FI106960B - Menetelmä terapeuttisesti aktiivisten 1-fenyyli-pyrido[2,3-d]pyrimidiini-2,4-dioni- ja 2-onijohdannaisten valmistamiseksi - Google Patents
Menetelmä terapeuttisesti aktiivisten 1-fenyyli-pyrido[2,3-d]pyrimidiini-2,4-dioni- ja 2-onijohdannaisten valmistamiseksi Download PDFInfo
- Publication number
- FI106960B FI106960B FI944305A FI944305A FI106960B FI 106960 B FI106960 B FI 106960B FI 944305 A FI944305 A FI 944305A FI 944305 A FI944305 A FI 944305A FI 106960 B FI106960 B FI 106960B
- Authority
- FI
- Finland
- Prior art keywords
- pyrido
- pyrimidine
- dione
- formula
- pyridylmethyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 89
- 238000002360 preparation method Methods 0.000 title claims description 75
- 230000008569 process Effects 0.000 title claims description 19
- IMHWTGUXZBPFDM-UHFFFAOYSA-N 1-phenylpyrido[2,3-d]pyrimidine-2,4-dione Chemical compound O=C1NC(=O)C2=CC=CN=C2N1C1=CC=CC=C1 IMHWTGUXZBPFDM-UHFFFAOYSA-N 0.000 title description 6
- -1 pyridyl N-oxide Chemical group 0.000 claims description 161
- 150000001875 compounds Chemical class 0.000 claims description 144
- 238000006243 chemical reaction Methods 0.000 claims description 52
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 22
- QGKGASXQTBQINX-UHFFFAOYSA-N 3,4-dihydro-1h-pyrimidin-2-one Chemical compound O=C1NCC=CN1 QGKGASXQTBQINX-UHFFFAOYSA-N 0.000 claims description 21
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 21
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 239000001257 hydrogen Substances 0.000 claims description 18
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 18
- DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 239000000460 chlorine Substances 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- 239000002585 base Substances 0.000 claims description 11
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 11
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- JISZFRZDAXTJGT-UHFFFAOYSA-N methyl 3-[2,4-dioxo-3-(pyridin-3-ylmethyl)pyrido[2,3-d]pyrimidin-1-yl]benzoate Chemical compound COC(=O)C1=CC=CC(N2C(N(CC=3C=NC=CC=3)C(=O)C3=CC=CN=C32)=O)=C1 JISZFRZDAXTJGT-UHFFFAOYSA-N 0.000 claims description 10
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- YLHRMVRLIOIWTO-UHFFFAOYSA-N 1-(3-nitrophenyl)-3-(pyridin-4-ylmethyl)pyrido[2,3-d]pyrimidine-2,4-dione Chemical compound [O-][N+](=O)C1=CC=CC(N2C(N(CC=3C=CN=CC=3)C(=O)C3=CC=CN=C32)=O)=C1 YLHRMVRLIOIWTO-UHFFFAOYSA-N 0.000 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 150000001204 N-oxides Chemical class 0.000 claims description 7
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 5
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 claims description 5
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 5
- QTVKLFYTISVDOC-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-(pyridin-4-ylmethyl)pyrido[2,3-d]pyrimidine-2,4-dione Chemical compound ClC1=CC=CC(N2C(N(CC=3C=CN=CC=3)C(=O)C3=CC=CN=C32)=O)=C1 QTVKLFYTISVDOC-UHFFFAOYSA-N 0.000 claims description 4
- DAGZOMMSVOOPMS-UHFFFAOYSA-N 3-[2,4-dioxo-3-(pyridin-4-ylmethyl)pyrido[2,3-d]pyrimidin-1-yl]benzonitrile Chemical compound O=C1C2=CC=CN=C2N(C=2C=C(C=CC=2)C#N)C(=O)N1CC1=CC=NC=C1 DAGZOMMSVOOPMS-UHFFFAOYSA-N 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 4
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims description 4
- GMQNXISAYIRAFJ-UHFFFAOYSA-N 1-(3-nitrophenyl)-3-(pyridin-3-ylmethyl)pyrido[2,3-d]pyrimidine-2,4-dione Chemical compound [O-][N+](=O)C1=CC=CC(N2C(N(CC=3C=NC=CC=3)C(=O)C3=CC=CN=C32)=O)=C1 GMQNXISAYIRAFJ-UHFFFAOYSA-N 0.000 claims description 3
- ROSFKXDQMBPYQQ-UHFFFAOYSA-N 1-(3-nitrophenyl)-3-(pyridin-4-ylmethyl)pyrido[2,3-d]pyrimidine-2,4-dione;hydrochloride Chemical compound Cl.[O-][N+](=O)C1=CC=CC(N2C(N(CC=3C=CN=CC=3)C(=O)C3=CC=CN=C32)=O)=C1 ROSFKXDQMBPYQQ-UHFFFAOYSA-N 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 239000012458 free base Substances 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- SVRNPMAYXZNRHD-UHFFFAOYSA-N methyl 3-[2,4-dioxo-3-(pyridin-4-ylmethyl)pyrido[2,3-d]pyrimidin-1-yl]benzoate Chemical compound COC(=O)C1=CC=CC(N2C(N(CC=3C=CN=CC=3)C(=O)C3=CC=CN=C32)=O)=C1 SVRNPMAYXZNRHD-UHFFFAOYSA-N 0.000 claims description 3
- UUDZSOQPKQTJPR-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-(pyridin-4-ylmethyl)-4h-pyrido[2,3-d]pyrimidin-2-one Chemical compound ClC1=CC=CC(N2C3=NC=CC=C3CN(CC=3C=CN=CC=3)C2=O)=C1 UUDZSOQPKQTJPR-UHFFFAOYSA-N 0.000 claims description 2
- 125000004620 quinolinyl-N-oxide group Chemical group 0.000 claims description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims 3
- MBYULSWQNLZIAJ-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-(pyridin-3-ylmethyl)pyrido[2,3-d]pyrimidine-2,4-dione Chemical compound ClC1=CC=CC(N2C(N(CC=3C=NC=CC=3)C(=O)C3=CC=CN=C32)=O)=C1 MBYULSWQNLZIAJ-UHFFFAOYSA-N 0.000 claims 2
- DCKMUXFLBIAEAH-UHFFFAOYSA-N 1-phenyl-3-(pyridin-4-ylmethyl)pyrido[2,3-d]pyrimidine-2,4-dione Chemical compound O=C1C2=CC=CN=C2N(C=2C=CC=CC=2)C(=O)N1CC1=CC=NC=C1 DCKMUXFLBIAEAH-UHFFFAOYSA-N 0.000 claims 2
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims 2
- ALZKIYWRMWPNAN-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-(pyridin-3-ylmethyl)-4h-pyrido[2,3-d]pyrimidin-2-one Chemical compound ClC1=CC=CC(N2C3=NC=CC=C3CN(CC=3C=NC=CC=3)C2=O)=C1 ALZKIYWRMWPNAN-UHFFFAOYSA-N 0.000 claims 1
- TXLLMXXVURYZIR-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-(pyridin-4-ylmethyl)-2,4-dihydropyrido[2,3-d]pyrimidine Chemical compound ClC1=CC=CC(N2C3=NC=CC=C3CN(CC=3C=CN=CC=3)C2)=C1 TXLLMXXVURYZIR-UHFFFAOYSA-N 0.000 claims 1
- 125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims 1
- 241000277284 Salvelinus fontinalis Species 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
- 150000001413 amino acids Chemical class 0.000 claims 1
- 239000003086 colorant Substances 0.000 claims 1
- CPPKAGUPTKIMNP-UHFFFAOYSA-N cyanogen fluoride Chemical compound FC#N CPPKAGUPTKIMNP-UHFFFAOYSA-N 0.000 claims 1
- 239000003337 fertilizer Substances 0.000 claims 1
- 102000013370 fibrillin Human genes 0.000 claims 1
- 108060002895 fibrillin Proteins 0.000 claims 1
- JAIDNXCWLNECBZ-UHFFFAOYSA-N fluoro thiocyanate Chemical compound FSC#N JAIDNXCWLNECBZ-UHFFFAOYSA-N 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 239000000243 solution Substances 0.000 description 86
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 80
- 239000002904 solvent Substances 0.000 description 67
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 63
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 60
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- 239000011541 reaction mixture Substances 0.000 description 51
- 239000003153 chemical reaction reagent Substances 0.000 description 38
- 239000000725 suspension Substances 0.000 description 37
- JQPYINKVAWEQDQ-UHFFFAOYSA-N 1h-pyrido[2,3-d]pyrimidine-2,4-dione Chemical class C1=CC=C2C(=O)NC(=O)NC2=N1 JQPYINKVAWEQDQ-UHFFFAOYSA-N 0.000 description 35
- 239000007787 solid Substances 0.000 description 32
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- 235000019439 ethyl acetate Nutrition 0.000 description 27
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 27
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 23
- 239000000047 product Substances 0.000 description 21
- XISPDDYROWQPHI-UHFFFAOYSA-N 3,4-dihydro-1h-pyrido[2,3-d]pyrimidin-2-one Chemical class C1=CN=C2NC(=O)NCC2=C1 XISPDDYROWQPHI-UHFFFAOYSA-N 0.000 description 20
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
- 238000003756 stirring Methods 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- 238000003556 assay Methods 0.000 description 17
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 15
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- IVOMOUWHDPKRLL-KQYNXXCUSA-M 3',5'-cyclic AMP(1-) Chemical compound C([C@H]1O2)OP([O-])(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-M 0.000 description 14
- 239000002244 precipitate Substances 0.000 description 14
- 238000001914 filtration Methods 0.000 description 13
- 239000000203 mixture Substances 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
- 230000003110 anti-inflammatory effect Effects 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
- 241000699670 Mus sp. Species 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- 230000004048 modification Effects 0.000 description 10
- 238000012986 modification Methods 0.000 description 10
- 238000012746 preparative thin layer chromatography Methods 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- 210000001772 blood platelet Anatomy 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 9
- 229910000104 sodium hydride Inorganic materials 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 230000000694 effects Effects 0.000 description 8
- 210000000265 leukocyte Anatomy 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 7
- 238000000605 extraction Methods 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 125000001072 heteroaryl group Chemical group 0.000 description 7
- 230000007935 neutral effect Effects 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 239000008188 pellet Substances 0.000 description 7
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 7
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 229910052782 aluminium Inorganic materials 0.000 description 6
- 239000000010 aprotic solvent Substances 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 230000001506 immunosuppresive effect Effects 0.000 description 6
- 210000004698 lymphocyte Anatomy 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- UDJFFSGCRRMVFH-UHFFFAOYSA-N pyrido[2,3-d]pyrimidine Chemical compound N1=CN=CC2=CC=CN=C21 UDJFFSGCRRMVFH-UHFFFAOYSA-N 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 5
- GASMSRQSLYKUHV-UHFFFAOYSA-N 1-(3-nitrophenyl)pyrido[2,3-d]pyrimidine-2,4-dione Chemical compound [O-][N+](=O)C1=CC=CC(N2C(NC(=O)C3=CC=CN=C32)=O)=C1 GASMSRQSLYKUHV-UHFFFAOYSA-N 0.000 description 5
- CNQCWYFDIQSALX-UHFFFAOYSA-N 3-(chloromethyl)pyridine Chemical compound ClCC1=CC=CN=C1 CNQCWYFDIQSALX-UHFFFAOYSA-N 0.000 description 5
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 5
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 5
- 235000019270 ammonium chloride Nutrition 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 125000006501 nitrophenyl group Chemical group 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 4
- GUKZTMNMNAOZOX-UHFFFAOYSA-N 1-(3-chlorophenyl)-3,4-dihydropyrido[2,3-d]pyrimidin-2-one Chemical compound ClC1=CC=CC(N2C3=NC=CC=C3CNC2=O)=C1 GUKZTMNMNAOZOX-UHFFFAOYSA-N 0.000 description 4
- XYTDWEFEUCVUHK-UHFFFAOYSA-N 2-(3-nitroanilino)pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=C1NC1=CC=CC([N+]([O-])=O)=C1 XYTDWEFEUCVUHK-UHFFFAOYSA-N 0.000 description 4
- HXKWWDAWOMOFHB-UHFFFAOYSA-N 2-anilinopyridine-3-carboxamide Chemical class NC(=O)C1=CC=CN=C1NC1=CC=CC=C1 HXKWWDAWOMOFHB-UHFFFAOYSA-N 0.000 description 4
- 108010054479 3',5'-Cyclic-AMP Phosphodiesterases Proteins 0.000 description 4
- 102000001707 3',5'-Cyclic-AMP Phosphodiesterases Human genes 0.000 description 4
- SACUGYGVTSZFEA-UHFFFAOYSA-N 3-(aminomethyl)-n-(3-chlorophenyl)pyridin-2-amine Chemical compound NCC1=CC=CN=C1NC1=CC=CC(Cl)=C1 SACUGYGVTSZFEA-UHFFFAOYSA-N 0.000 description 4
- DECBEECYBHUSOO-UHFFFAOYSA-N 3-(aminomethyl)-n-phenylpyridin-2-amine Chemical class NCC1=CC=CN=C1NC1=CC=CC=C1 DECBEECYBHUSOO-UHFFFAOYSA-N 0.000 description 4
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 150000001450 anions Chemical class 0.000 description 4
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 125000001309 chloro group Chemical group Cl* 0.000 description 4
- 125000004802 cyanophenyl group Chemical group 0.000 description 4
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 4
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 239000003226 mitogen Substances 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 230000001590 oxidative effect Effects 0.000 description 4
- OXAIIPJGBIWVIM-UHFFFAOYSA-M potassium;2-chloropyridine-3-carboxylate Chemical compound [K+].[O-]C(=O)C1=CC=CN=C1Cl OXAIIPJGBIWVIM-UHFFFAOYSA-M 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 210000000952 spleen Anatomy 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 4
- XCHAALHRVVUHRS-UHFFFAOYSA-N 1-(3-methylsulfanylphenyl)-3-(pyridin-4-ylmethyl)pyrido[2,3-d]pyrimidine-2,4-dione Chemical compound CSC1=CC=CC(N2C(N(CC=3C=CN=CC=3)C(=O)C3=CC=CN=C32)=O)=C1 XCHAALHRVVUHRS-UHFFFAOYSA-N 0.000 description 3
- GZFVXWJVRLWUKL-UHFFFAOYSA-N 2-(3-nitroanilino)pyridine-3-carboxamide Chemical compound NC(=O)C1=CC=CN=C1NC1=CC=CC([N+]([O-])=O)=C1 GZFVXWJVRLWUKL-UHFFFAOYSA-N 0.000 description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
- UUMMTMQODCACRH-UHFFFAOYSA-N 2-anilinopyridine-3-carboxylic acid Chemical class OC(=O)C1=CC=CN=C1NC1=CC=CC=C1 UUMMTMQODCACRH-UHFFFAOYSA-N 0.000 description 3
- RLQZIECDMISZHS-UHFFFAOYSA-N 2-phenylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C=CC(=O)C(C=2C=CC=CC=2)=C1 RLQZIECDMISZHS-UHFFFAOYSA-N 0.000 description 3
- ZDHKVKPZQKYREU-UHFFFAOYSA-N 4-(chloromethyl)pyridine;hydron;chloride Chemical compound Cl.ClCC1=CC=NC=C1 ZDHKVKPZQKYREU-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
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 229920001817 Agar Polymers 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 3
- 239000007868 Raney catalyst Substances 0.000 description 3
- 229910000564 Raney nickel Inorganic materials 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 239000008272 agar Substances 0.000 description 3
- 230000000202 analgesic effect Effects 0.000 description 3
- 229940121363 anti-inflammatory agent Drugs 0.000 description 3
- 239000002260 anti-inflammatory agent Substances 0.000 description 3
- 239000012736 aqueous medium Substances 0.000 description 3
- 230000001363 autoimmune Effects 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 150000001768 cations Chemical class 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 229960003444 immunosuppressant agent Drugs 0.000 description 3
- 239000003018 immunosuppressive agent Substances 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 3
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 3
- 229910052939 potassium sulfate Inorganic materials 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000011775 sodium fluoride Substances 0.000 description 3
- 235000013024 sodium fluoride Nutrition 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 239000011343 solid material Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 230000008961 swelling Effects 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- YKTYUHMWNUVAAM-UHFFFAOYSA-N (6-methoxypyridin-3-yl)methanol Chemical compound COC1=CC=C(CO)C=N1 YKTYUHMWNUVAAM-UHFFFAOYSA-N 0.000 description 2
- DJCJOWDAAZEMCI-UHFFFAOYSA-N (6-methylpyridin-3-yl)methanol Chemical compound CC1=CC=C(CO)C=N1 DJCJOWDAAZEMCI-UHFFFAOYSA-N 0.000 description 2
- ZTRPRQFOFYPVIN-UHFFFAOYSA-N 1-(3-acetylanilino)-n-benzyl-2h-pyridine-3-carboxamide Chemical compound CC(=O)C1=CC=CC(NN2C=CC=C(C2)C(=O)NCC=2C=CC=CC=2)=C1 ZTRPRQFOFYPVIN-UHFFFAOYSA-N 0.000 description 2
- HIZMMXWNQKBWTA-UHFFFAOYSA-N 1-(3-aminophenyl)-3-(pyridin-4-ylmethyl)pyrido[2,3-d]pyrimidine-2,4-dione Chemical compound NC1=CC=CC(N2C(N(CC=3C=CN=CC=3)C(=O)C3=CC=CN=C32)=O)=C1 HIZMMXWNQKBWTA-UHFFFAOYSA-N 0.000 description 2
- AAPIRHWNZXNDGK-UHFFFAOYSA-N 1-(3-methylsulfonylphenyl)-3-(pyridin-4-ylmethyl)pyrido[2,3-d]pyrimidine-2,4-dione Chemical compound CS(=O)(=O)C1=CC=CC(N2C(N(CC=3C=CN=CC=3)C(=O)C3=CC=CN=C32)=O)=C1 AAPIRHWNZXNDGK-UHFFFAOYSA-N 0.000 description 2
- ASLWETLNYXUFFL-UHFFFAOYSA-N 1-(3-nitrophenyl)-3,4-dihydropyrido[2,3-d]pyrimidin-2-one Chemical compound [O-][N+](=O)C1=CC=CC(N2C3=NC=CC=C3CNC2=O)=C1 ASLWETLNYXUFFL-UHFFFAOYSA-N 0.000 description 2
- ONKRRSMCUFOCMB-UHFFFAOYSA-N 1-(4-methyl-3-nitrophenyl)-3-(pyridin-3-ylmethyl)pyrido[2,3-d]pyrimidine-2,4-dione Chemical compound C1=C([N+]([O-])=O)C(C)=CC=C1N1C(=O)N(CC=2C=NC=CC=2)C(=O)C2=CC=CN=C21 ONKRRSMCUFOCMB-UHFFFAOYSA-N 0.000 description 2
- PRMFDDKXIJVBTF-UHFFFAOYSA-N 2-(3-chloroanilino)pyridine-3-carboxamide Chemical compound NC(=O)C1=CC=CN=C1NC1=CC=CC(Cl)=C1 PRMFDDKXIJVBTF-UHFFFAOYSA-N 0.000 description 2
- ABZUNABOAWEBFZ-UHFFFAOYSA-N 2-(3-chloroanilino)pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=C1NC1=CC=CC(Cl)=C1 ABZUNABOAWEBFZ-UHFFFAOYSA-N 0.000 description 2
- MHDZVXFWLPXYED-UHFFFAOYSA-N 2-(3-methoxycarbonylanilino)pyridine-3-carboxylic acid Chemical compound COC(=O)C1=CC=CC(NC=2C(=CC=CN=2)C(O)=O)=C1 MHDZVXFWLPXYED-UHFFFAOYSA-N 0.000 description 2
- XSJKCCUASQVUSD-UHFFFAOYSA-N 2-(3-methylsulfanylanilino)pyridine-3-carboxylic acid Chemical compound CSC1=CC=CC(NC=2C(=CC=CN=2)C(O)=O)=C1 XSJKCCUASQVUSD-UHFFFAOYSA-N 0.000 description 2
- FERVRTQRLPFPOC-UHFFFAOYSA-N 2-(3-nitroanilino)pyridine-3-carbonyl chloride Chemical compound [O-][N+](=O)C1=CC=CC(NC=2C(=CC=CN=2)C(Cl)=O)=C1 FERVRTQRLPFPOC-UHFFFAOYSA-N 0.000 description 2
- IBRSSZOHCGUTHI-UHFFFAOYSA-N 2-chloropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=C1Cl IBRSSZOHCGUTHI-UHFFFAOYSA-N 0.000 description 2
- UEOBHSBDULPHPR-UHFFFAOYSA-N 3-(2,4-dioxopyrido[2,3-d]pyrimidin-1-yl)benzonitrile Chemical compound O=C1NC(=O)C2=CC=CN=C2N1C1=CC=CC(C#N)=C1 UEOBHSBDULPHPR-UHFFFAOYSA-N 0.000 description 2
- JNICSHTXCGICKK-UHFFFAOYSA-N 3-(aminomethyl)-n-(3-nitrophenyl)pyridin-2-amine Chemical compound NCC1=CC=CN=C1NC1=CC=CC([N+]([O-])=O)=C1 JNICSHTXCGICKK-UHFFFAOYSA-N 0.000 description 2
- CMKLNFNSNNDDRA-UHFFFAOYSA-N 3-[2,4-dioxo-3-(pyridin-3-ylmethyl)pyrido[2,3-d]pyrimidin-1-yl]benzamide Chemical compound NC(=O)C1=CC=CC(N2C(N(CC=3C=NC=CC=3)C(=O)C3=CC=CN=C32)=O)=C1 CMKLNFNSNNDDRA-UHFFFAOYSA-N 0.000 description 2
- HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 2
- WIXZFNINVXFWRU-UHFFFAOYSA-N 4-nitro-2-(3-nitroanilino)pyridine-3-carboxamide Chemical compound [N+](=O)([O-])C1=C(C(=NC=C1)NC1=CC(=CC=C1)[N+](=O)[O-])C(N)=O WIXZFNINVXFWRU-UHFFFAOYSA-N 0.000 description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 206010012438 Dermatitis atopic Diseases 0.000 description 2
- 208000009386 Experimental Arthritis Diseases 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 208000009329 Graft vs Host Disease Diseases 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 239000007832 Na2SO4 Substances 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- 229920006926 PFC Polymers 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 2
- 229940035676 analgesics Drugs 0.000 description 2
- 150000001448 anilines Chemical class 0.000 description 2
- 239000000730 antalgic agent Substances 0.000 description 2
- 239000000043 antiallergic agent Substances 0.000 description 2
- 210000000628 antibody-producing cell Anatomy 0.000 description 2
- 239000002111 antiemetic agent Substances 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229940114079 arachidonic acid Drugs 0.000 description 2
- 235000021342 arachidonic acid Nutrition 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 201000008937 atopic dermatitis Diseases 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 239000002274 desiccant Substances 0.000 description 2
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 125000006575 electron-withdrawing group Chemical group 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 208000024908 graft versus host disease Diseases 0.000 description 2
- 230000002949 hemolytic effect Effects 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 230000002519 immonomodulatory effect Effects 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- XCFOZGDREOFFNT-UHFFFAOYSA-N methyl 3-(2,4-dioxopyrido[2,3-d]pyrimidin-1-yl)benzoate Chemical compound COC(=O)C1=CC=CC(N2C(NC(=O)C3=CC=CN=C32)=O)=C1 XCFOZGDREOFFNT-UHFFFAOYSA-N 0.000 description 2
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 230000006213 negative regulation of lymphocyte proliferation Effects 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 230000036407 pain Effects 0.000 description 2
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 206010039083 rhinitis Diseases 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 230000000451 tissue damage Effects 0.000 description 2
- 231100000827 tissue damage Toxicity 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- YXPVCSWOMRFRCS-UHFFFAOYSA-N (2-chloro-6-methylpyridin-4-yl)methanol Chemical compound CC1=CC(CO)=CC(Cl)=N1 YXPVCSWOMRFRCS-UHFFFAOYSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- UYBULCLJEWQLKE-UHFFFAOYSA-N 1-(1-nitrocyclohexa-2,4-dien-1-yl)pyrido[2,3-d]pyrimidine-2,4-dione Chemical compound C12=NC=CC=C2C(=O)NC(=O)N1C1([N+](=O)[O-])CC=CC=C1 UYBULCLJEWQLKE-UHFFFAOYSA-N 0.000 description 1
- YJCPPVRQIORSBL-UHFFFAOYSA-N 1-(2-aminophenyl)pyrido[2,3-d]pyrimidine-2,4-dione Chemical class NC1=CC=CC=C1N1C(=O)NC(=O)C2=CC=CN=C21 YJCPPVRQIORSBL-UHFFFAOYSA-N 0.000 description 1
- XZUUSUYWNHMZTM-UHFFFAOYSA-N 1-(2-methylsulfinylphenyl)pyrido[2,3-d]pyrimidine-2,4-dione Chemical compound CS(=O)C1=CC=CC=C1N1C(=O)NC(=O)C2=CC=CN=C21 XZUUSUYWNHMZTM-UHFFFAOYSA-N 0.000 description 1
- LMJBHQBOPUCWML-UHFFFAOYSA-N 1-(2-methylsulfonylphenyl)pyrido[2,3-d]pyrimidine-2,4-dione Chemical class CS(=O)(=O)C1=CC=CC=C1N1C(=O)NC(=O)C2=CC=CN=C21 LMJBHQBOPUCWML-UHFFFAOYSA-N 0.000 description 1
- OWLJFADHVWHGPG-UHFFFAOYSA-N 1-(3-chloroanilino)-2h-pyridine-3-carboxamide Chemical compound C1C(C(=O)N)=CC=CN1NC1=CC=CC(Cl)=C1 OWLJFADHVWHGPG-UHFFFAOYSA-N 0.000 description 1
- JZJKXAYUMVPBIL-UHFFFAOYSA-N 1-(3-chlorophenyl)pyrido[2,3-d]pyrimidine-2,4-dione Chemical compound ClC1=CC=CC(N2C(NC(=O)C3=CC=CN=C32)=O)=C1 JZJKXAYUMVPBIL-UHFFFAOYSA-N 0.000 description 1
- IIBRIHBGMXSWGI-UHFFFAOYSA-N 1-(3-cyanoanilino)-2h-pyridine-3-carboxamide Chemical compound C1C(C(=O)N)=CC=CN1NC1=CC=CC(C#N)=C1 IIBRIHBGMXSWGI-UHFFFAOYSA-N 0.000 description 1
- LPPJLEJIXTYPLI-UHFFFAOYSA-N 1-(3-fluorophenyl)-3-(pyridin-4-ylmethyl)pyrido[2,3-d]pyrimidine-2,4-dione Chemical compound FC1=CC=CC(N2C(N(CC=3C=CN=CC=3)C(=O)C3=CC=CN=C32)=O)=C1 LPPJLEJIXTYPLI-UHFFFAOYSA-N 0.000 description 1
- CGKFYXYFMYVHQW-UHFFFAOYSA-N 1-(3-fluorophenyl)pyrido[2,3-d]pyrimidine-2,4-dione Chemical compound FC1=CC=CC(N2C(NC(=O)C3=CC=CN=C32)=O)=C1 CGKFYXYFMYVHQW-UHFFFAOYSA-N 0.000 description 1
- NOYDSUBGNSMYIE-UHFFFAOYSA-N 1-(3-methylsulfanylanilino)-2h-pyridine-3-carboxamide Chemical compound CSC1=CC=CC(NN2C=CC=C(C2)C(N)=O)=C1 NOYDSUBGNSMYIE-UHFFFAOYSA-N 0.000 description 1
- XITNDRCZVAAUJJ-UHFFFAOYSA-N 1-(3-methylsulfanylphenyl)pyrido[2,3-d]pyrimidine-2,4-dione Chemical compound CSC1=CC=CC(N2C(NC(=O)C3=CC=CN=C32)=O)=C1 XITNDRCZVAAUJJ-UHFFFAOYSA-N 0.000 description 1
- GAJZKAXROBUCME-UHFFFAOYSA-N 1-(3-methylsulfinylphenyl)-3-(pyridin-4-ylmethyl)pyrido[2,3-d]pyrimidine-2,4-dione Chemical compound CS(=O)C1=CC=CC(N2C(N(CC=3C=CN=CC=3)C(=O)C3=CC=CN=C32)=O)=C1 GAJZKAXROBUCME-UHFFFAOYSA-N 0.000 description 1
- NEHOYJQSYJOLET-UHFFFAOYSA-N 1-(3-nitrophenyl)-3-(pyridin-2-ylmethyl)pyrido[2,3-d]pyrimidine-2,4-dione Chemical compound [O-][N+](=O)C1=CC=CC(N2C(N(CC=3N=CC=CC=3)C(=O)C3=CC=CN=C32)=O)=C1 NEHOYJQSYJOLET-UHFFFAOYSA-N 0.000 description 1
- UXMGWWASSFIEHE-UHFFFAOYSA-N 1-(3-nitrophenyl)-3-(pyridin-4-ylmethyl)-4h-pyrido[2,3-d]pyrimidin-2-one Chemical compound [O-][N+](=O)C1=CC=CC(N2C3=NC=CC=C3CN(CC=3C=CN=CC=3)C2=O)=C1 UXMGWWASSFIEHE-UHFFFAOYSA-N 0.000 description 1
- ILDVYSSPLJLKIZ-UHFFFAOYSA-N 1-(3-nitrophenyl)-3-(quinolin-2-ylmethyl)-4h-pyrido[2,3-d]pyrimidin-2-one Chemical compound [O-][N+](=O)C1=CC=CC(N2C3=NC=CC=C3CN(CC=3N=C4C=CC=CC4=CC=3)C2=O)=C1 ILDVYSSPLJLKIZ-UHFFFAOYSA-N 0.000 description 1
- CLCSIZYOXWVPIA-UHFFFAOYSA-N 1-(3-nitrophenyl)-3-(quinolin-2-ylmethyl)pyrido[2,3-d]pyrimidine-2,4-dione Chemical compound [O-][N+](=O)C1=CC=CC(N2C(N(CC=3N=C4C=CC=CC4=CC=3)C(=O)C3=CC=CN=C32)=O)=C1 CLCSIZYOXWVPIA-UHFFFAOYSA-N 0.000 description 1
- NTQPDBHBERZZGK-UHFFFAOYSA-N 1-(4-methyl-3-nitroanilino)-2h-pyridine-3-carboxamide Chemical compound C1=C([N+]([O-])=O)C(C)=CC=C1NN1C=CC=C(C(N)=O)C1 NTQPDBHBERZZGK-UHFFFAOYSA-N 0.000 description 1
- GVFXWELSLNNCTN-UHFFFAOYSA-N 1-(4-methyl-3-nitrophenyl)pyrido[2,3-d]pyrimidine-2,4-dione Chemical compound C1=C([N+]([O-])=O)C(C)=CC=C1N1C(=O)NC(=O)C2=CC=CN=C21 GVFXWELSLNNCTN-UHFFFAOYSA-N 0.000 description 1
- VWVZFHRDLPHBEG-UHFFFAOYSA-N 1-(chloromethyl)-4-methylsulfanylbenzene Chemical group CSC1=CC=C(CCl)C=C1 VWVZFHRDLPHBEG-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- XWMANWBPRFZVFB-UHFFFAOYSA-N 1-[3-(hydroxymethyl)phenyl]-3-(pyridin-3-ylmethyl)pyrido[2,3-d]pyrimidine-2,4-dione Chemical compound OCC1=CC=CC(N2C(N(CC=3C=NC=CC=3)C(=O)C3=CC=CN=C32)=O)=C1 XWMANWBPRFZVFB-UHFFFAOYSA-N 0.000 description 1
- BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-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
- NMELLURGURSXPO-UHFFFAOYSA-N 1h-1,6-naphthyridine-2,4-dione Chemical compound N1=CC=C2NC(=O)CC(=O)C2=C1 NMELLURGURSXPO-UHFFFAOYSA-N 0.000 description 1
- MHHOMHMNIRXARC-UHFFFAOYSA-N 1h-pyrido[2,3-d]pyrimidin-2-one Chemical class C1=CN=C2NC(=O)N=CC2=C1 MHHOMHMNIRXARC-UHFFFAOYSA-N 0.000 description 1
- SDQJTWBNWQABLE-UHFFFAOYSA-N 1h-quinazoline-2,4-dione Chemical compound C1=CC=C2C(=O)NC(=O)NC2=C1 SDQJTWBNWQABLE-UHFFFAOYSA-N 0.000 description 1
- ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 description 1
- FDXXZCRKXFGQPP-UHFFFAOYSA-N 2-(2,4-dioxopyrido[2,3-d]pyrimidin-1-yl)-n,n-dimethylbenzamide Chemical class CN(C)C(=O)C1=CC=CC=C1N1C(=O)NC(=O)C2=CC=CN=C21 FDXXZCRKXFGQPP-UHFFFAOYSA-N 0.000 description 1
- RPCFQCWDCOHBQY-UHFFFAOYSA-N 2-(3-acetylanilino)pyridine-3-carboxylic acid Chemical compound CC(=O)C1=CC=CC(NC=2C(=CC=CN=2)C(O)=O)=C1 RPCFQCWDCOHBQY-UHFFFAOYSA-N 0.000 description 1
- YDZJBTQPTZTCAT-UHFFFAOYSA-N 2-(3-cyanoanilino)pyridine-3-carboxamide Chemical compound NC(=O)C1=CC=CN=C1NC1=CC=CC(C#N)=C1 YDZJBTQPTZTCAT-UHFFFAOYSA-N 0.000 description 1
- NCFQWKWKPWAUFB-UHFFFAOYSA-N 2-(3-cyanoanilino)pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=C1NC1=CC=CC(C#N)=C1 NCFQWKWKPWAUFB-UHFFFAOYSA-N 0.000 description 1
- VIKDAUKRCJFPLV-UHFFFAOYSA-N 2-(3-methylsulfanylanilino)pyridine-3-carboxamide Chemical compound CSC1=CC=CC(NC=2C(=CC=CN=2)C(N)=O)=C1 VIKDAUKRCJFPLV-UHFFFAOYSA-N 0.000 description 1
- OSBQBRNMQSMSFD-UHFFFAOYSA-N 2-(4-methyl-3-nitroanilino)pyridine-3-carboxamide Chemical compound C1=C([N+]([O-])=O)C(C)=CC=C1NC1=NC=CC=C1C(N)=O OSBQBRNMQSMSFD-UHFFFAOYSA-N 0.000 description 1
- WYBYKMDKJNGTKE-UHFFFAOYSA-N 2-(4-methyl-3-nitroanilino)pyridine-3-carboxylic acid Chemical compound C1=C([N+]([O-])=O)C(C)=CC=C1NC1=NC=CC=C1C(O)=O WYBYKMDKJNGTKE-UHFFFAOYSA-N 0.000 description 1
- NJWIMFZLESWFIM-UHFFFAOYSA-N 2-(chloromethyl)pyridine Chemical compound ClCC1=CC=CC=N1 NJWIMFZLESWFIM-UHFFFAOYSA-N 0.000 description 1
- DDEAEWMDOSXKBX-UHFFFAOYSA-N 2-(chloromethyl)quinoline Chemical compound C1=CC=CC2=NC(CCl)=CC=C21 DDEAEWMDOSXKBX-UHFFFAOYSA-N 0.000 description 1
- ULQQGOGMQRGFFR-UHFFFAOYSA-N 2-chlorobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC=CC=C1Cl ULQQGOGMQRGFFR-UHFFFAOYSA-N 0.000 description 1
- CKQHAYFOPRIUOM-UHFFFAOYSA-N 3'-Aminoacetophenone Chemical compound CC(=O)C1=CC=CC(N)=C1 CKQHAYFOPRIUOM-UHFFFAOYSA-N 0.000 description 1
- KLPUJWLQGMDXDV-UHFFFAOYSA-N 3,4-dihydro-1h-1,6-naphthyridin-2-one Chemical class N1=CC=C2NC(=O)CCC2=C1 KLPUJWLQGMDXDV-UHFFFAOYSA-N 0.000 description 1
- SEYKDMQFAOGRJK-UHFFFAOYSA-N 3-[2,4-dioxo-3-(pyridin-4-ylmethyl)pyrido[2,3-d]pyrimidin-1-yl]benzamide Chemical compound NC(=O)C1=CC=CC(N2C(N(CC=3C=CN=CC=3)C(=O)C3=CC=CN=C32)=O)=C1 SEYKDMQFAOGRJK-UHFFFAOYSA-N 0.000 description 1
- NJXPYZHXZZCTNI-UHFFFAOYSA-N 3-aminobenzonitrile Chemical compound NC1=CC=CC(C#N)=C1 NJXPYZHXZZCTNI-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- RQDSQUBWIDXELE-UHFFFAOYSA-N 3-benzyl-1-(3-nitrophenyl)-4h-pyrido[2,3-d]pyrimidin-2-one Chemical compound [O-][N+](=O)C1=CC=CC(N2C3=NC=CC=C3CN(CC=3C=CC=CC=3)C2=O)=C1 RQDSQUBWIDXELE-UHFFFAOYSA-N 0.000 description 1
- PNPCRKVUWYDDST-UHFFFAOYSA-N 3-chloroaniline Chemical compound NC1=CC=CC(Cl)=C1 PNPCRKVUWYDDST-UHFFFAOYSA-N 0.000 description 1
- KCHLDNLIJVSRPK-UHFFFAOYSA-N 3-methylsulfanylaniline Chemical compound CSC1=CC=CC(N)=C1 KCHLDNLIJVSRPK-UHFFFAOYSA-N 0.000 description 1
- XJCVRTZCHMZPBD-UHFFFAOYSA-N 3-nitroaniline Chemical compound NC1=CC=CC([N+]([O-])=O)=C1 XJCVRTZCHMZPBD-UHFFFAOYSA-N 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- WZIYCIBURCPKAR-UHFFFAOYSA-N 4-(chloromethyl)pyridine Chemical group ClCC1=CC=NC=C1 WZIYCIBURCPKAR-UHFFFAOYSA-N 0.000 description 1
- GDIIPKWHAQGCJF-UHFFFAOYSA-N 4-Amino-2-nitrotoluene Chemical compound CC1=CC=C(N)C=C1[N+]([O-])=O GDIIPKWHAQGCJF-UHFFFAOYSA-N 0.000 description 1
- 102000004008 5'-Nucleotidase Human genes 0.000 description 1
- OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 244000291564 Allium cepa Species 0.000 description 1
- 235000002732 Allium cepa var. cepa Nutrition 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 108010062580 Concanavalin A Proteins 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 241000271537 Crotalus atrox Species 0.000 description 1
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical class [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 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
- 241000551547 Dione <red algae> Species 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 206010014025 Ear swelling Diseases 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- 206010020751 Hypersensitivity 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
- 229930182816 L-glutamine Natural products 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000186359 Mycobacterium Species 0.000 description 1
- 240000001307 Myosotis scorpioides Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 1
- 239000012425 OXONE® Substances 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 239000005662 Paraffin oil Substances 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229940099471 Phosphodiesterase inhibitor Drugs 0.000 description 1
- 235000017284 Pometia pinnata Nutrition 0.000 description 1
- 240000007653 Pometia tomentosa Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000176725 Pyrops Species 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 208000009205 Tinnitus Diseases 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- PNNAKABJIIIATC-UHFFFAOYSA-N [N+](=O)([O-])N1C(N(C2=C(C1)C=CC=N2)C1=CC(=CC=C1)[N+](=O)[O-])=O Chemical compound [N+](=O)([O-])N1C(N(C2=C(C1)C=CC=N2)C1=CC(=CC=C1)[N+](=O)[O-])=O PNNAKABJIIIATC-UHFFFAOYSA-N 0.000 description 1
- 229940008309 acetone / ethanol Drugs 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical group [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 230000003474 anti-emetic effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 229940125683 antiemetic agent Drugs 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000001722 carbon compounds Chemical class 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000002826 coolant Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000007368 endocrine function Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 239000011521 glass Substances 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
- 230000008588 hemolysis Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 210000005104 human peripheral blood lymphocyte Anatomy 0.000 description 1
- 125000001145 hydrido group Chemical group *[H] 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- UKOWSVWWNOROMJ-UHFFFAOYSA-N methyl 3-[(3-carbamoylpyridin-2-yl)amino]benzoate Chemical compound COC(=O)C1=CC=CC(NC=2C(=CC=CN=2)C(N)=O)=C1 UKOWSVWWNOROMJ-UHFFFAOYSA-N 0.000 description 1
- VZDNXXPBYLGWOS-UHFFFAOYSA-N methyl 3-aminobenzoate Chemical compound COC(=O)C1=CC=CC(N)=C1 VZDNXXPBYLGWOS-UHFFFAOYSA-N 0.000 description 1
- VYPPZXZHYDSBSJ-UHFFFAOYSA-N methyl 6-methylpyridine-3-carboxylate Chemical compound COC(=O)C1=CC=C(C)N=C1 VYPPZXZHYDSBSJ-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000002297 mitogenic effect Effects 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- SUJVKLGPMOZVMV-UHFFFAOYSA-N n-[3-(aminomethyl)pyridin-2-yl]-n-phenylnitramide Chemical compound NCC1=CC=CN=C1N([N+]([O-])=O)C1=CC=CC=C1 SUJVKLGPMOZVMV-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 230000005375 negative regulation of lymphocyte activation Effects 0.000 description 1
- 229960003057 nialamide Drugs 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229940124641 pain reliever Drugs 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- OKBMCNHOEMXPTM-UHFFFAOYSA-M potassium peroxymonosulfate Chemical compound [K+].OOS([O-])(=O)=O OKBMCNHOEMXPTM-UHFFFAOYSA-M 0.000 description 1
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004673 propylcarbonyl group Chemical group 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 108010043671 prostatic acid phosphatase Proteins 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000011369 resultant mixture Substances 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000012279 sodium borohydride Chemical class 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 238000005556 structure-activity relationship Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000012134 supernatant fraction Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 231100000886 tinnitus Toxicity 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
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 239000002435 venom Substances 0.000 description 1
- 210000001048 venom Anatomy 0.000 description 1
- 231100000611 venom Toxicity 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Pulmonology (AREA)
- Neurology (AREA)
- Transplantation (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/855,179 US5264437A (en) | 1992-03-20 | 1992-03-20 | Optionally substituted pyrido[2,3-d]pyridine-2,4(1H,3H)-diones and pyrido[2,]pyrimidine-2(1H,3H)-ones |
| US85517992 | 1992-03-20 | ||
| US9302273 | 1993-03-18 | ||
| PCT/US1993/002273 WO1993019068A1 (en) | 1992-03-20 | 1993-03-18 | PYRIDO[2,3-d]PYRIMIDINE DERIVATIVES AS PHOSPHODIESTERASE INHIBITORS |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI944305L FI944305L (fi) | 1994-09-16 |
| FI944305A0 FI944305A0 (fi) | 1994-09-16 |
| FI106960B true FI106960B (fi) | 2001-05-15 |
Family
ID=25320543
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI944305A FI106960B (fi) | 1992-03-20 | 1994-09-16 | Menetelmä terapeuttisesti aktiivisten 1-fenyyli-pyrido[2,3-d]pyrimidiini-2,4-dioni- ja 2-onijohdannaisten valmistamiseksi |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US5264437A (OSRAM) |
| EP (2) | EP0631580A1 (OSRAM) |
| JP (1) | JP3241384B2 (OSRAM) |
| KR (1) | KR100274104B1 (OSRAM) |
| CN (1) | CN1040327C (OSRAM) |
| AU (1) | AU669520B2 (OSRAM) |
| CA (1) | CA2132297C (OSRAM) |
| FI (1) | FI106960B (OSRAM) |
| HU (2) | HUT67552A (OSRAM) |
| IL (1) | IL105092A (OSRAM) |
| MX (1) | MX9301530A (OSRAM) |
| NO (1) | NO301763B1 (OSRAM) |
| NZ (1) | NZ251525A (OSRAM) |
| TW (1) | TW240226B (OSRAM) |
| WO (1) | WO1993019068A1 (OSRAM) |
| ZA (1) | ZA931945B (OSRAM) |
Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5672622A (en) * | 1994-04-21 | 1997-09-30 | Berlex Laboratories, Inc. | Treatment of multiple sclerosis |
| US6060501A (en) * | 1994-06-02 | 2000-05-09 | Schering Aktiengesellschaft | Combined treatment of multiple sclerosis |
| US5817670A (en) * | 1994-08-29 | 1998-10-06 | Yamanouchi Pharmaceutical Co., Ltd. | Naphthyridine derivatives and pharmaceutical compositions thereof |
| IL117090A (en) * | 1995-02-10 | 2000-07-26 | Schering Ag | Pharmaceutical compositions containing oxazolidinone derivatives |
| DE19540475A1 (de) * | 1995-10-20 | 1997-04-24 | Schering Ag | Chirale Methylphenyloxazolidinone |
| NZ322197A (en) * | 1995-11-21 | 1999-02-25 | Yamanouchi Pharma Co Ltd | Pyrido[2,3-d] pyrimidine derivatives and pharmaceutical compositions thereof |
| WO2001013953A2 (en) | 1999-08-21 | 2001-03-01 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Synergistic combination of pde inhibitors and beta 2 adrenoceptor agonist |
| JP2000119272A (ja) | 1998-10-15 | 2000-04-25 | Nippon Zoki Pharmaceut Co Ltd | 新規７−アミノピリド〔２，３−ｄ〕ピリミジン誘導体 |
| US6455554B1 (en) | 1999-06-07 | 2002-09-24 | Targacept, Inc. | Oxopyridinyl pharmaceutical compositions and methods for use |
| TWI243055B (en) | 2000-04-13 | 2005-11-11 | Nippon Zoki Pharmaceutical Co | Pharmaceutical composition for use in treatment of dermatitis |
| US6825180B2 (en) * | 2001-05-18 | 2004-11-30 | Cell Therapeutics, Inc. | Pyridopyrimidine compounds and their uses |
| US7183288B2 (en) * | 2001-11-01 | 2007-02-27 | Herwig Josephus Margareta Janssen, legal representative | Amide derivatives as glycogen synthase kinase 3-β inhibitors |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| WO2004087211A2 (en) | 2003-04-01 | 2004-10-14 | Applied Research Systems Ars Holding N.V. | Inhibitors of phosphodiesterases in infertility |
| WO2006019965A2 (en) * | 2004-07-16 | 2006-02-23 | Takeda San Diego, Inc. | Dipeptidyl peptidase inhibitors |
| TW200726767A (en) * | 2005-07-04 | 2007-07-16 | Astrazeneca Ab | Chemical compounds 2 |
| TW200800997A (en) * | 2006-03-22 | 2008-01-01 | Astrazeneca Ab | Chemical compounds |
| AU2007297212B8 (en) * | 2006-09-15 | 2011-04-28 | Pfizer Products Inc. | Pyrido (2, 3-d) pyrimidinone compounds and their use as pi3 inhibitors |
| SA08280783B1 (ar) * | 2007-01-11 | 2011-04-24 | استرازينيكا ايه بي | مشتقات بيريدوبيريميدين كمثبطات pde4 |
| TW200835497A (en) * | 2007-01-11 | 2008-09-01 | Astrazeneca Ab | Chemical compounds 636 |
| WO2008084236A1 (en) * | 2007-01-11 | 2008-07-17 | Astrazeneca Ab | Chemical compounds 635 : pyridopyrimidinediones as pde4 inhibitors |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| AU2008261102B2 (en) | 2007-06-04 | 2013-11-28 | Bausch Health Ireland Limited | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| US8034782B2 (en) | 2008-07-16 | 2011-10-11 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| FR2921926B1 (fr) * | 2007-10-03 | 2009-12-04 | Sanofi Aventis | Derives de quinazolinedione,leur preparation et leurs applications therapeutiques. |
| PL2297106T3 (pl) | 2008-05-27 | 2015-01-30 | Galderma Sa | Pochodne fenoksypirydynyloamidu i ich zastosowania w leczeniu chorób, w których pośredniczy pde4 |
| CA2930674A1 (en) | 2008-06-04 | 2009-12-10 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| FR2944282B1 (fr) | 2009-04-09 | 2013-05-03 | Sanofi Aventis | Derives de quinazolinedione, leur preparation et leurs diverses applications therapeutiques |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| CA2828346C (en) | 2011-03-01 | 2021-01-26 | Synergy Pharmaceuticals Inc. | Process of preparing guanylate cyclase c agonists |
| CA2902348C (en) | 2013-02-25 | 2021-11-30 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase and their uses |
| US9486494B2 (en) | 2013-03-15 | 2016-11-08 | Synergy Pharmaceuticals, Inc. | Compositions useful for the treatment of gastrointestinal disorders |
| EP2970384A1 (en) | 2013-03-15 | 2016-01-20 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase and their uses |
| EP4424697A3 (en) | 2013-06-05 | 2024-12-25 | Bausch Health Ireland Limited | Ultra-pure agonists of guanylate cyclase c, method of making and using same |
| EP3492106B1 (en) | 2013-08-09 | 2021-02-17 | Ardelyx, Inc. | Compounds and methods for inhibiting phosphate transport |
| EP3972599B1 (en) | 2019-05-21 | 2025-10-22 | Ardelyx, Inc. | Combination for lowering serum phosphate in a patient |
| JPWO2023042879A1 (OSRAM) * | 2021-09-17 | 2023-03-23 | ||
| CN113831491B (zh) * | 2021-09-30 | 2023-03-24 | 南昌大学 | 一种嘧啶唑共价有机框架的制备方法及吸附应用 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5649917B2 (OSRAM) * | 1973-12-18 | 1981-11-25 | ||
| JPS58428B2 (ja) * | 1974-07-05 | 1983-01-06 | ヒサミツセイヤク カブシキガイシヤ | シンキナ ２− オキソ −１，２，３，４− テトラヒドロピリド （ ２，３−ｄ ） ピリミジンユウドウタイノ セイゾウホウ |
| DE2523730A1 (de) * | 1974-06-12 | 1976-02-12 | Hisamitsu Pharmaceutical Co | Pyrido eckige klammer auf 2,3-d eckige klammer zu pyrimidinonen |
| ES2031513T3 (es) * | 1986-08-21 | 1992-12-16 | Pfizer Inc. | Quinazolindionas y piridopirimidinadionas. |
| JPH07506369A (ja) * | 1992-04-29 | 1995-07-13 | エス・アール・アイ・インターナシヨナル | 炎症を処置するためのデアザアミノプテリン |
-
1992
- 1992-03-20 US US07/855,179 patent/US5264437A/en not_active Expired - Lifetime
-
1993
- 1993-03-18 KR KR1019940703294A patent/KR100274104B1/ko not_active Expired - Fee Related
- 1993-03-18 JP JP51663493A patent/JP3241384B2/ja not_active Expired - Fee Related
- 1993-03-18 WO PCT/US1993/002273 patent/WO1993019068A1/en not_active Ceased
- 1993-03-18 CA CA002132297A patent/CA2132297C/en not_active Expired - Fee Related
- 1993-03-18 MX MX9301530A patent/MX9301530A/es not_active IP Right Cessation
- 1993-03-18 EP EP93908322A patent/EP0631580A1/en not_active Ceased
- 1993-03-18 EP EP05023665A patent/EP1770093A1/en not_active Withdrawn
- 1993-03-18 IL IL105092A patent/IL105092A/en not_active IP Right Cessation
- 1993-03-18 ZA ZA931945A patent/ZA931945B/xx unknown
- 1993-03-18 TW TW082101993A patent/TW240226B/zh active
- 1993-03-18 NZ NZ251525A patent/NZ251525A/en unknown
- 1993-03-18 CN CN93103352A patent/CN1040327C/zh not_active Expired - Fee Related
- 1993-03-18 AU AU39186/93A patent/AU669520B2/en not_active Ceased
- 1993-03-18 HU HU9402653A patent/HUT67552A/hu unknown
-
1994
- 1994-09-16 NO NO943456A patent/NO301763B1/no not_active IP Right Cessation
- 1994-09-16 FI FI944305A patent/FI106960B/fi not_active IP Right Cessation
-
1995
- 1995-04-24 HU HU95P/P00114P patent/HU210873A9/hu unknown
Also Published As
| Publication number | Publication date |
|---|---|
| HU210873A9 (en) | 1995-08-28 |
| MX9301530A (es) | 1994-01-31 |
| HUT67552A (en) | 1995-04-28 |
| NO943456L (no) | 1994-09-16 |
| NZ251525A (en) | 1996-09-25 |
| EP1770093A1 (en) | 2007-04-04 |
| WO1993019068A1 (en) | 1993-09-30 |
| KR100274104B1 (ko) | 2000-12-15 |
| CA2132297C (en) | 2006-01-03 |
| AU669520B2 (en) | 1996-06-13 |
| CA2132297A1 (en) | 1993-09-30 |
| IL105092A (en) | 1998-06-15 |
| IL105092A0 (en) | 1993-07-08 |
| ZA931945B (en) | 1994-09-18 |
| JP3241384B2 (ja) | 2001-12-25 |
| TW240226B (OSRAM) | 1995-02-11 |
| FI944305L (fi) | 1994-09-16 |
| EP0631580A1 (en) | 1995-01-04 |
| AU3918693A (en) | 1993-10-21 |
| KR950700909A (ko) | 1995-02-20 |
| HU9402653D0 (en) | 1994-11-28 |
| CN1078470A (zh) | 1993-11-17 |
| CN1040327C (zh) | 1998-10-21 |
| FI944305A0 (fi) | 1994-09-16 |
| NO943456D0 (no) | 1994-09-16 |
| US5264437A (en) | 1993-11-23 |
| JPH07504676A (ja) | 1995-05-25 |
| NO301763B1 (no) | 1997-12-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| FI106960B (fi) | Menetelmä terapeuttisesti aktiivisten 1-fenyyli-pyrido[2,3-d]pyrimidiini-2,4-dioni- ja 2-onijohdannaisten valmistamiseksi | |
| AU2019201352B2 (en) | Bromodomain inhibitors | |
| AU2004268625B2 (en) | Aryloxy and arylalkyleneoxy substituted imidazoquinolines | |
| JP5820882B2 (ja) | キナーゼインヒビターとしてのキノリン及びキノキサリン誘導体 | |
| CA2446820C (en) | Novel pyrrole derivatives as pharmaceutical agents | |
| KR20220068243A (ko) | 포스포디에스테라제 억제제 및 용도 | |
| JP3110765B2 (ja) | ピリド［２，３−ｄ］ピリミジン誘導体及びその医薬組成物 | |
| CZ292311B6 (cs) | Pyridazinové deriváty, způsob jejich výroby a farmaceutické prostředky, které je obsahují | |
| JP2022526854A (ja) | ホスファチジルイノシトール３－キナーゼ阻害剤 | |
| JP2006519877A (ja) | １−アミノ１ｈ−イミダゾキノリン | |
| AU2018391833A1 (en) | Compound functioning as bromodomain protein inhibitor, and composition | |
| EP2222661A2 (en) | Non-nucleoside reverse transcriptase inhibitors | |
| CZ20012338A3 (cs) | Imidazolové sloučeniny | |
| CN115151550B (zh) | 外核苷酸焦磷酸酶/磷酸二酯酶1(enpp1)调节剂及其用途 | |
| FR2479225A1 (fr) | Imidazopyridines, leur preparation et leur utilisation comme agents cardiotoniques | |
| EP4332101A1 (en) | Methionine adenosyltransferase inhibitor, preparation method therefor and application thereof | |
| CZ20011981A3 (cs) | Sulfonamidové sloučeniny | |
| SU1362402A3 (ru) | Способ получени производных имидазола или их солей с кислотами | |
| EP3810597B1 (en) | 1,2,4-triazole derivatives as tankyrase inhibitors | |
| EA007226B1 (ru) | Производные имидазохинолина | |
| EP4578857A1 (en) | Cryptolepine salt derivative, and preparation method therefor and use thereof | |
| US20040158066A1 (en) | Novel pyridylmethylaminopyrimidines | |
| JPWO2019078246A1 (ja) | Ｉｄｏ／ｔｄｏ阻害剤 | |
| CN118994146A (zh) | 一类含吡啶并环结构的化合物及其作为泛素特异性蛋白酶1抑制剂的用途 | |
| EP4501912A1 (en) | Novel heterocyclic compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MA | Patent expired |