HRP20220913T1 - Inhibitori rho kinaze - Google Patents

Inhibitori rho kinaze Download PDF

Info

Publication number
HRP20220913T1
HRP20220913T1 HRP20220913TT HRP20220913T HRP20220913T1 HR P20220913 T1 HRP20220913 T1 HR P20220913T1 HR P20220913T T HRP20220913T T HR P20220913TT HR P20220913 T HRP20220913 T HR P20220913T HR P20220913 T1 HRP20220913 T1 HR P20220913T1
Authority
HR
Croatia
Prior art keywords
alkyl
group
independently selected
halo
alkenyl
Prior art date
Application number
HRP20220913TT
Other languages
English (en)
Inventor
Masha POYUROVSKY
Ji-In Kim
Kevin Liu
Alexandra Zanin-Zhorov
Original Assignee
Kadmon Corporation, Llc
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=50435589&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=HRP20220913(T1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Kadmon Corporation, Llc filed Critical Kadmon Corporation, Llc
Publication of HRP20220913T1 publication Critical patent/HRP20220913T1/hr

Links

Classifications

    • 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
    • C07D403/12—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 chain containing hetero atoms as chain links
    • 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
    • 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
    • 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
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • 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
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
    • 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
    • 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
    • A61P17/04—Antipruritics
    • 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
    • A61P17/06—Antipsoriatics
    • 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
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • 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
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • 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
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • 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
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • 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
    • 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
    • A61P9/08—Vasodilators for multiple indications
    • 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
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • 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
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/42—One nitrogen atom
    • 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
    • C07D401/14—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 three or more hetero rings
    • 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
    • C07D403/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pulmonology (AREA)
  • Cardiology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Dermatology (AREA)
  • Epidemiology (AREA)
  • Psychology (AREA)
  • Urology & Nephrology (AREA)
  • Rheumatology (AREA)
  • Hematology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pain & Pain Management (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Diabetes (AREA)
  • Psychiatry (AREA)
  • Oncology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Vascular Medicine (AREA)
  • Hospice & Palliative Care (AREA)

Claims (4)

1. Spoj koji inhibira ROCK 2 za upotrebu u liječenju autoimunog poremećaja kod subjekta, pri čemu je autoimuni poremećaj psorijaza, atopijski dermatitis, ekcem ili bolest transplantata protiv domaćina (GVHD), te pri čemu je spoj koji inhibira ROCK2 spoj s formulom (XXXII): [image] ili njegova farmaceutski prihvatljiva sol, pri čemu: R1 je odabran iz skupine koja sadrži -O-(CH2)y-CO2R12, -O-(CH2)y-C(=O)NR13R14, -O-(CH2)y-heteroaril, -O-(CH2)y-cikloalkil, -O-C(=O)-(CH2)y-NR13R14, -O-(CH2)z-NR13R14, -NH-C(=O)-(CH2)y-NR13R14, -NH-C(=O)-X-R15, -NH-(CH2)y-NR13R14; R12 je odabran iz skupine koja sadrži C1-C6 alkil, -(C1-C6 alkil)-O-(C1-C6 alkil), -(C1-C6 alkil)-NR16R17, -(C1-C6 alkil)-C(=O)NR16R17, -(C1-C6 alkil)-O-(C1-C6 alkil)-O-(C1-C6 alkil), aril, aralkil, heteroaril, C3-C7 cikloalkil, tro- do dvanaesteročlani heterociklički prsten koji sadrži do 3 heteroatoma, od kojih svaki može biti izborno supstituiran na jednom ili više atoma ugljika s od 1 do 3 supstituenta neovisno odabrana iz niza koji sadrži halo, C1-C6 alkoksi, hidroksi, amino, cijano i C1-C3 perfluoro alkil; R13 i R14 su neovisno odabrani iz skupine koju čine H, C1-C8 alkil, C2-C8 alkenil, C2-C8 alkinil, -(C1-C6 alkil)-O-(C1-C6 alkil), -(C1-C6 alkil)-NR16R17, -(C1-C6 alkil)-C(=O)NR16R17 , aril, aralkil, heteroaril, C3-C7 cikloalkil, tro- do dvanaesteročlani heterociklički prsten koji sadrži do 3 heteroatoma, od kojih svaki može biti po izboru supstituiran s od 1 do 3 supstituenta neovisno odabrana iz niza koji sadrži halo, C1-C6 alkil, C2-C6 alkenil, C3-C7 cikloalkil, C1-C6 alkoksi, hidroksi, amino, cijano i C1-C3 perfluoro alkil; ili R13 i R14 mogu se uzeti zajedno da tvore tro- do dvanaesteročlani heterociklički prsten koji ima do 3 heteroatoma koji je po izboru supstituiran s od 1 do 3 supstituenta neovisno odabrana iz niza koji sadrži halo, C1-C6 alkil, C2-C6 alkenil, C1-C6 alkoksi, C3-C7 cikloalkil, okso, hidroksi, amino, cijano i C1-C3 perfluoro alkil; X je odabran od kovalentne veze, O, NH, i C1-C6 alkil; R15 je odabran iz skupine koja sadrži heteroaril, C3-C7 cikloalkil, tro- do dvanaesteročlani heterociklički prsten koji sadrži do 3 heteroatoma, od kojih svaki može biti po izboru supstituiran s od 1 do 3 supstituenta neovisno odabrana iz niza koji sadrži halo, C1-C6 alkil, C2-C6 alkenil, C1-C6 alkoksi, hidroksi, amino, cijano i C1-C3 perfluoro alkil, ili R15 je odabran od -(C1-C6 alkil)-O-(C1-C6 alkil), -(C1-C6 alkil)-NR16R17, -CO2R18, -O-(CH2)x-CO2R18, i -C(=O)NR16R17; R16 i R17 su neovisno odabrani iz skupine koju čine H, C1-C8 alkil, C2-C8 alkenil, C2-C8 alkinil, -(C1-C6 alkil)-O-(C1-C6 alkil), aril, aralkil, heteroaril, C3-C7 cikloalkil, tro- do dvanaesteročlani heterociklički prsten koji sadrži do 3 heteroatoma, od kojih svaki može biti po izboru supstituiran s od 1 do 3 supstituenta neovisno odabrana iz niza koji sadrži halo, C1-C6 alkil, C2-C6 alkenil, C1-C6 alkoksi, hidroksi, amino, cijano i C1-C3 perfluoro alkil; ili R16 i R17 mogu se uzeti zajedno da tvore tro- do dvanaesteročlani heterociklički prsten koji ima do 3 heteroatoma koji je po izboru supstituiran s od 1 do 3 supstituenta neovisno odabrana iz niza koji sadrži halo, C1-C6 alkil, C2-C6 alkenil, C1-C6 alkoksi, okso, hidroksi, amino, cijano i C1-C3 perfluoro alkil; R18 je odabran iz skupine koja sadrži H, aril, aralkil, heteroaril, C1-C6 alkil, -(C1-C6 alkil)-O-(C1-C6 alkil), -(C1-C6 alkil)-NR16R17, -(C1-C6 alkil)-O-(C1-C6 alkil)-O-(C1-C6 alkil), od kojih svaki može biti po izboru supstituiran s od 1 do 3 supstituenta neovisno odabrana iz niza koji sadrži halo, C1-C6 alkoksi, hidroksi, amino, cijano i C1-C3 perfluoroalkil; x je odabran od 0 do 6; y je odabran od 0 do 6; z je odabran od 2 do 6; svaki R2 je neovisno odabran iz skupine koja sadrži niži alkil, CN, halo, hidroksi, niži alkoksi, amino, i perfluoro niži alkil; svaki R3 je neovisno odabran iz skupine koja sadrži niži alkil, CN, halo, hidroksi, niži alkoksi, amino, i perfluoro niži alkil; n je odabran od 0 do 4; i m je odabran od 0 do 3.
2. Spoj za upotrebu prema zahtjevu 1, naznačen time što je spoj koji inhibira ROCK2 spoj s formulom [image]
3. Spoj za upotrebu prema zahtjevu 1, naznačen time što je spoj koji inhibira ROCK2 spoj s formulom XXXIV: [image] ili njegova farmaceutski prihvatljiva sol, pri čemu: R13 i R14 su neovisno odabrani iz skupine koju čine H, C1-C8 alkil, C2-C8 alkenil, C2-C8 alkinil, -(C1-C6 alkil)-O-(C1-C6 alkil), -(C1-C6 alkil)-NR16R17, -(C1-C6 alkil)-C(=O)NR16R17 , aril, aralkil, heteroaril, C3-C7 cikloalkil, tro- do dvanaesteročlani heterociklički prsten koji sadrži do 3 heteroatoma, od kojih svaki može biti po izboru supstituiran s od 1 do 3 supstituenta neovisno odabrana iz niza koji sadrži halo, C1-C6 alkil, C2-C6 alkenil, C3-C7 cikloalkil, C1-C6 alkoksi, hidroksi, amino, cijano i C1-C3 perfluoro alkil; ili R13 i R14 mogu se uzeti zajedno da tvore tro- do dvanaesteročlani heterociklički prsten koji ima do 3 heteroatoma koji je po izboru supstituiran s od 1 do 3 supstituenta neovisno odabrana iz niza koji sadrži halo, C1-C6 alkil, C2-C6 alkenil, C1-C6 alkoksi, C3-C7 cikloalkil, okso, hidroksi, amino, cijano i C1-C3 perfluoro alkil; R16 i R17 su neovisno odabrani iz skupine koju čine H, C1-C8 alkil, C2-C8 alkenil, C2-C8 alkinil, -(C1-C6 alkil)-O-(C1-C6 alkil), aril, aralkil, heteroaril, C3-C7 cikloalkil, tro- do dvanaesteročlani heterociklički prsten koji sadrži do 3 heteroatoma, od kojih svaki može biti po izboru supstituiran s od 1 do 3 supstituenta neovisno odabrana iz niza koji sadrži halo, C1-C6 alkil, C2-C6 alkenil, C1-C6 alkoksi, hidroksi, amino, cijano i C1-C3 perfluoro alkil; ili R16 i R17 mogu se uzeti zajedno da tvore tro- do dvanaesteročlani heterociklički prsten koji ima do 3 heteroatoma koji je po izboru supstituiran s od 1 do 3 supstituenta neovisno odabrana iz niza koji sadrži halo, C1-C6 alkil, C2-C6 alkenil, C1-C6 alkoksi, okso, hidroksi, amino, cijano i C1-C3 perfluoro alkil; svaki R2 je neovisno odabran iz skupine koja sadrži niži alkil, CN, halo, hidroksi, niži alkoksi, amino, i perfluoro niži alkil; svaki R3 je neovisno odabran iz skupine koja sadrži niži alkil, CN, halo, hidroksi, niži alkoksi, amino, i perfluoro niži alkil; n je odabran od 0 do 4; i m je odabran od 0 do 3.
4. Spoj za upotrebu prema zahtjevu 1, naznačen time što je spoj koji inhibira ROCK2 spoj s formulom XXXIVa: [image] ili njegova farmaceutski prihvatljiva sol, pri čemu: R13 i R14 su neovisno odabrani iz skupine koju čine H, C1-C8 alkil, C2-C8 alkenil, C2-C8 alkinil, -(C1-C6 alkil)-O-(C1-C6 alkil), -(C1-C6 alkil)-NR16R17, -(C1-C6 alkil)-C(=O)NR16R17 , aril, aralkil, heteroaril, C3-C7 cikloalkil, tro- do dvanaesteročlani heterociklički prsten koji sadrži do 3 heteroatoma, od kojih svaki može biti po izboru supstituiran s od 1 do 3 supstituenta neovisno odabrana iz niza koji sadrži halo, C1-C6 alkil, C2-C6 alkenil, C3-C7 cikloalkil, C1-C6 alkoksi, hidroksi, amino, cijano i C1-C3 perfluoro alkil; ili R13 i R14 mogu se uzeti zajedno da tvore tro- do dvanaesteročlani heterociklički prsten koji ima do 3 heteroatoma koji je po izboru supstituiran s od 1 do 3 supstituenta neovisno odabrana iz niza koji sadrži halo, C1-C6 alkil, C2-C6 alkenil, C1-C6 alkoksi, okso, hidroksi, amino, cijano i C1-C3 perfluoro alkil; R16 i R17 su neovisno odabrani iz skupine koju čine H, C1-C8 alkil, C2-C8 alkenil, C2-C8 alkinil, -(C1-C6 alkil)-O-(C1-C6 alkil), aril, aralkil, heteroaril, C3-C7 cikloalkil, tro- do dvanaesteročlani heterociklički prsten koji sadrži do 3 heteroatoma, od kojih svaki može biti po izboru supstituiran s od 1 do 3 supstituenta neovisno odabrana iz niza koji sadrži halo, C1-C6 alkil, C2-C6 alkenil, C1-C6 alkoksi, hidroksi, amino, cijano i C1-C3 perfluoro alkil; ili R16 i R17 mogu se uzeti zajedno da tvore tro- do dvanaesteročlani heterociklički prsten koji ima do 3 heteroatoma koji je po izboru supstituiran s od 1 do 3 supstituenta neovisno odabrana iz niza koji sadrži halo, C1-C6 alkil, C2-C6 alkenil, C1-C6 alkoksi, okso, hidroksi, amino, cijano i C1-C3 perfluoro alkil.
HRP20220913TT 2012-10-05 2013-10-07 Inhibitori rho kinaze HRP20220913T1 (hr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201261710373P 2012-10-05 2012-10-05
US201361840288P 2013-06-27 2013-06-27
PCT/US2013/063752 WO2014055996A2 (en) 2012-10-05 2013-10-07 Rho kinase inhibitors
EP13843426.1A EP2903618B1 (en) 2012-10-05 2013-10-07 Rho kinase inhibitors

Publications (1)

Publication Number Publication Date
HRP20220913T1 true HRP20220913T1 (hr) 2022-10-28

Family

ID=50435589

Family Applications (1)

Application Number Title Priority Date Filing Date
HRP20220913TT HRP20220913T1 (hr) 2012-10-05 2013-10-07 Inhibitori rho kinaze

Country Status (16)

Country Link
US (4) US9815820B2 (hr)
EP (2) EP4116293A3 (hr)
JP (2) JP6419076B2 (hr)
CN (5) CN113637008A (hr)
CA (2) CA2926478C (hr)
DK (1) DK2903618T3 (hr)
EA (1) EA201500362A1 (hr)
ES (1) ES2924915T3 (hr)
HR (1) HRP20220913T1 (hr)
HU (1) HUE059305T2 (hr)
LT (1) LT2903618T (hr)
PL (1) PL2903618T3 (hr)
PT (1) PT2903618T (hr)
RS (1) RS63503B1 (hr)
SI (1) SI2903618T1 (hr)
WO (1) WO2014055996A2 (hr)

Families Citing this family (46)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11008359B2 (en) 2002-08-23 2021-05-18 Illumina Cambridge Limited Labelled nucleotides
LT2903618T (lt) 2012-10-05 2022-08-25 Kadmon Corporation, Llc Rho kinazės inhibitoriai
WO2015157556A1 (en) * 2014-04-09 2015-10-15 Kadmon Corporation, Llc Treatment of gvhd
WO2016028971A1 (en) 2014-08-21 2016-02-25 Bristol-Myers Squibb Company Tied-back benzamide derivatives as potent rock inhibitors
WO2016057726A2 (en) * 2014-10-07 2016-04-14 Kadmon Corporation, Llc Human anti-vegfr-2/kdr antibodies
WO2016138335A1 (en) 2015-02-27 2016-09-01 Lycera Corporation Indazolyl thiadiazolamines and related compounds for inhibition of rho-associated protein kinase and the treatment of disease
US11021468B2 (en) * 2015-04-01 2021-06-01 Rigel Pharmaceuticals, Inc. TGF-ß inhibitors
US9937154B2 (en) * 2015-06-10 2018-04-10 Hackensak University Medical Center Use of telmisartan to prevent and treat graft versus host disease and other alloimmune and autoimmune diseases
EA201890153A1 (ru) * 2015-06-26 2018-06-29 КАДМОН КОРПОРЕЙШН, ЭлЭлСи Ингибиторы поглощения глюкозы
EA201891732A1 (ru) * 2016-02-02 2019-02-28 Кадмон Корпорейшн, Ллк Биспецифичные связывающие белки для pd-l1 и kdr
WO2018027124A1 (en) * 2016-08-05 2018-02-08 Medimmune, Llc Anti-o2 antibodies and uses thereof
EP3504204A4 (en) 2016-08-26 2020-05-27 Lycera Corporation INDAZOLYL-L, 2,4-THIADIAZOLAMINE AND RELATED COMPOUNDS FOR INHIBITING RHO-ASSOCIATED PROTEIN KINASES AND FOR TREATING DISEASES
CA3039686A1 (en) 2016-10-19 2018-04-26 Medimmune, Llc Anti-o1 antibodies and uses thereof
CN106916145B (zh) * 2017-03-06 2019-06-04 上海应用技术大学 SLx-2119的合成方法
IT201700047189A1 (it) * 2017-05-02 2018-11-02 Fondazione St Italiano Tecnologia Composti e composizioni per il trattamento di cancro, disordini della retina e cardiomiopatie
EP3421464B1 (en) * 2017-06-30 2021-11-24 Beijing Tide Pharmaceutical Co., Ltd. Rho-associated protein kinase inhibitor, pharmaceutical composition comprising the same, as well as preparation method and use thereof
JP7311228B2 (ja) 2017-06-30 2023-07-19 ベイジン タイド ファーマシューティカル カンパニー リミテッド Ｒｈｏ－関連プロテインキナーゼ阻害剤、それを含む医薬組成物並びにその調製方法及び使用
WO2019000682A1 (zh) 2017-06-30 2019-01-03 北京泰德制药股份有限公司 Rho相关蛋白激酶抑制剂、包含其的药物组合物及其制备方法和用途
US11613531B2 (en) * 2017-09-01 2023-03-28 Kadmon Corporation, Llc Inhibitors of RHO associated coiled-coil containing protein kinase
CA3073956A1 (en) 2017-09-03 2019-03-07 Angion Biomedica Corp. Vinylheterocycles as rho-associated coiled-coil kinase (rock) inhibitors
US11345678B2 (en) 2018-04-18 2022-05-31 Medshine Discovery Inc. Benzopyrazole compound used as RHO kinase inhibitor
US11248004B2 (en) 2018-11-06 2022-02-15 Cervello Therapeutics, Llc. Substituted isoquinolines as rock kinase inhibitors
DK3877364T3 (da) 2018-11-06 2024-09-23 Cervello Therapeutics LLC Rock-kinasehæmmere
US20220202827A1 (en) * 2019-04-08 2022-06-30 The General Hospital Corporation Enhancement of Melanocyte Migration Using ROCK Inhibitors
WO2021073592A1 (zh) 2019-10-18 2021-04-22 南京明德新药研发有限公司 作为rho激酶抑制剂的苯并吡唑类化合物的盐型、晶型及其制备方法
CN114746412A (zh) * 2019-12-27 2022-07-12 广东东阳光药业有限公司 Kd-025的新晶型及其制备方法
US12014835B2 (en) 2020-02-19 2024-06-18 Vanderbilt University Methods for evaluating therapeutic benefit of combination therapies
WO2022020850A1 (en) 2020-07-22 2022-01-27 Teva Pharmaceuticals International Gmbh Solid state forms of belumosudil and belumosudil salts
WO2022017412A1 (zh) * 2020-07-22 2022-01-27 北京泰德制药股份有限公司 治疗造血干细胞移植后的移植物抗宿主病的方法
CN114105976B (zh) * 2020-08-28 2024-04-26 杭州邦顺制药有限公司 选择性rock2激酶抑制剂
MX2023008141A (es) 2021-01-11 2023-10-20 Incyte Corp Terapia combinada que comprende el inhibidor de la vía de proteínas tirosina cinasas de janus cinasas (jak) y el inhibidor de la proteína cinasa asociada a rho (rock).
WO2022170864A1 (zh) * 2021-02-09 2022-08-18 苏州科睿思制药有限公司 Belumosudil甲磺酸盐的晶型及其制备方法和用途
WO2022229351A1 (en) 2021-04-28 2022-11-03 Graviton Bioscience Bv Selective inhibitors of rock2 for the treatment of muscular dystrophy
WO2023285706A1 (en) 2021-07-16 2023-01-19 Sandoz Ag Solid-state forms of 2-(3-(4-(1h-indazol-5-ylamino)quinazolin-2-yl )phenoxy)-n- isopropylacetamide methane sulfonic acid salt
CA3238227A1 (en) 2021-11-11 2023-05-19 The Doshisha Cryopreservation preparation for corneal endothelial cells and method for producing said cryopreservation preparation
WO2023205153A1 (en) 2022-04-19 2023-10-26 Kadmon Corporation, Llc Belumosudil for treating chronic lung allograft dysfunction
WO2024015066A1 (en) 2022-07-14 2024-01-18 Kadmon Corporation, Llc Methods of administering belumosudil in combination with cyp3a inducers and/or proton pump inhibitors
WO2024015065A1 (en) 2022-07-14 2024-01-18 Kadmon Corporation, Llc Methods of administering belumosudil for treatment of chronic graft versus host disease in patient subpopulations
CA3178096A1 (en) 2022-07-14 2024-01-14 Kadmon Corporation, Llc Methods of administering belumosudil for treatment of chronic graft versus host disease
WO2024015068A1 (en) 2022-07-14 2024-01-18 Kadmon Corporation, Llc Belumosudil metabolites and uses thereof in the treatment of chronic graft-versus-host disease
WO2024023276A1 (en) 2022-07-27 2024-02-01 Graviton Bioscience Bv Rock2 inhibitors for the treatment of viral infections
WO2024063770A1 (en) * 2022-09-21 2024-03-28 Kadmon Corporation, Llc Liquid formulation of belumosudil
CN117243959A (zh) * 2022-10-13 2023-12-19 山东大学 治疗骨质疏松的方法和药物组合物
WO2024110851A1 (en) * 2022-11-21 2024-05-30 Graviton Bioscience Bv Inhibitors of rock2
WO2024118556A1 (en) 2022-11-29 2024-06-06 Kadmon Corporation, Llc Solid dispersion comprising amorphous 2-[3-[4-(lh-indazol-5- ylamino)quinazolin-2-yl]phenoxy]-n-propan-2-yl-acetamide
WO2024124084A1 (en) 2022-12-09 2024-06-13 Kadmon Corporation, Llc Methods of administering belumosudil for treatment of multiple myeloma

Family Cites Families (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS59115488A (ja) * 1982-12-22 1984-07-03 Hitachi Ltd 密閉形スクロ−ル圧縮機の軸受装置
MXPA04007191A (es) 2002-01-23 2005-03-31 Bayer Pharmaceuticals Corp Derivados de pirimidina como inhibidores de rho-quinasa.
CA2569404A1 (en) 2004-06-04 2005-12-22 Amphora Discovery Corporation Quinoline- and isoquinoline-based compounds exhibiting atp-utilizing enzyme inhibitory activity, and compositions, and uses thereof
CR9465A (es) * 2005-03-25 2008-06-19 Surface Logix Inc Compuestos mejorados farmacocineticamente
US8216575B2 (en) 2006-03-31 2012-07-10 Chengdu Kanghong Biotechnologies Co., Ltd. Inhibition of neovascularization with a soluble chimeric protein comprising VEGF FLT-1 and KDR domains
WO2008054599A2 (en) * 2006-09-27 2008-05-08 Surface Logix, Inc. Rho kinase inhibitors
US8648069B2 (en) 2007-06-08 2014-02-11 Abbvie Inc. 5-substituted indazoles as kinase inhibitors
JP5767965B2 (ja) 2008-06-10 2015-08-26 プレキシコン インコーポレーテッドＰｌｅｘｘｉｋｏｎ Ｉｎｃ． キナーゼを調節する５ｈ−ピロロ［２，３−ｂ］ピラジン誘導体、およびその適応症
JP5856064B2 (ja) 2009-11-17 2016-02-09 ザ リージェンツ オブ ザ ユニバーシティ オブ ミシガン 治療特性を有する１，４−ベンゾジアゼピン−２，５−ジオンおよび関連化合物
EA031616B1 (ru) * 2010-03-02 2019-01-31 пиЭйч ФАРМА Ко., ЛТД. Новые ингибиторы rock
US9079880B2 (en) * 2010-07-07 2015-07-14 Boehringer Ingelheim International Gmbh Rho kinase inhibitors
WO2012040499A2 (en) 2010-09-22 2012-03-29 Surface Logix, Inc. Metabolic inhibitors
EP2640698A1 (en) 2010-11-15 2013-09-25 AbbVie Inc. Nampt and rock inhibitors
GB201107223D0 (en) 2011-04-29 2011-06-15 Amakem Nv Novel rock inhibitors
GB201114854D0 (en) 2011-08-29 2011-10-12 Amakem Nv Novel rock inhibitors
EA201490515A1 (ru) 2011-08-31 2014-08-29 Амакем Нв Новые ингибиторы rock-киназ
LT2903618T (lt) 2012-10-05 2022-08-25 Kadmon Corporation, Llc Rho kinazės inhibitoriai
JP2016502502A (ja) * 2012-10-05 2016-01-28 カドモン コーポレイション，リミティド ライアビリティ カンパニー 眼疾患の治療
WO2015157556A1 (en) * 2014-04-09 2015-10-15 Kadmon Corporation, Llc Treatment of gvhd

Also Published As

Publication number Publication date
JP6703075B2 (ja) 2020-06-03
JP2019034949A (ja) 2019-03-07
LT2903618T (lt) 2022-08-25
EP2903618A2 (en) 2015-08-12
US10183931B2 (en) 2019-01-22
EP4116293A2 (en) 2023-01-11
CN113773308A (zh) 2021-12-10
CN113637008A (zh) 2021-11-12
CN113620933A (zh) 2021-11-09
ES2924915T3 (es) 2022-10-11
HUE059305T2 (hu) 2022-11-28
EP4116293A3 (en) 2023-03-29
CA3151343A1 (en) 2014-04-10
US20150252025A1 (en) 2015-09-10
US9815820B2 (en) 2017-11-14
WO2014055996A3 (en) 2014-06-19
JP2015533125A (ja) 2015-11-19
JP6419076B2 (ja) 2018-11-14
US20180244657A1 (en) 2018-08-30
US20210147391A1 (en) 2021-05-20
PT2903618T (pt) 2022-08-19
EP2903618A4 (en) 2017-05-10
CA2926478A1 (en) 2014-04-10
CN113637007A (zh) 2021-11-12
US10696660B2 (en) 2020-06-30
SI2903618T1 (sl) 2022-09-30
RS63503B1 (sr) 2022-09-30
DK2903618T3 (da) 2022-08-22
CA2926478C (en) 2022-05-24
CN105120869A (zh) 2015-12-02
PL2903618T3 (pl) 2022-09-19
US20190308953A1 (en) 2019-10-10
EP2903618B1 (en) 2022-06-01
WO2014055996A2 (en) 2014-04-10
EA201500362A1 (ru) 2015-08-31

Similar Documents

Publication Publication Date Title
HRP20220913T1 (hr) Inhibitori rho kinaze
HRP20171453T1 (hr) Derivati imidazotiadiazola i imidazopirazina kao inhibitori proteazom aktiviranog receptora 4 (par4) za liječenje agregacije trombocita
HRP20191579T1 (hr) Spojevi kao modulatori za ror gama
PE20070848A1 (es) Derivados de pirimidina como ligandos del receptor de histamina h4
PE20090288A1 (es) Derivados de quinoxalina como inhibidores de la pi3 quinasa
RS54425B1 (en) Pyridine and Pyrazine Derivatives for Cystic Fibrosis (CF) Treatment
AR077417A1 (es) Compuesto triazolopiridina y su accion como inhibidor de prolil hidroxilasa o agente inductor de la produccion de eritropoyetina
RS54358B1 (en) PYROLOPYRIDINES AS KINASE INHIBITORS
RS52596B (en) SUBSTITUTED AMID DERIVATIVES AS PROTEIN KINASE INHIBITORS
RS53677B1 (en) TRIAZOLOPYRIDINE UNITS
NZ587926A (en) Pyridines and pyrazines as inhibitors of pi3k
RS52949B (en) ADDITIONAL SALTS OF AMINS CONTAINING HYDROXYL AND / OR CARBOXYL GROUPS WITH AMINONICOTINIC ACID DERIVATIVES AS DHODH INHIBITORS
RS53350B (en) SUBSTITUTED COMPOUNDS OF IMIDASO [1,2-B] PYRIDASINE AS INK KINASE INHIBITORS
CO6251283A2 (es) Pirimidil ciclopentanos como inhibidores de proteina cinasa akt
RS52605B (en) Benzoic Acids (1-Phenyl-2-pyridin-4-yl) -ETHYL ESTERS AS PHOSPHODIESTERASE INHIBITORS
PH12014502866A1 (en) Fungicidal heterocyclic carboxamides
RS53028B (en) PYRASOLO PIRIDINE DERIVATIVES AS NADPH OXIDASE INHIBITORS
MY194307A (en) Pyridone derivative having tetrahydropyranylmethyl group
RS52210B (en) CYCLOPENT [D] PYRIMIDINS AS PROTEIN KINASE ACTION INHIBITORS
MX2015015893A (es) 2-fenilimidazo[1,2-a]pirimidinas como agentes formadores de imagen.
AR074052A1 (es) Compuestos pirazolo{1,5-a}pirimidina sustituida como inhibidores de trk cinasa
RS53275B (en) ARYL-PYRIDINE AS AN ALDOSTERON SYNTHASE INHIBITOR
BR112015015812A2 (pt) derivados de pirimidina fundidos a pirido ou pirrolo como inibidores de autotaxina para tratamento de dor
RS52520B (en) ACT AND P70 S6 KINASE INHIBITORS
BRPI1009212B8 (pt) Composto de piperazina capaz de inibir a prostaglandina d sintase, seus usos e composição farmacêutica