HRP20150932T2 - Heterociklički spojevi - Google Patents

Heterociklički spojevi Download PDF

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Publication number
HRP20150932T2
HRP20150932T2 HRP20150932TT HRP20150932T HRP20150932T2 HR P20150932 T2 HRP20150932 T2 HR P20150932T2 HR P20150932T T HRP20150932T T HR P20150932TT HR P20150932 T HRP20150932 T HR P20150932T HR P20150932 T2 HRP20150932 T2 HR P20150932T2
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alkyl
alkylene
attached
compound
heterocycloalkyl
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HRP20150932TT
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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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Publication of HRP20150932T1 publication Critical patent/HRP20150932T1/hr
Publication of HRP20150932T2 publication Critical patent/HRP20150932T2/hr

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24Heterocyclic 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
    • C07D239/28Heterocyclic 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
    • C07D239/46Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/50Three nitrogen atoms
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/18Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
    • AHUMAN NECESSITIES
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    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/06Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
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    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/14Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D251/00Heterocyclic compounds containing 1,3,5-triazine rings
    • C07D251/02Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
    • C07D251/12Heterocyclic 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
    • C07D251/26Heterocyclic 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
    • C07D251/40Nitrogen atoms
    • C07D251/54Three nitrogen atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic 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
    • C07D403/04Heterocyclic 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)
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  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Engineering & Computer Science (AREA)
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  • Diabetes (AREA)
  • Cardiology (AREA)
  • Immunology (AREA)
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  • Urology & Nephrology (AREA)
  • Neurology (AREA)
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  • Ophthalmology & Optometry (AREA)
  • Pain & Pain Management (AREA)
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  • 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. Spoj prema slijedećoj formuli: [image] naznačen time da svaki Q i U je CH ili N, pod uvjetom da barem jedan od Q i U je N; svaki X, Y, i Z, neovisno, je C1-5 alkilen ili izbrisan; m je 0, 1, 2, 3, 4, ili 5; n je 0, 1 ili 2; p je 1 ili 2; R1 je H, C1-C10 alkil, C3-C20 cikloalkil, C1-C20 heterocikloalkil, aril, heteroaril, halo, CN, ORa, COORa, OC(O)Ra, C(O)Ra, C(O)NRaRb, ili NRaRb; R2 je C1-C10 alkil, C3-C20 cikloalkil, C1-C20 heterocikloalkil, aril, heteroaril, ili C1-C10 alkil, proizvoljno supstituiran s C1-C10 alkil, C3-C20 cikloalkil, C1-C20 heterocikloalkil, ili N(RCRd); R3, neovisno, je C1-C10 alkil, C3-C20 cikloalkil, C1-C20 heterocikloalkil, aril, heteroaril, halo, CN, ORe, COORe, OC(O)Re, C(O)Re, C(O)NReRf, ili NReRf; ili R3 je C1-5 alkilen vezan na dva ugljikova atoma prstena na koji je vezan ili C2-8 alkilen vezan na jedan ugljikov atom prstena na koji je vezan; i R4 je P(=O)(ORg)(ORi), P(=O)(NHRg)(ORi), P(=O)(NRg)(NRi); gdje svaki od Ra, Rb, RC, Rd, Re, Rf, Rg i Ri, neovisno, je H, C1-C10 alkil, C3-C20 cikloalkil, C1-C20 heterocikloalkil, aril, heteroaril, ili -C(O)R, R je H, C1-C10 alkil, C3-C20 cikloalkil, C1-C20 heterocikloalkil, aril, ili heteroaril; ili Ra i Rb su vezani i zajedno tvore C2-8 alkilen, RC i Rd su vezani i zajedno tvore C2-8 alkilen, Re i Rf su vezani i zajedno tvore C2-8 alkilen, ili Rg i Ri su vezani i zajedno tvore C1-5 alkilen.
2. Spoj prema zahtjevu 1, naznačen time da Q je CH ili N i U je N.
3. Spoj prema zahtjevu 1, naznačen time da X je -CH2-, -CH2CH2- ili -CH2CH2CH2- i p je 1.
4. Spoj prema zahtjevu 1, naznačen time da Y je -CH2 ili izbrisan i Z je -CH2-.
5. Spoj prema zahtjevu 1, naznačen time da R2 je C1-5 alkil supstituiran s N(RCRd), poželjno -CH2CH2CH2-N(RCRd), gdje RC je H i Rd je C1-C10 alkil, C3-C20 cikloalkil, C1-C20 heterocikloalkil, aril, ili heteroaril, ili RC i Rd su vezani i zajedno tvore C4-6 alkilen.
6. Spoj prema zahtjevu 1, naznačen time da m je 0, 1, ili 2; n je 1 ili 2; R1 je NH2; i R3 je C1-C3 alkil, C3-C8 cikloalkil, C1-C8 heterocikloalkil, aril, heteroaril, halo, CN, ORe, ili C(O)NReRf; ili R3 je C1-2 alkilen vezan na dva ugljikova atoma prstena na koji je vezan ili C2-5 alkilen vezan na jedan ugljikov atom prstena na koji je vezan.
7. Spoj prema zahtjevu 1, naznačen time da R4 je P(=O)(OH)2, P(=O)(OH)(OCH2CH3), P(=O)(OCH2CH3)2, [image] i pri čemu poželjno m je 0, 1, ili 2; n je 1; p je 1; X je -CH2CH2- ili -CH2CH2CH2-; Y je -CH2 ili izbrisan i Z je -CH2-; R1 je NH2; R2 je C1-5 alkil supstituiran N(RCRd); i R3 je C1-C3 alkil, C3-C8 cikloalkil, C1-C8 heterocikloalkil, aril, heteroaril, halo, CN, ORe, ili C(O)NReRf; ili C1-2 alkilen vezan na dva ugljikova atoma prstena na koji je vezan ili C2-5 alkilen vezan na jedan ugljikov atom prstena na koji je vezan.
8. Spoj prema zahtjevu 1, naznačen time da je spoj odabran iz skupine koja se sastoji od slijedećih spojeva [image] [image] [image] [image] [image]
9. Spoj kao što je definirano u bilo kojem od zahtjeva 1 do 8, naznačen time da je za uporabu u liječenju medicinskog stanja povezanog s CXCR4, pri čemu je stanje upalna ili imunološka bolest, razvojna ili degenerativna bolest, ili oštećenje tkiva, poželjno izabrano iz skupine koja sadrži dijabetes melitus tipa I, ozljedu mozga, ozljedu živca, ozljedu srca, oštećenje jetre, ozljedu skeletnih mišića, oštećenje bubrega, oštećenje gušterače, ozljedu pluća, ozljedu kože, ishemiju udova, tihu ishemiju, srčanu ishemiju, ili ozljedu gastrointestinalnog trakta, pri čemu se spoj poželjno primjenjuje u kombinaciji s faktorom rasta G-CSF.
10. Spoj za uporabu u liječenju medicinskog stanja povezanog s CXCR4 prema zahtjevu 9, naznačen time da medicinsko stanje je dijabetička retinopatija, proliferativna retinopatija, makularna degeneracija povezna sa starenjem, makularni edem, neovaskularizacija rožnice, ili neovaskularizacija šarenice.
11. Spoj za uporabu u liječenju medicinskog stanja povezanog s CXCR4 prema zahtjevu 10, naznačen time da je spoj u pripravku formuliranom kao kapi za oči, pomast, injekcijska tekućina, mikročestice, ili oblik s produljenim otpuštanjem.
12. Spoj kao što je definirano u zahtjevima 1 do 8, za uporabu za liječenje raka, naznačen time da se spoj daje u kombinaciji s učinkovitom količinom kemoterapeutskog sredstva.
HRP20150932TT 2008-04-21 2015-09-07 Heterociklički spojevi HRP20150932T2 (hr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US4649608P 2008-04-21 2008-04-21
EP08874003.0A EP2268635B1 (en) 2008-04-21 2008-11-03 Heterocyclic compounds
PCT/US2008/082202 WO2009131598A1 (en) 2008-04-21 2008-11-03 Heterocyclic compounds

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HRP20150932T1 HRP20150932T1 (en) 2015-10-09
HRP20150932T2 true HRP20150932T2 (hr) 2017-10-20

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US (1) US8372849B2 (hr)
EP (1) EP2268635B1 (hr)
JP (1) JP5661607B2 (hr)
KR (1) KR101579999B1 (hr)
CN (1) CN101565404B (hr)
AU (1) AU2008355098B2 (hr)
CA (1) CA2720229C (hr)
CY (1) CY1116802T1 (hr)
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NZ (1) NZ588989A (hr)
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SI (1) SI2268635T1 (hr)
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CA2720229C (en) 2015-02-17
PL2268635T3 (pl) 2015-11-30
CN101565404B (zh) 2012-12-05
US8372849B2 (en) 2013-02-12
AU2008355098B2 (en) 2012-11-15
KR101579999B1 (ko) 2015-12-23
PT2268635E (pt) 2015-10-06
HK1138269A1 (en) 2010-08-20
TWI444188B (zh) 2014-07-11
US20090264339A1 (en) 2009-10-22
EP2268635B1 (en) 2015-06-10
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WO2009131598A1 (en) 2009-10-29
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KR20110008085A (ko) 2011-01-25
JP5661607B2 (ja) 2015-01-28
CN101565404A (zh) 2009-10-28
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HUE025179T2 (en) 2016-02-29
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SI2268635T1 (sl) 2015-10-30
EP2268635A1 (en) 2011-01-05
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