HRP20160172T1 - Spojevi koji su inhibitori metaloenzima - Google Patents

Spojevi koji su inhibitori metaloenzima Download PDF

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HRP20160172T1
HRP20160172T1 HRP20160172TT HRP20160172T HRP20160172T1 HR P20160172 T1 HRP20160172 T1 HR P20160172T1 HR P20160172T T HRP20160172T T HR P20160172TT HR P20160172 T HRP20160172 T HR P20160172T HR P20160172 T1 HRP20160172 T1 HR P20160172T1
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difluorophenyl
difluoro
pyridin
tetrazol
propan
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HRP20160172TT
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William J. Hoekstra
Robert J. Schotzinger
Stephen William Rafferty
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Viamet Pharmaceuticals, Inc.
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Publication of HRP20160172T1 publication Critical patent/HRP20160172T1/hr

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    • 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
    • C07D401/06—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 only aliphatic carbon atoms
    • 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
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    • A—HUMAN NECESSITIES
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    • A61P17/06—Antipsoriatics
    • 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
    • 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
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A61P31/08—Antibacterial agents for leprosy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A61P33/06—Antimalarials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • 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
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
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  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Dermatology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Claims (15)

1. Spoj s formulom (I), ili njegova sol, naznačen time da: [image] MBG je proizvoljno supstituiran tetrazolil, proizvoljno supstituiran triazolil, ili proizvoljno supstituiran pirazolil; R1 je halo; R2 je halo; svaki R3 je neovisno alkil, cijano, haloalkil, alkoksi, halo, haloalkoksi, R4 je aril proizvoljno supstituiran s 0, 1, 2 ili 3 neovisnih R3; R5 je H, ili -C(O)alkil proizvoljno supstituiran s amino; n je 0, 1, 2 ili 3.
2. Spoj prema zahtjevu 1, naznačen time da R1 je fluoro.
3. Spoj prema zahtjevu 1, naznačen time da R2 je fluoro.
4. Spoj prema zahtjevu 1, naznačen time da R1 i R2 su fluoro.
5. Spoj prema zahtjevu 1, naznačen time da R4 je fenil proizvoljno supstituiran s 0, 1, 2 ili 3 neovisnih R3.
6. Spoj prema zahtjevu 1, naznačen time da R4 je fenil proizvoljno supstituiran s 0, 1, 2 ili 3 neovisnih halo.
7. Spoj prema zahtjevu 1, naznačen time da R4 je fenil proizvoljno supstituiran s 0, 1, 2 ili 3 neovisnih fluoro.
8. Spoj prema zahtjevu 1, naznačen time da R4 je 2,4-difluorofenil.
9. Spoj prema zahtjevu 1, naznačen time da R5 je H.
10. Spoj prema zahtjevu 1, naznačen time da R5 je amino supstituirani acil.
11. Spoj prema zahtjevu 1, naznačen time da: R1 je fluoro; R2 je fluoro; R4 je 2,4-difluorofenil; i R5 je H.
12. Spoj prema zahtjevu 1, naznačen time da: svaki R3 je neovisno cijano, haloalkil, alkoksi, halo, haloalkoksi, i n je 1 ili 2.
13. Spoj prema zahtjevu 11, naznačen time da: svaki R3 je neovisno cijano, haloalkil, alkoksi, halo, haloalkoksi, i n je 1.
14. Spoj prema zahtjevu 1, naznačen time da je jedan od: 4-(6-(2-(2,4-difluorofenil)-1,1-difluoro-2-hidroksi-3-(1H-tetrazol-1-il)propil) piridin-3-il)benzonitril (1); 2-(2,4-difluorofenil)-1,1-difluoro-3-(1H-tetrazol-1-il)-1-(5-(4-(trifluorometil)fenil)piridin-2-il)propan-2-ol (2); 3-(6-(2-(2,4-difluorofenil)-1,1-difluoro-2-hidroksi-3-(1H-tetrazol-1-il)propil)piridin-3-il)benzonitril (3); 2-(2,4-difluorofenil)-1,1-difluoro-1-(5-(4-izopropoksifenil)piridin-2-il)-3-(1H-tetrazol-1-il)propan-2-ol (4); 2-(2,4-difluorofenil)-1,1-difluoro-1-(5-(4-fluorofenil)piridin-2-il)-3-(1H-tetrazol-1-il)propan-2-ol (5); 2-(2,4-difluorofenil)-1,1-difluoro-3-(1H-tetrazol-1-il)-1-(5-(3-(trifluorometoksi)fenil)piridin-2-il)propan-2-ol (6); 2-(2,4-difluorofenil)-1,1-difluoro-3-(1H-tetrazol-1-il)-1-(5-(4-(trifluorometoksi) fenil)piridin-2-il) propan-2-ol (7); 1-(5-(3-klorofenil)piridin-2-il)-2-(2,4-difluorofenil)-1,1-difluoro-3-(1H-tetrazol-1-il)propan-2-ol (8); 1-(5-(4-klorofenil)piridin-2-il)-2-(2,4-difluorofenil)-1,1-difluoro-3-(1H-tetrazol-1-il)propan-2-ol (9); 2-(2,4-difluorofenil)-1-(5-(2,5-difluorofenil)piridin-2-il)-1,1-difluoro-3-(1H-tetrazol-1-il)propan-2-ol (10); 2-(2,4-difluorofenil)-1,1-difluoro-3-(1H-tetrazol-1-il)-1-(5-(4-(2,2,2-trifluoroethoksi)fenil)piridin-2-il)propan-2-ol (11); 2-(2,4-difluorofenil)-1,1-difluoro-1-(5-(4-(2,2,3,3,3-pentafluoropropoksi)fenil)piridin-2-il)-3-(1H-tetrazol-1-il)propan-2-ol (12); 2-(2, 4-difluorofenil)-1,1-difluoro-3-(1H-tetrazol-1-il)-1-(5-(4-(2,2,2-trifluoroethoksi)fenil)piridin-2-il)propan-2-il 3-aminopropanoat (13); 2-(2,4-difluorofenil)-1,1-difluoro-3-(1H-tetrazol-1-il)-1-(5-(4-(2,2,2-trifluoroethoksi)fenil)piridin-2-il)propan-2-il 2-aminoacetat hidroklorid (14); 2-(2,4-difluorofenil)-1,1-difluoro-3-(1H-pirazol-3-il)-1-(5-(4-(trifluoro metoksi) fenil) piridin-2-il)propan-2-ol (15); 2-(2,4-difluorofenil)-1,1-difluoro-1-(5-(4-fluorofenil)piridin-2-il)-3-(1H-1,2,4-triazol-1-il)propan-2-ol (16); 2-(2,4-difluorofenil)-1,1-difluoro-3-(1H-1,2,4-triazol-1-il)-1-(5-(4-(2,2,2-trifluoroethoksi) fenil)piridin-2-il)propan-2-ol (17); 2-(2,4-difluorofenil)-1,1-difluoro-3-(1H-1,2,4-triazol-1-il)-1-(5-(4-(trifluorometoksi)fenil)piridin-2-il)propan-2-ol (18); 2-(2,4-difluorofenil)-1,1-difluoro-3-(1H-1,2,3-triazol-1-il)-1-(5-(4-(trifluorometoksi)fenil)piridin-2-il)propan-2-ol (19); 2-(2,4-difluorofenil)-1,1-difluoro-3-(2H-tetrazol-1-il)-1-(5-(4-(2,2,2-trifluoroethoksi)fenil)piridin-2-il)propan-2-ol (20); 2-(2,4-difluorofenil)-1,1-difluoro-3-(2H-tetrazol-1-il)-1-(5-(3-fluorofenil) piridin-2-il)propan-2-ol (21); 2-(2,4-difluorofenil)-1,1-difluoro-3-(2H-tetrazol-1-il)-1-(5-(4-(trifluorometil)fenil)piridin-2-il)propan-2-ol (22); 2-(2,4-difluorofenil)-1,1-difluoro-3-(1H-1,2,3-triazol-1-il)-1-(5-(4-(trifluorometilfenil)piridin-2-il)propan-2-ol (23); 4-(6-(2-(2,4-difluorofenil)-1,1-difluoro-2-hidroksi-3-(1H-tetrazol-1-il)propil) piridin-3-il)fenol (24); 2-(2,4-difluorofenil)-1,1-difluoro-1-(5-(3-izopropilfenil)piridin-2-il)-3-(1H-tetrazol-1-il)propan-2-ol (25); 2-(2,4-difluorofenil)-1-(5-(3,4-difluorofenil)piridin-2-il)-1,1-difluoro-3-(1H-tetrazol-1-il)propan-2-ol (26); 1-(5-(3-(difluorometoksi)fenil)piridin-2-il)-2-(2,4-difluorofenil)-1,1-difluoro-3-(1H-tetrazol-1-il)propan-2-ol (27); 2-(2,4-difluorofenil)-1,1-difluoro-3-(1H-tetrazol-1-il)-1-(5-(4-((trifluorometil)tio)fenil)piridin-2-il)propan-2-ol (28).
15. Pripravak naznačen time da sadrži spoj prema zahtjevu 1 i farmaceutski prihvatljiv nosač.
HRP20160172TT 2010-04-24 2016-02-16 Spojevi koji su inhibitori metaloenzima HRP20160172T1 (hr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US32766310P 2010-04-24 2010-04-24
EP11772772.7A EP2563771B1 (en) 2010-04-24 2011-04-22 Metalloenzyme inhibitor compounds
PCT/US2011/033597 WO2011133875A2 (en) 2010-04-24 2011-04-22 Metalloenzyme inhibitor compounds

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HRP20160172T1 true HRP20160172T1 (hr) 2016-05-06

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HRP20160172TT HRP20160172T1 (hr) 2010-04-24 2016-02-16 Spojevi koji su inhibitori metaloenzima

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US (2) US8236962B2 (hr)
EP (1) EP2563771B1 (hr)
JP (2) JP5266430B2 (hr)
KR (1) KR101379370B1 (hr)
CN (1) CN103097374B (hr)
AU (1) AU2011242562B2 (hr)
BR (1) BR112012027308B1 (hr)
CA (2) CA2837400C (hr)
CY (1) CY1117678T1 (hr)
DK (1) DK2563771T3 (hr)
EA (1) EA024341B1 (hr)
ES (1) ES2563319T3 (hr)
HR (1) HRP20160172T1 (hr)
HU (1) HUE026474T2 (hr)
PL (1) PL2563771T3 (hr)
PT (1) PT2563771E (hr)
RS (1) RS55010B1 (hr)
SI (1) SI2563771T1 (hr)
TW (1) TWI578987B (hr)
WO (1) WO2011133875A2 (hr)

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