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THIENO[2,3-b]PYRIDINE DERIVATIVE AND QUINOLINE DERIVATIVE, AND USE THEREOF NEW

外国特許コード F180009321
整理番号 (S2016-0779-N0)
掲載日 2018年1月24日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2017JP021895
国際公開番号 WO 2017217439
国際出願日 平成29年6月14日(2017.6.14)
国際公開日 平成29年12月21日(2017.12.21)
優先権データ
  • 特願2016-117807 (2016.6.14) JP
発明の名称 (英語) THIENO[2,3-b]PYRIDINE DERIVATIVE AND QUINOLINE DERIVATIVE, AND USE THEREOF NEW
発明の概要(英語) The purpose of the invention is to provide a compound that inhibits the binding of the ALS-related mutant SOD1 and Derlin-1, a drug containing the compound, and a method for treating ALS by administering the drug to a patient. More specifically, the compound is represented by general formula (1). [In formula (1), X represents a sulfur atom or -CH=CH-, A1-A4 each independently are a carbon atom or nitrogen atom and at least one of A1-A4 is a nitrogen atom, R1 is a 1,2,3,4-tetrahydroquinolyl group (or 3,4-dihydro-1(2H-quinolyl group), 3,4-dihydro-4,4-dimethyl-1(2H)-quinolyl group, 2,3,4,5-tetrahydro-1H-1-benzazepinyl group, or substituent represented by formula (2) (in formula (2), R4 is an unsubstituted or optionally substituted phenyl group, unsubstituted or optionally substituted pyridyl group, or unsubstituted or optionally substituted naphthyl group, R5 is a hydrogen atom, lower alkyl group, lower alkenyl group, lower alkynyl group (optionally including an oxygen atom and/or double bond), or an unsubstituted or optionally substituted aromatic lower alkyl group), R2 represents a hydrogen atom, lower alkyl group, lower acyl group, or an unsubstituted or optionally substituted aromatic lower alkyl group, R3 represents a hydrogen atom, or R2 and R3 may bond to each other to form a ring.]
特許請求の範囲(英語) [claim1]
1. The compound represented by the following general formula of (1) a salt, hydrate or solvate.
Formulae (1), represents a sulfur atom or - CH=CH - X, A1-A4each independently represents a carbon atom or nitrogen atom A1-A41 is a nitrogen atom and at least one of the two, R11, 2, 3, 4 - tetrahydroquinolyl group is (or, -1 - dihydro - 3,4 - (2H) - quinolyl group), -4,4 - - dihydro - -1 - dimethyl - 3,4 - (2H) - quinolyl group, 2, 3, 4, 5 - tetrahydro - 1H-1 - benzazepinyl group or a substituent represented by the following equation (2)
(formulae (2), R4may have a substituent or a substituted or unsubstituted phenyl group, an unsubstituted or substituted with a pyridyl group which may have a substituent or an unsubstituted or substituted naphthyl group which may have a substituent, R5is preferably a hydrogen atom, a lower alkyl group, alkenyl group, lower alkynyl group (oxygen atoms and/or may contain a double bond) or an unsubstituted or substituted aromatic group which may have a lower alkyl group) is any one of the, R2represents a hydrogen atom, a lower alkyl group, an acyl group or a substituted or unsubstituted alkyl group optionally having a substituent or an aromatic or a lower alkyl group, R3represents a hydrogen atom and, alternatively, R2R and3are bound to each other may form a ring.
[claim2]
2. By the following general formula (1a) according to claim 1 compound or its salt represented by the following, or a solvate or hydrate thereof. Formula (1a) in, A1-A4each independently represents a carbon atom or a nitrogen atom, A1-A41 is a nitrogen atom and at least one of the two, R1tetrahydroquinolyl group 1, 2, 3, 4 - is (or, -1 - dihydro - 3,4 - (2H) - quinolyl group), -4,4 - - dihydro - -1 - dimethyl - 3,4 - (2H) - quinolyl group, 2, 3, 4, 5 - tetrahydro - 1H-1 - benzazepinyl group or a substituent represented by the following equation (2) (formulae (2), R4may have a substituent and may be unsubstituted or substituted phenyl group, an unsubstituted or substituted with a pyridyl group which may have a substituent or an unsubstituted or substituted naphthyl group which may have a substituent, R5is preferably a hydrogen atom, a lower alkyl group, a lower alkenyl, lower alkynyl group (oxygen atoms and/or may contain a double bond) or an unsubstituted or substituted aromatic group which may have a substituent and a lower alkyl group) is any one of, R2represents a hydrogen atom, a lower alkyl group, an acyl group or a substituted or unsubstituted alkyl group having a substituent or an aromatic or a lower alkyl group, R3represents a hydrogen atom and, alternatively, R2R and3are bound to each other may form a ring.
[claim3]
3. R2and R3according to claim 2 compound is a hydrogen atom or a salt, hydrate or solvate.
[claim4]
4. A1nitrogen atom, A2、A3and A4carbon atom, R1tetrahydrofolic 2, 3, 4, 5 - is - 1H-1 - benzazepinyl group, tetrahydroquinolyl group 1, 2, 3, 4 - (3,4 - - dihydro - -1 (2H) quinolyl group) or 3,4 - (2H) - -4,4 - - dihydro - -1 - dimethyl - quinolyl group compound or a salt thereof according to claim 2 or 3, hydrate or solvate.
[claim5]
5. A2nitrogen atom, A1、A3and A4carbon atom, R1-1 dimethyl - 3,4 - - (2H) is -4,4 - - dihydro - quinolyl group according to claim 2 or 3 compound or a salt thereof, or a solvate or hydrate thereof.
[claim6]
6. A1nitrogen atom, A2、A3and A4carbon atom, R4is 4 - pyridyl group, 2 - - iodo -4 - pyridyl group, a phenyl group, 4 - - fluorophenyl group, 2, 3, 4 - trifluorophenyl group, 4 - Iodophenyl group, 2,4 - - difluorophenyl group, 2,3 - - difluorophenyl group, 2,5 - - difluorophenyl group, 3,5 - - difluorophenyl group, 5 - fluoro -2 - methylphenyl group, 3 - group, 2,6 - - dimethylphenyl group, 4 - Benzyloxyphenyl group, 4 - - trifluoromethylphenyl group, 3,5 - - bis (trifluoromethyl) biphenyl group or a naphthyl group 1 -, R5hydrogen atom, propyl groups 1 -, 2 - butenyl group, -2 - - methyl - 3 - - butenyl group, a propenyl 2 -, -2 - - methyl groups having 2 -, 2 - cyclopentylidene ethyl groups, 2 - propynyl group, 2 - group butyny, (Z) -4 - -2 - (prop .rho.yridin -2 -) enyl group-butoxy, butoxy (E) -4 - -2 - (prop .rho.yridin -2 -) according to claim 2 or 3 enyl group or a benzyl group the compound or its salt, hydrate or solvate.
[claim7]
7. A2nitrogen atom, A1、A3and A4carbon atom, R4is 4 - pyridyl group, a phenyl group, 3 - - trifluoromethylphenyl group, 2,5 - - difluorophenyl group, 3,5 - - difluorophenyl group, 3,4 - - difluorophenyl group, 3 - - trifluoromethylphenyl group, 3 - - methoxyphenyl group, 4 - - methoxyphenyl group, 4-tert - butylphenyl group, 3 - group or 3,5 - - bis (trifluoromethyl) biphenyl, R5is a hydrogen atom, 2 - - propenyl group, 2 - or -2 - - methyl - -2 - - methyl - 3 - - butenyl group of the compound or the salt thereof according to claim 2 or 3 propenyl group, or a solvate or hydrate thereof.
[claim8]
8. A4nitrogen atom, A1、A2and A3carbon atom, R44 - is a pyridyl group, R5according to claim 2 or 3 compound is a hydrogen atom or a salt thereof, or a solvate or hydrate thereof.
[claim9]
9. A1and A3nitrogen atom, A2and A4carbon atom, R44 - is a pyridyl group, R5according to claim 2 or 3 compound is a hydrogen atom or a salt thereof, or a solvate or hydrate thereof.
[claim10]
10. (1a) Of the compound represented by the general formula is, amino -N- -6 - - phenyl - -3 --allyhc N- (3 - - pyridinyl) Thieno 2, 3-b: -2 - carboxamideI pyridine, -6 - - phenyl - -3 - -N- amino propargylation N- (3 - - pyridinyl) Thieno 2, 3-b: pyridine -2 - carboxamide, (3 - amino - 6 - (3 - - pyridinyl) Thieno 2, 3-b: 2 - - pyridinyl) (3,4 - - dihydro - -1 (2H) quinolinyl) methanone, amino -N- (4 - - pyridinyl) -6-3 - (3 - - pyridinyl) Thieno 2, 3-b: -2 - carboxamideI pyridine, 3 - -N- amino - -6 - - phenyl (trans-2 - butenyl) -N- (3 - - pyridinyl) Thieno 2, 3-b: pyridine -2 - carboxamide, amino -N- (4 - - pyridinyl) -6-3 - (2 - - pyridinyl) Thieno 2, 3-b: pyridine -2 - carboxamide, amino -N- 3 - (4 - (3 ', 5' - bis (trifluoromethyl) biphenyl) -6 - (4 - - pyridinyl) Thieno 2, 3-b: pyridine -2 - carboxamide, allyl N- (2,5 - - difluorophenyl) -N- amino - -6-3 - (4 - - pyridinyl) Thieno 2, 3-b: -2 - carboxamideI pyridine, 3 - -N- amino - -6 - - phenyl (2 - - butynyl) -N- (3 - - pyridinyl) Thieno 2, 3-b: -2 - carboxamideI pyridine, -3 - -N- amino propyl N-n - (3 - - pyridinyl) phenyl - -6 --thieno 2, 3-b: pyridine -2 - carboxamide, N-n - propyl -3 - amino -N- (3 - - pyridinyl) -6 - (2, 3, 4 - trifluorophenyl) thieno 2, 3-b: pyridine -2 - carboxamide, allyl N- -3 - -6 - (4 - - iodophenyl) amino -N- (3 - - pyridinyl) Thieno 2, 3-b: pyridine -2 - carboxamide, N- -3 - (-2 - - methyl - 3 - - butenyl) -N- -6 - (3 - - pyridinyl) phenyl-amino Thieno 2, 3-b: pyridine -2 - carboxamide, [3 - amino -6 - (3 - - pyridinyl) Thieno 2, 3-b: 2 - pyridinyl] (2, 3, 4, 5 - benzo b -1H - - tetrahydro -: - yl -1 - azepine) methanone, 3 - amino -N- (2,4 - - difluorophenyl) allyl N- -6 - (3 - - pyridinyl) Thieno 2, 3-b: pyridine -2 - carboxamide, amino -N- 3 - allyl N- (2, 3- Difluorophenyl) -6 - (3 - - pyridinyl) Thieno 2, 3-b: pyridine -2 - carboxamide, 3 - (2,5 - - difluorophenyl) -N- amino allyhc N- -6 - (3 - - pyridinyl) Thieno 2, 3-b: pyridine -2 - carboxamide, amino -N- -3 - allyl N- (-2 - - fluoro - 5 - - methylphenyl) -6 - (3 - - pyridinyl) Thieno 2, 3-b: pyridine -2 - carboxamide, allyl N- 3 - -6 - (3,4 - - difluorophenyl) -N- amino - (4 - - pyridinyl) Thieno 2, 3-b: pyridine -2 - carboxamide, allyl N- (3,5 - - difluorophenyl) -N- amino - -6-3 - (3 - - pyridinyl) Thieno 2, 3-b: pyridine -2 - carboxamide, allyl N- amino -N- 3 - (3 - (pentafluoro - λ6-sulfanyl) phenyl) -6 - (3 - - pyridinyl) Thieno 2, 3-b: pyridine -2 - carboxamide, N- allyl 3 - amino -N- (3,5 - - difluorophenyl) -6 - (4 - - pyridinyl) Thieno 2, 3-b: pyridine -2 - carboxamide, N- allyl 3 - amino -N- (3 - (pentafluoro - λ6-sulfanyl) phenyl) -6 - (4 - - pyridinyl) Thieno 2, 3-b: -2 - carboxamideI pyridine, 3 - -N- (1 - - naphthyl) amino phenyl -6 - -N- (3 - - pyridinyl) Thieno 2, 3-b: pyridine -2 - carboxamide, amino -N- (2,6 - dimethylphenyl) -6-3 - (3 - - pyridinyl) Thieno 2, 3-b: pyridine -2 - carboxamide, 3 - [4 - (benzyloxy) phenyl] amino -N- -6 - (3 - - pyridinyl) Thieno 2, 3-b: pyridine -2 - carboxamide, amino -N- 3 - (3 - - pyridinyl) -6 - (4 - - iodophenyl) thieno 2, 3-b: pyridine -2 - carboxamide, amino -N- 3 - (2 - -4 - iodoacetate pyridinyl) -6 - (3 - - pyridinyl) Thieno 2, 3-b: -2 - carboxamideI pyridine, 3 - -N- (3 - - pyridinyl) amino -6 - (4 - (trifluoromethyl) phenyl) Thieno 2, 3-b: pyridine -2 - carboxamide, amino -N- 3 - (3 ', 5' - bis (trifluoromethyl) [1,1 ' - biphenyl] - -4 - - yl) -6 - (3 - - pyridinyl) thieno [2, 3-b] pyridine -2 - carboxamide, 3 - (4 - - pyridinyl) -N- amino - -6 - (3 - (trifluoromethyl) phenyl) Thieno 2, 3-b: pyridine -2 - carboxamide, amino -N- (4 - - pyridinyl) -6-3 - (4 - - pyridinyl) Thieno 2, 3-b: pyridine -2 - carboxamide, amino -N- (4 - - pyridinyl) -6-3 - (5 - - pyrimidinyl) Thieno 2, 3-b: pyridine -2 - carboxamide, amino -N- 3 - (4 - - fluorophenyl) -N- -6 - (2 - -1 - -2 - methylprop ENED yl) (3 - - pyridinyl) Thieno 2, 3-b: -2 - carboxamideI pyridine, 3 - -N- (4 - - fluorophenyl) amino -N- (prop - -2 - - yl--1 -) -6 - (3 - - pyridinyl) Thieno 2, 3-b: -2 - carboxamideI pyridine, 3 - -N- amino-phenyl -N- ((Z) -4 - -2 - (prop .rho.yridin -2 -) dimethylpent butqxy) -6 - (3 - - pyridinyl) Thieno 2, 3-b: -2 - carboxamideI pyridine, -6 - - phenyl - 3 - -N- amino - (3 - - pyridinyl) -N- benzyl Thieno 2, 3-b: pyridine -2 - carboxamide, amino -N- 3 - ((E) -4 - -2 - (pent -4 - ynyloxy) dimethylpent butqxy) -N- (3 - - pyridinyl) phenyl - - 6 - Thieno 2, 3-b: -2 - carboxamideI pyridine, 3 - -N- (4 - - pyridinyl) -N- prenyl -6 - - amino - (3 - - pyridinyl) Thieno 2, 3-b: -2 - carboxamideI pyridine, 3 - -N- phenyl -6 - -N- amino (2 - cyclopentylidene ethyl) (3 - - pyridinyl) Thieno 2, 3-b: pyridine -2 - carboxamide, amino - (3 - - pyridinyl) 3 - -6 - Thieno 2, 3-b: 2 - - pyridinyl) (3,4 - (2H) - -1 - dimethyl - -4,4 - - dihydro - quinolinyl) methanone, amino -N- 3 - (4-tert - butylphenyl) -N- -6 - (3 - -1 - -2 - methylbut ENED yl) (4 - - pyridinyl) Thieno 2, 3-b: -2 - carboxamideI pyridine, 3 - - amino - (4 - - pyridinyl) Thieno 2, 3-b -6 -: 2 - - pyridinyl) (3,4 - - dihydro - -1 (2H) dimethyl -4,4 - - quinolyl) methanone, prenyl 3 - -N- (3 - - methoxyphenyl) amino - -6 - -N- (4 - - pyridinyl) Thieno 2, 3-b: -2 - carboxamideI pyridine, 3 - -N- (4 - - methoxyphenyl) amino -N- -6 - prenyl (4 - - pyridinyl) thieno [2, 3-b] pyridine -2 - -N- amino phenyl -6 - -N- carboxamide and 3 - (4 - - pyridinyl) methallyl Thieno 2, 3-b: selected from the group consisting of pyridine -2 - carboxamideI Reovirus, according to claim 2 compound or its salt, hydrate or solvate thereof.
[claim11]
11. By the following general formula (1b) according to claim 1 compound or its salt represented by the following, or a solvate or hydrate thereof. Formula (1b) in, A1-A4each independently represents a carbon atom or a nitrogen atom, A1-A4of at least 1 one nitrogen atom, R1denotes a (2) substituent represented by the(formulae (2), R4is a non-substituted or substituted groups and a phenyl group, R5is preferably a hydrogen atom, a lower alkyl group, alkenyl group, alkynyl group), R2is preferably a hydrogen atom, a lower alkyl group, with a lower acyl group or an unsubstituted or substituted alkyl groups may be aromatic and a lower alkyl group, R3represents a hydrogen atom and, alternatively, R2R and3are bound to each other may form a ring.
[claim12]
12. A1nitrogen atom, A2、A3and A4carbon atom, R2and R3is a hydrogen atom, R4is a phenyl group, R5-2 - butenyl group is methyl 3 - according to claim 11 compound or a salt thereof, or a solvate or hydrate thereof.
[claim13]
13. (1b) Of the compound represented by the general formula 5 - is -2 - -N- prenyl amino phenyl -N- -6 - carboxamide (pyridine -3 - yl) according to claim 11 quinoline compound or its salt, or a solvate or hydrate thereof.
[claim14]
14. According to any one of claims 1-13 compound or a salt thereof, or their hydrates solvate thereof as an active ingredient, ALS SOD1-Derlin-1 variant associated with the binding inhibitor.
[claim15]
15. According to any one of claims 1-13 compound or a salt thereof, or a solvate or a hydrate of any pharmaceutical or pharmaceutical composition comprising as an active ingredient.
  • 出願人(英語)
  • ※2012年7月以前掲載分については米国以外のすべての指定国
  • UNIVERSITY OF TOKYO
  • NAGOYA CITY UNIVERSITY
  • 発明者(英語)
  • ICHIJO HIDENORI
  • HOMMA KENGO
  • TSUBURAYA NAOMI
  • NAGANO TETSUO
  • OKABE TAKAYOSHI
  • KOJIMA HIROTATSU
  • SHIMONISHI MANABU
  • FUJISAWA TAKAO
  • SHIBATA NORIO
  • HIGUCHI TSUNEHIKO
  • NAKAMURA SEIICHI
  • NAKAGAWA HIDEHIKO
  • IKEDA SHIN-ICHI
国際特許分類(IPC)
指定国 (WO2017217439)
National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL CN CO CR CU CZ DE DJ DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JO JP KE KG KH KN KP KR KW KZ LA LC LK LR LS LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PA PE PG PH PL PT QA RO RS RU RW SA SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW KM ML MR NE SN ST TD TG

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