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RU2002122335A - Азотсодержащее циклическое соединение и фармацевтическая композиция, включающая указанное соединение - Google Patents

Азотсодержащее циклическое соединение и фармацевтическая композиция, включающая указанное соединение

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Publication number
RU2002122335A
RU2002122335A RU2002122335/04A RU2002122335A RU2002122335A RU 2002122335 A RU2002122335 A RU 2002122335A RU 2002122335/04 A RU2002122335/04 A RU 2002122335/04A RU 2002122335 A RU2002122335 A RU 2002122335A RU 2002122335 A RU2002122335 A RU 2002122335A
Authority
RU
Russia
Prior art keywords
group
substituted
ring
cyano
hydrate
Prior art date
Application number
RU2002122335/04A
Other languages
English (en)
Other versions
RU2230060C2 (ru
Inventor
Нобуру ЯМАМОТО (JP)
Нобуру ЯМАМОТО
Юити СУДЗУКИ (JP)
Юити СУДЗУКИ
Манами КИМУРА (JP)
Манами КИМУРА
Тецухиро НИДОМЕ (JP)
Тецухиро НИДОМЕ
Йоити ИЙМУРА (JP)
Йоити ИЙМУРА
Тецуюки ТЕРАМОТО (US)
Тецуюки ТЕРАМОТО
Йосихиса КАНЕДА (JP)
Йосихиса КАНЕДА
Тосихико КАНЕКО (JP)
Тосихико Канеко
Нобуюки КУРУСУ (JP)
Нобуюки КУРУСУ
Даисуке СИНМИО (JP)
Даисуке СИНМИО
Юкие ЙОСИКАВА (JP)
Юкие ЙОСИКАВА
Синдзи ХАТАКЕЯМА (JP)
Синдзи Хатакеяма
Original Assignee
Эйсай Ко., Лтд. (JP)
Эйсай Ко., Лтд.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Эйсай Ко., Лтд. (JP), Эйсай Ко., Лтд. filed Critical Эйсай Ко., Лтд. (JP)
Publication of RU2002122335A publication Critical patent/RU2002122335A/ru
Application granted granted Critical
Publication of RU2230060C2 publication Critical patent/RU2230060C2/ru

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D207/337—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • 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
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • 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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    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
    • C07D207/09—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
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    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/14—Nitrogen atoms not forming part of a nitro radical
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    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
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    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
    • C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/26—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms
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    • C07—ORGANIC CHEMISTRY
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    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/30—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom
    • C07D211/32—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom by oxygen atoms
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    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
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    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D211/40—Oxygen atoms
    • C07D211/44—Oxygen atoms attached in position 4
    • C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
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    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
    • C07D211/64—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4 having an aryl radical as the second substituent in position 4
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    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
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    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
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    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
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Claims (43)

1. Соединение формулы (I), его соль или гидрат
Figure 00000001
где в указанной формуле Ar означает (1) С6-14 ароматическую углеводородную циклическую группу, которая может быть замещена, (2) 5-14-членную ароматическую гетероциклическую группу, которая может быть замещена, (3) C1-6 алкильную группу, замещенную C6-14 ароматической углеводородной циклической группой, которая может быть замещена, или (4) C1-6 алкильную группу, замещенную 5-14-членной ароматической гетероциклической группой, которая может быть замещена;
кольцо А представляет соответственно пиперазиновое кольцо, гомопиперазиновое кольцо, пиперидиновое кольцо, гомопиперидиновое кольцо, пирролидиновое кольцо или диазабицикло[2,2,1]гептановое кольцо, которые, соответственно, могут быть замещены;
кольцо В представляет (1) С3-14 углеводородное кольцо, которое может быть замещено, или (2) 5-14-членное гетероциклическое кольцо, которое может быть замещено;
Е означает (1) простую связь, группу формулы (2) -СО- или (3) -СН(ОН)-;
Х означает (1) простую связь, (2) атом кислорода, (3) атом серы, (4) C1-6 алкиленовую цепь, которая может быть замещена, группу формулы (5) -NR2- (где R2 означает атом водорода или C1-6 алкильную группу, С3-8 циклоалкильную группу, низшую ацильную группу или C1-6 алкилсульфонильную группу, которые могут быть замещены), (6) -СО-, (7) -COO-, (8) -ООС-, (9) -CONR3- (где R3 означает атом водорода или C1-6 алкильную группу, которые могут быть замещены), (10) -NR4CO- (где R4 означает атом водорода или C1-6 алкильную группу, которая может быть замещена), (11) -SO-, (12) -SO2-, (13) -SONR5- (где R5 означает атом водорода или C1-6 алкильную группу, которая может быть замещена), (14) -NR6SO- (где R6 означает атом водорода или C1-6 алкильную группу, которая может быть замещена), (15) -SO2NR7 (где R7 означает атом водорода или C1-6 алкильную группу, которая может быть замещена), (16) -NR8SO2- (где R8 означает атом водорода или C1-6 алкильную группу, которая может быть замещена), (17) >C=N-OR9 (где R9 означает атом водорода или C1-6 алкильную группу, которая может быть замещена), (18) -NR10W3-O- (где R10 означает атом водорода или C1-6 алкильную группу, С3-8 циклоалкильную группу, низшую ацильную группу или C1-6 алкилсульфонильную группу, которая может быть замещена; и W3 означает C1-6 алкиленовую группу, которая может быть замещена), (19) -NH-CO-NH-, (20) -NH-CS-NH-, (21) -C(=NR15)NR16- (где R15 и R16 имеют одинаковые или разные значения и представляют атом водорода, нитрильную группу, C1-6 алкильную группу, С2-6 алкенильную группу, С3-8 циклоалкильную группу или С3-8 циклоалкенильную группу), (22) -NHC(=NH)-, (23) -O-CO-S-, (24) -S-CO-O-, (25) -ОСОО-, (26) -NHCOO-, (27) -OCONH-, (28) -CO(CH2)mO- (где m означает 0 или целое число от 1 до 6), (29) -СНОН- или (30) -СНОН (СН2)nО- (где n означает 0 или целое число от 1 до 6); R1 означает (1) атом водорода, (2) атом галогена, (3) гидроксильную группу, (4) C1-6 алкильную группу, которая может быть замещена одной или несколькими группами, выбираемыми из гидроксильной группы, атома галогена и нитрильной группы, (5) C2-6 алкенильную группу, которая может быть замещена одной или несколькими группами, выбираемыми из гидроксильной группы, атома галогена и нитрильной группы, (6) C2-6 алкинильную группу, которая может быть замещена одной или несколькими группами, выбираемыми из гидроксильной группы, атома галогена и нитрильной группы, (7) С3-8 циклоалкильную группу, которая может быть замещена одной или несколькими группами, выбираемыми из гидроксильной группы, атома галогена и нитрильной группы, (9) C1-6 алкокси-C1-6 алкильную группу, (10) амино-C1-6 алкильную группу, в которой атом азота может быть замещен, (11) группу формулы -N(R11)R12- (где R11 и R12 имеют одинаковые или разные значения и представляют, каждый, атом водорода или C1-6 алкильную группу), (12) аралкильную группу, (13) морфолинильную группу, (14) тиоморфолинильную группу, (15) пиперидильную группу, (16) пирролидинильную группу или (17) пиперазинильную группу; и
D1, D1, W1 и W2 имеют одинаковые или разные значения и представляют (1) простую связь или (2) C1-6 алкиленовую цепь, которая может быть замещена;
при условии, что из приведенного выше определения исключены 1-[4-циано-5-метил-4-(2-циано-5-тиенил)гексил]-4-[2-(4-фторфенокси)этил]пиперазин; 1-[4-циано-5-метил-4-(2-циано-5-тиенил)гексил]-4-[2-(3-фторфенокси)этил]пиперазин и 1-[4-циано-5-метил-4-(2-тиенил)гексил]-4-[2-(3-фторфенокси)этил]пиперазин.
2. Соединение по п.1, его соль или гидрат, где Ar означает C6-14 ароматическое углеводородное кольцо или 5-14-членное ароматическое гетероциклическое кольцо, которое может быть замещено.
3. Соединение по п.1, его соль или гидрат, где Ar означает тиофеновое кольцо или бензольное кольцо, которое может быть замещено.
4. Соединение по п.1, его соль или гидрат, где Ar означает С6-14 ароматическое углеводородное кольцо или 5-14-членное ароматическое углеводородное кольцо, которое может быть замещено одной или несколькими группами, выбираемыми из нитрильной группы и атома галогена.
5. Соединение по п.1, его соль или гидрат, где Ar означает тиофеновое кольцо или бензольное кольцо, которое может быть замещено одной или несколькими группами, выбираемыми, соответственно, из нитрильной группы и атома галогена.
6. Соединение по п.1, его соль или гидрат, где кольцо А представляет собой пиперазиновое кольцо, гомопиперазиновое кольцо или пиперидиновое кольцо.
7. Соединение по п.1, его соль или гидрат, где кольцо А представляет пиперазиновое кольцо.
8. Соединение по п.1, его соль или гидрат, где кольцо А представляет пиперазиновое кольцо, гомопиперазиновое кольцо или пиперидиновое кольцо, которое может быть замещено одной или несколькими группами, выбираемыми из гидроксильной группы, атома галогена, цианогруппы, C1-6 алкильной группы, которая может быть замещена, С2-6 алкенильной группы, которая может быть замещена, C2-6 алкинильной группы, которая может быть замещена, C1-6 алкоксильной группы, которая может быть замещена, C2-6 алкенилоксигруппы, которая может быть замещена, C1-6 алкилкарбонильной группы, которая может быть замещена, C2-6 алкенилкарбонильной группы, которая может быть замещена, C1-6 алкоксикарбонильной группы, которая может быть замещена, и С2-6 алкенилоксикарбонильной группы, которая может быть замещена.
9. Соединение по п.1, его соль или гидрат, где кольцо В представляет С6-14 ароматическое углеводородное кольцо или 5-14-членное ароматическое гетероциклическое кольцо, которые, соответственно, могут быть замещены.
10. Соединение по п.1, его соль или гидрат, где кольцо В представляет бензол, тиофен, пиридин, 1,4-бензодиоксан, индол, бензотиазол, бензоксазол, бензимидазол, 2-кето-1-бензимидазол, тиазол, оксазол, изоксазол, 1,2,4-оксадиазол, инданон, бензофуран, хинолин, 1,2,3,4-тетрагидрохинолин, нафталин или 1,2,3,4-тетрагидронафталин, которые, соответственно, могут быть замещены.
11. Соединение по п.1, его соль или гидрат, где кольцо В представляет С6-14 ароматическое углеводородное кольцо или 5-14-членное ароматическое гетероциклическое кольцо, которые, соответственно, могут быть замещены одной или несколькими группами, выбираемыми из атома галогена, нитрильной группы, C1-6 алкильной группы, низшей ацильной группы, C1-6 алкилсульфонильной группы и аралкильной группы.
12. Соединение по п.1, его соль или гидрат, где D1 и D2 имеют одинаковые или разные значения и представляют (1) простую связь или (2) C1-6 алкиленовую цепь, которая может быть замещена одной или несколькими группами, выбираемыми из гидроксильной группы, атома галогена, нитрильной группы, C1-6 алкильной группы, C2-6 алкенильной группы и C1-6 алкоксильной группы.
13. Соединение по п.1, его соль или гидрат, где Е означает простую связь.
14. Соединение по п.1, его соль или гидрат, где D1 и D2 означают C1-6 алкиленовую цепь и Е означает простую связь.
15. Соединение по п.1, его соль или гидрат, где частичная структура -D1-E-D2- представляет C1-4 алкиленовую группу.
16. Соединение по п.1, его соль или гидрат, где W1 и W2 имеют одинаковые или разные значения и представляют, каждый, (1) простую связь или (2) C1-6 алкиленовую цепь, которая может быть замещена одной или несколькими группами, выбираемыми из гидроксильной группы, атома галогена, нитрильной группы, C1-6 алкилоксигруппы и С2-6 алкенилоксигруппы.
17. Соединение по п.1, его соль или гидрат, где W1 означает (1) простую связь или (2) C1-6 алкиленовую цепь, которая может быть замещена одной или несколькими группами, выбираемыми из (i) нитрильной группы, (ii) C1-6 алкильной группы, которая может быть замещена одной или несколькими группами, выбираемыми из C1-6 алкоксильной группы и С2-6 алкенилоксигруппы, и (iii) С2-6 алкенильной группы; и W2 означает простую связь.
18. Соединение по п.1, его соль или гидрат, где W1 и W2 имеют одинаковые или разные значения и представляют, каждый, C1-6 алкиленовую цепь, замещенную одной или несколькими группами, выбираемыми из C1-6 алкильной группы и С2-6 алкенильной группы, причем вышеуказанные C1-6 алкильная группа и/или С2-6 алкенильная группа могут быть связаны друг с другом с образованием кольца либо вышеуказанная C1-6 алкильная группа или С2-6 алкенильная группа может быть связана с кольцом В или Х с образованием кольца.
19. Соединение по п.1, его соль или гидрат, где Х означает (1) простую связь, (2) атом кислорода, группу формулы (3) -NR2- (где R2 означает атом водорода, C1-6 алкильную группу, С3-8 циклоалкильную группу, низшую ацильную группу или C1-6 алкилсульфонильную группу, которые могут быть замещены), (4) -NR10-W3-O- (где R10 означает атом водорода, C1-6 алкильную группу, С3-8 циклоалкильную группу, низшую ацильную группу или C1-6 алкилсульфонильную группу, которые могут быть замещены; и W3 означает C1-6 алкиленовую группу, которая может быть замещена) или (5) -NH-SO2-.
20. Соединение по п.1, его соль или гидрат, где Х означает (1) атом кислорода, группу формулы (2) -NR2- (где R2 означает атом водорода, C1-6 алкильную группу, С3-8 циклоалкильную группу, низшую ацильную группу или C1-6 алкилсульфонильную группу, которая может быть замещена) или (3) -NH-SO2-.
21. Соединение по п.1, его соль или гидрат, где частичная структура -W1-X-W2- представляет C1-6 алкиленовую группу, которая может быть замещена.
22. Соединение по п.1, его соль или гидрат, где W1 означает C1-6 алкиленовую цепь, которая может быть замещена; W2 означает простую связь; и Х означает кислород или группу формулы -NR2- (где R2 имеет указанные выше значения).
23. Соединение по п. 22, его соль или гидрат, где заместитель W1 представляет одну или несколько групп, выбираемых из (1) нитрильной группы, (2) C1-6 алкильной группы, которая может быть замещена C1-6 алкилоксигруппой или С2-6 алкенилоксигруппой, и (3) С2-6 алкенильной группы; и R2 означает C1-6 алкильную группу, которая может быть замещена.
24. Соединение по п.1, его соль или гидрат, где R1 означает C1-6 алкильную группу.
25. Соединение по п.1, его соль или гидрат, где R1 означает метильную, этильную, н-пропильную или изопропильную группу.
26. Соединение формулы (II), его соль или гидрат
Figure 00000002
где в указанной формуле R1 имеет приведенные выше значения;
R13 и R14 имеют одинаковые или разные значения и представляют (1) атом водорода, (2) атом галогена, (3) гидроксильную группу, (4) меркаптогруппу, 5) C1-6 алкильную группу, которая может быть замещена одной или несколькими группами, выбираемыми из гидроксильной группы и атома галогена, (6) C1-6 алкоксильную группу, которая может быть замещена одной или несколькими группами, выбираемыми из гидроксильной группы, атома галогена и C1-6 алкоксикарбонильной группы, (7) нитрогруппу, (8) аминогруппу, которая может быть замещена, (9) цианогруппу, (10) карбоксильную группу, (11) C1-6 алкоксикарбонильную группу, (12) C1-6 тиоалкоксильную группу, (13) C1-6 алкилсульфонильную группу, (14) низшую ацильную группу, (15) С6-14 ароматическую углеводородную циклическую группу, которая может быть замещена, (16) 5-14-членную ароматическую гетероциклическую группу, которая может быть необязательно замещена, (17) арилоксигруппу или (18) аралкилоксигруппу либо (19) все вместе элементы R13 или все вместе элементы R14 связаны друг с другом с образованием (i) алифатического кольца, которое может быть замещено, (ii) гетероциклического кольца, которое может быть замещено, или (iii) алкилендиоксигруппы;
n означает 0 или целое число от 1 до 3;
р означает целое число от 1 до 6;
q означает целое число от 1 до 6; и
r означает 0 или целое число от 1 до 5;
при условии, что из приведенного выше определения исключены 1-[4-циано-5-метил-4-(2-циано-5-тиенил)гексил]-4-[2-(4-фторфенокси)этил]пиперазин; 1-[4-циано-5-метил-4-(2-циано-5-тиенил)гексил]-4-[2-(3-фторфенокси)этил]пиперазин и 1-[4-циано-5-метил-4-(2-тиенил)гексил]-4-[2-(3-фторфенокси)этил]пиперазин.
27. Соединение формулы (III), его соль или гидрат
Figure 00000003
где в указанной формуле R1 и R2 имеют приведенные выше значения;
R13 и R14 имеют одинаковые или разные значения и представляют (1) атом водорода, (2) атом галогена, (3) гидроксильную группу, (4) меркаптогруппу, (5) C1-6 алкильную группу, которая может быть замещена одной или несколькими группами, выбираемыми из гидроксильной группы и атома галогена, (6) C1-6 алкоксильную группу, которая может быть замещена одной или несколькими группами, выбираемыми из гидроксильной группы, атома галогена и C1-6 алкоксикарбонильной группы, (7) нитрогруппу, (8) аминогруппу, которая может быть замещена, (9) цианогруппу, (10) карбоксильную группу, (11) C1-6 алкоксикарбонильную группу, (12) C1-6 тиоалкоксильную группу, (13) C1-6 алкилсульфонильную группу, (14) низшую ацильную группу, (15) С6-14 ароматическую углеводородную циклическую группу, которая может быть замещена, (16) 5-14-членную ароматическую гетероциклическую группу, которая может быть замещена, (17) арилоксигруппу, (18) аралкилоксигруппу или (19) все вместе элементы R13 или все вместе элементы R14 могут быть связаны друг с другом с образованием (i) алифатического кольца, которое может быть замещено, (ii) гетероциклического кольца, которое может быть замещено, или (iii) алкилендиоксигруппы;
n означает 0 или целое число от 1 до 3;
р означает целое число от 1 до 6;
q означает целое число от 1 до 6;
r означает 0 или целое число от 1 до 5.
28. Соединение по п.1, его соль или гидрат, которое выбирают из группы, включающей
4-[(4-циано-5-метил-4-фенил)гексил]-N-(4-фторфенил)-N’-(2-метилпропил)-1(2Н)-пиразинкарбоксиимидамид,
1-изопропил-4-[4-(1-изобутил-1Н-бензо[d]имидазол-2-ил)пиперазино]-1-фенилбутилцианид,
1-[4-циано-5-метил-4-(5-циано-2-тиенил)гексил]-4-[2-(3-цианофенокси)этил]пиперазин,
1-[4-циано-5-метил-4-(2-тиенил)гексил]-4-[2-(3-цианофенокси)этил]пиперазин,
1-[4-циано-5-метил-4-(5-циано-2-тиенил)гексил]-4-[3-(5-циано-2-тиенил)пропил]пиперазин,
1-[4-циано-5-метил-4-(3-тиенил)гексил]-4-[2-(3-цианофенокси)этил]пиперазин,
1-{4-циано-5-метил-4-[4-(2-циано)тиенил]гексил}-4-[2-(3-цианофенокси)этил]пиперазин,
1-[(4-циано-5-метил-4-фенил)гексил]-4-[(2-бензоксазолил)амино]пиперидин,
1-[4-циано-4-(5-циано-2-тиенил)-5-метилгексил]-(3S)-3-[N-(2-цианоэтил)-N-бензиламино]пирролидин,
1-[4-циано-4-(5-циано-2-тиенил)-5-метилгексил]-(3R)-3-[N-(2-цианоэтил)-N-бензиламино]пирролидин,
1-[(4-циано-5-метил-4-фенил)гексил]-4-(бензотиазолил]пиперазин,
1-[(4-циано-5-метил-4-фенил)гексил]-4-[2-(6-метокси)бензотиазолил]пиперазин,
1-[(4-циано-5-метил-4-фенил)гексил]-4-(2-бензоксазолил)пиперазин,
1-[(4-циано-5-метил-4-фенил)гексил]-4-(2-хинолинил)пиперазин,
4-[4-(1-метил-1Н-бензо[d]имидазол-2-ил)-1,4-диазепан-1-ил]-1-изопропил-1-фенилбутилцианид,
4-[4-(1-этил-1Н-бензо[d]имидазол-2-ил)-1,4-диазепан-1-ил]-1-изопропил-1-фенилбутилцианид,
этил-4-(4-циано-5-метил-4-фенилгексил)-1-[2-(4-фторфенокси)этил]-2-пиперазинкарбоксилат,
1-[(2-оксо-1,2-дигидро-3-хинолил)метил]-4-[(4-циано-5-метил-4-фенил)гексил]пиперидин,
4-[(4-циано-5-метил-4-фенил)гексил]-1-{[2-(метансульфониламино)фенил]метил}пиперазин,
4-[(4-циано-5-метил-4-фенил)гексил]-1-{[2-(метансульфониламино)фенил]метил}пиперидин,
{1-[4-циано-5-метил-5-(2-тионил)гексил]пиперазинил}амид(S)-3-фенил-2-аминопропановой кислоты,
4-[4-(4-фенилпиперидинил)пиперидинил]-1-изопропил-1-фенилбутилцианид,
4-[4-(4-циано-4-фенилпиперидинил)пиперидинил]-1-изопропил-1-фенилбутилцианид, и
4-[4-(4-бензилпиперидинил)пиперидинил]-1-изопропил-1-фенилбутилцианид.
29. Фармацевтическая композиция, содержащая соединение формулы (I), его соль или гидрат
Figure 00000004
где в указанной формуле Ar означает (1) С6-14 ароматическую углеводородную циклическую группу, которая может быть замещена, (2) 5-14-членную ароматическую гетероциклическую группу, которая может быть замещена, (3) C1-6 алкильную группу, замещенную C6-14 ароматической углеводородной циклической группой, которая может быть замещена, или (4) C1-6 алкильную группу, замещенную 5-14-членной ароматической гетероциклической группой, которая может быть замещена;
кольцо А представляет пиперазиновое кольцо, гомопиперазиновое кольцо, пиперидиновое кольцо, гомопиперидиновое кольцо, пирролидиновое кольцо или диазабицикло[2,2,1]гептановое кольцо, которые, соответственно, могут быть замещены;
кольцо В представляет (1) С3-14 углеводородное кольцо, которое может быть замещено, или (2) 5-14-членное гетероциклическое кольцо, которое может быть замещено;
Е означает (1) простую связь, группу формулы (2) -СО- или (3) -СН(ОН)-;
Х означает (1) простую связь, (2) атом кислорода, (3) атом серы, (4) C1-6 алкиленовую цепь, которая может быть замещена, группу формулы (5) -NR2- (где R2 означает атом водорода или C1-6 алкильную группу, С3-8 циклоалкильную группу, низшую ацильную группу или C1-6 алкилсульфонильную группу, которые могут быть замещены), (6) -СО-, (7) -COO-, (8) -ООС-, (9) -CONR3- (где R3 означает атом водорода или C1-6 алкильную группу, которая может быть замещена), (10) -NR4CO-(где R4 означает атом водорода или C1-6 алкильную группу, которая может быть замещена), (11) -SO-, (12) -SO2-, (13) -SONR5- (где R5 означает атом водорода или C1-6 алкильную группу, которая может быть замещена), (14) -NR6SO- (где R6 означает атом водорода или C1-6 алкильную группу, которая может быть замещена), (15) -SO2NR7- (где R7 означает атом водорода или C1-6 алкильную группу, которая может быть замещена), (16) -NR8SO2- (где R8 означает атом водорода или C1-6 алкильную группу, которая может быть замещена), (17) >C=N-OR9 (где R9 означает атом водорода или C1-6 алкильную группу, которая может быть замещена), (18) -NR10W3-O- (где R10 означает атом водорода или C1-6 алкильную группу, С3-8 циклоалкильную группу, низшую ацильную группу или C1-6 алкилсульфонильную группу, которые могут быть замещены; и W3 означает C1-6 алкиленовую группу, которая может быть замещена), (19) -NH-CO-NH-, (20) -NH-CS-NH-, (21) -С (=NRl5)NR16- (где R15 и R16 имеют одинаковые или разные значения и представляют, каждый, атом водорода, нитрильную группу,C1-6 алкильную группу, С2-6 алкенильную группу, С3-8 циклоалкильную группу или С3-8 циклоалкенильную группу), (22) -NHC(=NH)-, (23) -O-CO-S-, (24) -S-CO-O-, (25) -ОСОО-, (26) -NHCOO-, (27) -OCONH-, (28) -СО(СН2)mО- (где m означает 0 или целое число от 1 до 6), (29) -СНОН- или (30) -СНОН (СН2)nО- (где n означает 0 или целое число от 1 до 6); R1 означает (1) атом водорода, (2) атом галогена, (3) гидроксильную группу, (4) C1-6 алкильную группу, которая может быть замещена одной или несколькими группами, выбираемыми из гидроксильной группы, атома галогена и нитрильной группы, (5) С2-6 алкенильную группу, которая может быть замещена одной или несколькими группами, выбираемыми из гидроксильной группы, атома галогена и нитрильной группы, (6) С2-6 алкинильную группу, которая может быть замещена одной или несколькими группами, выбираемыми из гидроксильной группы, атома галогена и нитрильной группы, (7) С3-8 циклоалкильную группу, которая может быть замещена одной или несколькими группами, выбираемыми из гидроксильной группы, атома галогена и нитрильной группы, (9) C1-6 алкокси-C1-6 алкильную группу, (10) амино-C1-6 алкильную группу, в которой атом азота может быть замещен, (11) группу формулы -N(R11)R12-(где R11 и R12 имеют одинаковые или разные значения и представляют атом водорода или C1-6 алкильную группу), (12) аралкильную группу, (13) морфолинильную группу, (14) тиоморфолинильную группу, (15) пиперидильную группу, (16) пирролидинильную группу или (17) пиперазинильную группу; и D1, D2, W1 и W2 имеют одинаковые или разные значения и представляют каждый (1) простую связь или (2) C1-6 алкиленовую цепь, которая может быть замещена; при условии, что из приведенного выше определения исключены 1-[4-циано-5-метил-4-(2-циано-5-тиенил)гексил]-4-[2-(4-фторфенокси)этил]пиперазин; 1-[4-циано-5-метил-4-(2-циано-5-тиенил)гексил]-4-[2-(3-фторфенокси)этил]пиперазин и 1-[4-циано-5-метил-4-(2-тиенил)гексил]-4-[2-(3-фторфенокси)этил]пиперазин.
30. Композиция по п.29, которая является антагонистом кальция.
31. Композиция по п.29, которая является нейронизбирательным антагонистом кальция.
32. Композиция по п.29, которая является ингибитором, по крайней мере, одного кальциевого канала P/Q-типа и N-типа.
33. Композиция по п.29, которая является средством для лечения, профилактики или улучшения состояния при заболевании, при котором эффективно ингибирующее действие в отношении, по крайней мере, одного кальциевого канала P/Q-типа и одного кальциевого канала N-типа.
34. Композиция по п.29, которая является средством, препятствующим гибели нервных клеток или защищающим нервные клетки головного мозга.
35. Композиция по п.29, которая является средством для лечения, профилактики или улучшения состояния в случае нервного заболевания.
36. Композиция по п.35, воздействующая на любое нервное заболевание, выбираемое из группы, включающей острый ишемический инсульт, кровоизлияние в мозг, инфаркт головного мозга, травму головы, гибель нервных клеток головного мозга, болезнь Альцгеймера, болезнь Паркинсона, боковой амиотрофический склероз, болезнь Хантингтона, метаболическое расстройство кровообращения головного мозга, нарушение функции головного мозга, болевой синдром, спазмы, шизофрению, мигрень, эпилепсию, маниакально-депрессивный синдром, дегенеративные нервные заболевания, ишемию головного мозга, слабоумие, вызванное СПИДом, отек мозга, состояние страха, диабетическую невропатию, слабоумие вследствие поражения сосудов головного мозга и рассеянный склероз.
37. Композиция по п.29, которая является аналгетиком.
38. Соединение по п.1, его соль или гидрат для получения антагониста кальция, нейронизбирательного антагониста кальция, ингибитора кальциевого канала P/Q-типа и/или N-типа, средства для лечения, профилактики или улучшения состояния в случае заболевания, восприимчивого к ингибированию кальциевого канала P/Q-типа и/или N-типа, средства, препятствующего гибели нервных клеток или защищающего нервные клетки головного мозга, средства для лечения, профилактики или улучшения состояния в случае нервных заболеваний или аналгетика.
39. Соединение по п.38, в котором нервное заболевание является любым заболеванием, выбираемым из группы, включающей острый ишемический инсульт, кровоизлияние в мозг, инфаркт головного мозга, травму головы, гибель нервных клеток головного мозга, болезнь Альцгеймера, болезнь Паркинсона, боковой амиотрофический склероз, болезнь Хантингтона, метаболическое расстройство кровообращения головного мозга, нарушение функции головного мозга, болевой синдром, спазмы, шизофрению, мигрень, эпилепсию, маниакально-депрессивный синдром, дегенеративные нервные заболевания, ишемию головного мозга, слабоумие, вызванное СПИДом, отек мозга, состояние страха, диабетическую невропатию, слабоумие вследствие поражения сосудов головного мозга и рассеянный склероз.
40. Способ профилактики, лечения или улучшения состояния в случае заболевания, восприимчивого к антагонизму в отношении кальция, нейронизбирательному антагонизму в отношении кальция и ингибирующему действию в отношении кальциевого канала P/Q-типа и/или N-типа, путем введения нуждающемуся субъекту фармакологически эффективного количества соединения по п.1, его соли или гидрата.
41. Способ предотвращения гибели нервных клеток или защиты нервных клеток головного мозга путем введения нуждающемуся субъекту фармакологически эффективного количества соединения по п.1, его соли или гидрата.
42. Способ профилактики, лечения или улучшения состояния в случае нервного заболевания или болевого синдрома путем введения нуждающемуся субъекту фармакологически эффективного количества соединения по п.1, его соли или гидрата.
43. Способ по п.42, в котором нервное заболевание является любым заболеванием, выбираемым из группы, включающей острый ишемический инсульт, кровоизлияние в мозг, инфаркт головного мозга, травму головы, гибель нервных клеток головного мозга, болезнь Альцгеймера, болезнь Паркинсона, боковой амиотрофический склероз, болезнь Хантингтона, метаболическое расстройство кровообращения головного мозга, нарушение функции головного мозга, болевой синдром, спазмы, шизофрению, мигрень, эпилепсию, маниакально-депрессивный синдром, дегенеративные нервные заболевания, ишемию головного мозга, слабоумие, вызванное СПИДом, отек мозга, состояние страха, диабетическую невропатию, слабоумие вследствие поражения сосудов головного мозга и рассеянный склероз.
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