JP2008525500A - ホスホジエステラーゼ１０阻害剤としてのチエノピリミジン誘導体 - Google Patents
ホスホジエステラーゼ１０阻害剤としてのチエノピリミジン誘導体 Download PDFInfo
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- JP2008525500A JP2008525500A JP2007548601A JP2007548601A JP2008525500A JP 2008525500 A JP2008525500 A JP 2008525500A JP 2007548601 A JP2007548601 A JP 2007548601A JP 2007548601 A JP2007548601 A JP 2007548601A JP 2008525500 A JP2008525500 A JP 2008525500A
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- Prior art keywords
- alkyl
- substituted
- phenyl
- alkoxy
- pyrimidin
- Prior art date
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- RBNBDIMXFJYDLQ-UHFFFAOYSA-N thieno[3,2-d]pyrimidine Chemical class C1=NC=C2SC=CC2=N1 RBNBDIMXFJYDLQ-UHFFFAOYSA-N 0.000 title abstract description 3
- 239000003112 inhibitor Substances 0.000 title description 28
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 title description 13
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 title description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 33
- 201000010099 disease Diseases 0.000 claims abstract description 29
- 102000004190 Enzymes Human genes 0.000 claims abstract description 20
- 108090000790 Enzymes Proteins 0.000 claims abstract description 20
- 208000018737 Parkinson disease Diseases 0.000 claims abstract description 18
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims abstract description 13
- 208000028017 Psychotic disease Diseases 0.000 claims abstract description 12
- 230000005764 inhibitory process Effects 0.000 claims abstract description 12
- 208000011580 syndromic disease Diseases 0.000 claims abstract description 7
- 230000000926 neurological effect Effects 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 519
- -1 cyano, hydroxyl Chemical group 0.000 claims description 448
- 125000003545 alkoxy group Chemical group 0.000 claims description 413
- 125000003282 alkyl amino group Chemical group 0.000 claims description 242
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 199
- 125000001424 substituent group Chemical group 0.000 claims description 196
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 161
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 160
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 143
- 238000000034 method Methods 0.000 claims description 133
- 150000001875 compounds Chemical class 0.000 claims description 103
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 102
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 98
- 125000003118 aryl group Chemical group 0.000 claims description 91
- 239000000126 substance Substances 0.000 claims description 91
- 125000000623 heterocyclic group Chemical group 0.000 claims description 88
- 239000000203 mixture Substances 0.000 claims description 82
- 125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 81
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 81
- 125000004043 oxo group Chemical group O=* 0.000 claims description 80
- 125000004076 pyridyl group Chemical group 0.000 claims description 74
- 125000001072 heteroaryl group Chemical group 0.000 claims description 72
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 61
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 60
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 53
- 150000005829 chemical entities Chemical class 0.000 claims description 51
- 125000003342 alkenyl group Chemical group 0.000 claims description 46
- 125000000304 alkynyl group Chemical group 0.000 claims description 46
- 125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims description 45
- 125000002541 furyl group Chemical group 0.000 claims description 44
- 125000000335 thiazolyl group Chemical group 0.000 claims description 43
- 125000001425 triazolyl group Chemical group 0.000 claims description 41
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 39
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 36
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 35
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 claims description 31
- 239000004202 carbamide Substances 0.000 claims description 31
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 29
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 29
- 206010012289 Dementia Diseases 0.000 claims description 27
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 26
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 24
- 208000010877 cognitive disease Diseases 0.000 claims description 23
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 22
- 206010027175 memory impairment Diseases 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 19
- 201000000980 schizophrenia Diseases 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 18
- 229910052736 halogen Inorganic materials 0.000 claims description 18
- 150000002367 halogens Chemical class 0.000 claims description 18
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 17
- 208000028698 Cognitive impairment Diseases 0.000 claims description 17
- 150000001350 alkyl halides Chemical class 0.000 claims description 17
- 125000004414 alkyl thio group Chemical group 0.000 claims description 17
- 125000004423 acyloxy group Chemical group 0.000 claims description 16
- 210000004227 basal ganglia Anatomy 0.000 claims description 16
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 208000023105 Huntington disease Diseases 0.000 claims description 15
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 15
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 15
- 125000004422 alkyl sulphonamide group Chemical group 0.000 claims description 15
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 15
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 15
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 15
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 15
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 15
- 125000005112 cycloalkylalkoxy group Chemical group 0.000 claims description 15
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 15
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 14
- 239000012453 solvate Substances 0.000 claims description 14
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 13
- 239000000651 prodrug Substances 0.000 claims description 13
- 229940002612 prodrug Drugs 0.000 claims description 13
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 13
- 125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 claims description 12
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 12
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 12
- 125000005874 benzothiadiazolyl group Chemical group 0.000 claims description 12
- 150000003857 carboxamides Chemical class 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 229910052717 sulfur Inorganic materials 0.000 claims description 12
- 208000020925 Bipolar disease Diseases 0.000 claims description 11
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 10
- 208000024827 Alzheimer disease Diseases 0.000 claims description 10
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 claims description 10
- 125000001070 dihydroindolyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 10
- 201000006417 multiple sclerosis Diseases 0.000 claims description 10
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 9
- 125000003107 substituted aryl group Chemical group 0.000 claims description 9
- 206010012601 diabetes mellitus Diseases 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 8
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 7
- HFFFLSISAQUYCX-UHFFFAOYSA-N 5-(4-fluorophenyl)-4-[3-(3-nitrophenoxy)propoxy]thieno[2,3-d]pyrimidine Chemical compound [O-][N+](=O)C1=CC=CC(OCCCOC=2C=3C(C=4C=CC(F)=CC=4)=CSC=3N=CN=2)=C1 HFFFLSISAQUYCX-UHFFFAOYSA-N 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 206010015037 epilepsy Diseases 0.000 claims description 6
- 230000006870 function Effects 0.000 claims description 6
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- UKQOFEREGIIHCF-UHFFFAOYSA-N 3-[3-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxypropoxy]aniline Chemical compound NC1=CC=CC(OCCCOC=2C=3C(C=4C=CC(F)=CC=4)=CSC=3N=CN=2)=C1 UKQOFEREGIIHCF-UHFFFAOYSA-N 0.000 claims description 5
- NYDGMGDUUUCXPO-UHFFFAOYSA-N 3-[3-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxypropoxy]benzoic acid Chemical compound OC(=O)C1=CC=CC(OCCCOC=2C=3C(C=4C=CC(F)=CC=4)=CSC=3N=CN=2)=C1 NYDGMGDUUUCXPO-UHFFFAOYSA-N 0.000 claims description 5
- MUQAAKGTOJWWPL-UHFFFAOYSA-N 5-[3-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxypropoxy]pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=CC(OCCCOC=2C=3C(C=4C=CC(F)=CC=4)=CSC=3N=CN=2)=C1 MUQAAKGTOJWWPL-UHFFFAOYSA-N 0.000 claims description 5
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Natural products C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 239000000463 material Substances 0.000 claims description 5
- FHFJIUXXXLIHCD-UHFFFAOYSA-N n-[4-[3-[[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]amino]propyl]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1CCCNC1=NC=NC2=C1C(C=1C=CC(F)=CC=1)=CS2 FHFJIUXXXLIHCD-UHFFFAOYSA-N 0.000 claims description 5
- 125000005188 oxoalkyl group Chemical group 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- KMPCEWAWKJUGGR-UHFFFAOYSA-N 3-[3-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxypropoxy]benzohydrazide Chemical compound NNC(=O)C1=CC=CC(OCCCOC=2C=3C(C=4C=CC(F)=CC=4)=CSC=3N=CN=2)=C1 KMPCEWAWKJUGGR-UHFFFAOYSA-N 0.000 claims description 4
- DSQDKPIOTLAMLN-UHFFFAOYSA-N 4-but-3-enyl-5-(4-fluorophenyl)thieno[2,3-d]pyrimidine Chemical compound C1=CC(F)=CC=C1C1=CSC2=NC=NC(CCC=C)=C12 DSQDKPIOTLAMLN-UHFFFAOYSA-N 0.000 claims description 4
- ZKALPSBKAGJIAF-UHFFFAOYSA-N 5-[4-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]butoxy]-n-methylpyridine-3-carboxamide Chemical compound CNC(=O)C1=CN=CC(OCCCCC=2C=3C(C=4C=CC(F)=CC=4)=CSC=3N=CN=2)=C1 ZKALPSBKAGJIAF-UHFFFAOYSA-N 0.000 claims description 4
- 230000006999 cognitive decline Effects 0.000 claims description 4
- 208000035475 disorder Diseases 0.000 claims description 4
- REMQACVQKFUNKD-UHFFFAOYSA-N methyl 5-[4-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]butoxy]pyridine-3-carboxylate Chemical compound COC(=O)C1=CN=CC(OCCCCC=2C=3C(C=4C=CC(F)=CC=4)=CSC=3N=CN=2)=C1 REMQACVQKFUNKD-UHFFFAOYSA-N 0.000 claims description 4
- LCIUBJUOVIIFTR-UHFFFAOYSA-N n-[(3-nitrophenyl)methyl]-n'-(5-phenylthieno[2,3-d]pyrimidin-4-yl)ethane-1,2-diamine Chemical compound [O-][N+](=O)C1=CC=CC(CNCCNC=2C=3C(C=4C=CC=CC=4)=CSC=3N=CN=2)=C1 LCIUBJUOVIIFTR-UHFFFAOYSA-N 0.000 claims description 4
- LVHUHEUOMRAXBI-UHFFFAOYSA-N n-[3-[3-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxyphenoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC(OC=2C=C(OC=3C=4C(C=5C=CC(F)=CC=5)=CSC=4N=CN=3)C=CC=2)=C1 LVHUHEUOMRAXBI-UHFFFAOYSA-N 0.000 claims description 4
- XDPJVACQLSQIPI-UHFFFAOYSA-N n-[3-[3-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxypropoxy]phenyl]acetamide Chemical compound CC(=O)NC1=CC=CC(OCCCOC=2C=3C(C=4C=CC(F)=CC=4)=CSC=3N=CN=2)=C1 XDPJVACQLSQIPI-UHFFFAOYSA-N 0.000 claims description 4
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 4
- JXCZNCZXBUPYKF-UHFFFAOYSA-N 1-[3-[3-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxypropoxy]phenyl]-3-hydroxyurea Chemical compound ONC(=O)NC1=CC=CC(OCCCOC=2C=3C(C=4C=CC(F)=CC=4)=CSC=3N=CN=2)=C1 JXCZNCZXBUPYKF-UHFFFAOYSA-N 0.000 claims description 3
- MELRXBKNVPEXRS-UHFFFAOYSA-N 1-[3-[3-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxypropoxy]phenyl]-3-methylurea Chemical compound CNC(=O)NC1=CC=CC(OCCCOC=2C=3C(C=4C=CC(F)=CC=4)=CSC=3N=CN=2)=C1 MELRXBKNVPEXRS-UHFFFAOYSA-N 0.000 claims description 3
- BWOQFALLHSXGCX-UHFFFAOYSA-N 1-[4-[3-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxypropoxy]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1OCCCOC1=NC=NC2=C1C(C=1C=CC(F)=CC=1)=CS2 BWOQFALLHSXGCX-UHFFFAOYSA-N 0.000 claims description 3
- RIMMTXOYGBAVGQ-UHFFFAOYSA-N 1-amino-3-[3-[3-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxypropoxy]phenyl]urea Chemical compound NNC(=O)NC1=CC=CC(OCCCOC=2C=3C(C=4C=CC(F)=CC=4)=CSC=3N=CN=2)=C1 RIMMTXOYGBAVGQ-UHFFFAOYSA-N 0.000 claims description 3
- VWKXLLWUKHPSEF-UHFFFAOYSA-N 1-amino-3-[4-[3-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxypropoxy]phenyl]urea Chemical compound C1=CC(NC(=O)NN)=CC=C1OCCCOC1=NC=NC2=C1C(C=1C=CC(F)=CC=1)=CS2 VWKXLLWUKHPSEF-UHFFFAOYSA-N 0.000 claims description 3
- YAIKPAGNERAPOQ-UHFFFAOYSA-N 1-ethyl-3-[4-[3-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxypropoxy]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1OCCCOC1=NC=NC2=C1C(C=1C=CC(F)=CC=1)=CS2 YAIKPAGNERAPOQ-UHFFFAOYSA-N 0.000 claims description 3
- JAPSOFJPZTZOKU-UHFFFAOYSA-N 2-methoxy-4-[2-[(5-phenylthieno[2,3-d]pyrimidin-4-yl)amino]ethyliminomethyl]phenol Chemical compound C1=C(O)C(OC)=CC(C=NCCNC=2C=3C(C=4C=CC=CC=4)=CSC=3N=CN=2)=C1 JAPSOFJPZTZOKU-UHFFFAOYSA-N 0.000 claims description 3
- JYSDTQNYAABJEX-UHFFFAOYSA-N 3-[2-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxyethoxy]-n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC(OCCOC=2C=3C(C=4C=CC(F)=CC=4)=CSC=3N=CN=2)=C1 JYSDTQNYAABJEX-UHFFFAOYSA-N 0.000 claims description 3
- ZKDHQCWALNJRAV-UHFFFAOYSA-N 3-[3-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxypropoxy]-n,n-dimethylbenzamide Chemical compound CN(C)C(=O)C1=CC=CC(OCCCOC=2C=3C(C=4C=CC(F)=CC=4)=CSC=3N=CN=2)=C1 ZKDHQCWALNJRAV-UHFFFAOYSA-N 0.000 claims description 3
- ZXZCMQKCBYXJFM-UHFFFAOYSA-N 3-[3-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxypropoxy]-n-hydroxybenzamide Chemical compound ONC(=O)C1=CC=CC(OCCCOC=2C=3C(C=4C=CC(F)=CC=4)=CSC=3N=CN=2)=C1 ZXZCMQKCBYXJFM-UHFFFAOYSA-N 0.000 claims description 3
- VRCJHDOBEHWIQN-UHFFFAOYSA-N 3-[3-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]oxypropoxy]-n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC(OCCCOC=2C=3C(C=4C=CC(F)=CC=4)=CSC=3N=CN=2)=C1 VRCJHDOBEHWIQN-UHFFFAOYSA-N 0.000 claims description 3
- HDILMKJHAHEKRB-UHFFFAOYSA-N 3-[[2-[(5-phenylthieno[2,3-d]pyrimidin-4-yl)amino]ethylamino]methyl]benzonitrile Chemical compound N#CC1=CC=CC(CNCCNC=2C=3C(C=4C=CC=CC=4)=CSC=3N=CN=2)=C1 HDILMKJHAHEKRB-UHFFFAOYSA-N 0.000 claims description 3
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 3
- IIONUEOGNZKNAS-UHFFFAOYSA-N 4-[3-(1,2-benzothiazol-3-yloxy)propoxy]-5-(4-fluorophenyl)thieno[2,3-d]pyrimidine Chemical compound C1=CC(F)=CC=C1C1=CSC2=NC=NC(OCCCOC=3C4=CC=CC=C4SN=3)=C12 IIONUEOGNZKNAS-UHFFFAOYSA-N 0.000 claims description 3
- POAZBDQRENJPTB-UHFFFAOYSA-N 4-[3-(3,4-dimethoxyphenoxy)propoxy]-5-(4-fluorophenyl)thieno[2,3-d]pyrimidine Chemical compound C1=C(OC)C(OC)=CC=C1OCCCOC1=NC=NC2=C1C(C=1C=CC(F)=CC=1)=CS2 POAZBDQRENJPTB-UHFFFAOYSA-N 0.000 claims description 3
- KRHWFIKMFNNPLI-UHFFFAOYSA-N 4-[3-(3,5-difluorophenoxy)propoxy]-5-(4-fluorophenyl)thieno[2,3-d]pyrimidine Chemical compound C1=CC(F)=CC=C1C1=CSC2=NC=NC(OCCCOC=3C=C(F)C=C(F)C=3)=C12 KRHWFIKMFNNPLI-UHFFFAOYSA-N 0.000 claims description 3
- NAMZLNCGEWXEAY-UHFFFAOYSA-N 4-[3-(3-ethylphenoxy)propoxy]-5-(4-fluorophenyl)thieno[2,3-d]pyrimidine Chemical compound CCC1=CC=CC(OCCCOC=2C=3C(C=4C=CC(F)=CC=4)=CSC=3N=CN=2)=C1 NAMZLNCGEWXEAY-UHFFFAOYSA-N 0.000 claims description 3
- CIUBDWZQZZSFQF-UHFFFAOYSA-N 4-[3-(4-chlorophenoxy)propoxy]-5-(4-fluorophenyl)thieno[2,3-d]pyrimidine Chemical compound C1=CC(F)=CC=C1C1=CSC2=NC=NC(OCCCOC=3C=CC(Cl)=CC=3)=C12 CIUBDWZQZZSFQF-UHFFFAOYSA-N 0.000 claims description 3
- AZHBPFURRAAKBS-UHFFFAOYSA-N 4-[3-(4-fluorophenoxy)propoxy]-5-(4-fluorophenyl)thieno[2,3-d]pyrimidine Chemical compound C1=CC(F)=CC=C1OCCCOC1=NC=NC2=C1C(C=1C=CC(F)=CC=1)=CS2 AZHBPFURRAAKBS-UHFFFAOYSA-N 0.000 claims description 3
- RCUDCNNBMDZSCL-UHFFFAOYSA-N 4-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]butan-1-ol Chemical compound C1=2C(CCCCO)=NC=NC=2SC=C1C1=CC=C(F)C=C1 RCUDCNNBMDZSCL-UHFFFAOYSA-N 0.000 claims description 3
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
- ZRECHBAMRMTXJQ-UHFFFAOYSA-N 5-(2-chlorophenyl)-4-(4-phenylmethoxyphenoxy)thieno[2,3-d]pyrimidine Chemical compound ClC1=CC=CC=C1C1=CSC2=NC=NC(OC=3C=CC(OCC=4C=CC=CC=4)=CC=3)=C12 ZRECHBAMRMTXJQ-UHFFFAOYSA-N 0.000 claims description 3
- SXGFENWNHKBEKR-UHFFFAOYSA-N 5-(4-fluorophenyl)-4-(3-phenoxypropoxy)thieno[2,3-d]pyrimidine Chemical compound C1=CC(F)=CC=C1C1=CSC2=NC=NC(OCCCOC=3C=CC=CC=3)=C12 SXGFENWNHKBEKR-UHFFFAOYSA-N 0.000 claims description 3
- SFJYZAMUKNWMQY-UHFFFAOYSA-N 5-(4-fluorophenyl)-4-[3-(3-methoxyphenoxy)propoxy]thieno[2,3-d]pyrimidine Chemical compound COC1=CC=CC(OCCCOC=2C=3C(C=4C=CC(F)=CC=4)=CSC=3N=CN=2)=C1 SFJYZAMUKNWMQY-UHFFFAOYSA-N 0.000 claims description 3
- NIQYCFLTUPCEDK-UHFFFAOYSA-N 5-(4-fluorophenyl)-4-[3-(3-methylphenoxy)propoxy]thieno[2,3-d]pyrimidine Chemical compound CC1=CC=CC(OCCCOC=2C=3C(C=4C=CC(F)=CC=4)=CSC=3N=CN=2)=C1 NIQYCFLTUPCEDK-UHFFFAOYSA-N 0.000 claims description 3
- ODSKNVMHALFYOO-UHFFFAOYSA-N 5-(4-fluorophenyl)-4-[3-[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]oxypropoxy]thieno[2,3-d]pyrimidine Chemical compound C1=C(C(F)(F)F)N(C)N=C1OCCCOC1=NC=NC2=C1C(C=1C=CC(F)=CC=1)=CS2 ODSKNVMHALFYOO-UHFFFAOYSA-N 0.000 claims description 3
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Classifications
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- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
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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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- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/12—Antidiuretics, e.g. drugs for diabetes insipidus
Landscapes
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
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- Emergency Medicine (AREA)
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- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US63817904P | 2004-12-23 | 2004-12-23 | |
| PCT/US2005/047439 WO2006071988A1 (en) | 2004-12-23 | 2005-12-27 | Thienopyrimidine derivatives as phosphodiesterase 10 inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008525500A true JP2008525500A (ja) | 2008-07-17 |
| JP2008525500A5 JP2008525500A5 (enExample) | 2009-03-05 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| JP2007548601A Pending JP2008525500A (ja) | 2004-12-23 | 2005-12-27 | ホスホジエステラーゼ１０阻害剤としてのチエノピリミジン誘導体 |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US7576080B2 (enExample) |
| EP (1) | EP1831229A1 (enExample) |
| JP (1) | JP2008525500A (enExample) |
| AU (1) | AU2005321903A1 (enExample) |
| CA (1) | CA2594676A1 (enExample) |
| MX (1) | MX2007007387A (enExample) |
| WO (1) | WO2006071988A1 (enExample) |
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| EP2923734B1 (en) | 2009-03-13 | 2018-01-10 | Katholieke Universiteit Leuven, K.U. Leuven R&D | Purine analogues and their use as immunosuppressive agents |
| CA2768924A1 (en) * | 2009-09-21 | 2011-03-24 | F. Hoffmann-La Roche Ag | Heterocyclic antiviral compounds |
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| JP2004534827A (ja) * | 2001-06-22 | 2004-11-18 | バイエル・ヘルスケア・アクチェンゲゼルシャフト | イミダゾトリアジン |
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