KR20090112627A - 에이1 아데노신 수용체의 알로스테릭 조절제 - Google Patents

에이1 아데노신 수용체의 알로스테릭 조절제 Download PDF

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Publication number: KR20090112627A
Authority: KR; South Korea
Prior art keywords: chlorophenyl; methyl; amino; methanone; thiophen
Prior art date: 2006-11-13
Legal status (The legal status 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 Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Withdrawn

Application number

KR1020097009765A

Other languages

English (en)

Korean (ko)

Inventor

피에르 지오바니 바랄디

알. 무어만 알란

로마뇰리 로메오

Original Assignee

킹 파머슈티칼스 리서치 앤드 디벨로프먼트 아이엔씨

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.)

2006-11-13

Filing date

2007-11-13

Publication date

2009-10-28

2007-11-12 Priority claimed from US11/938,465 external-priority patent/US7855209B2/en

2007-11-12 Priority claimed from US11/938,514 external-priority patent/US7897596B2/en

2007-11-13 Application filed by 킹 파머슈티칼스 리서치 앤드 디벨로프먼트 아이엔씨 filed Critical 킹 파머슈티칼스 리서치 앤드 디벨로프먼트 아이엔씨

2009-10-28 Publication of KR20090112627A publication Critical patent/KR20090112627A/ko

Status Withdrawn legal-status Critical Current

Links

101150007969 ADORA1 gene Proteins 0.000 title claims abstract description 27
230000003281 allosteric effect Effects 0.000 title abstract description 8
150000001875 compounds Chemical class 0.000 claims abstract description 307
208000002193 Pain Diseases 0.000 claims abstract description 37
230000036407 pain Effects 0.000 claims abstract description 29
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 23
201000010099 disease Diseases 0.000 claims abstract description 20
208000004296 neuralgia Diseases 0.000 claims abstract description 17
208000021722 neuropathic pain Diseases 0.000 claims abstract description 17
208000019622 heart disease Diseases 0.000 claims abstract description 16
208000012902 Nervous system disease Diseases 0.000 claims abstract description 11
208000025966 Neurological disease Diseases 0.000 claims abstract description 11
208000006011 Stroke Diseases 0.000 claims abstract description 11
230000006378 damage Effects 0.000 claims abstract description 11
206010015037 epilepsy Diseases 0.000 claims abstract description 11
208000010125 myocardial infarction Diseases 0.000 claims abstract description 11
208000019116 sleep disease Diseases 0.000 claims abstract description 10
210000003462 vein Anatomy 0.000 claims abstract description 10
206010002383 Angina Pectoris Diseases 0.000 claims abstract description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 117
-1 4- (4-chlorophenyl) piperidin-1-yl Chemical group 0.000 claims description 115
150000003839 salts Chemical class 0.000 claims description 101
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 97
229910052739 hydrogen Inorganic materials 0.000 claims description 90
239000001257 hydrogen Substances 0.000 claims description 89
125000000217 alkyl group Chemical group 0.000 claims description 57
150000002431 hydrogen Chemical class 0.000 claims description 56
125000003118 aryl group Chemical group 0.000 claims description 53
125000000547 substituted alkyl group Chemical group 0.000 claims description 42
125000003107 substituted aryl group Chemical group 0.000 claims description 42
125000004093 cyano group Chemical group *C#N 0.000 claims description 41
229910052736 halogen Inorganic materials 0.000 claims description 41
150000002367 halogens Chemical class 0.000 claims description 41
238000000034 method Methods 0.000 claims description 39
125000000753 cycloalkyl group Chemical group 0.000 claims description 35
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 35
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 33
239000008194 pharmaceutical composition Substances 0.000 claims description 31
125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 28
239000003814 drug Substances 0.000 claims description 21
125000002252 acyl group Chemical group 0.000 claims description 18
150000001721 carbon Chemical group 0.000 claims description 18
229910052799 carbon Inorganic materials 0.000 claims description 18
125000004432 carbon atom Chemical group C* 0.000 claims description 17
125000001072 heteroaryl group Chemical group 0.000 claims description 16
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
208000027418 Wounds and injury Diseases 0.000 claims description 15
125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 15
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 14
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 14
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 14
125000003545 alkoxy group Chemical group 0.000 claims description 14
125000004475 heteroaralkyl group Chemical group 0.000 claims description 14
239000001301 oxygen Substances 0.000 claims description 13
229910052760 oxygen Inorganic materials 0.000 claims description 13
125000001424 substituent group Chemical group 0.000 claims description 13
AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 claims description 12
241000124008 Mammalia Species 0.000 claims description 12
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
229910052717 sulfur Chemical group 0.000 claims description 11
239000011593 sulfur Chemical group 0.000 claims description 11
208000014674 injury Diseases 0.000 claims description 9
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
125000002947 alkylene group Chemical group 0.000 claims description 8
238000002360 preparation method Methods 0.000 claims description 8
WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 claims description 7
239000000126 substance Substances 0.000 claims description 7
239000003937 drug carrier Substances 0.000 claims description 6
229910052757 nitrogen Inorganic materials 0.000 claims description 6
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 6
125000005415 substituted alkoxy group Chemical group 0.000 claims description 6
WBVSHKCZLDSJBP-UHFFFAOYSA-N [2-amino-4-[(4-phenylpiperazin-1-yl)methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN(CC1)CCN1C1=CC=CC=C1 WBVSHKCZLDSJBP-UHFFFAOYSA-N 0.000 claims description 5
230000001105 regulatory effect Effects 0.000 claims description 5
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 3
LRNXGDCNTQAXDV-UHFFFAOYSA-N [2-amino-4-[(4-pyridin-2-ylpiperazin-1-yl)methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN(CC1)CCN1C1=CC=CC=N1 LRNXGDCNTQAXDV-UHFFFAOYSA-N 0.000 claims description 3
FJHGONQMXVSBES-UHFFFAOYSA-N [2-amino-4-[(4-pyrimidin-2-ylpiperazin-1-yl)methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN(CC1)CCN1C1=NC=CC=N1 FJHGONQMXVSBES-UHFFFAOYSA-N 0.000 claims description 3
HZIBFSCCTZORDE-UHFFFAOYSA-N [2-amino-4-[[4-(3,4-dichlorophenyl)piperazin-1-yl]methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN(CC1)CCN1C1=CC=C(Cl)C(Cl)=C1 HZIBFSCCTZORDE-UHFFFAOYSA-N 0.000 claims description 3
IIEVNVFDTPPXOR-UHFFFAOYSA-N [2-amino-4-[[4-[3-(4-chlorophenyl)propyl]piperazin-1-yl]methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN(CC1)CCN1CCCC1=CC=C(Cl)C=C1 IIEVNVFDTPPXOR-UHFFFAOYSA-N 0.000 claims description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
230000002981 neuropathic effect Effects 0.000 claims description 3
WGSAKPFHJLTQFG-UHFFFAOYSA-N 1-[4-[[5-amino-4-(4-chlorobenzoyl)thiophen-3-yl]methyl]piperazin-1-yl]-2-(4-chlorophenyl)ethanone Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN(CC1)CCN1C(=O)CC1=CC=C(Cl)C=C1 WGSAKPFHJLTQFG-UHFFFAOYSA-N 0.000 claims description 2
BTURCFCECILJTE-UHFFFAOYSA-N 2-[4-[[5-amino-4-(4-chlorobenzoyl)thiophen-3-yl]methyl]piperazin-1-yl]-1-(4-chlorophenyl)ethanone Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN(CC1)CCN1CC(=O)C1=CC=C(Cl)C=C1 BTURCFCECILJTE-UHFFFAOYSA-N 0.000 claims description 2
ITIPXEQVFANBBI-UHFFFAOYSA-N 4-[4-[[5-amino-4-(4-chlorobenzoyl)-2-methylthiophen-3-yl]methyl]piperazin-1-yl]benzonitrile Chemical compound C1CN(C=2C=CC(=CC=2)C#N)CCN1CC1=C(C)SC(N)=C1C(=O)C1=CC=C(Cl)C=C1 ITIPXEQVFANBBI-UHFFFAOYSA-N 0.000 claims description 2
GBEKMUYDTMZKOO-UHFFFAOYSA-N 4-[4-[[5-amino-4-(4-chlorobenzoyl)thiophen-3-yl]methyl]piperazin-1-yl]benzonitrile Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN(CC1)CCN1C1=CC=C(C#N)C=C1 GBEKMUYDTMZKOO-UHFFFAOYSA-N 0.000 claims description 2
HYXHXEHHOZDASV-UHFFFAOYSA-N [2-amino-4-[(4-benzylpiperazin-1-yl)methyl]-5-methylthiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C1CN(CC=2C=CC=CC=2)CCN1CC1=C(C)SC(N)=C1C(=O)C1=CC=C(Cl)C=C1 HYXHXEHHOZDASV-UHFFFAOYSA-N 0.000 claims description 2
VLUIIUMESZDQJJ-UHFFFAOYSA-N [2-amino-4-[(4-benzylpiperazin-1-yl)methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN(CC1)CCN1CC1=CC=CC=C1 VLUIIUMESZDQJJ-UHFFFAOYSA-N 0.000 claims description 2
AZYUIXUQGNQGEY-UHFFFAOYSA-N [2-amino-4-[(4-cycloheptylpiperazin-1-yl)methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN(CC1)CCN1C1CCCCCC1 AZYUIXUQGNQGEY-UHFFFAOYSA-N 0.000 claims description 2
PNTFMBLZDHRWEH-UHFFFAOYSA-N [2-amino-4-[(4-cyclohexylpiperazin-1-yl)methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN(CC1)CCN1C1CCCCC1 PNTFMBLZDHRWEH-UHFFFAOYSA-N 0.000 claims description 2
MLBNYNHTFZBWOO-UHFFFAOYSA-N [2-amino-4-[(4-cyclopentylpiperazin-1-yl)methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN(CC1)CCN1C1CCCC1 MLBNYNHTFZBWOO-UHFFFAOYSA-N 0.000 claims description 2
UUYUBKMEGGSUJJ-UHFFFAOYSA-N [2-amino-4-[(4-fluorospiro[1,3-benzodioxole-2,4'-piperidine]-1'-yl)methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound NC=1SC=C(CN2CCC3(CC2)OC2=C(F)C=CC=C2O3)C=1C(=O)C1=CC=C(Cl)C=C1 UUYUBKMEGGSUJJ-UHFFFAOYSA-N 0.000 claims description 2
FBLJFWZLJFATLC-UHFFFAOYSA-N [2-amino-4-[(4-methylpiperazin-1-yl)methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C1CN(C)CCN1CC1=CSC(N)=C1C(=O)C1=CC=C(Cl)C=C1 FBLJFWZLJFATLC-UHFFFAOYSA-N 0.000 claims description 2
FVCNDFNVEXZHJO-UHFFFAOYSA-N [2-amino-4-[(4-methylspiro[1,3-benzodioxole-2,4'-piperidine]-1'-yl)methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound O1C=2C(C)=CC=CC=2OC1(CC1)CCN1CC1=CSC(N)=C1C(=O)C1=CC=C(Cl)C=C1 FVCNDFNVEXZHJO-UHFFFAOYSA-N 0.000 claims description 2
JKXQLDDFLKSYTM-UHFFFAOYSA-N [2-amino-4-[(4-pyridin-3-ylpiperazin-1-yl)methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN(CC1)CCN1C1=CC=CN=C1 JKXQLDDFLKSYTM-UHFFFAOYSA-N 0.000 claims description 2
PTDILEGANSBTSE-UHFFFAOYSA-N [2-amino-4-[(4-pyridin-4-ylpiperazin-1-yl)methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN(CC1)CCN1C1=CC=NC=C1 PTDILEGANSBTSE-UHFFFAOYSA-N 0.000 claims description 2
VGTGXMREKQFXNQ-UHFFFAOYSA-N [2-amino-4-[(5-methylspiro[1,3-benzodioxole-2,4'-piperidine]-1'-yl)methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound O1C2=CC(C)=CC=C2OC1(CC1)CCN1CC1=CSC(N)=C1C(=O)C1=CC=C(Cl)C=C1 VGTGXMREKQFXNQ-UHFFFAOYSA-N 0.000 claims description 2
LXZNFZIWNXAXPF-UHFFFAOYSA-N [2-amino-4-[(5-tert-butylspiro[1,3-benzodioxole-2,4'-piperidine]-1'-yl)methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound O1C2=CC(C(C)(C)C)=CC=C2OC1(CC1)CCN1CC1=CSC(N)=C1C(=O)C1=CC=C(Cl)C=C1 LXZNFZIWNXAXPF-UHFFFAOYSA-N 0.000 claims description 2
XEJIHQOMTYJWCT-UHFFFAOYSA-N [2-amino-4-[[2-(4-chlorophenyl)-2,7-diazaspiro[4.4]nonan-7-yl]methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN(C1)CCC1(C1)CCN1C1=CC=C(Cl)C=C1 XEJIHQOMTYJWCT-UHFFFAOYSA-N 0.000 claims description 2
VETJLOKKGTWBFO-UHFFFAOYSA-N [2-amino-4-[[4-(1,3-benzodioxol-5-yl)piperazin-1-yl]methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound NC=1SC=C(CN2CCN(CC2)C=2C=C3OCOC3=CC=2)C=1C(=O)C1=CC=C(Cl)C=C1 VETJLOKKGTWBFO-UHFFFAOYSA-N 0.000 claims description 2
BRWGCTMCYZVICL-UHFFFAOYSA-N [2-amino-4-[[4-(2,3-dichlorophenyl)piperazin-1-yl]methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN(CC1)CCN1C1=CC=CC(Cl)=C1Cl BRWGCTMCYZVICL-UHFFFAOYSA-N 0.000 claims description 2
SKVYUUPKEQJOOR-UHFFFAOYSA-N [2-amino-4-[[4-(2,3-difluorophenyl)piperazin-1-yl]methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN(CC1)CCN1C1=CC=CC(F)=C1F SKVYUUPKEQJOOR-UHFFFAOYSA-N 0.000 claims description 2
QLXKABIMWDIRKB-UHFFFAOYSA-N [2-amino-4-[[4-(2,4,6-trifluorophenyl)piperazin-1-yl]methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN(CC1)CCN1C1=C(F)C=C(F)C=C1F QLXKABIMWDIRKB-UHFFFAOYSA-N 0.000 claims description 2
VUSWZWCZLQPKBC-UHFFFAOYSA-N [2-amino-4-[[4-(2,4-difluorophenyl)piperazin-1-yl]methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN(CC1)CCN1C1=CC=C(F)C=C1F VUSWZWCZLQPKBC-UHFFFAOYSA-N 0.000 claims description 2
RRXKFDQOOZHJTF-UHFFFAOYSA-N [2-amino-4-[[4-(2,5-dichlorophenyl)piperazin-1-yl]methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN(CC1)CCN1C1=CC(Cl)=CC=C1Cl RRXKFDQOOZHJTF-UHFFFAOYSA-N 0.000 claims description 2
DXGZCDTWBDRRKI-UHFFFAOYSA-N [2-amino-4-[[4-(2,5-difluorophenyl)piperazin-1-yl]methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN(CC1)CCN1C1=CC(F)=CC=C1F DXGZCDTWBDRRKI-UHFFFAOYSA-N 0.000 claims description 2
BHNZEYVIYRIQCZ-UHFFFAOYSA-N [2-amino-4-[[4-(2,6-dichlorophenyl)piperazin-1-yl]methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN(CC1)CCN1C1=C(Cl)C=CC=C1Cl BHNZEYVIYRIQCZ-UHFFFAOYSA-N 0.000 claims description 2
DHAUTGJWCQUFII-UHFFFAOYSA-N [2-amino-4-[[4-(2,6-difluorophenyl)piperazin-1-yl]methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN(CC1)CCN1C1=C(F)C=CC=C1F DHAUTGJWCQUFII-UHFFFAOYSA-N 0.000 claims description 2
HDQFEKGOVIJERJ-UHFFFAOYSA-N [2-amino-4-[[4-(2,6-difluorophenyl)piperazin-1-yl]methyl]thiophen-3-yl]-[3-(trifluoromethyl)phenyl]methanone Chemical compound C=1C=CC(C(F)(F)F)=CC=1C(=O)C1=C(N)SC=C1CN(CC1)CCN1C1=C(F)C=CC=C1F HDQFEKGOVIJERJ-UHFFFAOYSA-N 0.000 claims description 2
FJERGVLETHXCBK-UHFFFAOYSA-N [2-amino-4-[[4-(2-chloro-4-fluorophenyl)piperazin-1-yl]methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN(CC1)CCN1C1=CC=C(F)C=C1Cl FJERGVLETHXCBK-UHFFFAOYSA-N 0.000 claims description 2
ZGNUUPGCNLNRGC-UHFFFAOYSA-N [2-amino-4-[[4-(2-chlorophenyl)piperazin-1-yl]methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN(CC1)CCN1C1=CC=CC=C1Cl ZGNUUPGCNLNRGC-UHFFFAOYSA-N 0.000 claims description 2
KFWAXNAVBQKIAZ-UHFFFAOYSA-N [2-amino-4-[[4-(2-fluorophenyl)piperazin-1-yl]methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN(CC1)CCN1C1=CC=CC=C1F KFWAXNAVBQKIAZ-UHFFFAOYSA-N 0.000 claims description 2
NQOCPHPCHPECPX-UHFFFAOYSA-N [2-amino-4-[[4-(3,4-dichlorophenyl)piperazin-1-yl]methyl]-5-methylthiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C1CN(C=2C=C(Cl)C(Cl)=CC=2)CCN1CC1=C(C)SC(N)=C1C(=O)C1=CC=C(Cl)C=C1 NQOCPHPCHPECPX-UHFFFAOYSA-N 0.000 claims description 2
RQMCCXLNHOFIBT-UHFFFAOYSA-N [2-amino-4-[[4-(3,4-difluorophenyl)piperazin-1-yl]methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN(CC1)CCN1C1=CC=C(F)C(F)=C1 RQMCCXLNHOFIBT-UHFFFAOYSA-N 0.000 claims description 2
ACGNVIYHWCNNLW-UHFFFAOYSA-N [2-amino-4-[[4-(3,5-dichlorophenyl)piperazin-1-yl]methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN(CC1)CCN1C1=CC(Cl)=CC(Cl)=C1 ACGNVIYHWCNNLW-UHFFFAOYSA-N 0.000 claims description 2
UFSBQTGZKIHMDQ-UHFFFAOYSA-N [2-amino-4-[[4-(3,5-difluorophenyl)piperazin-1-yl]methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN(CC1)CCN1C1=CC(F)=CC(F)=C1 UFSBQTGZKIHMDQ-UHFFFAOYSA-N 0.000 claims description 2
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Classifications

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- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur 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
- C07D333/30—Hetero atoms other than halogen
- C07D333/36—Nitrogen atoms
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- 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
- C—CHEMISTRY; METALLURGY
- 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
- C07D409/12—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 chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/10—Spiro-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/113—Spiro-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Pain & Pain Management (AREA)
Psychiatry (AREA)
Hospice & Palliative Care (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)

KR1020097009765A 2006-11-13 2007-11-13 에이1 아데노신 수용체의 알로스테릭 조절제 Withdrawn KR20090112627A (ko)

Applications Claiming Priority (7)

Application Number	Priority Date	Filing Date	Title
US85850506P	2006-11-13	2006-11-13
US60/858,505		2006-11-13
US11/938,465 US7855209B2 (en)	2006-11-13	2007-11-12	Allosteric modulators of the A1 adenosine receptor
US11/938,465		2007-11-12
US11/938,514 US7897596B2 (en)	2006-11-13	2007-11-12	Allosteric modulators of the A1 adenosine receptor
US11/938,514		2007-11-12
PCT/US2007/084490 WO2008063984A2 (fr)	2006-11-13	2007-11-13	Modulateurs allostériques du récepteur de l'adénosine a1

Publications (1)

Publication Number	Publication Date
KR20090112627A true KR20090112627A (ko)	2009-10-28

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KR1020097009765A Withdrawn KR20090112627A (ko)	2006-11-13	2007-11-13	에이1 아데노신 수용체의 알로스테릭 조절제

Country Status (9)

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EP (1)	EP2081575A4 (fr)
JP (1)	JP2010509402A (fr)
KR (1)	KR20090112627A (fr)
AU (1)	AU2007323888A1 (fr)
BR (1)	BRPI0718520A2 (fr)
CA (1)	CA2669447A1 (fr)
IL (1)	IL198402A0 (fr)
MX (1)	MX2009004763A (fr)
WO (1)	WO2008063984A2 (fr)

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CN103739588B (zh) *	2014-01-04	2015-07-01	新发药业有限公司	一种2-氨基噻吩衍生物的简便合成方法
US10434099B2 (en)	2016-09-22	2019-10-08	The National Institute for Biotechnology in the Negev Ltd.	Methods for treating central nervous system disorders using VDAC inhibitors
ES2815539T3 (es) *	2015-09-14	2021-03-30	Nat Inst Biotechnology Negev Ltd	Nuevos derivados de piperazina y piperidina, síntesis y uso de los mismos en la inhibición de la oligomerización de VDAC, la apoptosis y la disfunción mitocondrial
US10787423B2 (en)	2015-09-14	2020-09-29	The National Institute For Biotechnolgy In The Negev Ltd.	Piperazine and piperidine derivatives, their synthesis and use thereof in inhibiting VDAC oligomerization, apoptosis and mitochondria dysfunction
US11220505B2 (en) *	2017-03-21	2022-01-11	Temple University-Of The Commonwealth System Of Higher Education	5-hydroxytryptamine receptor 7 modulators and their use as therapeutic agents
JP7365237B2 (ja) *	2017-03-21	2023-10-19	テンプル・ユニバーシティ－オブ・ザ・コモンウェルス・システム・オブ・ハイアー・エデュケイション	シグマ－２受容体の新規調節物質およびその使用方法

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US5332732A (en) *	1992-09-11	1994-07-26	Mcneilab, Inc.	Thiophene and pyridine antipsychotic agents
EP0595150B1 (fr) *	1992-10-29	1996-07-31	Hoechst Aktiengesellschaft	Procédé de préparation de composés aromatiques ayant des groupes bromomethyl
US5939432A (en) *	1997-10-29	1999-08-17	Medco Research, Inc.	Thiophenes useful for modulating the adenosine receptor

2007
- 2007-11-13 EP EP07864306A patent/EP2081575A4/fr not_active Withdrawn
- 2007-11-13 KR KR1020097009765A patent/KR20090112627A/ko not_active Withdrawn
- 2007-11-13 CA CA002669447A patent/CA2669447A1/fr not_active Abandoned
- 2007-11-13 MX MX2009004763A patent/MX2009004763A/es not_active Application Discontinuation
- 2007-11-13 AU AU2007323888A patent/AU2007323888A1/en not_active Abandoned
- 2007-11-13 BR BRPI0718520-0A patent/BRPI0718520A2/pt not_active IP Right Cessation
- 2007-11-13 WO PCT/US2007/084490 patent/WO2008063984A2/fr not_active Ceased
- 2007-11-13 JP JP2009537305A patent/JP2010509402A/ja not_active Withdrawn
2009
- 2009-04-26 IL IL198402A patent/IL198402A0/en unknown

Also Published As

Publication number	Publication date
EP2081575A2 (fr)	2009-07-29
BRPI0718520A2 (pt)	2013-11-19
CA2669447A1 (fr)	2008-05-29
IL198402A0 (en)	2010-02-17
WO2008063984A3 (fr)	2008-08-14
AU2007323888A1 (en)	2008-05-29
MX2009004763A (es)	2009-05-21
EP2081575A4 (fr)	2010-01-06
JP2010509402A (ja)	2010-03-25
WO2008063984A2 (fr)	2008-05-29

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CA2565238C (fr)	2014-08-05	Composes amido et leur utilisation comme produits pharmaceutiques
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TW200418801A (en)	2004-10-01	Isoquinolinone derivatives and their use as therapeutic agents
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Legal Events

Date	Code	Title	Description
2009-05-13	PA0105	International application	Patent event date: 20090513 Patent event code: PA01051R01D Comment text: International Patent Application
2009-10-28	PG1501	Laying open of application
2012-12-14	PC1203	Withdrawal of no request for examination
2012-12-14	WITN	Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid