CA2968874C - Small molecule inhibitors of fibrosis - Google Patents

Small molecule inhibitors of fibrosis Download PDF

Info

Publication number
CA2968874C
CA2968874C CA2968874A CA2968874A CA2968874C CA 2968874 C CA2968874 C CA 2968874C CA 2968874 A CA2968874 A CA 2968874A CA 2968874 A CA2968874 A CA 2968874A CA 2968874 C CA2968874 C CA 2968874C
Authority
CA
Canada
Prior art keywords
compound
formula
alkyl
alkylene
nr13r14
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.)
Active
Application number
CA2968874A
Other languages
English (en)
French (fr)
Other versions
CA2968874A1 (en
Inventor
Luke LAIRSON
Arnab K. Chatterjee
Michael BOLLONG
Baiyuan Yang
Peter G. Schultz
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.)
Scripps Research Institute
Original Assignee
Scripps Research Institute
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 Scripps Research Institute filed Critical Scripps Research Institute
Publication of CA2968874A1 publication Critical patent/CA2968874A1/en
Application granted granted Critical
Publication of CA2968874C publication Critical patent/CA2968874C/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero 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
    • A61K31/41—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
    • A61K31/4192—1,2,3-Triazoles
    • 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
    • A61K31/4196—1,2,4-Triazoles
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • 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
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • 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
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • 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
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N57/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Rheumatology (AREA)
  • Cardiology (AREA)
  • Pain & Pain Management (AREA)
  • Pulmonology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Dermatology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
CA2968874A 2014-12-10 2015-12-09 Small molecule inhibitors of fibrosis Active CA2968874C (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201462090267P 2014-12-10 2014-12-10
US62/090,267 2014-12-10
US201562117846P 2015-02-18 2015-02-18
US62/117,846 2015-02-18
PCT/US2015/064814 WO2016094570A1 (en) 2014-12-10 2015-12-09 Small molecule inhibitors of fibrosis

Publications (2)

Publication Number Publication Date
CA2968874A1 CA2968874A1 (en) 2016-06-16
CA2968874C true CA2968874C (en) 2024-06-18

Family

ID=56108132

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2968874A Active CA2968874C (en) 2014-12-10 2015-12-09 Small molecule inhibitors of fibrosis

Country Status (9)

Country Link
US (1) US10336735B2 (enExample)
EP (1) EP3250036B1 (enExample)
JP (1) JP6706023B2 (enExample)
KR (1) KR102548066B1 (enExample)
CN (1) CN107404878B (enExample)
AU (1) AU2015360583B2 (enExample)
CA (1) CA2968874C (enExample)
ES (1) ES2879963T3 (enExample)
WO (1) WO2016094570A1 (enExample)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11028078B2 (en) * 2011-09-07 2021-06-08 The Johns Hopkins University Itraconazole analogs and use thereof
US11571431B2 (en) 2013-12-04 2023-02-07 Galmed Research And Development Ltd Aramchol salts
WO2015116947A1 (en) * 2014-02-01 2015-08-06 University Of Connecticut Itraconazole analogues and methods of use thereof
IL243707A0 (en) 2016-01-20 2016-05-01 Galmed Res And Dev Ltd Treatment to regulate the microbiota in the intestine
US11197870B2 (en) 2016-11-10 2021-12-14 Galmed Research And Development Ltd Treatment for hepatic fibrosis
EP3669191A4 (en) 2017-08-20 2021-04-14 University of Connecticut NITROGEN-TYPE COMPOUND ANALOGUES AND THEIR METHODS OF USE
JP2021517558A (ja) 2018-03-19 2021-07-26 シェオ ファーマスーティカルズ 特発性肺線維症を治療するための方法および組成物
EP3886854A4 (en) 2018-11-30 2022-07-06 Nuvation Bio Inc. Pyrrole and pyrazole compounds and methods of use thereof
WO2021030174A1 (en) 2019-08-09 2021-02-18 University Of Connecticut Truncated itraconazole analogues and methods of use thereof

Family Cites Families (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4267179A (en) 1978-06-23 1981-05-12 Janssen Pharmaceutica, N.V. Heterocyclic derivatives of (4-phenylpiperazin-1-yl-aryloxymethyl-1,3-dioxolan-2-yl)methyl-1H-imidazoles and 1H-1,2,4-triazoles
US4619931A (en) 1983-02-28 1986-10-28 Janssen Pharmaceutica, N.V. [[4-[4-(4-phenyl-1-piperazinyl)phenoxymethyl]-1,3-dioxolan-2-yl]methyl]-1H-imidazoles and 1H-1,2,4-triazoles
US4791111A (en) 1985-12-23 1988-12-13 Janssen Pharmaceutica, N.V. [[4-[4-(4-phenyl-1-piperazinyl)phenoxymethyl]-1,3-dioxolan-2-yl]methyl]-1H-imidazoles and 1H-1,2,4-triazoles having anti-microbial properties
CN1041425C (zh) 1993-11-19 1998-12-30 国际壳牌研究有限公司 氧化稳定的聚酮聚合物组合物及其应用
US5521186A (en) * 1994-10-27 1996-05-28 Janssen Pharmaceutica N.V. Apolipoprotein-β synthesis inhibitors
TW457240B (en) 1995-04-20 2001-10-01 Janssen Pharmaceutica Nv Novel triazolones as apolipoprotein-B synthesis inhibitors
EP0957101A1 (en) 1998-05-14 1999-11-17 Janssen Pharmaceutica N.V. Water soluble azoles as broad-spectrum antifungals
DE60006541D1 (de) 1999-06-30 2003-12-18 Merck & Co Inc Src-kinase hemmende verbindungen
US6414013B1 (en) 2000-06-19 2002-07-02 Pharmacia & Upjohn S.P.A. Thiophene compounds, process for preparing the same, and pharmaceutical compositions containing the same background of the invention
EP1511490A4 (en) 2002-05-31 2009-03-11 Transform Pharmaceuticals Inc NOVEL CONAZOLE CRYSTALLINE FORMS AND RELATED METHODS, PHARMACEUTICAL COMPOSITIONS AND METHODS
EP1655295A1 (en) * 2004-11-03 2006-05-10 Schering Aktiengesellschaft Anthranilamide pyridinureas as VEGF receptor kinase inhibitors
AU2007296740B2 (en) * 2006-09-11 2012-09-27 Curis, Inc. Substituted 2-indolinone as PTK inhibitors containing a zinc binding moiety
WO2009074300A2 (en) 2007-12-13 2009-06-18 Siena Biotech S.P.A. Hedgehog pathway antagonists and therapeutic applications thereof
US20100092479A1 (en) * 2008-08-18 2010-04-15 Combinatorx (Singapore) Pte. Ltd. Compositions and methods for treatment of viral diseases
JO3182B1 (ar) 2009-07-29 2018-03-08 Regeneron Pharma مضادات حيوية بشرية عالية الالفة مع تولد الاوعية البشرية - 2
US20110183948A1 (en) 2010-01-15 2011-07-28 Infinity Pharmaceuticals, Inc. Treatment of fibrotic conditions using hedgehog inhibitors
WO2012047762A2 (en) 2010-10-08 2012-04-12 Amplyx Pharmaceuticals, Inc. Antifungal agents
US9346791B2 (en) 2011-09-07 2016-05-24 The Johns Hopkins University Itraconazole analogs and use thereof
US10774132B2 (en) 2012-01-09 2020-09-15 The Scripps Research Instittue Ultralong complementarity determining regions and uses thereof
CA2891280C (en) 2012-11-24 2018-03-20 Hangzhou Dac Biotech Co., Ltd. Hydrophilic linkers and their uses for conjugation of drugs to cell binding molecules
KR102240329B1 (ko) 2013-06-07 2021-04-14 더 스크립스 리서치 인스티튜트 섬유증의 소분자 억제제
US9790224B2 (en) 2013-06-07 2017-10-17 Rhizen Pharmaceuticals Sa Dual selective PI3 delta and gamma kinase inhibitors

Also Published As

Publication number Publication date
ES2879963T3 (es) 2021-11-23
EP3250036A4 (en) 2018-06-27
CA2968874A1 (en) 2016-06-16
JP6706023B2 (ja) 2020-06-03
KR102548066B1 (ko) 2023-06-26
US20170362211A1 (en) 2017-12-21
US10336735B2 (en) 2019-07-02
EP3250036B1 (en) 2021-05-12
CN107404878B (zh) 2021-03-30
CN107404878A (zh) 2017-11-28
HK1249361A1 (zh) 2018-11-02
EP3250036A1 (en) 2017-12-06
WO2016094570A1 (en) 2016-06-16
AU2015360583B2 (en) 2020-01-23
AU2015360583A1 (en) 2017-06-22
JP2017537937A (ja) 2017-12-21
KR20170091154A (ko) 2017-08-08

Similar Documents

Publication Publication Date Title
CA2968874C (en) Small molecule inhibitors of fibrosis
CA2913634C (en) Small molecule inhibitors of fibrosis
US12559493B2 (en) PGDH inhibitors and methods of making and using
CN110352188B (zh) 氟代烯丙胺衍生物及其用途
AU2017336523B2 (en) Calpain modulators and therapeutic uses thereof
US10919885B2 (en) Compounds and uses thereof
CA2957046C (en) Optionally fused heterocyclyl-substituted derivatives of pyrimidine useful for the treatment of inflammatory, metabolic, oncologic and autoimmune diseases
EP2617715A1 (en) Glycine transporter inhibitor
CA3127791A1 (en) Compounds and uses thereof
NL1027084C2 (nl) Gesubstitueerde triazoolderivaten als oxytocine-antagonisten.
US20240199623A1 (en) SUBSTITUTED PYRAZOLO[1,5-a]PYRIMIDINES AS CFTR MODULATORS
KR20250023339A (ko) 페닐 트라이아졸 mll1-wdr5 단백질-단백질 상호작용 저해제
WO2011007899A1 (en) Glycine transporter inhibitors
US20230286948A1 (en) Haloalkylpyridyl triazole mll1-wdr5 protein-protein interaction inhibitor
CN121405680A (zh) 取代苯并咪唑衍生物及其制备方法和用途
KR101121662B1 (ko) 도파민 ｄ3, ｄ4 수용체 길항제인 신규 3-(메톡시메틸)피라졸 유도체, 이의 제조방법 및 이를 포함하는 약학적 조성물

Legal Events

Date Code Title Description
EEER Examination request

Effective date: 20201116

EEER Examination request

Effective date: 20201116

EEER Examination request

Effective date: 20201116

EEER Examination request

Effective date: 20201116

EEER Examination request

Effective date: 20201116

EEER Examination request

Effective date: 20201116

EEER Examination request

Effective date: 20201116

EEER Examination request

Effective date: 20201116

EEER Examination request

Effective date: 20201116

EEER Examination request

Effective date: 20201116

EEER Examination request

Effective date: 20201116

MPN Maintenance fee for patent paid

Free format text: FEE DESCRIPTION TEXT: MF (PATENT, 9TH ANNIV.) - STANDARD

Year of fee payment: 9

U00 Fee paid

Free format text: ST27 STATUS EVENT CODE: A-4-4-U10-U00-U101 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: MAINTENANCE REQUEST RECEIVED

Effective date: 20241122

U11 Full renewal or maintenance fee paid

Free format text: ST27 STATUS EVENT CODE: A-4-4-U10-U11-U102 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: MAINTENANCE FEE PAYMENT DETERMINED COMPLIANT

Effective date: 20241122