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DK2776038T3 - Acc-hæmmere og anvendelser deraf - Google Patents

Acc-hæmmere og anvendelser deraf Download PDF

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DK2776038T3
DK2776038T3 DK12848361.7T DK12848361T DK2776038T3 DK 2776038 T3 DK2776038 T3 DK 2776038T3 DK 12848361 T DK12848361 T DK 12848361T DK 2776038 T3 DK2776038 T3 DK 2776038T3
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compound
nitrogen
sulfur
oxygen
independently selected
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DK12848361.7T
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Geraldine C Harriman
Craig E Masse
James Harwood
Sathesh Bhat
Jeremy Robert Greenwood
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Gilead Apollo Llc
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    • 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
    • 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
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dentistry (AREA)
  • Environmental Sciences (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Agronomy & Crop Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Claims (10)

  1. ACC-HÆMMERE OG ANVENDELSER DERAF
    1. Forbindelse med formlen Π:
    II eller et farmaceutisk acceptabelt salt deraf, hvor: R1 er hydrogen eller Ci_4 alifatisk, eventuelt substitueret med ét eller flere halogener, -OR, -SR, -N(R)2, -N(R)C(0)R, -C(0)N(R)2, -N(R)C(0)N(R)2, -N(R)C(0)0R, -0C(0)N(R)2, -N(R)S02R, -S02N(R)2, -C(0)R, -C(0)0R, -0C(0)R, -S(0)R eller -S02R; R2 er Fly, hvor Fly er udvalgt fra 4-8-leddet mættet eller delvist umættet monocyklisk heterocyklisk ring med 1-2 heteroatomer, der er uafhængigt udvalgt fra nitrogen, oxygen eller svovl, en 5-6-leddet monocyklisk heteroaromatisk ring med 1-4 heteroatomer, der er uafhængigt udvalgt fra nitrogen, oxygen eller svovl, eller en 8-10-leddet bicyklisk heteroaromatisk ring med 1-5 heteroatomer, der er uafhængigt udvalgt fra nitrogen, oxygen eller svovl; hver R uafhængigt er hydrogen eller en eventuelt substitueret gruppe, der er udvalgt fra Ci_6 alifatisk, en 3-8-leddet mættet eller delvist umættet monocyklisk carbocyklisk ring, phenyl, en 8-10-leddet bicyklisk aromatisk carbocyklisk ring; en 4-8-leddet mættet eller delvist umættet monocyklisk heterocyklisk ring med 1-2 heteroatomer, der er uafhængigt udvalgt fra nitrogen, oxygen eller svovl, en 5-6-leddet monocyklisk heteroaromatisk ring med 1-4 heteroatomer, der er uafhængigt udvalgt fra nitrogen, oxygen eller svovl, eller en 8-10-leddet bicyklisk heteroaromatisk ring med 1-5 heteroatomer, der er uafhængigt udvalgt fra nitrogen, oxygen eller svovl; R3 er hydrogen, halogen, -CN, -OR, -SR, -N(R)2, -N(R)C(0)R, -C(0)N(R)2, -N(R)C(0)N(R)2, -N(R)C(0)0R, -0C(0)N(R)2, -N(R)S02R, -S02N(R)2, -C(0)R, -C(0)0R, -0C(0)R, -S(0)R, -so2r, -B(OFl)2 eller en eventuelt substitueret ring, der er udvalgt fra phenyl eller 5-6-leddet heteroaryl med 1-4 heteroatomer, der er uafhængigt udvalgt fra nitrogen, oxygen eller svovl; R4 er en eventuelt substitueret phenyl- eller naphthylring; hver af R5 og R5' uafhængigt er -R, -OR, -SR, -N(R)2, -N(R)C(0)R, -C(0)N(R)2, -N(R)C(0)N(R)2, -N(R)C(0)0R, -0C(0)N(R)2, -N(R)S02R, -S02N(R)2, -C(0)R, -C(0)0R, -0C(0)R, -S(0)R eller -S02R; eller R5 og R5 tages sammen for at danne en cyclopropylenyl-, cyclobutylenyl- eller oxetanylgruppe; og hver af R7 og R7 uafhængigt er hydrogen, -R, -OR, -SR, -N(R)2, -N(R)C(0)R, -C(0)N(R)2, -N(R)C(0)N(R)2, -N(R)C(0)0R, -0C(0)N(R)2, -N(R)S02R, -S02N(R)2, -C(0)R, -C(0)0R, -0C(0)R, -S(0)R eller -S02R; eller R7 og R7 tages sammen for at danne en 3-8-leddet mættet eller delvist umættet monocyklisk carbocyklisk ring, eller en 4-8-leddet mættet eller delvist umættet monocyklisk heterocyklisk ring med 1-2 heteroatomer, der er uafhængigt udvalgt fra nitrogen, oxygen eller svovl.
  2. 2. Forbindelse med formlen III:
    Ill eller et farmaceutisk acceptabelt salt deraf, hvor: R1 er hydrogen eller Ci_4 alifatisk, eventuelt substitueret med ét eller flere halogener, -OR, -SR, -N(R)2, -N(R)C(0)R, -C(0)N(R)2, -N(R)C(0)N(R)2, -N(R)C(0)0R, -0C(0)N(R)2, -N(R)S02R, -S02N(R)2, -C(0)R, -C(0)0R, -0C(0)R, -S(0)R eller -S02R; R2 er Hy, hvor Hy er udvalgt fra en 4-8-leddet mættet eller delvist umættet monocyklisk heterocyklisk ring med 1-2 heteroatomer, der er uafhængigt udvalgt fra nitrogen, oxygen eller svovl, en 5-6-leddet monocyklisk heteroaromatisk ring med 1-4 heteroatomer, der er uafhængigt udvalgt fra nitrogen, oxygen eller svovl, eller en 8-10-leddet bicyklisk heteroaromatisk ring med 1-5 heteroatomer, der er uafhængigt udvalgt fra nitrogen, oxygen eller svovl; hver R uafhængigt er hydrogen eller en eventuelt substitueret gruppe, der er udvalgt fra Ci_6 alifatisk, en 3-8-leddet mættet eller delvist umættet monocyklisk carbocyklisk ring, phenyl, en 8-10-leddet bicyklisk aromatisk carbocyklisk ring; en 4-8-leddet mættet eller delvist umættet monocyklisk heterocyklisk ring med 1-2 heteroatomer, der er uafhængigt udvalgt fra nitrogen, oxygen eller svovl, en 5-6-leddet monocyklisk heteroaromatisk ring med 1-4 heteroatomer, der er uafhængigt udvalgt fra nitrogen, oxygen eller svovl, eller en 8-10-leddet bicyklisk heteroaromatisk ring med 1-5 heteroatomer, der er uafhængigt udvalgt fra nitrogen, oxygen eller svovl; R3 er hydrogen, halogen, -CN, -OR, -SR, -N(R)2, -N(R)C(0)R, -C(0)N(R)2, -N(R)C(0)N(R)2, -N(R)C(0)0R, -0C(0)N(R)2, -N(R)S02R, -S02N(R)2, -C(0)R, -C(0)0R, -0C(0)R, -S(0)R, -so2r, -B(OH)2 eller en eventuelt substitueret ring, der er udvalgt fra phenyl eller 5-6-leddet heteroaryl med 1-4 heteroatomer, der er uafhængigt udvalgt fra nitrogen, oxygen eller svovl; hver af R5 og R5' uafhængigt er -R, -OR, -SR, -N(R)2, -N(R)C(0)R, -C(0)N(R)2, -N(R)C(0)N(R)2, -N(R)C(0)0R, -0C(0)N(R)2, -N(R)S02R, -S02N(R)2, -C(0)R, -C(0)0R, -0C(0)R, -S(0)R eller -S02R; eller R5 og R5 tages sammen for at danne en cyclopropylenyl-, cyclobutylenyl- eller oxetanylgruppe; R6 er -R, -C(0)N(R)2 eller -C(0)R; hver R8 uafhængigt er udvalgt fra halogen, -R, -OR, -SR, -N(R)2 eller deuterium; og n er 0-5.
  3. 3. Forbindelse med formlen IV:
    iv eller et farmaceutisk acceptabelt salt deraf, hvor: R1 er hydrogen eller C1A alifatisk, eventuelt substitueret med ét eller flere halogener, -OR, -SR, -N(R)2, -N(R)C(0)R, -C(0)N(R)2, -N(R)C(0)N(R)2, -N(R)C(0)0R, -0C(0)N(R)2, -N(R)S02R, -S02N(R)2, -C(0)R, -C(0)0R, -0C(0)R, -S(0)R eller -S02R; R2 er Hy, hvor Hy er udvalgt fra 4-8-leddet mættet eller delvist umættet monocyklisk heterocyklisk ring med 1-2 heteroatomer, der er uafhængigt udvalgt fra nitrogen, oxygen eller svovl, en 5-6-leddet monocyklisk heteroaromatisk ring med 1-4 heteroatomer, der er uafhængigt udvalgt fra nitrogen, oxygen eller svovl, eller en 8-10-leddet bicyklisk heteroaromatisk ring med 1-5 heteroatomer, der er uafhængigt udvalgt fra nitrogen, oxygen eller svovl; hver R uafhængigt er hydrogen eller en eventuelt substitueret gruppe, der er udvalgt fra Ci_6 alifatisk, en 3-8-leddet mættet eller delvist umættet monocyklisk carbocyklisk ring, phenyl, en 8-10-leddet bicyklisk aromatisk carbocyklisk ring; en 4-8-leddet mættet eller delvist umættet monocyklisk heterocyklisk ring med 1-2 heteroatomer, der er uafhængigt udvalgt fra nitrogen, oxygen eller svovl, en 5-6-leddet monocyklisk heteroaromatisk ring med 1-4 heteroatomer, der er uafhængigt udvalgt fra nitrogen, oxygen eller svovl, eller en 8-10-leddet bicyklisk heteroaromatisk ring med 1-5 heteroatomer, der er uafhængigt udvalgt fra nitrogen, oxygen eller svovl; R3 er hydrogen, halogen, -CN, -OR, -SR, -N(R)2, -N(R)C(0)R, -C(0)N(R)2, -N(R)C(0)N(R)2, -N(R)C(0)0R, -0C(0)N(R)2, -N(R)S02R, -S02N(R)2, -C(0)R, -C(0)0R, -0C(0)R, -S(0)R, -so2r, -B(OH)2, eller en eventuelt substitueret ring, der er udvalgt fra phenyl eller 5-6-leddet heteroaryl med 1-4 heteroatomer, der er uafhængigt udvalgt fra nitrogen, oxygen eller svovl; hver af R5 og R5' uafhængigt er -R, -OR, -SR, -N(R)2, -N(R)C(0)R, -C(0)N(R)2, -N(R)C(0)N(R)2, -N(R)C(0)0R, -0C(0)N(R)2, -N(R)S02R, -S02N(R)2, -C(0)R, -C(0)0R, -0C(0)R, -S(0)R, eller -S02R; eller R5 og R5 tages sammen for at danne en cyclopropylenyl-, cyclobutylenyl- eller oxetanylgruppe; R6 er -R, -C(0)N(R)2 eller -C(0)R; hver R8 uafhængigt er udvalgt fra halogen, -R, -OR, -SR, -N(R)2 eller deuterium; og n er 0-5.
  4. 4. Forbindelse ifølge et hvilket som helst af kravene 1, 2 eller 3, hvor R1 er methyl eller trifluormethyl.
  5. 5. Forbindelse ifølge et hvilket som helst af kravene 1, 2, 3 eller 4, hvor R2 er oxazolyl.
  6. 6. Forbindelse ifølge et hvilket som helst af kravene 1, 2, 3 eller 4, hvor R3 er tetrazolyl, -C(0)0R, -C(0)N(R)2 eller -OR.
  7. 7. Forbindelse ifølge et hvilket som helst af kravene 1, 2, 3, 4, 5 eller 6, hvor R5 og R5 hver er methyl, eller et farmaceutisk acceptabelt salt deraf.
  8. 8. Forbindelse ifølge et hvilket som helst af kravene 1,2, 3, 4, 5, 6 eller 7, hvor R3 er -C(0)0R eller -C(0)N(R)2 eller et farmaceutisk acceptabelt salt deraf.
  9. 9. Forbindelse ifølge et hvilket som helst af kravene 1, 2, 3, 4, 5, 6 eller 7, hvor R3 er -C(0)0H eller et farmaceutisk acceptabelt salt deraf.
  10. 10. Sammensætning, der omfatter en forbindelse ifølge et hvilket som helst af kravene 1, 2, 3, 4, 5, 6, 7, 8 eller 9, og et farmaceutisk acceptabelt bærestof, adjuvans eller vehikel.
DK12848361.7T 2011-11-11 2012-11-09 Acc-hæmmere og anvendelser deraf DK2776038T3 (da)

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US201161559023P 2011-11-11 2011-11-11
US201261615092P 2012-03-23 2012-03-23
US201261651878P 2012-05-25 2012-05-25
US201261675513P 2012-07-25 2012-07-25
PCT/US2012/064528 WO2013071169A1 (en) 2011-11-11 2012-11-09 Acc inhibitors and uses thereof

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EP (3) EP2776038B1 (da)
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KR (3) KR102033806B1 (da)
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CL (1) CL2014001241A1 (da)
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EA (2) EA030264B1 (da)
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HR (2) HRP20180534T1 (da)
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MX (3) MX390746B (da)
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