AP248A - Azole derivatives. - Google Patents
Azole derivatives. Download PDFInfo
- Publication number
- AP248A AP248A APAP/P/1991/000266A AP9100266A AP248A AP 248 A AP248 A AP 248A AP 9100266 A AP9100266 A AP 9100266A AP 248 A AP248 A AP 248A
- Authority
- AP
- ARIPO
- Prior art keywords
- furyl
- amino
- triazine
- formula
- alkyl
- Prior art date
Links
- 150000007980 azole derivatives Chemical class 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 183
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 88
- 125000005843 halogen group Chemical group 0.000 claims abstract description 24
- 125000001424 substituent group Chemical group 0.000 claims abstract description 21
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims abstract description 6
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 claims description 175
- -1 tetrafluorophenyl Chemical group 0.000 claims description 145
- 238000000034 method Methods 0.000 claims description 82
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 80
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 48
- 229910052739 hydrogen Inorganic materials 0.000 claims description 45
- 239000001257 hydrogen Substances 0.000 claims description 44
- 239000007858 starting material Substances 0.000 claims description 39
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 34
- 150000003839 salts Chemical class 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
- 125000002541 furyl group Chemical group 0.000 claims description 22
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
- 230000008569 process Effects 0.000 claims description 15
- 125000001544 thienyl group Chemical group 0.000 claims description 15
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 14
- 239000003085 diluting agent Substances 0.000 claims description 12
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 150000003918 triazines Chemical class 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- 125000001246 bromo group Chemical group Br* 0.000 claims description 8
- 125000001589 carboacyl group Chemical group 0.000 claims description 8
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 8
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 claims description 8
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 7
- JIHQDMXYYFUGFV-UHFFFAOYSA-N 1,3,5-triazine Chemical compound C1=NC=NC=N1 JIHQDMXYYFUGFV-UHFFFAOYSA-N 0.000 claims description 7
- 125000001153 fluoro group Chemical group F* 0.000 claims description 7
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
- 125000004464 hydroxyphenyl group Chemical group 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- SMUCKGNXNFHMNW-UHFFFAOYSA-N triazolo[1,5-a][1,3,5]triazine Chemical compound C1=NC=NC2=CN=NN21 SMUCKGNXNFHMNW-UHFFFAOYSA-N 0.000 claims description 5
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 125000004423 acyloxy group Chemical group 0.000 claims description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 4
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000006325 2-propenyl amino group Chemical group [H]C([H])=C([H])C([H])([H])N([H])* 0.000 claims description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- 125000003143 4-hydroxybenzyl group Chemical group [H]C([*])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 125000005277 alkyl imino group Chemical group 0.000 claims description 2
- 125000005336 allyloxy group Chemical group 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 2
- 125000001072 heteroaryl group Chemical group 0.000 claims description 2
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 2
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000002971 oxazolyl group Chemical group 0.000 claims description 2
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims 1
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 392
- 238000005481 NMR spectroscopy Methods 0.000 description 197
- 238000004452 microanalysis Methods 0.000 description 182
- 239000007787 solid Substances 0.000 description 117
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 99
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 99
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 93
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 66
- 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 58
- 239000000243 solution Substances 0.000 description 58
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 53
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 51
- 238000012360 testing method Methods 0.000 description 48
- 239000002904 solvent Substances 0.000 description 47
- 239000013078 crystal Substances 0.000 description 46
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 43
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 30
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 29
- 229960005305 adenosine Drugs 0.000 description 29
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 29
- 239000000203 mixture Substances 0.000 description 29
- 229910001868 water Inorganic materials 0.000 description 29
- 239000000725 suspension Substances 0.000 description 23
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 22
- 239000000377 silicon dioxide Substances 0.000 description 19
- 238000004587 chromatography analysis Methods 0.000 description 18
- 230000000694 effects Effects 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 231100000673 dose–response relationship Toxicity 0.000 description 15
- 238000010992 reflux Methods 0.000 description 15
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 15
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 14
- BIXYYZIIJIXVFW-UUOKFMHZSA-N (2R,3R,4S,5R)-2-(6-amino-2-chloro-9-purinyl)-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O BIXYYZIIJIXVFW-UUOKFMHZSA-N 0.000 description 13
- 239000012267 brine Substances 0.000 description 13
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 238000000354 decomposition reaction Methods 0.000 description 12
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 12
- DBTDEFJAFBUGPP-UHFFFAOYSA-N Methanethial Chemical compound S=C DBTDEFJAFBUGPP-UHFFFAOYSA-N 0.000 description 11
- 239000005557 antagonist Substances 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- 230000002792 vascular Effects 0.000 description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 229960000278 theophylline Drugs 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 230000009471 action Effects 0.000 description 8
- 239000008280 blood Substances 0.000 description 8
- 210000004369 blood Anatomy 0.000 description 8
- DZGWFCGJZKJUFP-UHFFFAOYSA-N tyramine Chemical compound NCCC1=CC=C(O)C=C1 DZGWFCGJZKJUFP-UHFFFAOYSA-N 0.000 description 8
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 7
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 7
- 229910052783 alkali metal Inorganic materials 0.000 description 7
- 230000001746 atrial effect Effects 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 239000007789 gas Substances 0.000 description 7
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 230000024883 vasodilation Effects 0.000 description 7
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 102000009346 Adenosine receptors Human genes 0.000 description 6
- 108050000203 Adenosine receptors Proteins 0.000 description 6
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 6
- 241000282326 Felis catus Species 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 125000004414 alkyl thio group Chemical group 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- 210000003141 lower extremity Anatomy 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 6
- 239000000296 purinergic P1 receptor antagonist Substances 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 150000003573 thiols Chemical class 0.000 description 6
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 5
- 241000700199 Cavia porcellus Species 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
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- 229960001760 dimethyl sulfoxide Drugs 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
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- IOSAAWHGJUZBOG-UHFFFAOYSA-N 3-(6-amino-9h-purin-9-yl)nonan-2-ol Chemical compound N1=CN=C2N(C(C(C)O)CCCCCC)C=NC2=C1N IOSAAWHGJUZBOG-UHFFFAOYSA-N 0.000 description 4
- 125000003682 3-furyl group Chemical group O1C([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
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
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- 150000007513 acids Chemical class 0.000 description 4
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
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- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 4
- 229960001802 phenylephrine Drugs 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 210000002027 skeletal muscle Anatomy 0.000 description 4
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- SNTWKPAKVQFCCF-UHFFFAOYSA-N 2,3-dihydro-1h-triazole Chemical compound N1NC=CN1 SNTWKPAKVQFCCF-UHFFFAOYSA-N 0.000 description 3
- PKGWLCZTTHWKIZ-UHFFFAOYSA-N 4-Hydroxypheoxyacetate Chemical compound OC(=O)COC1=CC=C(O)C=C1 PKGWLCZTTHWKIZ-UHFFFAOYSA-N 0.000 description 3
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 3
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 102000055025 Adenosine deaminases Human genes 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical class OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 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 3
- DYCJFJRCWPVDHY-LSCFUAHRSA-N NBMPR Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(SCC=3C=CC(=CC=3)[N+]([O-])=O)=C2N=C1 DYCJFJRCWPVDHY-LSCFUAHRSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Natural products OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 230000003444 anaesthetic effect Effects 0.000 description 3
- 238000010009 beating Methods 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 229940124630 bronchodilator Drugs 0.000 description 3
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 3
- 230000000747 cardiac effect Effects 0.000 description 3
- 239000007810 chemical reaction solvent Substances 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
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- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 1
- DUYAAUVXQSMXQP-UHFFFAOYSA-M thioacetate Chemical compound CC([S-])=O DUYAAUVXQSMXQP-UHFFFAOYSA-M 0.000 description 1
- 229960000103 thrombolytic agent Drugs 0.000 description 1
- RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 1
- 101150068774 thyX gene Proteins 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 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
- 238000012546 transfer Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229960004928 xamoterol Drugs 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB909011913A GB9011913D0 (en) | 1990-05-29 | 1990-05-29 | Azole derivatives |
| GB909011914A GB9011914D0 (en) | 1990-05-29 | 1990-05-29 | Heterocyclic compounds |
| GB919101380A GB9101380D0 (en) | 1991-01-22 | 1991-01-22 | Azole derivatives |
| GB919101379A GB9101379D0 (en) | 1991-01-22 | 1991-01-22 | Heterocyclic compounds |
| GB919104125A GB9104125D0 (en) | 1991-02-27 | 1991-02-27 | Azole derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AP9100266A0 AP9100266A0 (en) | 1991-07-31 |
| AP248A true AP248A (en) | 1993-03-16 |
Family
ID=27516979
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| APAP/P/1991/000266A AP248A (en) | 1990-05-29 | 1991-05-28 | Azole derivatives. |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US5270311A (fr) |
| EP (1) | EP0459702A1 (fr) |
| JP (1) | JP2504879B2 (fr) |
| KR (1) | KR910020012A (fr) |
| CN (1) | CN1056879A (fr) |
| AP (1) | AP248A (fr) |
| AU (1) | AU642494B2 (fr) |
| CA (1) | CA2043424A1 (fr) |
| CS (1) | CS159591A3 (fr) |
| FI (1) | FI912563A7 (fr) |
| GB (1) | GB2244487B (fr) |
| HU (1) | HUT61311A (fr) |
| IE (1) | IE911818A1 (fr) |
| IL (1) | IL98316A (fr) |
| NO (1) | NO178401C (fr) |
| NZ (1) | NZ238288A (fr) |
| OA (1) | OA09358A (fr) |
| PT (1) | PT97776A (fr) |
| RO (1) | RO109542B1 (fr) |
| YU (1) | YU47812B (fr) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5356894A (en) * | 1990-05-29 | 1994-10-18 | Rodney Peter W | Morpholinyl substituted [1,2,4]-triazolo[1,5-a]triazine as antagonist |
| GB9226735D0 (en) * | 1992-12-22 | 1993-02-17 | Ici Plc | Azole derivatives |
| GB2244487B (en) * | 1990-05-29 | 1994-02-02 | Ici Plc | Azole derivatives |
| GB9111130D0 (en) * | 1991-05-23 | 1991-07-17 | Ici Plc | Azole derivatives |
| GB9111131D0 (en) * | 1991-05-23 | 1991-07-17 | Ici Plc | Heterocyclic compounds |
| GB9124968D0 (en) * | 1991-11-25 | 1992-01-22 | Ici Plc | Chemical process |
| GB9125002D0 (en) * | 1991-11-25 | 1992-01-22 | Ici Plc | Azole derivatives |
| GB9125001D0 (en) * | 1991-11-25 | 1992-01-22 | Ici Plc | Heterocyclic compounds |
| ATE208199T1 (de) * | 1993-07-27 | 2001-11-15 | Kyowa Hakko Kogyo Kk | Arzneimittel gegen parkinsonsche krankheit |
| CA2148502A1 (fr) * | 1993-09-06 | 1995-03-16 | Fumio Suzuki | Antidepresseurs |
| CA2284737C (fr) | 1997-03-24 | 2007-03-13 | Kyowa Hakko Kogyo Co., Ltd. | Derives [1,2,4]triazolo[1,5-c]pyrimidiniques |
| US6060481A (en) * | 1998-05-28 | 2000-05-09 | The Penn State Research Foundation | Method for improving insulin sensitivity using an adenosine receptor antagonist |
| WO2000017201A1 (fr) * | 1998-09-22 | 2000-03-30 | Kyowa Hakko Kogyo Co., Ltd. | DERIVES DE [1,2,4]TRIAZOLO[1,5-c]PYRIMIDINE |
| AU2003272886A1 (en) * | 2002-09-24 | 2004-04-19 | Kyowa Hakko Kogyo Co., Ltd. | (1,2,4)-TRIAZOLO(1,5-c)PYRIMIDINE DERIVATIVE |
| US7329658B2 (en) * | 2003-02-06 | 2008-02-12 | Pfizer Inc | Cannabinoid receptor ligands and uses thereof |
| DE602004018637D1 (de) | 2003-04-09 | 2009-02-05 | Biogen Idec Inc | A2a-adenosinrezeptorantagonisten |
| WO2004092177A1 (fr) | 2003-04-09 | 2004-10-28 | Biogen Idec Ma Inc. | Triazolopyrazines et procedes de preparation et d'utilisation ce celles-ci |
| EP1618109A2 (fr) * | 2003-04-09 | 2006-01-25 | Biogen Idec MA Inc. | Triazolo [1,5-c]pyrimidines et pyrazolo [1,5-c]pyrimidines et procedes de preparation et d'utilisation de celles-ci |
| US7285550B2 (en) | 2003-04-09 | 2007-10-23 | Biogen Idec Ma Inc. | Triazolotriazines and pyrazolotriazines and methods of making and using the same |
| WO2004110454A1 (fr) * | 2003-06-13 | 2004-12-23 | Ishihara Sangyo Kaisha, Ltd. | Composition de traitement ou de prevention de maladies necessitant l'administration d'un agoniste du recepteur a2a de l'adenosine |
| EP1856053A1 (fr) | 2005-01-14 | 2007-11-21 | Millennium Pharmaceuticals, Inc. | Derives de cinnamide et d'hydrocinnamide presentant une activite inhibitrice de raf-kinase |
| CA2893876A1 (fr) | 2012-12-06 | 2014-06-12 | Wintershall Holding GmbH | Systeme et procede permettant de faire entrer de la chaleur dans une formation geologique par induction electromagnetique |
| CN106916073A (zh) * | 2017-01-20 | 2017-07-04 | 上海巧坤化工科技有限公司 | 一种大麦芽碱盐酸盐的合成方法 |
| JP2021512959A (ja) * | 2018-02-06 | 2021-05-20 | 江▲蘇▼恒瑞医▲薬▼股▲フン▼有限公司Ｊｉａｎｇｓｕ Ｈｅｎｇｒｕｉ Ｍｅｄｉｃｉｎｅ Ｃｏ．， Ｌｔｄ． | ピラゾロ［１，５−ａ］［１，３，５］トリアジン−２−アミン誘導体、その製造法、およびその医薬用途 |
| CA3103068C (fr) * | 2018-06-26 | 2024-06-25 | Zhejiang Vimgreen Pharmaceuticals, Ltd | Derives de triazolotriazine en tant qu'antagonistes du recepteur a2a |
| CA3115900C (fr) * | 2018-06-26 | 2024-10-08 | Zhejiang Vimgreen Pharmaceuticals, Ltd | Derives de triazolotriazine en tant qu'antagonistes du recepteur a2a |
| BE1026602B1 (fr) | 2018-09-27 | 2020-06-18 | Iteos Therapeutics S A | Inhibiteurs d’a2a ne penetrant pas dans le cerveau et methodes d’utilisation dans le traitement de cancers |
| WO2020103939A1 (fr) * | 2018-11-22 | 2020-05-28 | 上海科技大学 | Composé à cycle triazolo, son procédé de préparation, intermédiaires de celui-ci et utilisation associée |
| CN112479956A (zh) * | 2019-07-30 | 2021-03-12 | 杭州阿诺生物医药科技有限公司 | 一种用于制备腺苷受体抑制剂中间体的方法 |
| EP4065590A4 (fr) * | 2019-11-26 | 2023-11-15 | Aurigene Oncology Limited | Composés de sulfonamide ciblant cd73 et les récepteurs d'adénosine |
| JP2023508182A (ja) * | 2019-12-26 | 2023-03-01 | チェジン ヴィムグリーン ファーマシューティカルズ リミテッド | トリアゾロトリアジン誘導体の疾患治療への応用 |
| KR102863028B1 (ko) * | 2021-04-23 | 2025-09-22 | 주식회사 종근당 | 아데노신 A2a 수용체 길항제로서의 화합물 및 이를 포함하는 약학적 조성물 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0269859A2 (fr) * | 1986-10-31 | 1988-06-08 | Otsuka Pharmaceutical Co., Ltd. | Composés de pyrazolotriazine |
| EP0281367A1 (fr) * | 1987-03-02 | 1988-09-07 | Riker Laboratories, Inc. | 1,2,4-Triazolo[1,5-a]triazines substituées comme dilatatrices des bronches |
| EP0297651A1 (fr) * | 1987-06-29 | 1989-01-04 | Duphar International Research B.V | Dérivés d'indole annulaires |
| EP0459702A1 (fr) * | 1990-05-29 | 1991-12-04 | Zeneca Limited | Dérivés d'azoles |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3846423A (en) * | 1972-06-08 | 1974-11-05 | Icn Pharmaceuticals | Pyrazolo (1,5a) 1,3,5-triazines |
| BE815405A (fr) * | 1973-05-22 | 1974-11-22 | NOUVEAUX DERIVES DE LA PYRAZOLO(1,5-a)-S-TRIAZINE LEUR PREPARATION ET LEUR APPLICATION COMME MEDICAMENTS | |
| US3995039A (en) * | 1975-05-27 | 1976-11-30 | Merck & Co., Inc. | Pyrazolo [1,5-a] [1,3,5] triazines |
| GB1579932A (en) * | 1976-05-12 | 1980-11-26 | Ici Ltd | Herbicidal triazolotriazines |
| GB2016002B (en) * | 1978-01-09 | 1982-05-06 | Aron Sa | Amino derivatives of pyrazolo(1,5-a)s triazine |
| AU2192683A (en) * | 1982-12-30 | 1984-07-05 | Biomeasure Incorporated | Pyrazolo(1,5-alpha)-1,3,5-triazines |
| CA1267143A (fr) * | 1985-06-06 | 1990-03-27 | Sun H. Kim | Derives de 7-phenylpyrazole[1,5-a]-1,3,5-triazine, agents anti-arthrite |
| DE3677445D1 (de) * | 1985-09-30 | 1991-03-14 | Ciba Geigy Ag | 2-substituierte-e-kondensierte(1,5-c)-pyrimidine, pharmazeutische zubereitungen und ihre verwendung. |
| EP0263071B1 (fr) * | 1986-09-30 | 1992-08-12 | Ciba-Geigy Ag | [1,2,4]Triazolo[1,5-c]pyrimidines condensées en e et substituées en 2, compositions pharmaceutiques et leur utilisation |
| DE8817122U1 (de) * | 1988-12-22 | 1993-02-04 | Boehringer Ingelheim Kg, 55218 Ingelheim | Neue Xanthinderivate mit Adenosinantogenistischer Wirkung |
| US4970142A (en) * | 1989-02-16 | 1990-11-13 | Konica Corporation | Silver halide photographic light-sensitive material containing cyan coupler |
-
1991
- 1991-05-23 GB GB9111132A patent/GB2244487B/en not_active Expired - Fee Related
- 1991-05-23 EP EP91304665A patent/EP0459702A1/fr not_active Withdrawn
- 1991-05-28 PT PT97776A patent/PT97776A/pt not_active Application Discontinuation
- 1991-05-28 FI FI912563A patent/FI912563A7/fi not_active Application Discontinuation
- 1991-05-28 CA CA002043424A patent/CA2043424A1/fr not_active Abandoned
- 1991-05-28 IE IE181891A patent/IE911818A1/en unknown
- 1991-05-28 RO RO147639A patent/RO109542B1/ro unknown
- 1991-05-28 US US07/708,265 patent/US5270311A/en not_active Expired - Lifetime
- 1991-05-28 CS CS911595A patent/CS159591A3/cs unknown
- 1991-05-28 AP APAP/P/1991/000266A patent/AP248A/en active
- 1991-05-28 NZ NZ238288A patent/NZ238288A/xx unknown
- 1991-05-28 YU YU94791A patent/YU47812B/sh unknown
- 1991-05-28 NO NO912051A patent/NO178401C/no unknown
- 1991-05-28 KR KR1019910008926A patent/KR910020012A/ko not_active Withdrawn
- 1991-05-28 AU AU77348/91A patent/AU642494B2/en not_active Ceased
- 1991-05-29 JP JP3235332A patent/JP2504879B2/ja not_active Expired - Fee Related
- 1991-05-29 OA OA60010A patent/OA09358A/fr unknown
- 1991-05-29 HU HU911789A patent/HUT61311A/hu unknown
- 1991-05-29 CN CN91103744A patent/CN1056879A/zh active Pending
- 1991-05-30 IL IL9831691A patent/IL98316A/en not_active IP Right Cessation
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0269859A2 (fr) * | 1986-10-31 | 1988-06-08 | Otsuka Pharmaceutical Co., Ltd. | Composés de pyrazolotriazine |
| EP0281367A1 (fr) * | 1987-03-02 | 1988-09-07 | Riker Laboratories, Inc. | 1,2,4-Triazolo[1,5-a]triazines substituées comme dilatatrices des bronches |
| EP0297651A1 (fr) * | 1987-06-29 | 1989-01-04 | Duphar International Research B.V | Dérivés d'indole annulaires |
| EP0459702A1 (fr) * | 1990-05-29 | 1991-12-04 | Zeneca Limited | Dérivés d'azoles |
Also Published As
| Publication number | Publication date |
|---|---|
| YU94791A (sh) | 1994-06-24 |
| IL98316A (en) | 1995-05-26 |
| YU47812B (sr) | 1996-01-09 |
| EP0459702A1 (fr) | 1991-12-04 |
| IE911818A1 (en) | 1991-12-04 |
| CN1056879A (zh) | 1991-12-11 |
| RO109542B1 (ro) | 1995-03-30 |
| JP2504879B2 (ja) | 1996-06-05 |
| HUT61311A (en) | 1992-12-28 |
| KR910020012A (ko) | 1991-12-19 |
| OA09358A (fr) | 1992-09-15 |
| AP9100266A0 (en) | 1991-07-31 |
| FI912563A0 (fi) | 1991-05-28 |
| CS159591A3 (en) | 1992-01-15 |
| NO912051L (no) | 1991-12-02 |
| GB2244487B (en) | 1994-02-02 |
| IL98316A0 (en) | 1992-06-21 |
| GB9111132D0 (en) | 1991-07-17 |
| FI912563A7 (fi) | 1991-11-30 |
| AU7734891A (en) | 1991-12-05 |
| NO178401C (no) | 1996-03-20 |
| NO912051D0 (no) | 1991-05-28 |
| HU911789D0 (en) | 1991-12-30 |
| GB2244487A (en) | 1991-12-04 |
| NZ238288A (en) | 1993-07-27 |
| CA2043424A1 (fr) | 1991-11-30 |
| PT97776A (pt) | 1992-03-31 |
| JPH0597855A (ja) | 1993-04-20 |
| NO178401B (no) | 1995-12-11 |
| US5270311A (en) | 1993-12-14 |
| AU642494B2 (en) | 1993-10-21 |
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