EA202191398A1 - 6-6-CONDENSED BICYCLIC HETEROARYL COMPOUNDS AND THEIR USE AS LATS INHIBITORS - Google Patents

6-6-CONDENSED BICYCLIC HETEROARYL COMPOUNDS AND THEIR USE AS LATS INHIBITORS

Info

Publication number
EA202191398A1
EA202191398A1 EA202191398A EA202191398A EA202191398A1 EA 202191398 A1 EA202191398 A1 EA 202191398A1 EA 202191398 A EA202191398 A EA 202191398A EA 202191398 A EA202191398 A EA 202191398A EA 202191398 A1 EA202191398 A1 EA 202191398A1
Authority
EA
Eurasian Patent Office
Prior art keywords
present
bicyclic heteroaryl
heteroaryl compounds
condensed bicyclic
lats
Prior art date
Application number
EA202191398A
Other languages
Russian (ru)
Inventor
Дирк Бенке
Фрада Беренштейн
Сюэши Хао
Тимоти Хоффман
Цихой Цзинь
Арно Лакост
Камерон Ли
Цзюнь ЛЮ
Яху Лю
Юрген Клаус Майбаум
Тинтин Мо
Цзяньфэн Пань
Синь Цюй
Ян Тхож
Юнь Фэн Се
Шаньшань Янь
Ефэнь Цзоу
Original Assignee
Новартис Аг
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 Новартис Аг filed Critical Новартис Аг
Publication of EA202191398A1 publication Critical patent/EA202191398A1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0048—Eye, e.g. artificial tears
    • 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
    • A61K31/4375—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 six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
    • 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
    • A61K31/47—Quinolines; Isoquinolines
    • 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed 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
    • A61K31/495—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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-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
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0618—Cells of the nervous system
    • C12N5/0621—Eye cells, e.g. cornea, iris pigmented cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/30—Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/52—Genes encoding for enzymes or proenzymes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/86—Viral vectors
    • C12N15/864—Parvoviral vectors, e.g. parvovirus, densovirus
    • C12N15/8645—Adeno-associated virus
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/20—Type of nucleic acid involving clustered regularly interspaced short palindromic repeats [CRISPRs]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2502/00—Coculture with; Conditioned medium produced by
    • C12N2502/08—Coculture with; Conditioned medium produced by cells of the nervous system
    • C12N2502/085—Coculture with; Conditioned medium produced by cells of the nervous system eye cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2502/00—Coculture with; Conditioned medium produced by
    • C12N2502/13—Coculture with; Conditioned medium produced by connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
    • C12N2502/1352—Mesenchymal stem cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2502/00—Coculture with; Conditioned medium produced by
    • C12N2502/27—Lung cells, respiratory tract cells

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Ophthalmology & Optometry (AREA)
  • Biotechnology (AREA)
  • Wood Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Cell Biology (AREA)
  • Biochemistry (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Microbiology (AREA)
  • General Engineering & Computer Science (AREA)
  • Dermatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

Настоящее изобретение относится к 6-6-конденсированным бициклическим гетероарильным соединениям формулы А2 или А1 и к их применению в качестве ингибиторов LATS, или к их соли, стереоизомеру или фармацевтической композиции; где переменные определены в данном документе.Настоящее изобретение дополнительно относится к способу ингибирования LATS в популяции клеток с использованием соединения формулы А1 или его соли, стереоизомера или фармацевтической композиции. В настоящем изобретении дополнительно представлены способ изготовления соединений по настоящему изобретению и их терапевтические применения. В настоящем изобретении дополнительно представлены способы их получения, их применение в медицине, их применение в лечении и контроле заболеваний или нарушений.The present invention relates to 6-6 fused bicyclic heteroaryl compounds of formula A2 or A1 and their use as LATS inhibitors, or a salt, stereoisomer or pharmaceutical composition thereof; where the variables are defined herein. The present invention further relates to a method for inhibiting LATS in a population of cells using a compound of formula A1 or a salt, stereoisomer or pharmaceutical composition thereof. The present invention further provides a method of making the compounds of the present invention and their therapeutic uses. The present invention further provides methods for their preparation, their use in medicine, their use in the treatment and control of diseases or disorders.

EA202191398A 2018-03-29 2018-04-26 6-6-CONDENSED BICYCLIC HETEROARYL COMPOUNDS AND THEIR USE AS LATS INHIBITORS EA202191398A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US201862650232P 2018-03-29 2018-03-29

Publications (1)

Publication Number Publication Date
EA202191398A1 true EA202191398A1 (en) 2021-09-08

Family

ID=69942860

Family Applications (2)

Application Number Title Priority Date Filing Date
EA201992571A EA038453B1 (en) 2018-03-29 2018-04-26 6-6 fused bicyclic heteroaryl compounds and their use as lats inhibitors
EA202191398A EA202191398A1 (en) 2018-03-29 2018-04-26 6-6-CONDENSED BICYCLIC HETEROARYL COMPOUNDS AND THEIR USE AS LATS INHIBITORS

Family Applications Before (1)

Application Number Title Priority Date Filing Date
EA201992571A EA038453B1 (en) 2018-03-29 2018-04-26 6-6 fused bicyclic heteroaryl compounds and their use as lats inhibitors

Country Status (1)

Country Link
EA (2) EA038453B1 (en)

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110319409A1 (en) * 2010-06-23 2011-12-29 Cox Christopher D 7-aza-quinazoline pde10 inhibitors
WO2013012087A1 (en) * 2011-07-15 2013-01-24 国立大学法人大阪大学 Method for preparing corneal endothelial cell
TWI675836B (en) * 2014-03-25 2019-11-01 美商伊格尼塔公司 Azaquinazoline inhibitors of atypical protein kinase c

Also Published As

Publication number Publication date
EA038453B1 (en) 2021-08-31
EA201992571A1 (en) 2020-03-02

Similar Documents

Publication Publication Date Title
PH12019502436A1 (en) 6-6 fused bicyclic heteroaryl compounds and their use as lats inhibitors
JOP20210154B1 (en) Kif18a inhibitors
EA201991399A1 (en) AMINOTRIAZOLOPYRIDINE COMPOUNDS AND THEIR APPLICATION IN TREATMENT OF CANCER
MX2021007104A (en) Kif18a inhibitors.
MX2022001302A (en) Pyridine derivatives as kif18a inhibitors.
MX2021007157A (en) Heteroaryl amides useful as kif18a inhibitors.
MX2021007158A (en) Heteroaryl amides useful as kif18a inhibitors.
EA201992126A1 (en) JAK INHIBITORS CONTAINING 4-MEMBER HETEROCYCLIC AMIDE
EA201691151A1 (en) CONNECTIONS FOR THE TREATMENT OF PATIENTS WITH ROS1-MUTANT CANCER CELLS
CO2022018811A2 (en) Kras g12c protein inhibitors and their uses
EA201891091A1 (en) JAK KINASE INHIBITOR COMPOUNDS FOR THE TREATMENT OF RESPIRATORY DISEASE
EA201891191A1 (en) 2-SUBSTITUTED HINAZOLIN COMPOUNDS CONTAINING A SUBSTITUTED HETEROCYCLIC GROUP AND METHODS OF THEIR APPLICATION
MX2022001181A (en) Kif18a inhibitors.
EA201892207A1 (en) INDOLKARBOXAMIDE CONNECTIONS
WO2014100071A3 (en) Substituted pyrrolopyrimidines as hdm2 inhibitors
EA200970611A1 (en) SUBSTITUTED PYRAZOLOHINAZYLINE DERIVATIVES, METHOD FOR THEIR PRODUCTION AND THEIR USE AS KINASE INHIBITORS
EA201790246A1 (en) HETEROCYCLIC CARBONIC ACIDS AS ACTIVATORS OF SOLUBLE GUANYLATZYCLIC
TR201816176T4 (en) Novel compounds as histone deacetylase 6 inhibitors and pharmaceutical compositions containing the same.
CO2021002976A2 (en) 5- to 7-membered heterocyclic amides as jak inhibitors
EA201790519A1 (en) THERAPEUTIC CONNECTIONS AS INTEGRATORS OF OREXIN-1 RECEPTOR
EA201692260A1 (en) 1,3,4-TIADIAZOLE COMPOUNDS AND THEIR APPLICATION IN CANCER TREATMENT
EA202190588A1 (en) HETEROAROMATIC COMPOUNDS AS VANIN INHIBITORS
EA202191478A1 (en) HETEROAROMATIC COMPOUNDS AS VANIN INHIBITORS
EA201792341A1 (en) DERIVATIVES OF PYRAZOLA SUITABLE AS INHIBITOR PROTEINS ACTIVATING 5-LIPOXYGENASE (FLAP)
EA201990678A1 (en) Heteroarylcarboxamide Compounds as Ripk2 Inhibitors