SI20691B - Triciklični inhibitorji poli(ADP-riboza) polimeraz - Google Patents

Triciklični inhibitorji poli(ADP-riboza) polimeraz Download PDF

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SI20691B
SI20691B SI200020013A SI200020013A SI20691B SI 20691 B SI20691 B SI 20691B SI 200020013 A SI200020013 A SI 200020013A SI 200020013 A SI200020013 A SI 200020013A SI 20691 B SI20691 B SI 20691B
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alkyl
pharmaceutically acceptable
compound
acceptable salt
aryl
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SI20691A (sl
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Stephen Evan Webber
Stacie S Canan-Koch
Jayashree Girish Tikhe
Lars Henrik Thoresen
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Agouron Pharma
Cancer Rec Tech Ltd
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    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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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
    • A61K31/435—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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4375—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
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    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A—HUMAN NECESSITIES
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    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
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    • A—HUMAN NECESSITIES
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    • A—HUMAN NECESSITIES
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    • A—HUMAN NECESSITIES
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/06—Peri-condensed systems

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Abstract

Spojine po formuli (I) so poli (ADP-ribozil)transferaze (PARP) inhibitorji in so uporabne kot terapevtska sredstva pri zdravljenju rakov in izboljšanju posledic šoka, poškodb glave in neurodegenerativnih bolezni. Kot zdravila proti raku se spojine po izumu lahko uporabijo na primer v kombinacijis citotoksini in/ali z obsevanjem.

Claims (14)

  1. -1- -1- Sl 20691 TRICIKLIČNI INHIBITORJI POLI(ADP-RIBOZA) POLIMERAZ Patentni zahtevki 1. Spojina izbrana iz skupine, ki sestoji iz:
    Br -2-
  2. 2. Farmacevtska učinkovina, ki obsega: a) učinkovito koliično PARP-inhibicijskega sredstva, ki je:
  3. 3. Spojina s formulo:
    halogen; -8- ciano; po izbiri substituirana alkilna, alkenilna, alkinilna, cikloalkilna, heterocikloalkilna, arilna ali heteroarilna skupina; ali -C(0)-R1°, pri čemer je R10: H; po izbiri substituirana alkilna, alkenilna, alkinilna, cikloalkilna, heterocikloalkilna, arilna ali heteroarilna skupina; ali OR100 ali NR100R110, pri čemer je R100 in R110 neodvisno H ali po izbiri substituirana alkilna, alkenilna, alkinilna, cikloalkilna, heterocikloalkilna, arilna ali heteroarilna skupina R2je H ali alkil; R3je H ali alkil; 4 R je H, halogen ali alkil; Xje O ali S; Y je (CR5R6)(CR7R8)n ali N=C(R5), pri čemer: n je 0 ali 1; 5 6 R in R sta vsak neodvisno H ali po izbiri substituirana alkilna, alkenilna, alkinilna, cikloalkilna, heterocikloalkilna, arilna ali heteroarilna skupina; in 7 8 R in R sta vsak neodvisno H ali po izbiri substituirana alkilna, alkenilna, alkinilna, cikloalkilna, heterocikloalkilna, arilna, ali heteroarilna skupina; kjer takrat, ko so R1, R4, R5, R6 in R7 vsak H, R8 ni nesubstituiran fenil; ali farmacevtsko sprejemljiva sol ali solvat spojine.
    -3- £Ζ
  4. 4. Spojina po zahtevku 3, označena s formulo: O
    (II) v kateri: P je 2; R11 je H ali alkil; R12 je halogen ali po izbiri substituiran aril, alkil, alkenil, alkinil, ali acilna skupina -C(0)-R1°, pri čemer je R10: H; po izbiri substituirana alkilna, alkenilna, alkinilna, cikloalkilna, heterocikloalkilna, arilna ali heteroarilna skupina; ali OR100 ali NR100R110, pri čemer je R100 in R110 neodvisno H ali po izbiri substituirana alkilna, alkenilna, alkinilna, cikloalkilna, heterocikloalkilna, arilna ali heteroarilna skupina -9- R13 je H ali alkil; in R14 je H ali halogen; ali farmacevtsko sprejemljiva sol ali solvat spojine. 5. Spojina po zahtevku 3, označena s formulo
    v kateri: 15 R je H ali alkilna, alkenilna, alkinilna, cikloalkilna, heterocikloalkilna, arilna ali heteroarilna skupina, nesubstituirana ali substituirana z enim ali več substituenti, izbranimi med halogenom, hidroksi, nitro, amino in alkilnimi in arilnimi skupinami, nesubstituiranimi ali substituiranimi z enim ali več substituenti, izbranimi med halogenom, hidroksi, nitro in amino; 16 R je halogen, ciano ali alkilna, alkenilna, alkinilna, cikloalkilna, heterocikloalkilna, arilna ali heteroarilna skupina, nesubstituirana ali substituirana z enim ali več substituenti, izbranimi med halogenom, hidroksi, nitro, amino in alkilnimi in arilnimi skupinami, nesubstituiranimi ali substituiranimi z enim ali več substituenti, izbranimi med halogenom, hidroksi, nitro in amino; R17 je H ali alkil; in 18 R je H, halogen ali alkil; pri čemer R , R , R in R niso vsi H.
    -4- ιη
    Η
    ali njena farmacevtsko sprejemljiva sol ali njen solvat.
  5. -5-
    F * -6- ΖΙ
  6. 6. Spojina izbrana iz skupine, ki jo sestavljajo -10- Η
    /
  7. 7. Spojina, ki ima strukturo:
    ali njena farmacevtsko sprejemljiva sol.
    -7- -7-
    Η
    ιη ali (ii) farmacevtsko sprejemljiva sol ali solvat le-teh; in (b) farmacevtsko sprejemljiv nosilec.
  8. 8. Farmacevtska učinkovina, ki sestoji iz: a) učinkovite količine PARP inhibicijskega sredstva, ki je spojina po kateremkoli od zahtevkov 3-7, ali njena farmacevstko sprejemljiva sol ali solvat; in b) farmacevtsko sprejemljivega nosilca za omenjeno PARP-inhibicijsko sredstvo.
  9. 9. Uporaba spojine, farmacevtsko sprejemljive soli ali solvata po kateremkoli od zahtevkov 1 in 3-7 za izdelavo zdravila za zdravljenje raka pri sesalcu.
  10. 10. Uporaba spojine, farmacevtsko sprejemljive soli ali solvata po kateremkoli od zahtevkov 1 in 3-7 za izdelavo zdravila za zdravljenje kapi, poškodbe glave in/ali nevrodegenerativnih bolezni pri sesalcu.
  11. 11. Uporaba spojine, farmacevtsko sprejemljive soli ali solvata po kateremkoli od zahtevkov 1 in 3-7 za izdelavo zdravila za zakasnitev nastanka staranja celic, povezanega s staranjem kože pri človeku.
    -11-
  12. 12. Uporaba spojine, farmacevtsko sprejemljive soli ali solvata po kateremkoli od zahtevkov 1 in 3-7 za izdelavo zdravila za preprečevanje razvoja inzulinsko odvisnega diabetesa mellitusa pri dovzetnem posamezniku.
    -12-
    Η Η
  13. 13. Uporaba spojine, farmacevtsko sprejemljive soli ali solvata po kateremkoli od zahtevkov 1 in 3-7 za izdelavo zdravila za zdravljenje vnetnega stanja pri sesalcu.
    -13-
    -14-
    -15- IZ
    -16-
    Η Η
    Η
    -17-
    ali farmacevtsko sprejemljiva sol ali solvat le-teh. -18-
  14. 14. Uporaba spojine, farmacevtsko sprejemljive soli ali solvata po kateremkoli od zahtevkov 1 in 3-7 za izdelavo zdravila za zdravljenje kardiovaskularne bolezni pri sesalcu.
SI200020013A 1999-01-11 2000-01-10 Triciklični inhibitorji poli(ADP-riboza) polimeraz SI20691B (sl)

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US11543199P 1999-01-11 1999-01-11
PCT/US2000/000411 WO2000042040A1 (en) 1999-01-11 2000-01-10 Tricyclic inhibitors of poly(adp-ribose) polymerases

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