HRP20171996T1 - Novi derivati fenil-tetrahidroizokinolina - Google Patents

Novi derivati fenil-tetrahidroizokinolina Download PDF

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HRP20171996T1
HRP20171996T1 HRP20171996TT HRP20171996T HRP20171996T1 HR P20171996 T1 HRP20171996 T1 HR P20171996T1 HR P20171996T T HRP20171996T T HR P20171996TT HR P20171996 T HRP20171996 T HR P20171996T HR P20171996 T1 HRP20171996 T1 HR P20171996T1
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phenyl
trifluoromethyl
propionamide
tetrahydroisoquinolin
rac
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HRP20171996TT
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Johannes Aebi
Kurt Amrein
Benoît HORNSPERGER
Bernd Kuhn
Yonfu LIU
Hans P. Maerki
Rainer E. Martin
Alexander V. Mayweg
Peter Mohr
Xuefei Tan
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F. Hoffmann - La Roche Ag
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Publication of HRP20171996T1 publication Critical patent/HRP20171996T1/hr

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    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
    • C07D217/14—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals
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    • 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
    • A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
    • A61P5/42—Drugs for disorders of the endocrine system of the suprarenal hormones for decreasing, blocking or antagonising the activity of mineralocorticosteroids
    • 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
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    • A61P5/46—Drugs for disorders of the endocrine system of the suprarenal hormones for decreasing, blocking or antagonising the activity of glucocorticosteroids
    • 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
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • 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
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
    • C07D217/24—Oxygen atoms
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
    • C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
    • C07D221/04—Ortho- or peri-condensed ring systems
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    • C07—ORGANIC CHEMISTRY
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    • C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
    • C07D221/04—Ortho- or peri-condensed ring systems
    • C07D221/06—Ring systems of three rings
    • C07D221/16—Ring systems of three rings containing carbocyclic rings other than six-membered
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
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    • 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
    • C07D405/12—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 chain containing hetero atoms as chain links

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Claims (15)

1. Spojevi, naznačeni time, da imaju formulu (I) [image] u kojoj R1, R2, R3 i R4 su neovisno odabrani između vodika, halogena, cijano skupine, nitro skupine, alkoksikarbonila, cikloalkoksikarbonila, supstituiranog aminokarbonila, supstituiranog aminosulfonila, alkila, haloalkila, cikloalkila, alkoksi, haloalkoksi i cikloalkoksi, pri čemu su supstituirani aminokarbonil i supstituirani aminosulfonil, supstituirani na atom dušika s jednim ili dva supstituenta neovisno odabrana između vodika, alkila, cikloalkila, hidroksialkila i alkoksialkila; R5 je H, halogen, alkil ili cikloalkil; R6 je H, alkil, haloalkil, cikloalkil, supstituirani aril ili supstituirani heteroaril, pri čemu su supstituirani aril ili supstituirani heteroaril supstituirani s R19, R20 i R21; R7, R8, R9, R10, R11 i R12 su neovisno odabrani od H, halogena, alkila i haloalkila; A je -(CR13R14)p-NR15R16 ili -(CR13R14)p-OR16; R13 i R14 su neovisno odabrani između vodika, alkila, haloalkila, cikloalkila i halocikloalkila; R15 je vodik, alkil, haloalkil, cikloalkil, hidroksialkil, alkoksialkil ili haloalkoksialkil; R16 je vodik, alkil, haloalkil, cikloalkil, hidroksialkil, alkoksialkil, haloalkoksialkil, oksetanilalkil, -CH2-C(O)OH, -CH2-C(O)OR17, -CH2-C(O)-NR17R18, -S(O)R17, -S(O)2R17, -S(O)2OR17, -S(O)2NR17R18, -C(O)R17, -C(O)OR17 ili -C(O)NR17R18; R17 je alkil, hidroksialkil, haloalkil, cikloalkil, alkilcikloalkil, alkilcikloalkilalkil, cikloalkilalkil, cikloalkoksialkil, cikloalkilalkoksialkil, alkoksialkil, haloalkoksialkil, alkoksialkoksialkil ili supstituirani heteroaril, pri čemu je supstituirani heteroaril supstituiran s R22, R23 i R24; R18 je vodik, alkil, haloalkil, cikloalkil, alkoksialkil, haloalkoksialkil ili hidroksialkil; R19, R20, R21, R22, R23 i R24 su neovisno odabrani između vodika, halogena, alkila, haloalkila, cikloalkila, alkoksi i haloalkoksi; n je nula, 1 ili 2; p je nula ili 1; ili njihove farmaceutski prihvatljive soli ili esteri; te time, da pojam „alkil“ označava monovalentnu linearnu ili razgranatu zasićenu ugljikovodikovu skupinu od 1 do 12 ugljikovih atoma.
2. Spoj u skladu s patentnim zahtjevom 1, naznačen time, da su R1, R2, R3 i R4 neovisno odabrani između vodika, halogena, cijano skupine, alkila i haloalkila.
3. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 2, naznačen time, da R6 predstavlja vodik.
4. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 3, naznačen time, da R16 je -S(O)2R17 ili -C(O)R17.
5. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 4, naznačen time, da R17 je alkil ili hidroksialkil.
6. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 5, naznačen time, da su R19, R20 i R21 neovisno odabrani između vodika i alkila.
7. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 6, naznačen time, da je odabran između sljedećih: (rac)-4-(8-amino-5,6,7,8-tetrahidroizokinolin-4-il)benzonitril; (rac)-N-(4-(4-cijanofenil)-5,6,7,8-tetrahidroizokinolin-8-il)etansulfonamid; (rac)-N-(4-(4-cijanofenil)-5,6,7,8-tetrahidroizokinolin-8-il)N'-propilsumporni diamid; (rac)--1-(4-(4-cijanofenil)-5,6,7,8-tetrahidroizokinolin-8-il)-3-etilurea; (rac)-N-(4-(4-cijanofenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (-)-(S ili R)-N-(4-(4-cijanofenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (+)-(R ili S)-N-(4-(4-cijanofenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (rac)-N-(4-(4-cijanofenil)-5,6,7,8-tetrahidroizokinolin-8-il)acetamid; (rac)-N-(4-(4-cijanofenil)-5,6,7,8-tetrahidroizokinolin-8-il)izobutiramid; (rac)-etil 4-(4-cijanofenil)-5,6,7,8-tetrahidroizokinolin-8-ilkarbamat; (rac)-4-(8-hidroksi-5,6,7,8-tetrahidroizokinolin-4-il)benzonitril; (rac)-4-(4-cijanofenil)-5,6,7,8-tetrahidroizokinolin-8-il-etilkarbamat; (rac)-4-(8-metoksi-5,6,7,8-tetrahidroizokinolin-4-il)benzonitril; (rac)-4-(8-(3,4-dimetilfenil)-8-hidroksi-5,6,7,8-tetrahidroizokinolin-4-il)benzonitril; (+)-(S ili R)-4-(8-(3,4-dimetilfenil)-8-hidroksi-5,6,7,8-tetrahidroizokinolin-4-il)benzonitril; (-)-(R ili S)-4-(8-(3,4-dimetilfenil)-8-hidroksi-5,6,7,8-tetrahidroizokinolin-4-il)benzonitril; (rac)-N-(4-(4-cijanofenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-il)propionamid; (-)-(S ili R)-N-(4-(4-cijanofenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-il)propionamid; (+)-(R ili S)-N-(4-(4-cijanofenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-il)propionamid; (rac)-N-(4-(3-kloro-4-fluorofenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (rac)-N-(4-(4-(trifluorometil)fenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (-)-(S ili R)-N-(4-(4-(trifluorometil)fenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (+)-(R ili S)-N-(4-(4-(trifluorometil)fenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (rac)-N-(4-(4-klorofenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (-)-(S ili R)-N-(4-(4-klorofenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (+)-(R ili S)-N-(4-(4-klorofenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (rac)-N-(4-(4-kloro-3-metilfenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (-)-(S ili R)-N-(4-(4-fluoro-3-metilfenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (+)-(R ili S)-N-(4-(4-fluoro-3-metilfenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (rac)-N-(4-(4-kloro-2-fluorofenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (-)-(S ili R)-N-(4-(4-kloro-2-metilfenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (+)-(R ili S)-N-(4-(4-kloro-2-fluorofenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (rac)-N-(4-(2-fluoro-4-(trifluorometil)fenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (-)-(S ili R)-N-(4-(2-fluoro-4-(trifluorometil)fenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (+)-(R ili S)-N-(4-(2-fluoro-4-(trifluorometil)fenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (rac)-N-(4-(4-kloro-3-fluorofenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (-)-(S ili R)-N-(4-(4-kloro-3-metilfenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (+)-(R ili S)-N-(4-(4-kloro-3-fluorofenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (rac)-N-(4-(3-fluoro-4-(trifluorometil)fenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (-)-(S ili R)-N-(4-(3-fluoro-4-(trifluorometil)fenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (+)-(R ili S)-N-(4-(3-fluoro-4-(trifluorometil)fenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (rac)-N-(4-(2,4-difluorofenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (rac)-N-(4-(2,4,5-trifluorofenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (rac)-N-(4-(3,4-difluorofenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (rac)-N-(4-(3,4-diklorofenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (R)-2-hidroksi-N-[(S,R)-4-(4-trifluorometil-fenil)-5,6,7,8-tetrahidro-izokinolin-8-il]-propionamid; (+)-(R)-2-hidroksi-N-[(R ili S)-4-(4-trifluorometil-fenil)-5,6,7,8-tetrahidro-izokinolin-8-il]-propionamid; (-)-(R)-2-hidroksi-N-[(S ili R)-4-(4-trifluorometil-fenil)-5,6,7,8-tetrahidro-izokinolin-8-il]-propionamid; (rac)-N-(4-(4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-il)propionamid; (-)-(S ili R)-N-(4-(4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-il)propionamid; (+)-(R ili S)-N-(4-(4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-il)propionamid; (R)-2-hidroksi-N-((R,S)-4-(4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-il)propanamid; (-)-(R)-2-hidroksi-N-((S ili R)-4-(4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-il) propanamid; (+)-(R)-2-hidroksi-N-((R ili S)-4-(4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-il) propanamid; (rac)-N-(4-(4-kloro-3-fluoropfenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-il)propionamid; (-)-(S ili R)-N-(4-(4-kloro-3-fluorofenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-il)propionamid; (+)-(R ili S)-N-(4-(4-kloro-3-fluorofenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-il)propionamid; (rac)-N-(4-(4-fluoro-3-metilfenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-il)propionamid; (-)-(S ili R)-N-(4-(4-fluoro-3-metilfenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-il)propionamid; (+)-(R ili S)-N-(4-(4-fluoro-3-metilfenil)-6,7-dihidro-5H-cikllopenta[c]piridin-7-il)propionamid; (rac)-N-(4-(2-fluoro-4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-il)propionamid; (-)-(S ili R)-N-(4-(2-fluoro-4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-il)propionamid; (+)-(R ili S)-N-(4-(2-fluoro-4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-il)propionamid; (rac)-N-(4-(4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-il)etansulfonamid; (-)-(S ili R)-N-(4-(4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-il)etansulfonamid; (+)-(R ili S)-N-(4-(4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-il)etansulfonamid; N-[(7R,8S ili 7S,8R)-7-metil-4-(4-trifluorometil-fenil)-5,6,7,8-tetrahidroizokinolin-8-il]-propionamid; N-[(7S,8S ili 7R,8R)-7-metil-4-(4-trifluorometil-fenil)-5,6,7,8-tetrahidroizokinolin-8-il]-propionamid; N-[(7S,8R ili 7R,8S)-7-metil-4-(4-trifluorometil-fenil)-5,6,7,8-tetrahidroizokinolin-8-il]-propionamid; N-[(7R,8R ili 7S,8S)-7-metil-4-(4-trifluorometil-fenil)-5,6,7,8-tetrahidroizokinolin-8-il]-propionamid; i njihove farmaceutski prihvatljive soli.
8. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 7, naznačen time, da je odabran između sljedećih: (rac)-N-(4-(3-fluoro-4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-il)etansulfonamid; (-)-(S ili R)-N-(4-(3-fluoro-4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-il)propionamid; (+)-(R ili S)-N-(4-(3-fluoro-4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-il)etansulfonamid; (+)-(R)-4-(2-fluoro-4-(trifluorometil)fenil)-5,6,7,8-tetrahidroizokinolin-8-amin; (+)-(R)-N-(4-(2-fluoro-4-(trifluorometil)fenil)-5,6,7,8-tetrahidroizokinolin-8-il)acetamid; (+)-(R)-N-(4-(2-fluoro-4-(trifluorometil)fenil)-5,6,7,8-tetrahidroizokinolin-8-il)metansulfonamid; (+)-(R)-N-(4-(4-(trifluorometil)fenil)-5,6,7,8-tetrahidroizokinolin-8-il)acetamid; (+)-(R)-N-(4-(4-cijanofenil)-5,6,7,8-tetrahidroizokinolin-8-il)acetamid; (+)-( R)-N-(4-(3-fluoro-4-(trifluorometil)fenil)-5,6,7,8-tetrahidroizokinolin-8-il)acetamid; (rac)-4-(2-fluoro-4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-ol; (rac)-4-(7-hidroksi-6,7-dihidro-5H-ciklopenta[c]piridin-4-il)benzonitril; (rac)-4-(3-fluoro-4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-ol; (rac)-4-(4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-ol; (rac)-7-metil-4-(4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-ol; (+)-(7R ili 7S)-6,6-dimetil-4-[4-(trifluorometil)fenil]-5,7-dihidrociklopenta[c]piridin-7-ol; (-)-(7S ili 7R)-6,6-dimetil-4-[4-(trifluorometil)fenil]-5,7-dihidrociklopenta[c]piridin-7-ol; (+)-4-[(7R ili 7S)-7-hidroksi-6,6-dimetil-5,7-dihidrociklopenta[c]piridin-4-il]benzonitril; (-)-4-[(7S ili 7R)-7-hidroksi-6,6-dimetil-5,7-dihidrociklopenta[c]piridin-4-il]benzonitril; (rac)-4-(3-fluoro-4-trifluorometil-fenil)-6,7-dihidro-5H-[2]piridin-7-ilamin; (rac)-N-(4-(3-fluoro-4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-il)propionamid; (rac)-ciklopropansulfonska kiselina-[4-(3-fluoro-4-trifluorometil-fenil)-6,7-dihidro-5H-[2]piridin-7-il]-amid; (rac)-propionska kiselina-4-(3-fluoro-4-trifluorometil-fenil)-6,7-dihidro-5H-[2]piridin-7-il-ester; (rac)-4-(4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-amin; (rac)-N-(4-(4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-il)ciklopropansulfonamid; (rac)-N-(4-(4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-il)metansulfonamid; (rac)-N-(4-(4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-il)propan-1-sulfonamid; (rac)-tert-butil-2-(4-(4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-iloksi)acetat; (rac)-metil 2-(4-(4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-iloksi)acetat; (rac)-2-(4-(4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-iloksi)-octena kiselina-hidroklorid; (rac)-N-metil-2-(4-(4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-iloksi)acetamid; (rac)-N,N-dimetil-2-(4-(4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-iloksi)acetamid; (rac)-2-(4-(4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-iloksi)acetamid; (rac)-7-((3-metiloksetan-3-il)metoksi)-4-(4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin; (rac)-4-(4-(trifluorometil)fenil)-5,6,7,8-tetrahidroizokinolin-8-ol; (-)-(S)-4-(4-(trifluorometil)fenil)-5,6,7,8-tetrahidroizokinolin-8-ol; (+)-(R)-4-(4-(trifluorometil)fenil)-5,6,7,8-tetrahidroizokinolin-8-ol; (R)-N-(4-(2-ciklopropil-4-(trifluorometil)fenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (+)-(7R ili 7S)-4-[3-fluoro-4-(trifluorometil)fenil]-6,6-dimetil-5,7-dihidrociklopenta[c]-piridin-7-ol; (-)-(7S ili 7R)-4-[3-fluoro-4-(trifluorometil)fenil]-6,6-dimetil-5,7-dihidrociklopenta[c]-piridin-7-ol; i njihove farmaceutski prihvatljive soli.
9. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 8, naznačen time, da je odabran između sljedećih: (+)-(R ili S)-N-(4-(4-cijanofenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (+)-(R ili S)-N-(4-(4-(trifluorometil)fenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (+)-(R ili S)-N-(4-(2-fluoro-4-(trifluorometil)fenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (+)-(R ili S)-N-(4-(3-fluoro-4-(trifluorometil)fenil)-5,6,7,8-tetrahidroizokinolin-8-il)propionamid; (+)-(R ili S)-N-(4-(4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-il)propionamid; (+)-(R ili S)-N-(4-(2-fluoro-4-(trifluorometil)fenil)-6,7-dihidro-5H-ciklopenta[c]piridin-7-il)propionamid; N-[(7S,8R ili 7R,8S)-7-metil-4-(4-trifluorometil-fenil)-5,6,7,8-tetrahidro-izokinolin-8-il]-propionamid; i njihove farmaceutski prihvatljive soli.
10. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 6 ili 8, naznačen time, da je odabran od sljedećih: (+)-(7R ili 7S)-6,6-dimetil-4-[4-(trifluorometil)fenil]-5,7-dihidrociklopenta[c]piridin-7-ol; i njegove farmaceutski prihvatljive soli.
11. Postupak za pripremu spoja u skladu s bilo kojim od patentnih zahtjeva 1 do 10, naznačen time, da obuhvaća reakciju spoja formule (II) u prisutnosti spoja formule (III); [image] pri čemu su R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, A i n, kako su prethodno definirani, R101 i R102 su neovisno odabrani između alkila i cikloalkila, ili R101 i R102 zajedno s borovim atomom na kojega su priključeni, tvore borolan, a X je halogen ili triflat.
12. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 10, naznačen time, da se upotrebljava kao terapeutski djelatna tvar.
13. Farmaceutski pripravak, naznačen time, da obuhvaća spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 10, kao i terapeutski inertni nosač.
14. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 od 10, naznačen time, da služi za liječenje ili profilaksu kronične bolesti bubrega, kongestivnog zatajenja srca, hipertenzije, primarnog hiperaldosteronizma i Cushingova sindroma.
15. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 10, naznačen time, da se proizvodi putem postupka definiranog u patentnom zahtjevu 11.
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