JP2002523511A - 新規化合物 - Google Patents
新規化合物Info
- Publication number
- JP2002523511A JP2002523511A JP2000567536A JP2000567536A JP2002523511A JP 2002523511 A JP2002523511 A JP 2002523511A JP 2000567536 A JP2000567536 A JP 2000567536A JP 2000567536 A JP2000567536 A JP 2000567536A JP 2002523511 A JP2002523511 A JP 2002523511A
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- pyrimidine
- methylpropyl
- dione
- thieno
- 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.)
- Pending
Links
- 150000001875 compounds Chemical class 0.000 title claims description 188
- 238000000034 method Methods 0.000 claims abstract description 54
- JGOOQALRLGHKIY-UHFFFAOYSA-N 1h-thieno[2,3-d]pyrimidine-2,4-dione Chemical class O=C1NC(=O)NC2=C1C=CS2 JGOOQALRLGHKIY-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- 238000002360 preparation method Methods 0.000 claims abstract description 5
- -1 or C1-6Alkyl Chemical group 0.000 claims description 77
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 59
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 46
- 125000000217 alkyl group Chemical group 0.000 claims description 35
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 33
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 31
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 30
- 238000006243 chemical reaction Methods 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 23
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 21
- 239000012453 solvate Substances 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 20
- 229910052799 carbon Inorganic materials 0.000 claims description 18
- 125000001424 substituent group Chemical group 0.000 claims description 18
- 125000004432 carbon atom Chemical group C* 0.000 claims description 17
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 17
- 239000002904 solvent Substances 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 12
- RAHZWNYVWXNFOC-UHFFFAOYSA-N sulfur dioxide Inorganic materials O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- 125000003342 alkenyl group Chemical group 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 10
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 10
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 125000004076 pyridyl group Chemical group 0.000 claims description 10
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 9
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 7
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 7
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 7
- 125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 claims description 6
- 238000007254 oxidation reaction Methods 0.000 claims description 6
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 5
- FYODULSKIARMEB-UHFFFAOYSA-N 6-[1,3-benzothiazol-2-yl(hydroxy)methyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=CC=C2SC(C(O)C=3SC=4N(C(N(C)C(=O)C=4C=3)=O)CC(C)C)=NC2=C1 FYODULSKIARMEB-UHFFFAOYSA-N 0.000 claims description 5
- JCNVVNANFIZEMZ-UHFFFAOYSA-N 6-[hydroxy-(1-methylbenzimidazol-2-yl)methyl]-3-methyl-1-propan-2-ylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=CC=C2N(C)C(C(O)C=3SC=4N(C(N(C)C(=O)C=4C=3)=O)C(C)C)=NC2=C1 JCNVVNANFIZEMZ-UHFFFAOYSA-N 0.000 claims description 5
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims description 5
- 239000002671 adjuvant Substances 0.000 claims description 5
- 239000003638 chemical reducing agent Substances 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims description 5
- 229910052717 sulfur Chemical group 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- LLAAJKFSLZKYHE-UHFFFAOYSA-N 1-(cyclopropylmethyl)-6-[hydroxy-(1-methylbenzimidazol-2-yl)methyl]-3-methylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound N=1C2=CC=CC=C2N(C)C=1C(O)C(S1)=CC(C(N(C)C2=O)=O)=C1N2CC1CC1 LLAAJKFSLZKYHE-UHFFFAOYSA-N 0.000 claims description 4
- AMUJWWSZSRTUKN-UHFFFAOYSA-N 5-(3-hydroxypropoxy)-3-methyl-1-(2-methylpropyl)-6-(pyridin-3-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound OCCCOC=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1CC1=CC=CN=C1 AMUJWWSZSRTUKN-UHFFFAOYSA-N 0.000 claims description 4
- NWMHICYOEMTIFL-OAHLLOKOSA-N 5-[(3r)-3-hydroxypyrrolidin-1-yl]sulfonyl-3-methyl-1-(2-methylpropyl)-6-(pyridin-3-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C([C@H](O)CC1)N1S(=O)(=O)C=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1CC1=CC=CN=C1 NWMHICYOEMTIFL-OAHLLOKOSA-N 0.000 claims description 4
- ARZUNQNWVZXAOQ-UHFFFAOYSA-N 6-(benzimidazol-1-ylmethyl)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=NC2=CC=CC=C2N1CC(S1)=CC2=C1N(CC(C)C)C(=O)N(C)C2=O ARZUNQNWVZXAOQ-UHFFFAOYSA-N 0.000 claims description 4
- LKJZWOJOQXWWMP-UHFFFAOYSA-N 6-(benzimidazol-1-ylmethyl)-3-methyl-1-propan-2-ylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=NC2=CC=CC=C2N1CC(S1)=CC2=C1N(C(C)C)C(=O)N(C)C2=O LKJZWOJOQXWWMP-UHFFFAOYSA-N 0.000 claims description 4
- UMDLABDUJBFKRM-UHFFFAOYSA-N 6-[hydroxy-(1-methylbenzimidazol-2-yl)methyl]-3-methyl-1-(2-methylpropyl)-5-propan-2-ylsulfanylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=CC=C2N(C)C(C(O)C=3SC=4N(C(N(C)C(=O)C=4C=3SC(C)C)=O)CC(C)C)=NC2=C1 UMDLABDUJBFKRM-UHFFFAOYSA-N 0.000 claims description 4
- HIGFITSDKNNWTJ-UHFFFAOYSA-N 6-[hydroxy-(1-methylbenzimidazol-2-yl)methyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=CC=C2N(C)C(C(O)C=3SC=4N(C(N(C)C(=O)C=4C=3)=O)CC(C)C)=NC2=C1 HIGFITSDKNNWTJ-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 150000001540 azides Chemical class 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 230000001506 immunosuppresive effect Effects 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 230000000414 obstructive effect Effects 0.000 claims description 4
- 239000001301 oxygen Chemical group 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- NKAMAKVCUVIVTK-UHFFFAOYSA-N 1-(cyclopropylmethyl)-3-methyl-6-[(1-methylbenzimidazol-2-yl)methyl]thieno[2,3-d]pyrimidine-2,4-dione Chemical compound N=1C2=CC=CC=C2N(C)C=1CC(S1)=CC(C(N(C)C2=O)=O)=C1N2CC1CC1 NKAMAKVCUVIVTK-UHFFFAOYSA-N 0.000 claims description 3
- JYHUMIJWSGSAPL-UHFFFAOYSA-N 3-methyl-1-(2-methylpropyl)-5-propan-2-ylsulfanyl-6-(pyridin-3-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound CC(C)SC=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1CC1=CC=CN=C1 JYHUMIJWSGSAPL-UHFFFAOYSA-N 0.000 claims description 3
- DGXSDNVECZHQAZ-UHFFFAOYSA-N 3-methyl-1-(2-methylpropyl)-6-(pyridin-3-ylmethyl)-5-thiophen-2-ylsulfanylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C=1C=CSC=1SC=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1CC1=CC=CN=C1 DGXSDNVECZHQAZ-UHFFFAOYSA-N 0.000 claims description 3
- CRWMCZHHOIGMNV-UHFFFAOYSA-N 3-methyl-1-(2-methylpropyl)-6-(pyridine-3-carbonyl)-5-thiophen-2-ylsulfanylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C=1C=CSC=1SC=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1C(=O)C1=CC=CN=C1 CRWMCZHHOIGMNV-UHFFFAOYSA-N 0.000 claims description 3
- DSQHABJZILXDLV-UHFFFAOYSA-N 3-methyl-6-[(1-methylbenzimidazol-2-yl)methyl]-1-(2-methylpropyl)-5-propan-2-ylsulfanylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=CC=C2N(C)C(CC=3SC=4N(C(N(C)C(=O)C=4C=3SC(C)C)=O)CC(C)C)=NC2=C1 DSQHABJZILXDLV-UHFFFAOYSA-N 0.000 claims description 3
- LITLXRLYLVSWBD-UHFFFAOYSA-N 3-methyl-6-[(1-methylbenzimidazol-2-yl)methyl]-1-(2-methylpropyl)-5-propan-2-ylsulfonylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=CC=C2N(C)C(CC=3SC=4N(C(N(C)C(=O)C=4C=3S(=O)(=O)C(C)C)=O)CC(C)C)=NC2=C1 LITLXRLYLVSWBD-UHFFFAOYSA-N 0.000 claims description 3
- BHJLMTLHXPSAQR-UHFFFAOYSA-N 3-methyl-6-[(1-methylbenzimidazol-2-yl)methyl]-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=CC=C2N(C)C(CC=3SC=4N(C(N(C)C(=O)C=4C=3)=O)CC(C)C)=NC2=C1 BHJLMTLHXPSAQR-UHFFFAOYSA-N 0.000 claims description 3
- BBYYQONNCAAMKA-UHFFFAOYSA-N 3-methyl-6-[(1-methylbenzimidazol-2-yl)methyl]-1-propan-2-ylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=CC=C2N(C)C(CC=3SC=4N(C(N(C)C(=O)C=4C=3)=O)C(C)C)=NC2=C1 BBYYQONNCAAMKA-UHFFFAOYSA-N 0.000 claims description 3
- NSJKRGJIUCTXFM-UHFFFAOYSA-N 5-(3-hydroxypropylsulfanyl)-3-methyl-1-(2-methylpropyl)-6-(pyridin-3-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound OCCCSC=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1CC1=CC=CN=C1 NSJKRGJIUCTXFM-UHFFFAOYSA-N 0.000 claims description 3
- KJDSEKFFXGDYOD-UHFFFAOYSA-N 5-(3-hydroxypropylsulfanyl)-3-methyl-1-(2-methylpropyl)-6-(pyridine-3-carbonyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound OCCCSC=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1C(=O)C1=CC=CN=C1 KJDSEKFFXGDYOD-UHFFFAOYSA-N 0.000 claims description 3
- UQVFEKVXIUKTIA-UHFFFAOYSA-N 6-(benzimidazol-1-ylmethyl)-1-(cyclopropylmethyl)-3-methylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=2SC(CN3C4=CC=CC=C4N=C3)=CC=2C(=O)N(C)C(=O)N1CC1CC1 UQVFEKVXIUKTIA-UHFFFAOYSA-N 0.000 claims description 3
- MQCHNBJYTPUQRP-UHFFFAOYSA-N 6-(benzimidazol-1-ylmethyl)-3-methyl-1-(2-methylpropyl)-5-thiophen-2-ylsulfanylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC(CN2C3=CC=CC=C3N=C2)=C1SC1=CC=CS1 MQCHNBJYTPUQRP-UHFFFAOYSA-N 0.000 claims description 3
- UHLNLJGYZGCXIZ-UHFFFAOYSA-N 6-[hydroxy-[6-(trifluoromethyl)pyridin-2-yl]methyl]-3-methyl-1-(2-methylpropyl)-5-thiophen-2-ylsulfanylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C=1C=CSC=1SC=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1C(O)C1=CC=CC(C(F)(F)F)=N1 UHLNLJGYZGCXIZ-UHFFFAOYSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- XIPCEWGRKCZHJT-UHFFFAOYSA-N S1C(=NC2=C1C=CC=C2)C1=C(C2=C(N(C(N(C2=O)C)=O)CC(C)C)S1)C Chemical compound S1C(=NC2=C1C=CC=C2)C1=C(C2=C(N(C(N(C2=O)C)=O)CC(C)C)S1)C XIPCEWGRKCZHJT-UHFFFAOYSA-N 0.000 claims description 3
- 229910006074 SO2NH2 Inorganic materials 0.000 claims description 3
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 3
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 3
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 230000003647 oxidation Effects 0.000 claims description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 3
- 125000005493 quinolyl group Chemical group 0.000 claims description 3
- 208000023504 respiratory system disease Diseases 0.000 claims description 3
- 230000002441 reversible effect Effects 0.000 claims description 3
- 239000011593 sulfur Chemical group 0.000 claims description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
- GJQRXSNYCXFEJD-UHFFFAOYSA-N 3-methyl-1-(2-methylpropyl)-6-(1,3-thiazol-2-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1CC1=NC=CS1 GJQRXSNYCXFEJD-UHFFFAOYSA-N 0.000 claims description 2
- XQRUPBHBUFCSNE-UHFFFAOYSA-N 3-methyl-1-(2-methylpropyl)-6-(1h-pyrrolo[2,3-b]pyridin-3-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=CC=C2C(CC=3SC=4N(C(N(C)C(=O)C=4C=3)=O)CC(C)C)=CNC2=N1 XQRUPBHBUFCSNE-UHFFFAOYSA-N 0.000 claims description 2
- XQGBWCSNZSTOGH-UHFFFAOYSA-N 3-methyl-1-(2-methylpropyl)-6-(pyridin-2-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1CC1=CC=CC=N1 XQGBWCSNZSTOGH-UHFFFAOYSA-N 0.000 claims description 2
- IMLLAPNOOLJMMH-UHFFFAOYSA-N 3-methyl-1-(2-methylpropyl)-6-(pyridin-3-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1CC1=CC=CN=C1 IMLLAPNOOLJMMH-UHFFFAOYSA-N 0.000 claims description 2
- SUQLZAAGFNNDBQ-UHFFFAOYSA-N 3-methyl-1-(2-methylpropyl)-6-(pyridin-4-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1CC1=CC=NC=C1 SUQLZAAGFNNDBQ-UHFFFAOYSA-N 0.000 claims description 2
- FPCROBDZIRUNIV-UHFFFAOYSA-N 3-methyl-1-(2-methylpropyl)-6-(thiophen-2-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1CC1=CC=CS1 FPCROBDZIRUNIV-UHFFFAOYSA-N 0.000 claims description 2
- FVELFONZJZPXTG-UHFFFAOYSA-N 3-methyl-1-(2-methylpropyl)-6-[(3-oxo-1,2-benzothiazol-2-yl)methyl]-5-propan-2-ylsulfanylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound S1C2=CC=CC=C2C(=O)N1CC(S1)=C(SC(C)C)C2=C1N(CC(C)C)C(=O)N(C)C2=O FVELFONZJZPXTG-UHFFFAOYSA-N 0.000 claims description 2
- XFWKMDVLXOAROG-UHFFFAOYSA-N 6-(benzotriazol-1-ylmethyl)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound N1=NC2=CC=CC=C2N1CC(S1)=CC2=C1N(CC(C)C)C(=O)N(C)C2=O XFWKMDVLXOAROG-UHFFFAOYSA-N 0.000 claims description 2
- HPVJZAYZQRPTDJ-UHFFFAOYSA-N 6-(benzotriazol-2-ylmethyl)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound N1=C2C=CC=CC2=NN1CC(S1)=CC2=C1N(CC(C)C)C(=O)N(C)C2=O HPVJZAYZQRPTDJ-UHFFFAOYSA-N 0.000 claims description 2
- HSCFYYZKGKEYCH-UHFFFAOYSA-N 6-(indazol-1-ylmethyl)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound N1=CC2=CC=CC=C2N1CC(S1)=CC2=C1N(CC(C)C)C(=O)N(C)C2=O HSCFYYZKGKEYCH-UHFFFAOYSA-N 0.000 claims description 2
- SJULOZMZRAUZMG-UHFFFAOYSA-N 6-(indazol-2-ylmethyl)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=C2C=CC=CC2=NN1CC(S1)=CC2=C1N(CC(C)C)C(=O)N(C)C2=O SJULOZMZRAUZMG-UHFFFAOYSA-N 0.000 claims description 2
- QYOXPODCRHMTOK-UHFFFAOYSA-N 6-[(1,3-dioxoisoindol-2-yl)methyl]-3-methyl-1-(2-methylpropyl)-5-thiophen-2-ylsulfanylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC(CN2C(C3=CC=CC=C3C2=O)=O)=C1SC1=CC=CS1 QYOXPODCRHMTOK-UHFFFAOYSA-N 0.000 claims description 2
- CARZRMQRFMKZSE-UHFFFAOYSA-N 6-[(1,4-dioxo-3h-phthalazin-2-yl)methyl]-3-methyl-1-(2-methylpropyl)-5-propan-2-ylsulfanylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound N1C(=O)C2=CC=CC=C2C(=O)N1CC(S1)=C(SC(C)C)C2=C1N(CC(C)C)C(=O)N(C)C2=O CARZRMQRFMKZSE-UHFFFAOYSA-N 0.000 claims description 2
- LODJBUNSQMNQBS-UHFFFAOYSA-N 6-[(2-chlorobenzimidazol-1-yl)methyl]-3-methyl-1-(2-methylpropyl)-5-thiophen-2-ylsulfanylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC(CN2C3=CC=CC=C3N=C2Cl)=C1SC1=CC=CS1 LODJBUNSQMNQBS-UHFFFAOYSA-N 0.000 claims description 2
- YAAMAAXAZWGTFW-UHFFFAOYSA-N 6-[(4-chloro-1-methylpyrazol-3-yl)-hydroxymethyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1C(O)C1=NN(C)C=C1Cl YAAMAAXAZWGTFW-UHFFFAOYSA-N 0.000 claims description 2
- DQVOETUVDDMBAJ-UHFFFAOYSA-N 6-[(4-chloro-1-methylpyrazol-3-yl)methyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1CC1=NN(C)C=C1Cl DQVOETUVDDMBAJ-UHFFFAOYSA-N 0.000 claims description 2
- FOGCVSIRJSFWJC-UHFFFAOYSA-N 6-[(5-chlorothiophen-2-yl)methyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1CC1=CC=C(Cl)S1 FOGCVSIRJSFWJC-UHFFFAOYSA-N 0.000 claims description 2
- WEIQMEUHRGBRFZ-UHFFFAOYSA-N 6-[hydroxy(1,3-thiazol-2-yl)methyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1C(O)C1=NC=CS1 WEIQMEUHRGBRFZ-UHFFFAOYSA-N 0.000 claims description 2
- VCBYSTZNJAZSMW-UHFFFAOYSA-N 6-[hydroxy(pyridin-2-yl)methyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1C(O)C1=CC=CC=N1 VCBYSTZNJAZSMW-UHFFFAOYSA-N 0.000 claims description 2
- BCZHYOXHQNCJEP-UHFFFAOYSA-N 6-[hydroxy(pyridin-3-yl)methyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1C(O)C1=CC=CN=C1 BCZHYOXHQNCJEP-UHFFFAOYSA-N 0.000 claims description 2
- IMGVYVFMNBEGTO-UHFFFAOYSA-N 6-[hydroxy(pyridin-4-yl)methyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1C(O)C1=CC=NC=C1 IMGVYVFMNBEGTO-UHFFFAOYSA-N 0.000 claims description 2
- NTPNEWWRXUIHCB-UHFFFAOYSA-N 6-[hydroxy(thiophen-2-yl)methyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1C(O)C1=CC=CS1 NTPNEWWRXUIHCB-UHFFFAOYSA-N 0.000 claims description 2
- HSVZZBLWYSPELB-UHFFFAOYSA-N 6-[hydroxy(thiophen-3-yl)methyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1C(O)C=1C=CSC=1 HSVZZBLWYSPELB-UHFFFAOYSA-N 0.000 claims description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 2
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
- 229910052744 lithium Inorganic materials 0.000 claims description 2
- 229910021645 metal ion Inorganic materials 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 219
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 108
- 239000000243 solution Substances 0.000 description 92
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 79
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 77
- 239000000203 mixture Substances 0.000 description 73
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 72
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 71
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 63
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 59
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 58
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 45
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 43
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 41
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 36
- 239000000284 extract Substances 0.000 description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
- 239000000377 silicon dioxide Substances 0.000 description 34
- 239000007787 solid Substances 0.000 description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 28
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 25
- 238000003756 stirring Methods 0.000 description 23
- 239000012267 brine Substances 0.000 description 22
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
- 239000003921 oil Substances 0.000 description 21
- 235000019198 oils Nutrition 0.000 description 21
- 238000004440 column chromatography Methods 0.000 description 20
- 239000012279 sodium borohydride Substances 0.000 description 19
- 229910000033 sodium borohydride Inorganic materials 0.000 description 19
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 17
- 235000017557 sodium bicarbonate Nutrition 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 16
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- 239000002585 base Substances 0.000 description 13
- 239000012074 organic phase Substances 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 12
- 238000004587 chromatography analysis Methods 0.000 description 12
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 12
- 235000019341 magnesium sulphate Nutrition 0.000 description 12
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 12
- 238000000746 purification Methods 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- 239000012312 sodium hydride Substances 0.000 description 12
- 229910000104 sodium hydride Inorganic materials 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 10
- 239000010410 layer Substances 0.000 description 10
- 239000012071 phase Substances 0.000 description 10
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 10
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000003960 organic solvent Substances 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
- 206010039083 rhinitis Diseases 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 238000005406 washing Methods 0.000 description 7
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
- 102000000588 Interleukin-2 Human genes 0.000 description 5
- 108010002350 Interleukin-2 Proteins 0.000 description 5
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 5
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 238000002953 preparative HPLC Methods 0.000 description 5
- 238000013518 transcription Methods 0.000 description 5
- 230000035897 transcription Effects 0.000 description 5
- SIRPHJCQZYVEES-UHFFFAOYSA-N 1-methylbenzimidazole-2-carbaldehyde Chemical compound C1=CC=C2N(C)C(C=O)=NC2=C1 SIRPHJCQZYVEES-UHFFFAOYSA-N 0.000 description 4
- 208000030507 AIDS Diseases 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
- LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 239000006071 cream Substances 0.000 description 4
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 239000006260 foam Substances 0.000 description 4
- 206010025135 lupus erythematosus Diseases 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- 238000010626 work up procedure Methods 0.000 description 4
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 description 3
- BVTVICZVVWVBGB-UHFFFAOYSA-N 3-methyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-6-carbaldehyde Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1C=C(C=O)S2 BVTVICZVVWVBGB-UHFFFAOYSA-N 0.000 description 3
- WBAKOAPFWILXJX-UHFFFAOYSA-N 3-methyl-6-(1-methylbenzimidazole-2-carbonyl)-1-(2-methylpropyl)-5-propan-2-ylsulfanylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=CC=C2N(C)C(C(=O)C=3SC=4N(C(N(C)C(=O)C=4C=3SC(C)C)=O)CC(C)C)=NC2=C1 WBAKOAPFWILXJX-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 108010018525 NFATC Transcription Factors Proteins 0.000 description 3
- 102000002673 NFATC Transcription Factors Human genes 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 3
- 239000012346 acetyl chloride Substances 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- 208000010668 atopic eczema Diseases 0.000 description 3
- 229910002092 carbon dioxide Inorganic materials 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- KJRCEJOSASVSRA-UHFFFAOYSA-N propane-2-thiol Chemical compound CC(C)S KJRCEJOSASVSRA-UHFFFAOYSA-N 0.000 description 3
- OKULHRWWYCFJAB-UHFFFAOYSA-N pyrimidine-4-carbaldehyde Chemical compound O=CC1=CC=NC=N1 OKULHRWWYCFJAB-UHFFFAOYSA-N 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- JOLCGCMNXTUBIS-UHFFFAOYSA-N 1-(cyclopropylmethyl)-3-methylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=2SC=CC=2C(=O)N(C)C(=O)N1CC1CC1 JOLCGCMNXTUBIS-UHFFFAOYSA-N 0.000 description 2
- HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 2
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- PKLKUFMDLWMZNF-UHFFFAOYSA-N 3-methyl-1-(2-methylpropyl)-5-[3-(oxan-2-yloxy)propoxy]-6-(pyridin-3-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1CCCOC1OCCCOC=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1CC1=CC=CN=C1 PKLKUFMDLWMZNF-UHFFFAOYSA-N 0.000 description 2
- MSCKSLUUHSXKCP-UHFFFAOYSA-N 3-methyl-1-(2-methylpropyl)-6-(pyridin-3-ylmethylidene)thieno[2,3-d]pyrimidine-2,4,5-trione Chemical compound O=C1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC1=CC1=CC=CN=C1 MSCKSLUUHSXKCP-UHFFFAOYSA-N 0.000 description 2
- VMIMPKCZFHNUQG-UHFFFAOYSA-N 3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1C=CS2 VMIMPKCZFHNUQG-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- SCWAQHDJVTWJEC-UHFFFAOYSA-N 5-(azetidine-1-carbonyl)-1-(cyclopropylmethyl)-3-methyl-6-[(1-methylbenzimidazol-2-yl)methyl]thieno[2,3-d]pyrimidine-2,4-dione Chemical compound N=1C2=CC=CC=C2N(C)C=1CC(=C(C=1C(=O)N(C)C2=O)C(=O)N3CCC3)SC=1N2CC1CC1 SCWAQHDJVTWJEC-UHFFFAOYSA-N 0.000 description 2
- ATZUWILUGGKKPA-UHFFFAOYSA-N 5-bromo-3-methyl-1-(2-methylpropyl)-6-(pyridine-3-carbonyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound BrC=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1C(=O)C1=CC=CN=C1 ATZUWILUGGKKPA-UHFFFAOYSA-N 0.000 description 2
- DAZOSFZMQSTKRC-UHFFFAOYSA-N 6-(benzimidazol-1-ylmethyl)-3-methyl-1-(2-methylpropyl)-5-(pyrrolidine-1-carbonyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC(CN2C3=CC=CC=C3N=C2)=C1C(=O)N1CCCC1 DAZOSFZMQSTKRC-UHFFFAOYSA-N 0.000 description 2
- FPEQZNUKJTYNCR-UHFFFAOYSA-N 6-(benzimidazol-1-ylmethyl)-3-methyl-1-(2-methylpropyl)-5-propan-2-ylsulfanylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=NC2=CC=CC=C2N1CC(S1)=C(SC(C)C)C2=C1N(CC(C)C)C(=O)N(C)C2=O FPEQZNUKJTYNCR-UHFFFAOYSA-N 0.000 description 2
- OIYPJLURNZBSQG-UHFFFAOYSA-N 6-(chloromethyl)-1-(cyclopropylmethyl)-3-methylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=2SC(CCl)=CC=2C(=O)N(C)C(=O)N1CC1CC1 OIYPJLURNZBSQG-UHFFFAOYSA-N 0.000 description 2
- CXNSXHRQTDNGNM-UHFFFAOYSA-N 6-(chloromethyl)-3-methyl-1-(2-methylpropyl)-5-(pyrrolidine-1-carbonyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC(CCl)=C1C(=O)N1CCCC1 CXNSXHRQTDNGNM-UHFFFAOYSA-N 0.000 description 2
- LQTUQKQSHVWMDW-UHFFFAOYSA-N 6-[hydroxy(pyridin-3-yl)methyl]-3-methyl-1-(2-methylpropyl)-5-propan-2-ylsulfanylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound CC(C)SC=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1C(O)C1=CC=CN=C1 LQTUQKQSHVWMDW-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- PIGFYZPCRLYGLF-UHFFFAOYSA-N Aluminum nitride Chemical compound [Al]#N PIGFYZPCRLYGLF-UHFFFAOYSA-N 0.000 description 2
- 201000008283 Atrophic Rhinitis Diseases 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- ZJKGXLPYZUBLOI-UHFFFAOYSA-N C=1C=2C(=O)NC(=O)N(CC(C)C)C=2SC=1C(=O)C1=CC=CN=C1 Chemical compound C=1C=2C(=O)NC(=O)N(CC(C)C)C=2SC=1C(=O)C1=CC=CN=C1 ZJKGXLPYZUBLOI-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 201000004624 Dermatitis Diseases 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 2
- 206010024229 Leprosy Diseases 0.000 description 2
- 206010039088 Rhinitis atrophic Diseases 0.000 description 2
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- SWEDAZLCYJDAGW-UHFFFAOYSA-N Thiophene-2-thiol Chemical compound SC1=CC=CS1 SWEDAZLCYJDAGW-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- MJBWDEQAUQTVKK-IAGOWNOFSA-N aflatoxin M1 Chemical compound C=1([C@]2(O)C=CO[C@@H]2OC=1C=C(C1=2)OC)C=2OC(=O)C2=C1CCC2=O MJBWDEQAUQTVKK-IAGOWNOFSA-N 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 230000002140 halogenating effect Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- SUVIGLJNEAMWEG-UHFFFAOYSA-N propane-1-thiol Chemical compound CCCS SUVIGLJNEAMWEG-UHFFFAOYSA-N 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 102220240796 rs553605556 Human genes 0.000 description 2
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 2
- 229940001584 sodium metabisulfite Drugs 0.000 description 2
- 235000010262 sodium metabisulphite Nutrition 0.000 description 2
- WRVHPSSSTBDGRK-UHFFFAOYSA-N sodium;sulfane;hydrate Chemical compound O.[Na].S WRVHPSSSTBDGRK-UHFFFAOYSA-N 0.000 description 2
- 239000011343 solid material Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- ZWWLLYJRPKYTDF-UHFFFAOYSA-N thiophene-3,4-dicarboxylic acid Chemical compound OC(=O)C1=CSC=C1C(O)=O ZWWLLYJRPKYTDF-UHFFFAOYSA-N 0.000 description 2
- JHHZLHWJQPUNKB-SCSAIBSYSA-N (3r)-pyrrolidin-3-ol Chemical compound O[C@@H]1CCNC1 JHHZLHWJQPUNKB-SCSAIBSYSA-N 0.000 description 1
- 125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 description 1
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 description 1
- YYQPTCSSUWHYOB-UHFFFAOYSA-N 1,3-bis(prop-2-ynyl)quinazoline-2,4-dione Chemical compound C1=CC=C2C(=O)N(CC#C)C(=O)N(CC#C)C2=C1 YYQPTCSSUWHYOB-UHFFFAOYSA-N 0.000 description 1
- MPWWUNWBNNDDBR-UHFFFAOYSA-N 1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound O=C1NC(=O)N(CC(C)C)C2=C1C=CS2 MPWWUNWBNNDDBR-UHFFFAOYSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
- BTUGGGLMQBJCBN-UHFFFAOYSA-N 1-iodo-2-methylpropane Chemical compound CC(C)CI BTUGGGLMQBJCBN-UHFFFAOYSA-N 0.000 description 1
- SDQJTWBNWQABLE-UHFFFAOYSA-N 1h-quinazoline-2,4-dione Chemical class C1=CC=C2C(=O)NC(=O)NC2=C1 SDQJTWBNWQABLE-UHFFFAOYSA-N 0.000 description 1
- HJNHUFQGDJLQRS-UHFFFAOYSA-N 2-(3-bromopropoxy)oxane Chemical compound BrCCCOC1CCCCO1 HJNHUFQGDJLQRS-UHFFFAOYSA-N 0.000 description 1
- DOWNSQADAFSSAR-UHFFFAOYSA-N 2-bromo-6-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=CC(Br)=N1 DOWNSQADAFSSAR-UHFFFAOYSA-N 0.000 description 1
- QSKPIOLLBIHNAC-UHFFFAOYSA-N 2-chloro-acetaldehyde Chemical compound ClCC=O QSKPIOLLBIHNAC-UHFFFAOYSA-N 0.000 description 1
- LDZYRENCLPUXAX-UHFFFAOYSA-N 2-methyl-1h-benzimidazole Chemical compound C1=CC=C2NC(C)=NC2=C1 LDZYRENCLPUXAX-UHFFFAOYSA-N 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- NZASCBIBXNPDMH-UHFFFAOYSA-N 3,3-diethyl-1H-pyridine-2,4-dione Chemical compound CCC1(CC)C(=O)NC=CC1=O NZASCBIBXNPDMH-UHFFFAOYSA-N 0.000 description 1
- ZYGXXTPJXIUCAP-UHFFFAOYSA-N 3-methyl-1-(2-methylpropyl)-2,4-dioxo-5-propan-2-ylsulfanylthieno[2,3-d]pyrimidine-6-carbaldehyde Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1C(SC(C)C)=C(C=O)S2 ZYGXXTPJXIUCAP-UHFFFAOYSA-N 0.000 description 1
- RPZUKOHEJSOUCW-UHFFFAOYSA-N 3-methyl-1-(2-methylpropyl)-2,4-dioxo-5-thiophen-2-ylsulfanylthieno[2,3-d]pyrimidine-6-carbaldehyde Chemical compound C1=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC(C=O)=C1SC1=CC=CS1 RPZUKOHEJSOUCW-UHFFFAOYSA-N 0.000 description 1
- DYVOXUZONYBZDN-UHFFFAOYSA-N 3-methyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-6-carbaldehyde;3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1C=CS2.O=C1N(C)C(=O)N(CC(C)C)C2=C1C=C(C=O)S2 DYVOXUZONYBZDN-UHFFFAOYSA-N 0.000 description 1
- QJQPZAOIKVISBN-UHFFFAOYSA-N 3-methyl-1-(2-methylpropyl)-5-(pyrrolidine-1-carbonyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=C1C(=O)N1CCCC1 QJQPZAOIKVISBN-UHFFFAOYSA-N 0.000 description 1
- IJOFJRNWCALZKL-UHFFFAOYSA-N 3-methyl-1-(2-methylpropyl)-6-(pyridin-3-ylmethyl)-5-pyrrolidin-1-ylsulfonylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1CCCN1S(=O)(=O)C=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1CC1=CC=CN=C1 IJOFJRNWCALZKL-UHFFFAOYSA-N 0.000 description 1
- PYOJMJKLFBEVAU-UHFFFAOYSA-N 3-methyl-1-(2-methylpropyl)-6-(pyridin-3-ylmethyl)-5-triethylsilyloxythieno[2,3-d]pyrimidine-2,4-dione Chemical compound S1C=2N(CC(C)C)C(=O)N(C)C(=O)C=2C(O[Si](CC)(CC)CC)=C1CC1=CC=CN=C1 PYOJMJKLFBEVAU-UHFFFAOYSA-N 0.000 description 1
- ASTLHPJOINAXRF-UHFFFAOYSA-N 3-methyl-1-(2-methylpropyl)-6-sulfanylidene-1,3-diazinane-2,4-dione Chemical compound CC(C)CN1C(=S)CC(=O)N(C)C1=O ASTLHPJOINAXRF-UHFFFAOYSA-N 0.000 description 1
- SHLSSLVZXJBVHE-UHFFFAOYSA-N 3-sulfanylpropan-1-ol Chemical compound OCCCS SHLSSLVZXJBVHE-UHFFFAOYSA-N 0.000 description 1
- GMAOFLBDXUFBSG-UHFFFAOYSA-N 5-(3-hydroxypropylsulfanyl)-6-[hydroxy(pyridin-3-yl)methyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound OCCCSC=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1C(O)C1=CC=CN=C1 GMAOFLBDXUFBSG-UHFFFAOYSA-N 0.000 description 1
- NPLRBOSMTSPITH-UHFFFAOYSA-N 5-(azetidine-1-carbonyl)-1-(cyclopropylmethyl)-3-methylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=2SC=C(C(=O)N3CCC3)C=2C(=O)N(C)C(=O)N1CC1CC1 NPLRBOSMTSPITH-UHFFFAOYSA-N 0.000 description 1
- HHDZJICTMAQRLQ-UHFFFAOYSA-N 5-(azetidine-1-carbonyl)-1-(cyclopropylmethyl)-6-[hydroxy-(1-methylbenzimidazol-2-yl)methyl]-3-methylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound N=1C2=CC=CC=C2N(C)C=1C(O)C(=C(C=1C(=O)N(C)C2=O)C(=O)N3CCC3)SC=1N2CC1CC1 HHDZJICTMAQRLQ-UHFFFAOYSA-N 0.000 description 1
- NQFGYSUUWVOIHN-UHFFFAOYSA-N 5-bromo-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1C(Br)=CS2 NQFGYSUUWVOIHN-UHFFFAOYSA-N 0.000 description 1
- BXVWQYCIEUKKQQ-UHFFFAOYSA-N 5-bromo-3-methyl-6-(1-methylbenzimidazole-2-carbonyl)-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=CC=C2N(C)C(C(=O)C=3SC=4N(C(N(C)C(=O)C=4C=3Br)=O)CC(C)C)=NC2=C1 BXVWQYCIEUKKQQ-UHFFFAOYSA-N 0.000 description 1
- HXYKODCZOHSSMQ-UHFFFAOYSA-N 5-bromo-6-[hydroxy(pyridin-3-yl)methyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound BrC=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1C(O)C1=CC=CN=C1 HXYKODCZOHSSMQ-UHFFFAOYSA-N 0.000 description 1
- YVTYEFMJAVLDRW-UHFFFAOYSA-N 5-bromo-6-[hydroxy-(1-methylbenzimidazol-2-yl)methyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=CC=C2N(C)C(C(O)C=3SC=4N(C(N(C)C(=O)C=4C=3Br)=O)CC(C)C)=NC2=C1 YVTYEFMJAVLDRW-UHFFFAOYSA-N 0.000 description 1
- FOJZXKAGMHUAHW-UHFFFAOYSA-N 5-chloro-3-methyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-6-carbaldehyde Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1C(Cl)=C(C=O)S2 FOJZXKAGMHUAHW-UHFFFAOYSA-N 0.000 description 1
- OFCDSAMAISBVHJ-UHFFFAOYSA-N 6-(chloromethyl)-3-methyl-1-(2-methylpropyl)-5-propan-2-ylsulfanylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1C(SC(C)C)=C(CCl)S2 OFCDSAMAISBVHJ-UHFFFAOYSA-N 0.000 description 1
- ZKDNDQZKGLLKIY-UHFFFAOYSA-N 6-(chloromethyl)-3-methyl-1-(2-methylpropyl)-5-thiophen-2-ylsulfanylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC(CCl)=C1SC1=CC=CS1 ZKDNDQZKGLLKIY-UHFFFAOYSA-N 0.000 description 1
- ZUGYHVQTOREIGF-UHFFFAOYSA-N 6-(chloromethyl)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1C=C(CCl)S2 ZUGYHVQTOREIGF-UHFFFAOYSA-N 0.000 description 1
- RMFWMFXHHJBZRO-UHFFFAOYSA-N 6-(chloromethyl)-3-methyl-1-propan-2-ylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound O=C1N(C)C(=O)N(C(C)C)C2=C1C=C(CCl)S2 RMFWMFXHHJBZRO-UHFFFAOYSA-N 0.000 description 1
- GXVYSANAPBKYMD-UHFFFAOYSA-N 6-(hydroxymethyl)-3-methyl-1-(2-methylpropyl)-5-(pyrrolidine-1-carbonyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC(CO)=C1C(=O)N1CCCC1 GXVYSANAPBKYMD-UHFFFAOYSA-N 0.000 description 1
- RLGDVNBEFMPMOW-UHFFFAOYSA-N 6-(hydroxymethyl)-3-methyl-1-(2-methylpropyl)-5-(thiophen-2-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC(CO)=C1CC1=CC=CS1 RLGDVNBEFMPMOW-UHFFFAOYSA-N 0.000 description 1
- WUKVVCUQPUAFJP-UHFFFAOYSA-N 6-(hydroxymethyl)-3-methyl-1-(2-methylpropyl)-5-propan-2-ylsulfanylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1C(SC(C)C)=C(CO)S2 WUKVVCUQPUAFJP-UHFFFAOYSA-N 0.000 description 1
- KLBJOSBKQSUDAO-UHFFFAOYSA-N 6-bromo-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1C=C(Br)S2 KLBJOSBKQSUDAO-UHFFFAOYSA-N 0.000 description 1
- 125000003341 7 membered heterocyclic group Chemical group 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 1
- 208000035939 Alveolitis allergic Diseases 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 206010003559 Asthma late onset Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000009137 Behcet syndrome Diseases 0.000 description 1
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 1
- STBNQTJNZNPRRX-UHFFFAOYSA-N CC(C)CN(C([S+](C)C(C1=CC=CN=C1)=C1S(Cl)(=O)=O)=C1C(N1C)=O)C1=O Chemical compound CC(C)CN(C([S+](C)C(C1=CC=CN=C1)=C1S(Cl)(=O)=O)=C1C(N1C)=O)C1=O STBNQTJNZNPRRX-UHFFFAOYSA-N 0.000 description 1
- NXYYPGSHUHACCC-UHFFFAOYSA-O CC(C)CN(C([S+](C)C(C1=CC=CN=C1)=C1S(O)=O)=C1C(N1C)=O)C1=O Chemical compound CC(C)CN(C([S+](C)C(C1=CC=CN=C1)=C1S(O)=O)=C1C(N1C)=O)C1=O NXYYPGSHUHACCC-UHFFFAOYSA-O 0.000 description 1
- 101100301076 Canis lupus familiaris RBM47 gene Proteins 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 206010011416 Croup infectious Diseases 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 206010012442 Dermatitis contact Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010014950 Eosinophilia Diseases 0.000 description 1
- 206010014954 Eosinophilic fasciitis Diseases 0.000 description 1
- 206010014989 Epidermolysis bullosa Diseases 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- XXRCUYVCPSWGCC-UHFFFAOYSA-N Ethyl pyruvate Chemical compound CCOC(=O)C(C)=O XXRCUYVCPSWGCC-UHFFFAOYSA-N 0.000 description 1
- 208000027445 Farmer Lung Diseases 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000879758 Homo sapiens Sjoegren syndrome nuclear autoantigen 1 Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 201000003838 Idiopathic interstitial pneumonia Diseases 0.000 description 1
- 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 241001024304 Mino Species 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 206010029164 Nephrotic syndrome Diseases 0.000 description 1
- 239000012425 OXONE® Substances 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 206010034277 Pemphigoid Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 206010036774 Proctitis Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 1
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 208000033464 Reiter syndrome Diseases 0.000 description 1
- 208000018569 Respiratory Tract disease Diseases 0.000 description 1
- 208000036284 Rhinitis seasonal Diseases 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 206010039793 Seborrhoeic dermatitis Diseases 0.000 description 1
- 208000009359 Sezary Syndrome Diseases 0.000 description 1
- 208000021388 Sezary disease Diseases 0.000 description 1
- 102100037330 Sjoegren syndrome nuclear autoantigen 1 Human genes 0.000 description 1
- 208000021386 Sjogren Syndrome Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- ICMGLRUYEQNHPF-UHFFFAOYSA-N Uraprene Chemical compound COC1=CC=CC=C1N1CCN(CCCNC=2N(C(=O)N(C)C(=O)C=2)C)CC1 ICMGLRUYEQNHPF-UHFFFAOYSA-N 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 208000004631 alopecia areata Diseases 0.000 description 1
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 230000003305 autocrine Effects 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 1
- HGQULGDOROIPJN-UHFFFAOYSA-N azetidin-1-ium;chloride Chemical compound Cl.C1CNC1 HGQULGDOROIPJN-UHFFFAOYSA-N 0.000 description 1
- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- RJTANRZEWTUVMA-UHFFFAOYSA-N boron;n-methylmethanamine Chemical compound [B].CNC RJTANRZEWTUVMA-UHFFFAOYSA-N 0.000 description 1
- AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 208000000594 bullous pemphigoid Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000012069 chiral reagent Substances 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- 208000017760 chronic graft versus host disease Diseases 0.000 description 1
- 201000009151 chronic rhinitis Diseases 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 201000010549 croup Diseases 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 201000001564 eosinophilic gastroenteritis Diseases 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 238000006266 etherification reaction Methods 0.000 description 1
- HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 1
- KPWIDYACZBVVRM-UHFFFAOYSA-N ethyl 1-(cyclopropylmethyl)-3-methyl-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxylate Chemical compound O=C1N(C)C(=O)C=2C(C(=O)OCC)=CSC=2N1CC1CC1 KPWIDYACZBVVRM-UHFFFAOYSA-N 0.000 description 1
- RGRWYVXOYWACTH-UHFFFAOYSA-N ethyl 2-(propan-2-ylamino)thiophene-3-carboxylate Chemical compound CCOC(=O)C=1C=CSC=1NC(C)C RGRWYVXOYWACTH-UHFFFAOYSA-N 0.000 description 1
- MKJQYFVTEPGXIE-UHFFFAOYSA-N ethyl 2-aminothiophene-3-carboxylate Chemical compound CCOC(=O)C=1C=CSC=1N MKJQYFVTEPGXIE-UHFFFAOYSA-N 0.000 description 1
- ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 1
- QFPLBRLCXPFSHN-UHFFFAOYSA-N ethyl 3-methyl-1-(2-methylpropyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxylate Chemical compound CC(C)CN1C(=O)N(C)C(=O)C2=C1SC=C2C(=O)OCC QFPLBRLCXPFSHN-UHFFFAOYSA-N 0.000 description 1
- 229940117360 ethyl pyruvate Drugs 0.000 description 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
- 208000022195 farmer lung disease Diseases 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 230000003463 hyperproliferative effect Effects 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- PGHMRUGBZOYCAA-ADZNBVRBSA-N ionomycin Chemical compound O1[C@H](C[C@H](O)[C@H](C)[C@H](O)[C@H](C)/C=C/C[C@@H](C)C[C@@H](C)C(/O)=C/C(=O)[C@@H](C)C[C@@H](C)C[C@@H](CCC(O)=O)C)CC[C@@]1(C)[C@@H]1O[C@](C)([C@@H](C)O)CC1 PGHMRUGBZOYCAA-ADZNBVRBSA-N 0.000 description 1
- PGHMRUGBZOYCAA-UHFFFAOYSA-N ionomycin Natural products O1C(CC(O)C(C)C(O)C(C)C=CCC(C)CC(C)C(O)=CC(=O)C(C)CC(C)CC(CCC(O)=O)C)CCC1(C)C1OC(C)(C(C)O)CC1 PGHMRUGBZOYCAA-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 201000011486 lichen planus Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- JDOZOOBCADNBIJ-UHFFFAOYSA-N lithium;2h-pyridin-2-ide Chemical compound [Li+].C1=CC=N[C-]=C1 JDOZOOBCADNBIJ-UHFFFAOYSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 208000008585 mastocytosis Diseases 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229940087646 methanolamine Drugs 0.000 description 1
- JVQGWRQXZNFKCB-UHFFFAOYSA-N methyl 2-(1,3-dimethyl-2,6-dioxopyrimidin-4-yl)sulfanylacetate Chemical compound COC(=O)CSC1=CC(=O)N(C)C(=O)N1C JVQGWRQXZNFKCB-UHFFFAOYSA-N 0.000 description 1
- MKIJJIMOAABWGF-UHFFFAOYSA-N methyl 2-sulfanylacetate Chemical compound COC(=O)CS MKIJJIMOAABWGF-UHFFFAOYSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 201000005962 mycosis fungoides Diseases 0.000 description 1
- 125000006501 nitrophenyl group Chemical group 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- OKBMCNHOEMXPTM-UHFFFAOYSA-M potassium peroxymonosulfate Chemical compound [K+].OOS([O-])(=O)=O OKBMCNHOEMXPTM-UHFFFAOYSA-M 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- KGAFDVVPNRSBFI-UHFFFAOYSA-N pyrimidine-5-sulfinic acid Chemical compound OS(=O)C1=CN=CN=C1 KGAFDVVPNRSBFI-UHFFFAOYSA-N 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 208000002574 reactive arthritis Diseases 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- QBERHIJABFXGRZ-UHFFFAOYSA-M rhodium;triphenylphosphane;chloride Chemical compound [Cl-].[Rh].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QBERHIJABFXGRZ-UHFFFAOYSA-M 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 208000008742 seborrheic dermatitis Diseases 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- LFAGQMCIGQNPJG-UHFFFAOYSA-N silver cyanide Chemical compound [Ag+].N#[C-] LFAGQMCIGQNPJG-UHFFFAOYSA-N 0.000 description 1
- 229940098221 silver cyanide Drugs 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 201000005671 spondyloarthropathy Diseases 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000007863 steatosis Effects 0.000 description 1
- 231100000240 steatosis hepatitis Toxicity 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- BUUPQKDIAURBJP-UHFFFAOYSA-N sulfinic acid Chemical compound OS=O BUUPQKDIAURBJP-UHFFFAOYSA-N 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 208000001319 vasomotor rhinitis Diseases 0.000 description 1
- 208000018464 vernal keratoconjunctivitis Diseases 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- 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
- C07D495/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A61P31/08—Antibacterial agents for leprosy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Pulmonology (AREA)
- Rheumatology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Dermatology (AREA)
- Virology (AREA)
- Pain & Pain Management (AREA)
- Neurology (AREA)
- AIDS & HIV (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Transplantation (AREA)
- Endocrinology (AREA)
- Biomedical Technology (AREA)
- Emergency Medicine (AREA)
- Neurosurgery (AREA)
- Molecular Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9802895-4 | 1998-08-28 | ||
| SE9802895 | 1998-08-28 | ||
| PCT/SE1999/001400 WO2000012514A1 (en) | 1998-08-28 | 1999-08-18 | Novel compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2002523511A true JP2002523511A (ja) | 2002-07-30 |
| JP2002523511A5 JP2002523511A5 (https=) | 2006-10-05 |
Family
ID=20412397
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000567536A Pending JP2002523511A (ja) | 1998-08-28 | 1999-08-18 | 新規化合物 |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US6300334B1 (https=) |
| EP (1) | EP1107973B1 (https=) |
| JP (1) | JP2002523511A (https=) |
| AT (1) | ATE253580T1 (https=) |
| AU (1) | AU763758B2 (https=) |
| CA (1) | CA2339664A1 (https=) |
| DE (1) | DE69912618T2 (https=) |
| DK (1) | DK1107973T3 (https=) |
| ES (1) | ES2211161T3 (https=) |
| NZ (1) | NZ509809A (https=) |
| PT (1) | PT1107973E (https=) |
| WO (1) | WO2000012514A1 (https=) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006515880A (ja) * | 2003-01-17 | 2006-06-08 | アストラゼネカ・アクチエボラーグ | 自己免疫疾患の調節におけるチエノピリダジノンとその使用 |
| JP2006516974A (ja) * | 2003-01-17 | 2006-07-13 | アストラゼネカ・アクチエボラーグ | 自己免疫疾患の調節におけるチエノピリミジンジオンとその使用 |
| JP2009528389A (ja) * | 2006-03-02 | 2009-08-06 | シーブイ・セラピューティクス・インコーポレイテッド | Ａ２ａアデノシン受容体拮抗剤 |
| JP2012521407A (ja) * | 2009-03-23 | 2012-09-13 | グレンマーク ファーマシューティカルズ， エセ．アー． | Ｔｒｐａ１調節因子としてのチエノピリミジンジオン誘導体 |
| JP2018509443A (ja) * | 2015-03-26 | 2018-04-05 | バイエル ファーマ アクチエンゲゼルシャフト | アデノシン−Ａ２ｂ受容体の拮抗薬としての複素環メチル−チエノウラシル |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE9801399D0 (sv) | 1998-04-21 | 1998-04-21 | Astra Pharma Prod | Method and apparatus for filling containers |
| EP1280806B1 (en) * | 2000-05-04 | 2004-08-04 | AstraZeneca AB | THIENO 2,3-d]PYRIMIDINEDIONES AND THEIR USE AS PHARMACEUTICALS |
| GB2361917A (en) * | 2000-05-04 | 2001-11-07 | Astrazeneca Ab | Novel thieno[2,3-d]pyrimidinediones |
| GB2363377B (en) * | 2000-06-14 | 2004-06-09 | Astrazeneca Ab | Novel thieno[2,3-d]pyrimidinediones and therapeutic uses thereof |
| EP1370562A1 (en) * | 2001-02-14 | 2003-12-17 | Warner-Lambert Company LLC | Thieno[2,3-d]pyrimidindione derivatives as matrix metalloproteinase inhibitors |
| GB0117583D0 (en) * | 2001-07-19 | 2001-09-12 | Astrazeneca Ab | Novel compounds |
| GB0118479D0 (en) * | 2001-07-28 | 2001-09-19 | Astrazeneca Ab | Novel compounds |
| SE0300120D0 (sv) * | 2003-01-17 | 2003-01-17 | Astrazeneca Ab | Novel compounds |
| CN1925855B (zh) | 2003-12-19 | 2010-06-16 | 普莱希科公司 | 开发Ret调节剂的化合物和方法 |
| US7498342B2 (en) | 2004-06-17 | 2009-03-03 | Plexxikon, Inc. | Compounds modulating c-kit activity |
| WO2006115509A2 (en) | 2004-06-24 | 2006-11-02 | Novartis Vaccines And Diagnostics Inc. | Small molecule immunopotentiators and assays for their detection |
| WO2008063888A2 (en) | 2006-11-22 | 2008-05-29 | Plexxikon, Inc. | Compounds modulating c-fms and/or c-kit activity and uses therefor |
| WO2009012283A1 (en) | 2007-07-17 | 2009-01-22 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| MY172424A (en) | 2009-04-03 | 2019-11-25 | Hoffmann La Roche | Propane- i-sulfonic acid {3- (4-chloro-phenyl)-1h-pyrrolo [2, 3-b] pyridine-3-carconyl] -2, 4-difluoro-phenyl} -amide compositions and uses thereof |
| CN106220623A (zh) | 2009-11-06 | 2016-12-14 | 普莱希科公司 | 用于激酶调节的化合物和方法及其适应症 |
| US9624213B2 (en) | 2011-02-07 | 2017-04-18 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
| AR085279A1 (es) | 2011-02-21 | 2013-09-18 | Plexxikon Inc | Formas solidas de {3-[5-(4-cloro-fenil)-1h-pirrolo[2,3-b]piridina-3-carbonil]-2,4-difluor-fenil}-amida del acido propano-1-sulfonico |
| US9150570B2 (en) | 2012-05-31 | 2015-10-06 | Plexxikon Inc. | Synthesis of heterocyclic compounds |
| KR20160065957A (ko) | 2013-10-07 | 2016-06-09 | 바이엘 파마 악티엔게젤샤프트 | 시클릭 티에노우라실-카르복스아미드 및 그의 용도 |
| WO2018041771A1 (de) | 2016-09-02 | 2018-03-08 | Bayer Pharma Aktiengesellschaft | (1-methylcyclopropyl)methyl-substituierte thienouracile und ihre verwendung |
| CA3037642A1 (en) | 2016-09-23 | 2018-03-29 | Bayer Aktiengesellschaft | N 3 -cyclically substituted thienouraciles and use thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01213284A (ja) * | 1988-02-22 | 1989-08-28 | Sankyo Co Ltd | チエノピリミジン−２，４−ジオン誘導体 |
| DD293824A5 (de) * | 1990-04-24 | 1991-09-12 | Karl-Marx-Universitaet Leipzig,De | Verfahren zur herstellung von 3-(mercaptoalkyl)=thieno/2,3-d/pyrimidin-2,4(1h,3h)-dionen |
| TW276256B (https=) * | 1993-08-26 | 1996-05-21 | Takeda Pharm Industry Co Ltd |
-
1999
- 1999-08-18 DE DE69912618T patent/DE69912618T2/de not_active Expired - Fee Related
- 1999-08-18 CA CA002339664A patent/CA2339664A1/en not_active Abandoned
- 1999-08-18 DK DK99944964T patent/DK1107973T3/da active
- 1999-08-18 US US09/402,837 patent/US6300334B1/en not_active Expired - Fee Related
- 1999-08-18 NZ NZ509809A patent/NZ509809A/xx unknown
- 1999-08-18 ES ES99944964T patent/ES2211161T3/es not_active Expired - Lifetime
- 1999-08-18 AT AT99944964T patent/ATE253580T1/de not_active IP Right Cessation
- 1999-08-18 WO PCT/SE1999/001400 patent/WO2000012514A1/en not_active Ceased
- 1999-08-18 AU AU57677/99A patent/AU763758B2/en not_active Ceased
- 1999-08-18 PT PT99944964T patent/PT1107973E/pt unknown
- 1999-08-18 EP EP99944964A patent/EP1107973B1/en not_active Expired - Lifetime
- 1999-08-18 JP JP2000567536A patent/JP2002523511A/ja active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006515880A (ja) * | 2003-01-17 | 2006-06-08 | アストラゼネカ・アクチエボラーグ | 自己免疫疾患の調節におけるチエノピリダジノンとその使用 |
| JP2006516974A (ja) * | 2003-01-17 | 2006-07-13 | アストラゼネカ・アクチエボラーグ | 自己免疫疾患の調節におけるチエノピリミジンジオンとその使用 |
| JP2009528389A (ja) * | 2006-03-02 | 2009-08-06 | シーブイ・セラピューティクス・インコーポレイテッド | Ａ２ａアデノシン受容体拮抗剤 |
| JP2012521407A (ja) * | 2009-03-23 | 2012-09-13 | グレンマーク ファーマシューティカルズ， エセ．アー． | Ｔｒｐａ１調節因子としてのチエノピリミジンジオン誘導体 |
| JP2018509443A (ja) * | 2015-03-26 | 2018-04-05 | バイエル ファーマ アクチエンゲゼルシャフト | アデノシン−Ａ２ｂ受容体の拮抗薬としての複素環メチル−チエノウラシル |
Also Published As
| Publication number | Publication date |
|---|---|
| AU763758B2 (en) | 2003-07-31 |
| EP1107973B1 (en) | 2003-11-05 |
| US6300334B1 (en) | 2001-10-09 |
| PT1107973E (pt) | 2004-03-31 |
| NZ509809A (en) | 2002-11-26 |
| DK1107973T3 (da) | 2004-02-23 |
| ATE253580T1 (de) | 2003-11-15 |
| DE69912618T2 (de) | 2004-10-28 |
| AU5767799A (en) | 2000-03-21 |
| DE69912618D1 (de) | 2003-12-11 |
| ES2211161T3 (es) | 2004-07-01 |
| CA2339664A1 (en) | 2000-03-09 |
| WO2000012514A1 (en) | 2000-03-09 |
| EP1107973A1 (en) | 2001-06-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2002523511A (ja) | 新規化合物 | |
| CN100334093C (zh) | 噻吩并嘧啶二酮及其在调节自身免疫疾病中的用途 | |
| EP3080123B1 (en) | Imidazopyridine derivatives as modulators of tnf activity | |
| US9815797B2 (en) | Fused bicyclic heteroaromatic derivatives as modulators of TNF activity | |
| DE69628368T2 (de) | Heterocyclische Verbindungen, ihre Herstellung und Verwendung | |
| DE602005004287T2 (de) | Pyrrazolopyrimidinderivate | |
| JP2001525413A (ja) | 新規化合物 | |
| KR20200100719A (ko) | Lpa 길항제로서의 시클로헥실 산 트리아졸 아진 | |
| US6136974A (en) | Pyrrolo[3,4-D]Pyrimidinone derivatives and their use as medicaments | |
| JP2004537557A (ja) | 化学化合物 | |
| EA010487B1 (ru) | Производные тетрагидронафтиридина, пригодные в качестве лигандов рецептора hгистамина | |
| JPH06287188A (ja) | 新規複素環誘導体 | |
| JP2001520645A (ja) | 新規な化合物 | |
| JPWO1997019078A1 (ja) | ピリド［２，３−ｄ］ピリミジン誘導体及びその医薬組成物 | |
| US7763617B2 (en) | Pyrazolopyridine-4-yl pyridazinone derivatives and addition salts thereof, and PDE inhibitors comprising the same derivatives or salts as active ingredient | |
| IE61045B1 (en) | 4-aryl-5-carbamoyl-1, 4-dihydropyridines | |
| RU2685417C1 (ru) | Гидроксипуриновые соединения и их применение | |
| EP2168960A1 (en) | Pyrazolone derivative and pde inhibitor containing the same as active ingredient | |
| JP2009040711A (ja) | カルボスティリル誘導体及びそれらを有効成分とするｐｄｅ阻害剤 | |
| SK99794A3 (en) | Triazolopyrimidine derivatives as antiotensin ii receptor antagonists, method of their preparation, pharmaceutical agent and use | |
| JP2006117647A (ja) | ハロゲノピラゾロピリジンピリダジノン誘導体とその付加塩及びそれを有効成分とするｐｄｅ阻害剤 | |
| KR20050092761A (ko) | 티에노피리다지논 및 그들의 자가면역 질환 조절 용도 | |
| CN100354282C (zh) | 噻吩并哒嗪酮及其在调节自身免疫疾病中的用途 | |
| JPS6242983A (ja) | （ベンズイミダゾ−ル−２−イル）−ピリジニウム化合物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20060810 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20060810 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20081216 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090126 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090303 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20090728 |