LV11615B - Therapeutic amides - Google Patents

Therapeutic amides Download PDF

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Publication number
LV11615B
LV11615B LVP-96-176A LV960176A LV11615B LV 11615 B LV11615 B LV 11615B LV 960176 A LV960176 A LV 960176A LV 11615 B LV11615 B LV 11615B
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carboxylic acid
biphenyl
trifluoromethyl
trifluoromethylbiphenyl
tetrahydroisoquinolin
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LVP-96-176A
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LV11615A (lv
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George Chang
Peter H Dorf
George J Quallich
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Pfizer
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Priority claimed from CA002223574A external-priority patent/CA2223574C/en
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Publication of LV11615A publication Critical patent/LV11615A/lv
Publication of LV11615B publication Critical patent/LV11615B/en

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    • 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
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    • 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
    • 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
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
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    • C07D217/04—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
    • C07D217/06—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with the ring nitrogen atom acylated by carboxylic or carbonic acids, or with sulfur or nitrogen analogues thereof, e.g. carbamates
    • 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
    • C07D401/10—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 aromatic rings
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    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
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    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

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Claims (37)

1 1LV 11615 Izgudrojuma formula 1. Savienojums ar formulu (I)
kurā: X ir CH2, CO, CS vai S02; Y ņemts no rindas: saite starp X un Z; no alifātiska ogļūdeņraža atvasināta divvērtīga palieka, kas satur līdz 20 oglekļa atomus un neobligāti aizvietota ar vienu no aizvietotājiem: Ci-ioalkoksigrupa, Ci.10acilgrupa, Ci-i0aciloksigrupa, C6-ioarilgrupa; NH un 0, ar tādu noteikumu, ka tad, kad X ir CH2, Y ir saite starp X un Z; Z ir ņemts no rindas: (1) ūdeņraža atoms, halogēna atoms, ciāngrupa; (2) hidroksilgrupa, Ci-i0alkoksigrupa, Ci-i0alkiltiogrupa, Ci-i0acilgrupa, tiofenilkarbonilgrupa, Ci-i0alkoksikarbonilgrupa; (3) Ci-ioalkilaminogrupa, di(Ci-ioalkil)aminogrupa, Ce-ioaril-Ci-ioalkil-aminogrupa, ar noteikumu, ka Y nav 0 vai NH; (4) neaizvietota vinilgrupa, Ce-ioarilgrupa, C3.8cikloalkilgrupa un tās atvasinājumi ar kondensētu benzola gredzenu, C7-iopolicikloalkilgrupa, C^ecikloalkenilgrupa, C7-ioPolicikloalkenilgrupa; (5) Ce-ioariloksigrupa, Ce-ioahltiogrupa, C6.i0aril-Ci-i0alkoksigrupa, Ce-ioanl-Ci-ioalkiltiogrupa, C3-eCikloalkoksigrupa, C^ecikloalkeniloksi-grupa; (6) heterociklisks aizvietotājs, kas veidots no monocikliskiem vai policikliskiem heterocikliem, kuros ir 5 - 14 gredzenu veidojošie atomi, no kuriem 1 - 4 ir hēteroatomi, kas, neatkarīgi viens no otra, ņemti no rindas: skābeklis, slāpeklis un sērs, pie tam katrs no aizvietotājā esošajiem cikliem var būt, neatkarīgi no citiem, piesātināts, daļēji nepiesātināts vai aromātisks, ar noteikumu, ka X ir CH2, Z ir ūdeņraža atoms, vai viens no aizvietotājiem (4) vai (6), pie tam, kad Z satur vienu vai vairākus ciklus, katrs no šiem cikliem, neatkarīgi viens no otra, var būt aizvietots ar 0 - 4 aizvietotājiem, kas, neatkarīgi viens no otra, ņemti no rindas: halogēna atoms, hidroksilgrupa, ciāngrupa, nitrogrupa, oksogrupa, tioksogrupa, aminosulfonilgrupa, fenilgrupa, fenoksigrupa, feniltiogrupa, halogēntiofenilgrupa, benzilgrupa, benziloksigrupa, Ci.ioalkilgrupa, Ci-ioalkoksigrupa, Ci-ioalkoksikarbonil-grupa, Ci_i0alkiltiogrupa, Ci.ļoalkilaminogrupa, Ci_i0alkilaminokarbonil-grupa, di(Ci-ioalkil)aminogrupa, di(Ci-ioalkil)aminokarbonilgrupa, di-(Cļ-ioalkiljamino-Ci-ioalkoksigrupa, Ci-3perfluoralkilgrupa, Ci.3perfluor-alkoksigrupa, Ci.ioacilgrupa, Cļ.ioaciloksigrupa, Ci-ioaciloksi-Ci_ioalkilgrupa un pirolidinilgrupa, kā arī šī savienojuma farmaceitiski pieņemamās sālis.
2. Savienojums pēc 1. punkta, kā arī tā farmaceitiski pieņemamās sālis, kur: X ir CH2, CO vai S02; Y ņemts no rindas: Y ņemts no rindas: saite starp X un Z, NH; Ci.ioalkilēngrupa vai C2_ioalkenilēngrupa, kas neobligāti aizvietotas ar fenilgrupu; ar tādu noteikumu, ka tad, kad X ir CH2, Y ir saite starp X un Z; Z ir ņemts no rindas: (1) ūdeņraža atoms; (2) Ci.i0alkoksigrupa, Ci-i0alki!tiogrupa; (3) Ci.i0alkilaminogrupa, di(Ci-ioalkil)aminogrupa, C6-ioaril-Ci-ioalkil-aminogrupa, ar noteikumu, ka Y nav NH; (4) neaizvietota vinilgrupa, C6-ioarilgrupa, C3.8cikloalkilgrupa, C4-8Ciklo-alkenilgrupa, (5) C6.ioariloksigrupa; (6) heterociklisks aizvietotājs, kas veidots no 5 un 6 locekļu heterocikliem, kas var būt piesātināti, daļēji nepiesātināti vai aromātiski, kā arī to ar benzola gredzenu kondesētajiem atvasinājumiem, kas var saturēt 1 - 3 heteroatomus, kas, neatkarīgi viens no otra, ņemti no rindas: skābeklis, slāpeklis un sērs, ar noteikumu, ka, ja X ir CH2, tad Z ir viens no aizvietotājiem (4) vai (6), pie tam, kad Z satur vienu vai vairākus ciklus, katrs no šiem cikliem, neatkarīgi viens no otra, var būt aizvietots ar 0 - 3 aizvietotājiem, kas, neatkarīgi viens no otra, ņemti no rindas: halogēna atoms, hidroksilgrupa, nitrogrupa, Ci.6alkilgrupa, Ci.6alkoksi-grupa, di(Ci.6alkil)aminokarbonilgrupa, Ci.3perfluoralkoksigrupa, C-Moacilgrupa un Ci.ioaciloksigrupa. 2 LV 11615
3. Savienojums pēc 2. punkta, un tā farmaceitiski pieņemamās sālīs, kur X ir metilēngrupa, Y ir saite starp X un Z, un Z ņemts no rindas: C6-ioarilgrupa, C3-8cikloalk’ilgrupa un C4-ecikloalkenilgrupa, kuras neobligāti aizvietotas ar 0 - 3 jau minētajiem aizvietotājiem, kas ņemti neatkarīgi viens no otra.
4. Savienojums pēc 2. punkta un tā farmaceitiski pieņemamās sālis, kur X ir metilēngrupa vai CO, Y ir saite srarp X un Z, Z ir heterociklisks aizvietotājs no rindas: tiofenilgrupa, pirolidinilgrupa, pirolilgrupa, furanilgrupa, tiazolilgrupa, izoksazolilgrupa, imidazolilgrupa, 1,2,4-triazolilgrupa, piridinilgrupa, pirimidinilgrupa, kā arī to ar benzola gredzenu kondensētie bicikliskie atvasinājumi, pie tam šie aizvietotāji var būt aizvietoti ar 0 - 3 jau minētajiem aizvietotājiem, kas ņemti neatkarīgi viens no otra.
5. Savienojums pēc 5. punkta un tā farmaceitiski pieņemamās sālis, kur: X ir CH2 vai CO; Y ir saite starp X un Z; Z ir ūdeņraža atoms, neaizvietota vinilgrupa, fenilgrupa, imidazolilgrupa, tiazolilgrupa, tiofenilgrupa, 1,2,4-triazolilgrupa, piridinilgrupa vai pirimidinilgrupa.
6. Savienojums pēc 5. punkta, kurā X ir CO.
7. Savienojums pēc 5. punkta, kurā X ir CH2.
8. Savienojums pēc 1. punkta, kurā grupa, kas saista aizvietotāju -ΧΥΖ pie 1,2,3,4-tetrahidro-izohinolīna gredzena slāpekļa atoma, ir ņemta no rindas:
N-alkilgrupa, 3 s ο
karbamāti, tiourīnvielas
sulfonamīdi.
9. Savienojums pēc 8. punkta, kurā minētā saistoša grupa ir amīda grupa.
10. Savienojums pēc 9. punkta, kas ņemts no rindas: 4’-trifluormetilbifenil-2-karbonskābes 2-fenilacetil-1,2,3,4-tetrahidroizohinolin-6-ilamīds; 4’-trifluormetilbifenil-2-karbonskābes 2-fenoksiacetil-1,2,3,4-tetrahidroizohino-lin-6-ilamīds; 4’-trifluormetilbifenil-2-karbonskābes 2-pentanoil-1,2,3,4-tetrahidroizohinolin-6-ilamīds; 4’-trifluormetilbifenil-2-karbonskābes 2-ciklobutilkarbonil-1,2,3,4-tetrahidroizo-hinolin-6-ilamīds; 4'-trifluormetilbifenil-2-karbonskābes 2-(tiofen-2-ilacetil)-1,2,3,4-tetrahidroizo-hinolin-6-ilamTds; 4’-trifluormetilbifenil-2-karbonskābes 2-butiril-1,2,3,4-tetrahidroizohinolin-6-il-amīds; 4’-trifluormetilbifenil-2-karbonskābes 2-etoksiacetil-1,2,3,4-tetrahidroizohino-lin-6-ilamTds; 4’-trifluormetilbifenil-2-karbonskābes 2-(4-fluorfenil)acetil-1,2,3,4-tetrahidroizo-hinolin-6-ilamīds; 4'-trifluormetiibifenil-2-karbonskābes 2-(3-metilbutiril)-1,2,3,4-tetrahidroizo-hinolin-6-ilamīds; 4 LV 11615 4'-trifluormetilbifenil-2-karbonskābes 2-but-3-enoil-1,2,3,4-tetrahidroizohinolin-6-ilamīds; 4’-trifluormetilbifenil-2-karbonskābes 2-metoksiacetil-1,2,3,4-tetrahidroizohino-lin-6-ilamīds; 4’-trifluormetilbifenil-2-karbonskābes 2-etiItioacetil-1,2,3,4-tetrahidroizohiηolin-6-ilamīds; 4’-trifluormetilbifenil-2-karbonskābes 2-(6-dietilkarbamoilcikloheks-3-ēnkarbo-nil)-1,2,3,4-tetrahidroizohinolin-6-ilamTds; 4’-trifluormetilbifenil-2-karbonskābes 2-(ciklopent-1-enil)acetil-1,2,3,4-tetra-hidro-izohinolin-6-ilamTds; 4'-trifluormetilbifenil-2-karbonskābes 2-heks-3-enoil -1,2,3,4-tetrahidroizohino-lin-6-ilamTds; 4’-trifluormetilbifenil-2-karbonskābes 2-(tetrahidrofuril-3-karbonil)-1,2,3,4-tetra-hidroizohinolin-6-ilamīds; 4’-trifluormetilbifenil-2-karbonskābes 2-(tiofen-3-il)acetil-1,2,3,4-tetrahidroizo-hinolin-6-ilamTds; 4’-trifluormetilbifenil-2-karbonskābes 2-(piridinilii-2-karbonil)-1,2,3,4-tetrahidro-izohinolin-6-ilamTds.
11. Savienojums pēc 8. punkta, kurā saistītāja grupa ir urīnvielas grupa.
12. Savienojums pēc 11. punkta, kas ņemts no rindas: 6-[(4'-trifluormetilbifenil-2-karbonil)amino]-3,4-dihidro-1H-izohinolin-2-karbon-skābes fenilamīds; 6-[(4’-trifluormetilbifenil-2-karbonil)amino]-3,4-dihidro-1H-izohinolin-2-karbon-skābes heksilamīds; 6-[(4'-trifluormetilbifenil-2-karbonil)amino]-3,4-dihidro-1H-izohinolin-2-karbon-skābes benzilamīds; 6-[(4'-trifluormetilbifenil-2-karbonil)amino]-3,4-dihidro-1H-izohinolin-2-karbon-skābes [(R)-1-feniletil]amīds; 6-[(4'-trifluormetilbifenil-2-karbonil)amino]-3,4-dihidro-1H-izohinolin-2-karbon-skābes piridinil-2-amīds.
13. Savienojums pēc 8. punkta, kurā saistītāja grupa ir sulfonamīdgrupa. 5
14. Savienojums pēc 13. punkta, kas ņemts no rindas: 4'-trifluormetilbifenil-2-karb’onskābes 2-(propān-2-sulfonil)-1,2,3,4-tetrahidro-izo-hinolin-6-ilamīds; 4'-trifluormetilbifenil-2-karbonskābes 2-dimetilsulfamoil-1,2,3,4-tetrahidroizo-hinolin-6-ilamīds; 4’-trifluormetilbifenil-2-karbonskābes 2-(2-trifluormetoksibenzolsulfonil)- 1,2,3,4-tetrahidroizo-hinolin-6-ilamTds.
15. Savienojums pēc 8. punkta, kurā saistītāja grupa ir tiourīnvielas grupa.
16. Savienojums pēc 15. punkta, proti, 4’-trifluormetilbifenil-2-karbon-skābes 2-ciklopropiltiokarbamoil-1,2,3,4-tetrahidroizohinolin-6-ilamīds.
17. Savienojums pēc 8. punkta, kurā saistītāja grupa ir N-alkilamīna grupa.
18. Savienojums pēc 17. punkta, kas ņemts no rindas: 4’-trifluormetilbifenil-2-karbonskābes 2-(2,6,6-trimetilcikloheks-2-enilmetil)- 1.2.3.4- tetrahidroizohinolin-6-ilamīds; 4’-trifluormetilbifenil-2-karbonskābes 2-(2,4-dihlorbenzil)-1,2,3,4-tetrahidroizo-hinolin-6-ilamīds; 4’-trifluormetilbifenil-2-karbonskābes 2-(1,5a,6,9,9a,9b-heksahidro-4H-diben-zofuran-4a-ilmetil)-1,2,3,4-tetrahidroizo-hinolin-6-ilamīds; 4'-trifluormetilbifenil-2-karbonskābes 2-(tiofen-2-ilmetil)-1,2,3,4-tetrahidroizo-hinolin-6-ilamīds; 4’-trifluormetilbifenil-2-karbonskābes 2-(1 H-pirol-2-ilmetil)-1,2,3,4-tetrahidro-izohinolin-6-ilamīds; 4’-trifluormetilbifenil-2-karbonskābes 2-(furan-2-ilmetil)-1,2,3,4-tetrahidroizo-hinolin-6-ilamīds; 5-{6-[(4,-trifluormetilbifenil-2-karbonil)amino]-3,4-dihidro-1H-izohinolin-2-il-metil}-furanil-2-metanola etiķskābes esteris; 4’-trifluormetilbifenil-2-karbonskābes 2-(tiofen-3-ilmetil)-1,2,3,4-tetrahidroizo-hinolin-6-ilamīds; 4’-trifluormetilbifenil-2-karbonskābes 2-(2,5-dimetoksitetrahidrofuran-3-ilmetil)- 1.2.3.4- tetrahidroizo-hinolin-6-ilamīds; 6 LV 11615 4’-trifluormetilbifenil-2-karbonskābes 2-benzil-1,2,3,4-tetrahidroizo-hinolin-6-ilamīds; 4’-trifluormetilbifenil-2-karbonskābes 2-(piridin-2-ilmetil)-1,2,3,4-tetrahidroizo-hinolin-6-ilamTds; 4’-trifluormetilbifenil-2-karbonskābes 2-(hinolin-2-ilmetil)-1,2,3,4-tetrahidroizo-hinolin-6-ilamTds; 4’-trifluormetilbifenil-2-karbonskābes 2-(3-hlorbenzil)-1,2,3,4-tetrahidroizo-hinolin-6-ilamīds; 4’-trifluormetilbifenil-2-karbonskābes 2-(pirimidin-2-ilmetil)-1,2,3,4-tetrahidro-izohinolin-6-ilamīds; 4’-trifluormetilbifenil-2-karbonskābes 2-(3-nitrobenzil)-1,2,3,4-tetrahidroizohi-nolin-6-ilamTds; 4’-trifluormetilbifenil-2-karbonskābes 2-(1 H-imidazol-2-ilmetil)-1,2,3,4-tetra-hidroizohinolin-6-ilamīds; 4’-trifluormetilbifenil-2-karbonskābes 2-(1 -metilpirol-2-ilmetil)-1,2,3,4-tetra-hidroizohinolin-6-ilamīds; 4’-trifluormetilbifenil-2-karbonskābes 2-(1 H-benzimidazol-2-ilmetil)-1,2,3,4-tetra-hidroizohinolin-6-ilamīds; 4’-trifluormetilbifenil-2-karbonskābes 2-(tiazol-2-ilmetil)-1,2,3,4-tetrahidroizo-hinolin-6-ilamTds; 4’-trifluormetilbifenil-2-karbonskābes 2-(1-metilimidazol-2-ilmetil)-1,2,3,4-tetra-hidroizohinolin-6-ilamīds; 4'-trifluormetilbifenil-2-karbonskābes 2-(1 H-[1,2,4]triazol-3-ilmetil)-1,2,3,4-tetrahidroizohinolin-6-ilamīds; 4’-trifluormetilbifenil-2-karbonskābes 2-allil-1,2,3,4-tetrahidroizohinolin-6-il-amīds.
19. Savienojums pēc 8. punkta, kurā saistošā grupa ir karbamāta grupa.
20. Savienojums pēc 19. punkta, proti, 6-[(4’-trifluormetilbifenil-2-karbonil)amino]-3,4-dihidro-1H-izohinofīh-2-karbonskābes terc-butilesteris.
21. Savienojums pēc 8. punkta, kurā saistošā grupa ir tioamīda grupa.
22. Savienojums pēc 8. punkta, kas ņemts no rindas: 7 4’-trifluormetilbifenil-2-karbonskābes 2-(tiofen-2-ilacetil)-1,2,3,4-tetrahidroizo-hinolin-6-ilamTds; 6-[(4’-trifluormetilbifenil-2-karbonil)amino]-3,4-dihidro-1H-izohinofīn-2-karbon-skābes [(R)-1-feniletil)amīds; 4’-trifluormetilbifenil-2-karbonskābes 2-(piridin-2-ilmetil)-1,2,3,4-tetrahidroizo-hinolin-6-ilam7ds; 4’-trifluormetilbifenil-2-karbonskābes 2-(1 H-imidazol-2-ilmetil)-1,2,3,4-tetra-hidroizohinolin-6-ilamīds; 4’-trifluormetilbifenil-2-karbonskābes 2-(tiazol-2-ilmetil)-1,2,3,4-tetrahidroizo-hinolin-6-ilam7ds; 4’-trifluormetilbifenil-2-karbonskābes 2-(1 H-[1,2,4]triazol-3-ilmetil)-1,2,3,4-tetrahidroizohinolin-6-ilamīds.
23. Savienojums pēc 22. punkta, proti, 4’-trifluormetilbifenil-2- karbonskābes 2-(tiofen-2-ilacetil)-1,2,3,4-tetrahidroizohinolin-6-ilamīds;
24. Savienojums pēc 22. punkta, proti, 6-[(4’-trifluormetilbifenil-2-karbonil)amino]-3,4-dihidro-1H-izohinofīn-2-karbonskābes 1-feniletilamīds;
25. Savienojums pēc 22. punkta, proti, 4’-trifluormetilbifenil-2- karbonskābes 2-(piridin-2-ilmetil)-1,2,3,4-tetrahidroizohinolin-6-ilamTds;
26. Savienojums pēc 22. punkta, proti, 4’-trifluormetilbifenil-2- karbonskābes 2-(1 H-imidazol-2-ilmetil)-1,2,3,4-tetrahidroizohinolin-6-ilamīds;
27. Savienojums pēc 22. punkta, proti, 4'-trifluormetilbifenil-2- karbonskābes 2-(tiazol-2-ilmetil)-1,2,3,4-tetrahidroizohinolin-6-ilamīds;
28. Savienojums pēc 22. punkta, proti, 4’-trifluormetilbifenil-2- karbonskābes 2-(1 H-[1,2,4]triazol-3-ilmetil)-1,2,3,4-tetrahidroizohinolin-6-ilamTds.
29. Farmaceitiskā kompozīcija, kas satur savienojumu ar formulu (I) pēc 1. punkta, un farmaceitiski pieņemamu nesēju.
30. Farmaceitiskā kompozīcija pēc 29. punkta, kas satur papildus vēl kādu citu lipīdu līmeni pazeminošu aģentu.
31. Savienojuma ar formulu (I) pēc 1. punkta pielietojums tādu medikamentu ražošanai, kas paredzēti aterosklerozes, pankreatīta, aptaukošanās, hiperholesterēmijas, hipertriglicerīdēmijas, hiperlipidēmijas un diabēta ārstēšanai zīdītājiem, pazeminot apolipoproteīna B sekrēciju.
32. Pielietojums pēc 31. punkta, kurā medikamenti paredzēti aterosklerozes, pankreatīta, aptaukošanās un diabēta ārstēšanai. 8 LV 11615
33. Pielietojums pēc 32. punkta, kurā medikamenti paredzēti aterosklerozes ārstēšanai.
34. Savienojuma ar formulu (I) pēc 1. punkta pielietojums tādu medikamentu ražošanai, kas paredzēti apoB (apolipoproteīna B) sekrēcijas pazemināšanai zīdītājiem.
35. Savienojums, kas ņemts no rindas: 4’-trifluormetilbifenil-2-karbonskābes 1,2,3,4-tetrahidroizohinolin-6-ilamīds; 4’-trifluormetilbifenil-2-karbonskābes 3-(2-hidroksietil)-4-hidroksimetilfenil-amīds; 2-(2-hidroksimetil-5-nitrofenil)etanols; 6-nitro-3,4-dihidro-1H-izohinolīn-2-karbonskābes terc-butilesteris; 6-amino-3,4-dihidro-1H-izohinorTn-2-karbonskābes terc-butilesteris; 2-(5-amino-2-hidroksimetilfenil)etanols.
36. Savienojums pēc 35. punkta, kas ņemts no rindas: 4’-trifluormetilbifenil-2-karbonskābes 1,2,3,4-tetrahidroizohinolin-6-ilamīds; 4’-trifluormetilbifenil-2-karbonskābes 3-(2-hidroksietil)-4-hidroksimetilfenil-amīds.
37. Savienojums pēc 35. punkta, proti, 6-amino-3,4-dihidro-1H-izohinolīn-2-karbonskābes terc-butilesteris. 9
LVP-96-176A 1995-06-07 1996-06-06 Therapeutic amides LV11615B (en)

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CA002223574A CA2223574C (en) 1995-06-07 1995-06-07 Biphenyl-2-carboxylic acid-tetrahydro-isoquinolin-6-yl amide derivatives, their preparation and their use as inhibitors of microsomal triglyceride transfer protein and/or apolipoprotein b (apo b) secretion
PCT/IB1995/000448 WO1996040640A1 (en) 1995-06-07 1995-06-07 BIPHENYL-2-CARBOXYLIC ACID-TETRAHYDRO-ISOQUINOLIN-6-YL AMIDE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS INHIBITORS OF MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN AND/OR APOLIPOPROTEIN B (Apo B) SECRETION
HU9601566A HUP9601566A3 (en) 1995-06-07 1996-06-06 Therapeutic tetrahydro-isoquinolin derivatives, their intermediates and pharmaceutical compositions containing the active component

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