DK2268635T3 - Heterocykliske forbindelser - Google Patents

Heterocykliske forbindelser Download PDF

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Publication number
DK2268635T3
DK2268635T3 DK08874003.0T DK08874003T DK2268635T3 DK 2268635 T3 DK2268635 T3 DK 2268635T3 DK 08874003 T DK08874003 T DK 08874003T DK 2268635 T3 DK2268635 T3 DK 2268635T3
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compound
alkyl
solution
heteroaryl
aryl
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DK08874003.0T
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Chi-Feng Yen
Cheng-Kung Hu
Chang-Pin Huang
Ying-Huey Huang
Gholam Hossein Hakimelahi
Chi-Hsin Richard King
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Taigen Biotechnology Co Ltd
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    • 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
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/50—Three nitrogen atoms
    • 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
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
    • 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
    • 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
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P21/00—Drugs for disorders of the muscular or neuromuscular 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
    • 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
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • 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
    • 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
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
    • 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
    • A61P9/10—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
    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
    • C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
    • C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D251/26—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hetero atoms directly attached to ring carbon atoms
    • C07D251/40—Nitrogen atoms
    • C07D251/54—Three nitrogen atoms
    • 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
    • C07D403/04—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 directly linked by a ring-member-to-ring-member bond

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
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  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Diabetes (AREA)
  • Cardiology (AREA)
  • Immunology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Urology & Nephrology (AREA)
  • Neurology (AREA)
  • Vascular Medicine (AREA)
  • Endocrinology (AREA)
  • Neurosurgery (AREA)
  • Dermatology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Pain & Pain Management (AREA)
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  • Gastroenterology & Hepatology (AREA)
  • Obesity (AREA)
  • Pulmonology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Claims (12)

1. Forbindelse med følgende formel:
hvor hver Q og U er CH eller N, forudsat at mindst én af Q og U er N; hver af X, Y og Z uafhængigt er Ci-salkylen eller fjernet; m er 0, 1, 2, 3, 4 eller 5; n er 0, 1 eller 2; p er 1 eller 2; Ri er H, Ci-Cioalkyl, C3-C2ocycloalkyl, Ci-C2oheterocycloalkyl, aryl, heteroaryl, halo, CN, ORa, COORa, 0C(0)Ra, C(0)Ra, C(0)NRaRb eller NRaRb; R2 er Ci-Cioalkyl, C3-C2ocycloalkyl, Ci-C2oheterocycloalkyl, aryl, heteroaryl eller Ci-Cioalkyl, der eventuelt er substitueret med Ci-Cioalkyl, C3-C2ocycloalkyl, Ci-C2oheterocycloalkyl eller N(RcRd); R3 uafhængigt er Ci-Cioalkyl, C3_C2ocycloalkyl, C3- C2oheterocycloalkyl, aryl, heteroaryl, halo, CN, ORe, COORe, 0C(0)Re, C (O) Re, C (0) NReRf eller NReRf, eller R3 er Ci_5alkylen, der er bundet til to carbonatomer i ringen, hvortil den er bundet, eller C2-salkylen, der er bundet til ét carbonatom i ringen, hvortil den er bundet; og R4 er P(=0) (ORg) (OR±) , P (=0) (NHRg) (OR±) , P (=0) (NRg) (NRf) ; hvori hver af Ra, Rb, Rc, Rd, Re, Rf, Rg og Rd uafhængigt er H, Ci-Cioalkyl, C3_C2ocycloalkyl, Ci-C2oheterocycloalkyl, aryl, heteroaryl eller -C(0)R, idet R er H, Ci-Cioalkyl, C3_ C2ocycloalkyl, Ci-C2oheterocycloalkyl, aryl eller heteroaryl; eller Ra og Rb er koblet og sammen danner C2-salkylen, Rc og Rd er koblet og sammen danner C2-salkylen, Re og Rf er koblet og sammen danner C2-salkylen, eller Rg og R± er koblet og sammen danner Ci-salkylen.
2. Forbindelse ifølge krav 1, hvor Q er CH eller N, og U er N.
3. Forbindelse ifølge krav 1, hvor X er -CH2-, -CH2CH2- eller -CH2CH2CH2-, og p er 1.
4. Forbindelse ifølge krav 1, hvor Y er -CH2 eller fjernet, og Z er -CH2-.
5. Forbindelse ifølge krav 1, hvor R2 er Ci-salkyl, der er substitueret med N (RcRd) t fortrinsvis -CH2CH2CH2-N (RcRd) , hvori Rc er H, og Rd er Ci-Ci0alkyl, C3-C2ocycloalkyl, Ci-C2oheterocycloalkyl, aryl eller heteroaryl, eller Rc og Rd er koblet og sammen danner C^alkylen.
6. Forbindelse ifølge krav 1, hvor m er 0, 1 eller 2; n er 1 eller 2; Ri er NH2; og R3 er Ci-C3alkyl, C3-C8cycloalkyl, Ci-Cgheterocycloalkyl, aryl, heteroaryl, halo, CN, ORe eller C(0)NReRf; eller R3 er Ci_2alkylen, der er bundet til to carbonatomer i ringen, hvortil den er bundet, eller C2_ 5alkylen, der er bundet til ét carbonatom i ringen, hvortil den er bundet.
7. Forbindelse ifølge krav 1, hvor R4 er P (=0) (0H)2, P (=0) (OH) (OCH2CH3) , P(=0) (0CH2CH3)2
og hvor fortrinsvis m er 0, 1 eller 2; n er 1; p er 1; X er -CH2CH2- eller -CH2CH2CH2-; Y er -CH2 eller fjernet, og Z er -CH2-; Ri er NH2; R2 er Ci_5alkyl-substitueret N (RcRd) ; og R3 er Ci-C3alkyl, C3-C8cycloalkyl, Ci-C8heterocycloalkyl, aryl, heteroaryl, halo, CN, 0Re eller C (0) NReRf; eller Ci_2alkylen, der er bundet til to carbonatomer i ringen, hvortil den er bundet, eller C2-5alkylen, der er bundet til ét carbonatom i ringen, hvortil den er bundet.
8. Forbindelse ifølge krav 1, hvor forbindelsen er udvalgt fra gruppen, der består af følgende forbindelser
9. Forbindelse ifølge et hvilket som helst af kravene 1 til 8 til anvendelse til behandling af en medicinsk tilstand, der er forbundet med CXCR4, hvor tilstanden er inflammationseller immunsygdom, en udviklingsrelateret eller degenerativ sygdom eller vævsskade, fortrinsvis er udvalgt fra gruppen, der består af type I-diabetes mellitus, hjerneskade, nerveskade, skade på hjertet, leverskade, skeletmuskelskade, nyreskade, pankreasskade, lungeskade, hudskade, iskæmi i lemmerne, tavs iskæmi, hjerteiskæmi eller skade i mavetarmkanalen, hvor forbindelsen fortrinsvis administreres i kombination med en G-CSF-vækstfaktor.
10. Forbindelse til anvendelse til behandling af en medicinsk tilstand, der er forbundet med CXCR4, ifølge krav 9, hvor den medicinske tilstand er diabetisk retinopati, proliferativ retinopati, aldersrelateret makuladegeneration, makulaødem, cornea-neovaskularisering eller iris-neovaskularisering.
11. Forbindelse til anvendelse til behandling af en medicinsk tilstand, der er forbundet med CXCR4, ifølge krav 10, hvor forbindelsen er i et præparat, der er formuleret som øjendråber, salve, injicerbar væske, mikropartikler eller en depotform.
12. Forbindelse ifølge krav 1 til 8 til anvendelse til behandling af cancer, hvor forbindelsen er til administration i kombination med en effektiv mængde af et kemoterapeutisk middel.
DK08874003.0T 2008-04-21 2008-11-03 Heterocykliske forbindelser DK2268635T3 (da)

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US4649608P 2008-04-21 2008-04-21
PCT/US2008/082202 WO2009131598A1 (en) 2008-04-21 2008-11-03 Heterocyclic compounds

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US (1) US8372849B2 (da)
EP (1) EP2268635B1 (da)
JP (1) JP5661607B2 (da)
KR (1) KR101579999B1 (da)
CN (1) CN101565404B (da)
AU (1) AU2008355098B2 (da)
CA (1) CA2720229C (da)
CY (1) CY1116802T1 (da)
DK (1) DK2268635T3 (da)
EA (1) EA019289B1 (da)
ES (1) ES2545731T3 (da)
HK (1) HK1138269A1 (da)
HR (1) HRP20150932T2 (da)
HU (1) HUE025179T2 (da)
NZ (1) NZ588989A (da)
PL (1) PL2268635T3 (da)
PT (1) PT2268635E (da)
SI (1) SI2268635T1 (da)
TW (1) TWI444188B (da)
WO (1) WO2009131598A1 (da)
ZA (1) ZA201008262B (da)

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CA2720229C (en) 2015-02-17
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AU2008355098B2 (en) 2012-11-15
KR101579999B1 (ko) 2015-12-23
PT2268635E (pt) 2015-10-06
HK1138269A1 (en) 2010-08-20
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CN101565404A (zh) 2009-10-28
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SI2268635T1 (sl) 2015-10-30
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