IL105092A

IL105092A - 1-PHENYL-3- (HETEROARYLALKYL) PYRIDO (2,3-d) PYRIMIDINE-2,4- (1H, 3H)-DIONE AND PYRIDO £2,3-d| PYRIMIDINE-2- (1H, 3H)-ONE DERIVATIVES, THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

1-PHENYL-3- (HETEROARYLALKYL) PYRIDO (2,3-d) PYRIMIDINE-2,4- (1H, 3H)-DIONE AND PYRIDO £2,3-d| PYRIMIDINE-2- (1H, 3H)-ONE DERIVATIVES, THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

Info

Publication number: IL105092A
Authority: IL; Israel
Prior art keywords: pyrido; pyrimidine; formula; dione; pyridylmethyl
Prior art date: 1992-03-20

Application number

IL105092A

Other languages

English (en)

Other versions

IL105092A0 (en

Original Assignee

Syntex Inc

Priority date

1992-03-20

Filing date

1993-03-18

Publication date

1998-06-15

1993-03-18 Application filed by Syntex Inc filed Critical Syntex Inc

1993-07-08 Publication of IL105092A0 publication Critical patent/IL105092A0/xx

1998-06-15 Publication of IL105092A publication Critical patent/IL105092A/en

Links

239000008194 pharmaceutical composition Substances 0.000 title claims description 14
238000002360 preparation method Methods 0.000 title description 86
JQPYINKVAWEQDQ-UHFFFAOYSA-N 1h-pyrido[2,3-d]pyrimidine-2,4-dione Chemical compound C1=CC=C2C(=O)NC(=O)NC2=N1 JQPYINKVAWEQDQ-UHFFFAOYSA-N 0.000 title description 21
-1 carboxy, methoxycarbonyl Chemical group 0.000 claims description 223
150000001875 compounds Chemical class 0.000 claims description 157
UDJFFSGCRRMVFH-UHFFFAOYSA-N pyrido[2,3-d]pyrimidine Chemical compound N1=CN=CC2=CC=CN=C21 UDJFFSGCRRMVFH-UHFFFAOYSA-N 0.000 claims description 103
238000000034 method Methods 0.000 claims description 89
HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 claims description 86
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 41
239000001257 hydrogen Substances 0.000 claims description 36
229910052739 hydrogen Inorganic materials 0.000 claims description 36
125000000217 alkyl group Chemical group 0.000 claims description 31
DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 claims description 30
150000003839 salts Chemical class 0.000 claims description 26
239000003814 drug Substances 0.000 claims description 25
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 20
125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 18
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 16
241000124008 Mammalia Species 0.000 claims description 15
125000001072 heteroaryl group Chemical group 0.000 claims description 15
230000008569 process Effects 0.000 claims description 14
125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 claims description 13
150000001204 N-oxides Chemical class 0.000 claims description 12
125000005843 halogen group Chemical group 0.000 claims description 12
150000002148 esters Chemical class 0.000 claims description 11
239000000546 pharmaceutical excipient Substances 0.000 claims description 11
208000023275 Autoimmune disease Diseases 0.000 claims description 10
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
208000006673 asthma Diseases 0.000 claims description 7
125000004093 cyano group Chemical group *C#N 0.000 claims description 7
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 7
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 7
125000001309 chloro group Chemical group Cl* 0.000 claims description 6
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 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
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 claims description 5
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 5
208000002193 Pain Diseases 0.000 claims description 4
125000001153 fluoro group Chemical group F* 0.000 claims description 4
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 4
230000036407 pain Effects 0.000 claims description 4
125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 3
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 3
125000004076 pyridyl group Chemical group 0.000 claims description 3
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
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 claims description 2
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 2
239000012458 free base Substances 0.000 claims description 2
208000027866 inflammatory disease Diseases 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
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 2
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 1
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 1
239000000243 solution Substances 0.000 description 94
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 76
239000002904 solvent Substances 0.000 description 72
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 66
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 64
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 61
125000004446 heteroarylalkyl group Chemical group 0.000 description 58
238000006243 chemical reaction Methods 0.000 description 56
239000011541 reaction mixture Substances 0.000 description 51
239000000203 mixture Substances 0.000 description 49
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 42
239000000725 suspension Substances 0.000 description 40
239000003153 chemical reaction reagent Substances 0.000 description 35
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
239000007787 solid Substances 0.000 description 32
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 31
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 28
235000019439 ethyl acetate Nutrition 0.000 description 26
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
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 23
239000000047 product Substances 0.000 description 22
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 21
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
239000012298 atmosphere Substances 0.000 description 18
201000010099 disease Diseases 0.000 description 18
238000003756 stirring Methods 0.000 description 18
239000003795 chemical substances by application Substances 0.000 description 17
238000009472 formulation Methods 0.000 description 17
102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 16
108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 16
238000003556 assay Methods 0.000 description 16
239000002244 precipitate Substances 0.000 description 15
238000001914 filtration Methods 0.000 description 14
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 13
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
241000699670 Mus sp. Species 0.000 description 12
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
229940079593 drug Drugs 0.000 description 12
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
239000012074 organic phase Substances 0.000 description 12
238000010992 reflux Methods 0.000 description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 11
230000004048 modification Effects 0.000 description 11
238000012986 modification Methods 0.000 description 11
238000000746 purification Methods 0.000 description 11
229940124597 therapeutic agent Drugs 0.000 description 11
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
230000003110 anti-inflammatory effect Effects 0.000 description 10
239000002585 base Substances 0.000 description 10
239000003638 chemical reducing agent Substances 0.000 description 10
230000000694 effects Effects 0.000 description 10
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
238000012746 preparative thin layer chromatography Methods 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
210000004027 cell Anatomy 0.000 description 9
230000006870 function Effects 0.000 description 9
210000000265 leukocyte Anatomy 0.000 description 9
239000000463 material Substances 0.000 description 9
229920006395 saturated elastomer Polymers 0.000 description 9
238000012360 testing method Methods 0.000 description 9
230000015572 biosynthetic process Effects 0.000 description 8
230000001506 immunosuppresive effect Effects 0.000 description 8
208000009329 Graft vs Host Disease Diseases 0.000 description 7
ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 7
229910052782 aluminium Inorganic materials 0.000 description 7
239000000872 buffer Substances 0.000 description 7
238000000605 extraction Methods 0.000 description 7
208000024908 graft versus host disease Diseases 0.000 description 7
239000004615 ingredient Substances 0.000 description 7
210000004698 lymphocyte Anatomy 0.000 description 7
229910052943 magnesium sulfate Inorganic materials 0.000 description 7
239000008188 pellet Substances 0.000 description 7
239000000829 suppository Substances 0.000 description 7
210000001519 tissue Anatomy 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
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 6
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
239000000010 aprotic solvent Substances 0.000 description 6
SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 6
239000002775 capsule Substances 0.000 description 6
229910052799 carbon Inorganic materials 0.000 description 6
239000013078 crystal Substances 0.000 description 6
230000005764 inhibitory process Effects 0.000 description 6
239000008101 lactose Substances 0.000 description 6
239000000843 powder Substances 0.000 description 6
239000011780 sodium chloride Substances 0.000 description 6
PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 6
229910000104 sodium hydride Inorganic materials 0.000 description 6
239000007858 starting material Substances 0.000 description 6
239000003826 tablet Substances 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
HXKWWDAWOMOFHB-UHFFFAOYSA-N 2-anilinopyridine-3-carboxamide Chemical class NC(=O)C1=CC=CN=C1NC1=CC=CC=C1 HXKWWDAWOMOFHB-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
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 5
ZDHKVKPZQKYREU-UHFFFAOYSA-N 4-(chloromethyl)pyridine;hydron;chloride Chemical compound Cl.ClCC1=CC=NC=C1 ZDHKVKPZQKYREU-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
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
239000002253 acid Substances 0.000 description 5
235000019270 ammonium chloride Nutrition 0.000 description 5
230000000202 analgesic effect Effects 0.000 description 5
239000000730 antalgic agent Substances 0.000 description 5
238000004587 chromatography analysis Methods 0.000 description 5
239000012043 crude product Substances 0.000 description 5
238000011534 incubation Methods 0.000 description 5
239000003112 inhibitor Substances 0.000 description 5
238000002955 isolation Methods 0.000 description 5
239000007788 liquid Substances 0.000 description 5
235000019359 magnesium stearate Nutrition 0.000 description 5
239000003921 oil Substances 0.000 description 5
235000019198 oils Nutrition 0.000 description 5
239000000126 substance Substances 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
IBRSSZOHCGUTHI-UHFFFAOYSA-N 2-chloropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=C1Cl IBRSSZOHCGUTHI-UHFFFAOYSA-N 0.000 description 4
QGKGASXQTBQINX-UHFFFAOYSA-N 3,4-dihydro-1h-pyrimidin-2-one Chemical class O=C1NCC=CN1 QGKGASXQTBQINX-UHFFFAOYSA-N 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
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
102000004190 Enzymes Human genes 0.000 description 4
108090000790 Enzymes Proteins 0.000 description 4
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
206010061218 Inflammation Diseases 0.000 description 4
241000699666 Mus <mouse, genus> Species 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
239000007868 Raney catalyst Substances 0.000 description 4
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
229910000564 Raney nickel Inorganic materials 0.000 description 4
229920002472 Starch Polymers 0.000 description 4
230000004913 activation Effects 0.000 description 4
239000000443 aerosol Substances 0.000 description 4
150000001450 anions Chemical class 0.000 description 4
210000004369 blood Anatomy 0.000 description 4
239000008280 blood Substances 0.000 description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
239000000969 carrier Substances 0.000 description 4
150000001768 cations Chemical class 0.000 description 4
OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 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
150000002431 hydrogen Chemical class 0.000 description 4
230000004054 inflammatory process Effects 0.000 description 4
239000003226 mitogen Substances 0.000 description 4
229910052757 nitrogen Inorganic materials 0.000 description 4
125000006501 nitrophenyl group Chemical group 0.000 description 4
229910000027 potassium carbonate Inorganic materials 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
230000035755 proliferation Effects 0.000 description 4
150000008513 pyrimidine-2,4(1H,3H)-diones Chemical class 0.000 description 4
210000002345 respiratory system Anatomy 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
239000011343 solid material Substances 0.000 description 4
210000000952 spleen Anatomy 0.000 description 4
239000008107 starch Substances 0.000 description 4
235000019698 starch Nutrition 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
DJCJOWDAAZEMCI-UHFFFAOYSA-N (6-methylpyridin-3-yl)methanol Chemical compound CC1=CC=C(CO)C=N1 DJCJOWDAAZEMCI-UHFFFAOYSA-N 0.000 description 3
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 3
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