions for the treatment of pain and other alpha 2 adrenergic-mediated conditions
CN104030987B (zh) * 2009-04-02 2017-04-12 默克雪兰诺有限公司 二氢乳清酸脱氢酶抑制剂
ES2694829T3 (es) 2013-02-25 2018-12-27 Aurigene Discovery Technologies Limited Derivados de benzotriazol trisustituido como inhibidores de dihidroorotato oxigenasa

Also Published As

Publication number Publication date
EP3585772A1 (en) 2020-01-01
CN110325514B (zh) 2023-06-13
US11028054B2 (en) 2021-06-08
US20200140395A1 (en) 2020-05-07
JP2020508327A (ja) 2020-03-19
EP3585772B1 (en) 2023-10-11
IL268843B (en) 2022-03-01
CN110325514A (zh) 2019-10-11
KR20190120786A (ko) 2019-10-24
BR112019017567A2 (pt) 2020-03-24
MX2019010096A (es) 2020-01-09
WO2018154088A1 (en) 2018-08-30
AU2018223982A1 (en) 2019-08-29
AU2018223982B2 (en) 2022-02-03
IL268843A (en) 2019-10-31
JP7146785B2 (ja) 2022-10-04
MA47593A (fr) 2020-01-01
CA3053068A1 (en) 2018-08-30

Similar Documents

Publication Publication Date Title
EA201991916A1 (ru) 1,4,6-ТРИЗАМЕЩЕННЫЕ-2-АЛКИЛ-1H-БЕНЗО[d]ИМИДАЗОЛЬНЫЕ ПРОИЗВОДНЫЕ В КАЧЕСТВЕ ДИГИДРООРОТАТНЫХ ОКСИГЕНАЗНЫХ ИНГИБИТОРОВ
MX2022010011A (es) Inhibidores de prmt5 novedosos.
EA201691401A1 (ru) Индазольные соединения в качестве ингибиторов irak4
MX2023007192A (es) Inhibidores de prmt5.
GEP20237561B (en) Protein tyrosine phosphatase inhibitors
GEP20207105B (en) 1,1,1-trifluoro-3-hydroxypropan-2-yl carbamate derivatives and 1,1,1-trifluoro-4-hydroxybutan-2yl carbamate derivatives as magl inhibitors
EA201691428A1 (ru) Бициклические гетероциклические производные в качестве ингибиторов irak4
WO2014128669A3 (en) Trisubstituted benzotriazole derivatives as dihydroorotate oxygenase inhibitors
EA201691803A1 (ru) Ингибиторы калликреина плазмы человека
EA200702339A1 (ru) Замещенные амидные производные в качестве ингибиторов протеинкиназы
GEP20146146B (en) Pyrrolopyrimidine compounds as inhibitors of cdk4/6
EA201400358A1 (ru) Замещенные n-[1-циано-2-(фенил)этил]-2-азабицикло[2.2.1]гептан-3-карбоксамидные ингибиторы катепсина с
EA201100391A1 (ru) Соединения, ингибирующие активность семикарбазид-чувствительной аминооксидазы
WO2014106800A3 (en) Substituted 2-amino pyrimidine derivatives as kinase inhibitors
CL2023001461A1 (es) Inhibidores de prmt5 novedosos
WO2014125408A3 (en) Substituted 1h-pyrrolopyridinone derivatives as kinase inhibitors
EA201492170A1 (ru) Новые замещенные в цикле n-пиридиниламиды в качестве ингибиторов киназ
PH12021550825A1 (en) Quinoline derivatives as alpha4beta7 integrin inhibitors
EA201300250A1 (ru) Оксадиазольные ингибиторы продуцирования лейкотриена
EA201991894A1 (ru) ПИПЕРИДИН-ЗАМЕЩЕННЫЕ ИНГИБИТОРЫ Mnk И СВЯЗАННЫЕ С НИМИ СПОСОБЫ
MX2019006843A (es) Inhibidor de cdk4/6.
MX2020001531A (es) Nuevos compuestos hetorociclicos como inhibidores de cdk8/19.
MX2021003945A (es) Compuestos de indolinona para uso como inhibidores de map4k1.
EA201692557A1 (ru) Хинолизиноновые производные в качестве ингибиторов pi3k
EA201270816A1 (ru) Производные бензамида и их применение в качестве ингибиторов hsp90