ES2364328T3 - Compuesto de pirimidina y composición medicinal del mismo. - Google Patents
Compuesto de pirimidina y composición medicinal del mismo. Download PDFInfo
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- ES2364328T3 ES2364328T3 ES02802050T ES02802050T ES2364328T3 ES 2364328 T3 ES2364328 T3 ES 2364328T3 ES 02802050 T ES02802050 T ES 02802050T ES 02802050 T ES02802050 T ES 02802050T ES 2364328 T3 ES2364328 T3 ES 2364328T3
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- 239000000203 mixture Substances 0.000 title claims description 51
- 239000002131 composite material Substances 0.000 title 1
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 235
- 150000001875 compounds Chemical class 0.000 claims abstract description 209
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 56
- 150000003839 salts Chemical class 0.000 claims abstract description 50
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 44
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 36
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 36
- 239000012453 solvate Substances 0.000 claims abstract description 35
- 125000005843 halogen group Chemical group 0.000 claims abstract description 25
- 125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 12
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 11
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 9
- 125000003277 amino group Chemical group 0.000 claims abstract description 8
- 125000001424 substituent group Chemical group 0.000 claims abstract description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 6
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims abstract description 4
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims abstract description 3
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims abstract description 3
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims abstract description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 3
- 125000002541 furyl group Chemical group 0.000 claims abstract description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims abstract description 3
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 3
- 125000005412 pyrazyl group Chemical group 0.000 claims abstract description 3
- 125000005495 pyridazyl group Chemical group 0.000 claims abstract description 3
- 125000001544 thienyl group Chemical group 0.000 claims abstract description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 82
- 206010010774 Constipation Diseases 0.000 claims description 44
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 31
- 201000010099 disease Diseases 0.000 claims description 28
- 102000009346 Adenosine receptors Human genes 0.000 claims description 25
- 108050000203 Adenosine receptors Proteins 0.000 claims description 25
- 101150051188 Adora2a gene Proteins 0.000 claims description 23
- 101150078577 Adora2b gene Proteins 0.000 claims description 21
- 208000018737 Parkinson disease Diseases 0.000 claims description 15
- 230000013872 defecation Effects 0.000 claims description 13
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 13
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 13
- 239000000296 purinergic P1 receptor antagonist Substances 0.000 claims description 13
- 229940121359 adenosine receptor antagonist Drugs 0.000 claims description 12
- 208000008384 ileus Diseases 0.000 claims description 11
- 230000001737 promoting effect Effects 0.000 claims description 11
- 208000011231 Crohn disease Diseases 0.000 claims description 7
- 208000002249 Diabetes Complications Diseases 0.000 claims description 7
- 206010012655 Diabetic complications Diseases 0.000 claims description 7
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 7
- 229940122355 Insulin sensitizer Drugs 0.000 claims description 7
- 208000008589 Obesity Diseases 0.000 claims description 7
- 208000001132 Osteoporosis Diseases 0.000 claims description 7
- 230000001430 anti-depressive effect Effects 0.000 claims description 7
- 239000000935 antidepressant agent Substances 0.000 claims description 7
- 229940005513 antidepressants Drugs 0.000 claims description 7
- 239000003472 antidiabetic agent Substances 0.000 claims description 7
- 239000002220 antihypertensive agent Substances 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 208000006673 asthma Diseases 0.000 claims description 7
- 239000002934 diuretic Substances 0.000 claims description 7
- 229940126904 hypoglycaemic agent Drugs 0.000 claims description 7
- 235000020824 obesity Nutrition 0.000 claims description 7
- 208000024827 Alzheimer disease Diseases 0.000 claims description 6
- 208000002705 Glucose Intolerance Diseases 0.000 claims description 6
- 206010018429 Glucose tolerance impaired Diseases 0.000 claims description 6
- 206010012601 diabetes mellitus Diseases 0.000 claims description 6
- 206010010356 Congenital anomaly Diseases 0.000 claims description 5
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 5
- 230000004064 dysfunction Effects 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- GIIUUEOCDDLBQZ-UHFFFAOYSA-N 5-[2-amino-4-(3-fluorophenyl)pyrimidin-5-yl]-1-methylpyridin-2-one Chemical compound C1=CC(=O)N(C)C=C1C1=CN=C(N)N=C1C1=CC=CC(F)=C1 GIIUUEOCDDLBQZ-UHFFFAOYSA-N 0.000 claims description 3
- IYBPHHBXSLOGND-UHFFFAOYSA-N 5-[2-amino-4-(3-fluorophenyl)pyrimidin-5-yl]-1h-pyridin-2-one Chemical compound C=1C=CC(F)=CC=1C1=NC(N)=NC=C1C=1C=CC(=O)NC=1 IYBPHHBXSLOGND-UHFFFAOYSA-N 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- LXMGWNGPIIDYEZ-UHFFFAOYSA-N 5-(2-amino-4-phenylpyrimidin-5-yl)-1-methylpyridin-2-one Chemical compound C1=CC(=O)N(C)C=C1C1=CN=C(N)N=C1C1=CC=CC=C1 LXMGWNGPIIDYEZ-UHFFFAOYSA-N 0.000 claims description 2
- KXDNYLRDVSRARZ-UHFFFAOYSA-N 5-(2-amino-4-thiophen-2-ylpyrimidin-5-yl)-1-methylpyridin-2-one Chemical compound C1=CC(=O)N(C)C=C1C1=CN=C(N)N=C1C1=CC=CS1 KXDNYLRDVSRARZ-UHFFFAOYSA-N 0.000 claims description 2
- CTYOLHLKCVSGEG-UHFFFAOYSA-N 5-[2-amino-4,6-bis(furan-2-yl)pyrimidin-5-yl]-1-methylpyridin-2-one Chemical compound C1=CC(=O)N(C)C=C1C1=C(C=2OC=CC=2)N=C(N)N=C1C1=CC=CO1 CTYOLHLKCVSGEG-UHFFFAOYSA-N 0.000 claims description 2
- INNCIQWLGZENAG-UHFFFAOYSA-N 5-[2-amino-4-(furan-2-yl)pyrimidin-5-yl]-1-(2-pyrrol-1-ylethyl)pyridin-2-one Chemical compound C=1C=COC=1C1=NC(N)=NC=C1C(=C1)C=CC(=O)N1CCN1C=CC=C1 INNCIQWLGZENAG-UHFFFAOYSA-N 0.000 claims description 2
- LFOIYKKLYCWEDX-UHFFFAOYSA-N 5-[2-amino-4-(furan-2-yl)pyrimidin-5-yl]-1-benzylpyridin-2-one Chemical compound C=1C=COC=1C1=NC(N)=NC=C1C(=C1)C=CC(=O)N1CC1=CC=CC=C1 LFOIYKKLYCWEDX-UHFFFAOYSA-N 0.000 claims description 2
- RWOLMPQKNXRXFP-UHFFFAOYSA-N 5-[2-amino-4-(furan-2-yl)pyrimidin-5-yl]-1-ethylpyridin-2-one Chemical compound C1=CC(=O)N(CC)C=C1C1=CN=C(N)N=C1C1=CC=CO1 RWOLMPQKNXRXFP-UHFFFAOYSA-N 0.000 claims description 2
- KLQQNDZPIWTDSO-UHFFFAOYSA-N 5-[2-amino-4-(furan-2-yl)pyrimidin-5-yl]-1-methylpyridin-2-one Chemical compound C1=CC(=O)N(C)C=C1C1=CN=C(N)N=C1C1=CC=CO1 KLQQNDZPIWTDSO-UHFFFAOYSA-N 0.000 claims description 2
- LWPWANLSNUFFAH-UHFFFAOYSA-N 5-[2,4-diamino-6-(3-fluorophenyl)pyrimidin-5-yl]-1-methylpyridin-2-one Chemical compound C1=CC(=O)N(C)C=C1C1=C(N)N=C(N)N=C1C1=CC=CC(F)=C1 LWPWANLSNUFFAH-UHFFFAOYSA-N 0.000 claims 1
- WJNNXYLGOHCGCH-UHFFFAOYSA-N 5-[2-amino-4-(furan-2-yl)pyrimidin-5-yl]-1-(2-fluoroethyl)pyridin-2-one Chemical compound C=1C=COC=1C1=NC(N)=NC=C1C=1C=CC(=O)N(CCF)C=1 WJNNXYLGOHCGCH-UHFFFAOYSA-N 0.000 claims 1
- QONUMVWLFMVXOC-UHFFFAOYSA-N 5-[2-amino-4-(furan-2-yl)pyrimidin-5-yl]-1-(2-methoxyethyl)pyridin-2-one Chemical compound C1=CC(=O)N(CCOC)C=C1C1=CN=C(N)N=C1C1=CC=CO1 QONUMVWLFMVXOC-UHFFFAOYSA-N 0.000 claims 1
- 230000002757 inflammatory effect Effects 0.000 claims 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 abstract description 83
- 229910052799 carbon Inorganic materials 0.000 abstract description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract description 4
- 125000004429 atom Chemical group 0.000 abstract description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 171
- 238000006243 chemical reaction Methods 0.000 description 114
- -1 pyrimidine compound Chemical class 0.000 description 97
- 239000002904 solvent Substances 0.000 description 97
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 86
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 80
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 77
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 73
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 72
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 67
- 239000007858 starting material Substances 0.000 description 62
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 58
- 125000004122 cyclic group Chemical group 0.000 description 58
- 239000002585 base Substances 0.000 description 55
- 238000005481 NMR spectroscopy Methods 0.000 description 54
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 54
- 238000004519 manufacturing process Methods 0.000 description 46
- 238000000034 method Methods 0.000 description 42
- 238000012360 testing method Methods 0.000 description 40
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 38
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 34
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 33
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 31
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 30
- 229910052783 alkali metal Inorganic materials 0.000 description 29
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- 125000000753 cycloalkyl group Chemical group 0.000 description 23
- 239000007864 aqueous solution Substances 0.000 description 22
- 150000002357 guanidines Chemical class 0.000 description 22
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 22
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
- 239000011541 reaction mixture Substances 0.000 description 22
- 229920006395 saturated elastomer Polymers 0.000 description 22
- 125000000392 cycloalkenyl group Chemical group 0.000 description 21
- 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 20
- 239000003153 chemical reaction reagent Substances 0.000 description 20
- 150000003230 pyrimidines Chemical class 0.000 description 19
- 238000003756 stirring Methods 0.000 description 19
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 18
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 18
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 229910052757 nitrogen Inorganic materials 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 17
- 235000019270 ammonium chloride Nutrition 0.000 description 17
- 230000027455 binding Effects 0.000 description 17
- 239000007787 solid Substances 0.000 description 17
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 16
- 229910052717 sulfur Inorganic materials 0.000 description 16
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 15
- 238000001914 filtration Methods 0.000 description 14
- 239000012046 mixed solvent Substances 0.000 description 14
- 125000004433 nitrogen atom Chemical group N* 0.000 description 14
- 102000005962 receptors Human genes 0.000 description 14
- 108020003175 receptors Proteins 0.000 description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 13
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 13
- 150000001298 alcohols Chemical class 0.000 description 13
- 150000002170 ethers Chemical class 0.000 description 13
- 230000005764 inhibitory process Effects 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
- 230000001590 oxidative effect Effects 0.000 description 12
- 125000004430 oxygen atom Chemical group O* 0.000 description 12
- 229960003878 haloperidol Drugs 0.000 description 11
- 229910000027 potassium carbonate Inorganic materials 0.000 description 11
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 11
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 229960005305 adenosine Drugs 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 239000007800 oxidant agent Substances 0.000 description 10
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- 125000004434 sulfur atom Chemical group 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000012298 atmosphere Substances 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 9
- 229910001873 dinitrogen Inorganic materials 0.000 description 9
- 239000008187 granular material Substances 0.000 description 9
- 239000012074 organic phase Substances 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- 229910052708 sodium Inorganic materials 0.000 description 9
- 229910000029 sodium carbonate Inorganic materials 0.000 description 9
- 208000009132 Catalepsy Diseases 0.000 description 8
- 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 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 8
- 206010047853 Waxy flexibility Diseases 0.000 description 8
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 8
- 150000008041 alkali metal carbonates Chemical class 0.000 description 8
- NOPFSRXAKWQILS-UHFFFAOYSA-N docosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCO NOPFSRXAKWQILS-UHFFFAOYSA-N 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000000825 pharmaceutical preparation Substances 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 125000003373 pyrazinyl group Chemical group 0.000 description 8
- 125000002098 pyridazinyl group Chemical group 0.000 description 8
- 239000012312 sodium hydride Substances 0.000 description 8
- 229910000104 sodium hydride Inorganic materials 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- RRLMPLDPCKRASL-UHFFFAOYSA-N 3-(dimethylamino)prop-2-enal Chemical compound CN(C)C=CC=O RRLMPLDPCKRASL-UHFFFAOYSA-N 0.000 description 7
- ACFHETZZSOOPTG-UHFFFAOYSA-N 5-[2-amino-4,6-bis(furan-2-yl)pyrimidin-5-yl]-1h-pyridin-2-one Chemical compound C1=CC(=O)NC=C1C=1C(C=2OC=CC=2)=NC(N)=NC=1C1=CC=CO1 ACFHETZZSOOPTG-UHFFFAOYSA-N 0.000 description 7
- 102000001267 GSK3 Human genes 0.000 description 7
- 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 description 7
- JADDQZYHOWSFJD-FLNNQWSLSA-N N-ethyl-5'-carboxamidoadenosine Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NCC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 JADDQZYHOWSFJD-FLNNQWSLSA-N 0.000 description 7
- 150000001340 alkali metals Chemical class 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 238000010438 heat treatment Methods 0.000 description 7
- 229920000609 methyl cellulose Polymers 0.000 description 7
- 235000010981 methylcellulose Nutrition 0.000 description 7
- 239000001923 methylcellulose Substances 0.000 description 7
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical class OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 7
- 229940044551 receptor antagonist Drugs 0.000 description 7
- 239000002464 receptor antagonist Substances 0.000 description 7
- 101150007969 ADORA1 gene Proteins 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 6
- 238000009833 condensation Methods 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 230000009871 nonspecific binding Effects 0.000 description 6
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 6
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Classifications
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| JP2001324018 | 2001-10-22 | ||
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| ES02802050T Expired - Lifetime ES2364328T3 (es) | 2001-10-22 | 2002-10-22 | Compuesto de pirimidina y composición medicinal del mismo. |
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- 2002-10-22 AT AT02802050T patent/ATE507217T1/de active
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