DK2563771T3 - Metalloenzyminhibitorforbindelser - Google Patents

Metalloenzyminhibitorforbindelser Download PDF

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DK2563771T3
DK2563771T3 DK11772772.7T DK11772772T DK2563771T3 DK 2563771 T3 DK2563771 T3 DK 2563771T3 DK 11772772 T DK11772772 T DK 11772772T DK 2563771 T3 DK2563771 T3 DK 2563771T3
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difluorophenyl
difluoro
pyridin
propan
compound
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DK11772772.7T
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William J Hoekstra
Robert J Schotzinger
Stephen William Rafferty
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Viamet Pharmaceuticals Inc
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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
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    • 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
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    • 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
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    • A—HUMAN NECESSITIES
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    • A61P33/00—Antiparasitic agents
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    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A61P33/06—Antimalarials
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    • A—HUMAN NECESSITIES
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    • 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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Claims (15)

1. Forbindelse med formel (I) eller salt deraf, hvor: w
MBG er eventuelt substitueret tetrazolyl, eventuelt substitueret triazolyl eller eventuelt substitueret pyrazolyl; Ri er halogen; R2 er halogen; hver R3 uafhængigt er alkyl, cyano, halogenalkyl, alkoxy, halogen, halogenalkoxy; R4 er aryl eventuelt substitueret med 0, 1, 2 eller 3 uafhængige R3; R5 er H eller -C(O)alkyl eventuelt substitueret med amino; n er 0, 1, 2 eller 3.
2. Forbindelse ifølge krav 1, hvor R4 er fluor.
3. Forbindelse ifølge krav 1, hvor R2 er fluor.
4. Forbindelse ifølge krav 1, hvor Ri og R2 er fluor.
5. Forbindelse ifølge krav 1, hvor R4 er phenyl eventuelt substitueret med 0, 1, 2 eller 3 uafhængige R3.
6. Forbindelse ifølge krav 1, hvor R4 er phenyl eventuelt substitueret med 0, 1, 2 eller 3 uafhængige halogen.
7. Forbindelse ifølge krav 1, hvor R4 er phenyl eventuelt substitueret med 0, 1, 2 eller 3 uafhængige fluor.
8. Forbindelse ifølge krav 1, hvor R4 er 2,4-difluorphenyl.
9. Forbindelse ifølge krav 1, hvor R5 er H.
10. Forbindelse ifølge krav 1, hvor R5 er aminosubstitueret acyl.
11. Forbindelse ifølge krav 1, hvor: Ri er fluor; R2 er fluor; R4 er 2,4-difluorphenyl; og R5 er H.
12. Forbindelse ifølge krav 1, hvor: hver R3 uafhængigt er cyano, halogenalkyl, alkoxy, halogen, halogenalkoxy, og n er 1 eller 2.
13. Forbindelse ifølge krav 11, hvor: hver R3 uafhængigt er cyano, halogenalkyl, alkoxy, halogen, halogenalkoxy, og n er 1.
14. Forbindelse ifølge krav 1, som er én af: 4-(6-(2-(2,4-Difluorphenyl)-1,1-difluor-2-hydroxy-3-(1H-tetrazol-l-yl)propyl)pyridin-3-yl)benzonitril (1); 2- (2,4-Difluorphenyl)-1,l-difluor-3-(lff-tetrazol-l-yl)-1-(5-(4-(trifluormethyl) phenyl)pyridin-2-yl)propan-2-ol (2); 3- (6-(2-(2,4-Difluorphenyl)-1,1-difluor-2-hydroxy-3-(1H-tetrazol-l-yl)propyl)pyridin-3-yl)benzonitril (3); 2-(2,4-Difluorphenyl)-1,1-difluor-l-(5-(4- isopropoxyphenyl)pyridin-2-yl)-3-(lff-tetrazol-l-yl)propan-2-ol (4) ; 2-(2,4-Difluorphenyl)-1,1-difluor-l-(5-(4-fluorphenyl)pyridin-2-yl)-3-(lH-tetrazol-l-yl)propan-2-ol (5); 2-(2,4-Difluorphenyl)-1,l-difluor-3-(lH-tetrazol-l-yl)-1_(5-(3-(trifluormethoxy)phenyl)pyridin-2-yl)propan-2-ol (6); 2-(2,4-Difluorphenyl)-1,l-difluor-3-(lff-tetrazol-l-yl) "1“(5-(4-(trifluormethoxy)phenyl)pyridin-2-yl)propan-2-ol (7); 1-(5-(3-Chlorphenyl)pyridin-2-yl)-2-(2,4-difluorphenyl)-1,1-difluor-3-(lH-tetrazol-l-yl)propan-2-ol (8); 1-(5-(4-Chlorphenyl)pyridin-2-yl)-2-(2,4-difluorphenyl)-1,1 difluor-3-(lH-tetrazol-l-yl)propan-2-ol (9); 2-(2,4-Difluorphenyl)-1-(5-(2,5-difluorphenyl)pyridin-2-yl)-1, l-difluor-3-(lH-tetrazol-l-yl)propan-2-ol (10); 2-(2,4-Difluorphenyl)-1, l-difluor-3-(lH-tetrazol-l-yl) -1-(5-(4-(2,2,2-trifluorethoxy)phenyl)pyridin-2-yl)propan-2-ol (11); 2-(2,4-Difluorphenyl)-1,1-difluor-1-(5-(4-(2,2,3,3,3-pentafluorpropoxy)phenyl)pyridin-2-yl)-3-(lff-tetrazol-l-yl)propan-2-ol (12); 2- (2,4-difluorphenyl) -1, l-difluor-3- (lH-tetrazol-l-yl) _1_ (5-(4-(2,2,2-trifluorethoxy)phenyl)pyridin-2-yl)propan-2-yl-3-aminopropanoat (13); 2-(2,4-Difluorphenyl)-1,l-difluor-3-(lH-tetrazol-l-yl)-1_ (5-(4-(2,2,2-trifluorethoxy)phenyl)pyridin-2-yl)propan-2-yl-2-aminoacetathydrochlorid (14); 2-(2,4-Difluorphenyl)-1,l-difluor-3-(lH-pyrazol-3-yl)-1- (5- (4-(trifluormethoxy)phenyl)pyridin-2-yl)propan-2-ol (15); 2-(2,4-Difluorphenyl)-1,1-difluor-l-(5-(4 — fluorphenyl)pyridin-2-yl)-3-(1H-1,2,4-triazol-l-yl)propan-2-ol (16) ; 2-(2,4-Difluorphenyl)-1,l-difluor-3-(1H-1,2,4-triazol-l-yl)-1 (5-(4-(2,2,2-trifluorethoxy) phenyl)pyridin-2-yl) propan-2-ol (17) ; 2-(2,4-Difluorphenyl)-1,l-difluor-3-(lH-l,2,4-triazol-l-yl)-l (5-(4-(trifluormethoxy)phenyl)pyridin-2-yl)propan-2-ol (18); 2-(2,4-Difluorphenyl)-1,l-difluor-3-(lH-l,2,3-triazol-l-yl)_l (5-(4-(trifluormethoxy)phenyl)pyridin-2-yl)propan-2-ol (19); 2- (2,4-Difluorphenyl) -1, l-difluor-3- (2H-tetrazol-l-yl) -1“ (5_ (4-(2,2,2-trifluorethoxy)phenyl)pyridin-2-yl)propan-2-ol (20); 2- (2,4-Difluorphenyl)-1,l-difluor-3-(2H-tetrazol-l-yl) -1-(5-(3-fluorphenyl)pyridin-2-yl)propan-2-ol (21) ; 2- (2,4-Difluorphenyl)-1,l-difluor-3-(2H-tetrazol-l-yD-1“(5-(4-(trifluormethyl)phenyl)pyridin-2-yl)propan-2-ol (22) , 2-(2,4-Difluorphenyl)-1,l-difluor-3-(lH-l, 2,3-triazol-l yl) 1 (5-(4-(trifluormethylphenyl)pyridin-2-yl)propan-2-ol (23); 4-(6-(2-(2,4-Difluorphenyl)-1,1-difluor-2-hydroxy-3-(1H-tetrazol-l-yl)propyl)pyridin-3-yl) phenol (24); 2-(2,4-Difluorphenyl)-1,1-difluor-l- (5-(3- isopropylphenyl)pyridin-2-yl)-3-(lH-tetrazol-l-yl)Pr°Pan 2 ol (25) ; 2-(2,4-Difluorphenyl)-1-(5-(3,4-difluorphenyl)pyridin-2-yl)- 1,l-difluor-3-(lH-tetrazol-l-yl)propan-2-ol (26); 1- (5-(3-(Difluormethoxy)phenyl)pyridin-2-yl)-2-(2,4- difluorphenyl)-1,l-difluor-3-(lH-tetrazol-l-yl)propan-2-ol (27) ; 2- (2,4-Difluorphenyl)-1, l-difluor-3-(lH-tetrazol-l-yl) -1-(5- (4-((trifluormethyl) thio)phenyl)pyridin-2-yl)propan-2-ol (28) .
15. Sammensætning, der omfatter en forbindelse ifølge krav 1 og et farmaceutisk acceptabelt bæremateriale.
DK11772772.7T 2010-04-24 2011-04-22 Metalloenzyminhibitorforbindelser DK2563771T3 (da)

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US32766310P 2010-04-24 2010-04-24
PCT/US2011/033597 WO2011133875A2 (en) 2010-04-24 2011-04-22 Metalloenzyme inhibitor compounds

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

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