AU2018223982B2 - 1, 4, 6-trisubstituted-2-alkyl-1H-benzo[d]imidazole derivatives as dihydroorotate oxygenase inhibitors - Google Patents

1, 4, 6-trisubstituted-2-alkyl-1H-benzo[d]imidazole derivatives as dihydroorotate oxygenase inhibitors Download PDF

Info

Publication number
AU2018223982B2
AU2018223982B2 AU2018223982A AU2018223982A AU2018223982B2 AU 2018223982 B2 AU2018223982 B2 AU 2018223982B2 AU 2018223982 A AU2018223982 A AU 2018223982A AU 2018223982 A AU2018223982 A AU 2018223982A AU 2018223982 B2 AU2018223982 B2 AU 2018223982B2
Authority
AU
Australia
Prior art keywords
methyl
benzo
imidazole
biphenyl
carboxylic acid
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
AU2018223982A
Other languages
English (en)
Other versions
AU2018223982A1 (en
Inventor
Michael Arlt
Subramanya Hosahalli
Sunil Kumar Panigrahi
Matthias Schwarz
Siva Sanjeeva Rao Thunuguntla
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck Patent GmbH
Original Assignee
Merck Patent GmbH
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 Merck Patent GmbH filed Critical Merck Patent GmbH
Publication of AU2018223982A1 publication Critical patent/AU2018223982A1/en
Application granted granted Critical
Publication of AU2018223982B2 publication Critical patent/AU2018223982B2/en
Ceased legal-status Critical Current
Anticipated expiration legal-status Critical

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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Rheumatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pain & Pain Management (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
AU2018223982A 2017-02-24 2018-02-23 1, 4, 6-trisubstituted-2-alkyl-1H-benzo[d]imidazole derivatives as dihydroorotate oxygenase inhibitors Ceased AU2018223982B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
IN201741006586 2017-02-24
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 (2)

Publication Number Publication Date
AU2018223982A1 AU2018223982A1 (en) 2019-08-29
AU2018223982B2 true AU2018223982B2 (en) 2022-02-03

Family

ID=61563366

Family Applications (1)

Application Number Title Priority Date Filing Date
AU2018223982A Ceased AU2018223982B2 (en) 2017-02-24 2018-02-23 1, 4, 6-trisubstituted-2-alkyl-1H-benzo[d]imidazole derivatives as dihydroorotate oxygenase inhibitors

Country Status (13)

Country Link
US (1) US11028054B2 (cg-RX-API-DMAC7.html)
EP (1) EP3585772B1 (cg-RX-API-DMAC7.html)
JP (1) JP7146785B2 (cg-RX-API-DMAC7.html)
KR (1) KR20190120786A (cg-RX-API-DMAC7.html)
CN (1) CN110325514B (cg-RX-API-DMAC7.html)
AU (1) AU2018223982B2 (cg-RX-API-DMAC7.html)
BR (1) BR112019017567A2 (cg-RX-API-DMAC7.html)
CA (1) CA3053068A1 (cg-RX-API-DMAC7.html)
EA (1) EA201991916A1 (cg-RX-API-DMAC7.html)
IL (1) IL268843B (cg-RX-API-DMAC7.html)
MA (1) MA47593A (cg-RX-API-DMAC7.html)
MX (1) MX2019010096A (cg-RX-API-DMAC7.html)
WO (1) WO2018154088A1 (cg-RX-API-DMAC7.html)

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
CN113456817B (zh) * 2020-03-30 2024-05-10 华东理工大学 抗rna病毒药物的dhodh抑制剂及其应用
CN115485266A (zh) * 2020-04-16 2022-12-16 豪夫迈·罗氏有限公司 苯并咪唑衍生物
EP4136074A1 (en) * 2020-04-16 2023-02-22 F. Hoffmann-La Roche AG Indazole derivatives
WO2021209485A1 (en) * 2020-04-16 2021-10-21 F. Hoffmann-La Roche Ag Benzimidazole derivatives
CN115397813A (zh) * 2020-04-16 2022-11-25 豪夫迈·罗氏有限公司 联苯衍生物
EP4136081A1 (en) * 2020-04-16 2023-02-22 F. Hoffmann-La Roche AG Sulfamoylamide derivatives

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010115736A2 (en) * 2009-04-02 2010-10-14 Merck Serono S.A. Dihydroorotate dehydrogenase inhibitors
WO2014128669A2 (en) * 2013-02-25 2014-08-28 Aurigene Discovery Technologies Limited Trisubstituted benzotriazole derivatives as dihydroorotate oxygenase inhibitors

Family Cites Families (15)

* 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
JP2995086B2 (ja) 1990-05-18 1999-12-27 ヘキスト・アクチエンゲゼルシヤフト イソオキサゾール−４−カルボキサミド類およびヒドロキシアルキリデンシアノアセトアミド類を含有する製剤
GB9217295D0 (en) 1992-08-14 1992-09-30 Wellcome Found Controlled released tablets
US5541231A (en) 1993-07-30 1996-07-30 Glaxo Wellcome Inc. Stabilized Pharmaceutical
US5358970A (en) 1993-08-12 1994-10-25 Burroughs Wellcome Co. Pharmaceutical composition containing bupropion hydrochloride and a stabilizer
GB9315856D0 (en) 1993-07-30 1993-09-15 Wellcome Found Stabilized pharmaceutical
DK0999825T3 (da) 1997-07-29 2004-02-09 Alcon Lab Inc Oftalmiske sammensætninger indeholdende galactomannanpolymerer og borater
US5904937A (en) 1997-10-03 1999-05-18 Fmc Corporation Taste masked pharmaceutical compositions
EP1051167A1 (en) 1998-01-29 2000-11-15 Sepracor, Inc. Pharmaceutical uses of optically pure (-) -bupropion
US8889112B2 (en) 1999-09-16 2014-11-18 Ocularis Pharma, Llc Ophthalmic formulations including selective alpha 1 antagonists
AR025929A1 (es) * 1999-10-01 2002-12-18 Inst Of Molecul & Cell Biology Compuestos para el tratamiento de enfermedades mediadas por virus
US6841561B1 (en) 1999-10-01 2005-01-11 Institute Of Molecular And Cell Biology Dihydroorotate dehydrogenase inhibitors 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
US8512717B2 (en) 2003-08-07 2013-08-20 Allergan, Inc. Compositions for delivery of therapeutics into the eyes and methods for making and using same
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

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010115736A2 (en) * 2009-04-02 2010-10-14 Merck Serono S.A. Dihydroorotate dehydrogenase inhibitors
WO2014128669A2 (en) * 2013-02-25 2014-08-28 Aurigene Discovery Technologies Limited Trisubstituted benzotriazole derivatives as dihydroorotate oxygenase inhibitors

Also Published As

Publication number Publication date
MX2019010096A (es) 2020-01-09
US20200140395A1 (en) 2020-05-07
EP3585772B1 (en) 2023-10-11
EP3585772A1 (en) 2020-01-01
WO2018154088A1 (en) 2018-08-30
JP7146785B2 (ja) 2022-10-04
CN110325514A (zh) 2019-10-11
US11028054B2 (en) 2021-06-08
CA3053068A1 (en) 2018-08-30
IL268843A (en) 2019-10-31
CN110325514B (zh) 2023-06-13
EA201991916A1 (ru) 2020-01-21
MA47593A (fr) 2020-01-01
IL268843B (en) 2022-03-01
AU2018223982A1 (en) 2019-08-29
BR112019017567A2 (pt) 2020-03-24
JP2020508327A (ja) 2020-03-19
KR20190120786A (ko) 2019-10-24

Similar Documents

Publication Publication Date Title
AU2018223982B2 (en) 1, 4, 6-trisubstituted-2-alkyl-1H-benzo[d]imidazole derivatives as dihydroorotate oxygenase inhibitors
US9937155B2 (en) Methods of use for trisubstituted benzotriazole derivatives as dihydroorotate oxygenase inhibitors
CN105814052B (zh) 作为tnf活性调节剂的咪唑并吡啶衍生物
US9624215B2 (en) Amine derivative or salt thereof
JPH07138232A (ja) ベンゾヘテロ環化合物
HUP9903009A2 (hu) Szubsztituált indazolszármazékok és IV típusú foszfodiészteráz (PDE) és tumornekrózis faktor (TNF) inhibítorokként történő alkalmazásuk
CN105829307A (zh) 用作tnf活性调节剂的四氢咪唑并吡啶衍生物
CN111377873B (zh) 氨基嘧啶化合物及其制备方法和用途
EP0983263A1 (en) Novel benzimidazole derivatives as antiulcer agents, process for their preparation and pharmaceutical compositions containing them
AU2021261519A1 (en) 2-heteroarylaminoquinazolinone derivative
US6818642B2 (en) Benzylaminopyrimidines
TW201315731A (zh) 菸鹼乙醯膽鹼受體之新穎正向異位調節劑
JPH0753715B2 (ja) ベンゾヘテロ環化合物
US20250171452A1 (en) Tryptanthrin derivatives and uses thereof
WO2024220556A2 (en) Heterocyclic sumo1 small molecule degraders and use thereof
JPH0747575B2 (ja) ベンゼン誘導体
HK1141948A (en) Benzimidazoles and pharmaceutical compositions thereof
HK1142077A (en) Triazolopyridines as phosphodiesterase inhibitors for treatment of dermal diseases
JPH07165636A (ja) ベンゼン誘導体

Legal Events

Date Code Title Description
FGA Letters patent sealed or granted (standard patent)
MK14 Patent ceased section 143(a) (annual fees not paid) or expired