CA2669447A1 - Modulateurs allosteriques du recepteur de l'adenosine a1 - Google Patents
Modulateurs allosteriques du recepteur de l'adenosine a1 Download PDFInfo
- Publication number
- CA2669447A1 CA2669447A1 CA002669447A CA2669447A CA2669447A1 CA 2669447 A1 CA2669447 A1 CA 2669447A1 CA 002669447 A CA002669447 A CA 002669447A CA 2669447 A CA2669447 A CA 2669447A CA 2669447 A1 CA2669447 A1 CA 2669447A1
- Authority
- CA
- Canada
- Prior art keywords
- chlorophenyl
- methyl
- amino
- methanone
- thiophen
- Prior art date
- 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.)
- Abandoned
Links
- 101150007969 ADORA1 gene Proteins 0.000 title claims abstract description 10
- 230000003281 allosteric effect Effects 0.000 title abstract description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 297
- 208000002193 Pain Diseases 0.000 claims abstract description 36
- 238000011282 treatment Methods 0.000 claims abstract description 28
- 208000020446 Cardiac disease Diseases 0.000 claims abstract description 26
- 208000019622 heart disease Diseases 0.000 claims abstract description 26
- 230000036407 pain Effects 0.000 claims abstract description 26
- 208000027418 Wounds and injury 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
- 230000001404 mediated effect Effects 0.000 claims abstract description 16
- 230000006378 damage Effects 0.000 claims abstract description 14
- 208000014674 injury Diseases 0.000 claims abstract description 14
- 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
- 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 11
- 206010002383 Angina Pectoris Diseases 0.000 claims abstract description 10
- 230000000747 cardiac effect Effects 0.000 claims abstract description 10
- 150000003839 salts Chemical class 0.000 claims description 100
- 229910052739 hydrogen Inorganic materials 0.000 claims description 89
- 239000001257 hydrogen Substances 0.000 claims description 87
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 63
- -1 4-(pyridin-2-yl)piperazin-1-yl Chemical group 0.000 claims description 62
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 60
- 125000000217 alkyl group Chemical group 0.000 claims description 56
- 125000003118 aryl group Chemical group 0.000 claims description 55
- 150000002431 hydrogen Chemical group 0.000 claims description 55
- 229910052736 halogen Inorganic materials 0.000 claims description 44
- 150000002367 halogens Chemical class 0.000 claims description 44
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 42
- 125000003107 substituted aryl group Chemical group 0.000 claims description 42
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 38
- 238000000034 method Methods 0.000 claims description 38
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 36
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 32
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 28
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
- 229910052799 carbon Inorganic materials 0.000 claims description 27
- 239000008194 pharmaceutical composition Substances 0.000 claims description 27
- 150000001721 carbon Chemical group 0.000 claims description 24
- 125000002252 acyl group Chemical group 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 16
- 125000001072 heteroaryl group Chemical group 0.000 claims description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 15
- 241000124008 Mammalia Species 0.000 claims description 13
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 13
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 239000001301 oxygen Substances 0.000 claims description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
- 229910052717 sulfur Chemical group 0.000 claims description 10
- 125000002947 alkylene group Chemical group 0.000 claims description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 239000011593 sulfur Chemical group 0.000 claims description 9
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 8
- 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 8
- 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 7
- 238000002360 preparation method Methods 0.000 claims description 7
- VMLCVTIAPHRDMD-UHFFFAOYSA-N [2-amino-4-[[4-(4-fluorophenyl)piperazin-1-yl]methyl]-5-methylthiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C1CN(C=2C=CC(F)=CC=2)CCN1CC1=C(C)SC(N)=C1C(=O)C1=CC=C(Cl)C=C1 VMLCVTIAPHRDMD-UHFFFAOYSA-N 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 4
- FHMKBGPASICGMG-UHFFFAOYSA-N [2-amino-4-[[4-(3-fluorophenyl)piperazin-1-yl]methyl]-5-methylthiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C1CN(C=2C=C(F)C=CC=2)CCN1CC1=C(C)SC(N)=C1C(=O)C1=CC=C(Cl)C=C1 FHMKBGPASICGMG-UHFFFAOYSA-N 0.000 claims description 4
- 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 3
- 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 3
- 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 3
- LGTDDJCWKVBENO-UHFFFAOYSA-N [2-amino-4-(spiro[1,3-benzodioxole-2,4'-piperidine]-1'-ylmethyl)thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound NC=1SC=C(CN2CCC3(CC2)OC2=CC=CC=C2O3)C=1C(=O)C1=CC=C(Cl)C=C1 LGTDDJCWKVBENO-UHFFFAOYSA-N 0.000 claims description 3
- 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 3
- 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 3
- GZDAZWLRSGSJFO-UHFFFAOYSA-N [2-amino-4-[(4-cyclooctylpiperazin-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)CCN1C1CCCCCCC1 GZDAZWLRSGSJFO-UHFFFAOYSA-N 0.000 claims description 3
- 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 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
- 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 3
- BKVQQVAZXXNRAL-UHFFFAOYSA-N [2-amino-4-[[2-(4-chlorophenyl)-2,5-diazabicyclo[2.2.1]heptan-5-yl]methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C=1C=C(Cl)C=CC=1C(=O)C1=C(N)SC=C1CN1CC2CC1CN2C1=CC=C(Cl)C=C1 BKVQQVAZXXNRAL-UHFFFAOYSA-N 0.000 claims description 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- RLQCJMVZVOGKBW-UHFFFAOYSA-N [2-amino-4-[[4-(2,4-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=C1Cl RLQCJMVZVOGKBW-UHFFFAOYSA-N 0.000 claims description 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 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
- 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 3
- 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 3
- 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 3
- KFWLBGALSCQPIL-UHFFFAOYSA-N [2-amino-4-[[4-(3-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(Cl)=C1 KFWLBGALSCQPIL-UHFFFAOYSA-N 0.000 claims description 3
- NDWVFXKAKMRXDA-UHFFFAOYSA-N [2-amino-4-[[4-(3-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(Cl)=C1 NDWVFXKAKMRXDA-UHFFFAOYSA-N 0.000 claims description 3
- ALBMIWSWBYYXEY-UHFFFAOYSA-N [2-amino-4-[[4-(3-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(F)=C1 ALBMIWSWBYYXEY-UHFFFAOYSA-N 0.000 claims description 3
- GNWFQOVRVPCKAX-UHFFFAOYSA-N [2-amino-4-[[4-(3-fluorophenyl)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=CC=CC(F)=C1 GNWFQOVRVPCKAX-UHFFFAOYSA-N 0.000 claims description 3
- WNMUAILZTTXQCU-UHFFFAOYSA-N [2-amino-4-[[4-(4-chlorophenyl)-1,4-diazepan-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)CCCN1C1=CC=C(Cl)C=C1 WNMUAILZTTXQCU-UHFFFAOYSA-N 0.000 claims description 3
- VQGCSQVHKQRFTI-UHFFFAOYSA-N [2-amino-4-[[4-(4-chlorophenyl)piperidin-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)CCC1C1=CC=C(Cl)C=C1 VQGCSQVHKQRFTI-UHFFFAOYSA-N 0.000 claims description 3
- GTPCHQHXBLWZKO-UHFFFAOYSA-N [2-amino-4-[[4-(4-methoxyphenyl)piperazin-1-yl]methyl]-5-methylthiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C1=CC(OC)=CC=C1N1CCN(CC=2C(=C(N)SC=2C)C(=O)C=2C=CC(Cl)=CC=2)CC1 GTPCHQHXBLWZKO-UHFFFAOYSA-N 0.000 claims description 3
- QQBFTEIZJXNNOZ-UHFFFAOYSA-N [2-amino-4-[[4-(4-methylphenyl)piperazin-1-yl]methyl]thiophen-3-yl]-(4-chlorophenyl)methanone Chemical compound C1=CC(C)=CC=C1N1CCN(CC=2C(=C(N)SC=2)C(=O)C=2C=CC(Cl)=CC=2)CC1 QQBFTEIZJXNNOZ-UHFFFAOYSA-N 0.000 claims description 3
- QPOPDJJHKWFMOW-UHFFFAOYSA-N [2-amino-4-[[4-[(4-chlorophenyl)methyl]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)CCN1CC1=CC=C(Cl)C=C1 QPOPDJJHKWFMOW-UHFFFAOYSA-N 0.000 claims description 3
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- JDVSMSUWNCGANW-UHFFFAOYSA-N [2-amino-4-[[4-[4-(trifluoromethoxy)phenyl]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(OC(F)(F)F)C=C1 JDVSMSUWNCGANW-UHFFFAOYSA-N 0.000 claims description 3
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Classifications
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- 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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- C07—ORGANIC CHEMISTRY
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- 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
-
- 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)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US85850506P | 2006-11-13 | 2006-11-13 | |
US60/858,505 | 2006-11-13 | ||
US11/938,514 US7897596B2 (en) | 2006-11-13 | 2007-11-12 | Allosteric modulators of the A1 adenosine receptor |
US11/938,514 | 2007-11-12 | ||
US11/938,465 US7855209B2 (en) | 2006-11-13 | 2007-11-12 | Allosteric modulators of the A1 adenosine receptor |
US11/938,465 | 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 |
---|---|
CA2669447A1 true CA2669447A1 (fr) | 2008-05-29 |
Family
ID=39430473
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002669447A Abandoned CA2669447A1 (fr) | 2006-11-13 | 2007-11-13 | Modulateurs allosteriques du recepteur de l'adenosine a1 |
Country Status (9)
Country | Link |
---|---|
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) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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 |
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 |
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 |
CN108290889B (zh) * | 2015-09-14 | 2021-08-10 | 内盖夫国家生物技术研究所 | 新的哌嗪和哌啶衍生物、它们的合成及其在抑制vdac寡聚化、细胞凋亡和线粒体功能障碍中的用途 |
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 |
JP7365238B2 (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 | 5-ヒドロキシトリプタミン受容体7調節物質および治療剤としてのその使用 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5332732A (en) * | 1992-09-11 | 1994-07-26 | Mcneilab, Inc. | Thiophene and pyridine antipsychotic agents |
ES2092737T3 (es) * | 1992-10-29 | 1996-12-01 | Hoechst Ag | Procedimiento para la preparacion de compuestos bromometil-aromaticos. |
US5939432A (en) * | 1997-10-29 | 1999-08-17 | Medco Research, Inc. | Thiophenes useful for modulating the adenosine receptor |
-
2007
- 2007-11-13 CA CA002669447A patent/CA2669447A1/fr not_active Abandoned
- 2007-11-13 EP EP07864306A patent/EP2081575A4/fr not_active Withdrawn
- 2007-11-13 JP JP2009537305A patent/JP2010509402A/ja not_active Withdrawn
- 2007-11-13 AU AU2007323888A patent/AU2007323888A1/en not_active Abandoned
- 2007-11-13 WO PCT/US2007/084490 patent/WO2008063984A2/fr active Application Filing
- 2007-11-13 BR BRPI0718520-0A patent/BRPI0718520A2/pt not_active IP Right Cessation
- 2007-11-13 MX MX2009004763A patent/MX2009004763A/es not_active Application Discontinuation
- 2007-11-13 KR KR1020097009765A patent/KR20090112627A/ko not_active Application Discontinuation
-
2009
- 2009-04-26 IL IL198402A patent/IL198402A0/en unknown
Also Published As
Publication number | Publication date |
---|---|
EP2081575A4 (fr) | 2010-01-06 |
WO2008063984A3 (fr) | 2008-08-14 |
BRPI0718520A2 (pt) | 2013-11-19 |
JP2010509402A (ja) | 2010-03-25 |
AU2007323888A1 (en) | 2008-05-29 |
MX2009004763A (es) | 2009-05-21 |
KR20090112627A (ko) | 2009-10-28 |
WO2008063984A2 (fr) | 2008-05-29 |
IL198402A0 (en) | 2010-02-17 |
EP2081575A2 (fr) | 2009-07-29 |
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Effective date: 20131113 |