AP248A - Azole derivatives. - Google Patents

Azole derivatives. Download PDF

Info

Publication number: AP248A
Authority: AP; ARIPO
Prior art keywords: furyl; amino; triazine; formula; alkyl
Prior art date: 1990-05-29

Application number

APAP/P/1991/000266A

Other languages

English (en)

Other versions

AP9100266A0 (en

Inventor

Peter William Rodney Caulkett

Geraint Jones

Michael George Collis

Simon Martin Poucher

Original Assignee

Zeneca Ltd

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1990-05-29

Filing date

1991-05-28

Publication date

1993-03-16

1990-05-29 Priority claimed from GB909011914A external-priority patent/GB9011914D0/en

1990-05-29 Priority claimed from GB909011913A external-priority patent/GB9011913D0/en

1991-01-22 Priority claimed from GB919101380A external-priority patent/GB9101380D0/en

1991-01-22 Priority claimed from GB919101379A external-priority patent/GB9101379D0/en

1991-02-27 Priority claimed from GB919104125A external-priority patent/GB9104125D0/en

1991-05-28 Application filed by Zeneca Ltd filed Critical Zeneca Ltd

1991-07-31 Publication of AP9100266A0 publication Critical patent/AP9100266A0/xx

1993-03-16 Application granted granted Critical

1993-03-16 Publication of AP248A publication Critical patent/AP248A/en

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
210000004027 cell Anatomy 0.000 description 5
229960001760 dimethyl sulfoxide Drugs 0.000 description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
230000001965 increasing effect Effects 0.000 description 5
210000004731 jugular vein Anatomy 0.000 description 5
230000004044 response Effects 0.000 description 5
230000001225 therapeutic effect Effects 0.000 description 5
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
206010047141 Vasodilatation Diseases 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
150000001340 alkali metals Chemical class 0.000 description 4
238000004458 analytical method Methods 0.000 description 4
230000008485 antagonism Effects 0.000 description 4
230000027455 binding Effects 0.000 description 4
230000017531 blood circulation Effects 0.000 description 4
230000036772 blood pressure Effects 0.000 description 4
239000002775 capsule Substances 0.000 description 4
230000001010 compromised effect Effects 0.000 description 4
238000002425 crystallisation Methods 0.000 description 4
201000010099 disease Diseases 0.000 description 4
239000003112 inhibitor Substances 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
210000004379 membrane Anatomy 0.000 description 4
239000012528 membrane Substances 0.000 description 4
230000000144 pharmacologic effect Effects 0.000 description 4
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
238000003756 stirring Methods 0.000 description 4
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
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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)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
Life Sciences & Earth Sciences (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Pain & Pain Management (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Vascular Medicine (AREA)
Urology & Nephrology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

APAP/P/1991/000266A 1990-05-29 1991-05-28 Azole derivatives. AP248A (en)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
GB909011914A GB9011914D0 (en)	1990-05-29	1990-05-29	Heterocyclic compounds
GB909011913A GB9011913D0 (en)	1990-05-29	1990-05-29	Azole derivatives
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)

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GB9226735D0 (en) *	1992-12-22	1993-02-17	Ici Plc	Azole derivatives
US5356894A (en) *	1990-05-29	1994-10-18	Rodney Peter W	Morpholinyl substituted [1,2,4]-triazolo[1,5-a]triazine as antagonist
GB9111130D0 (en) *	1991-05-23	1991-07-17	Ici Plc	Azole derivatives
GB9111131D0 (en) *	1991-05-23	1991-07-17	Ici Plc	Heterocyclic compounds
GB9125001D0 (en) *	1991-11-25	1992-01-22	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
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AU7546794A (en) *	1993-09-06	1995-03-27	Kyowa Hakko Kogyo Co. Ltd.	Depression remedy
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
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AU2003272886A1 (en) *	2002-09-24	2004-04-19	Kyowa Hakko Kogyo Co., Ltd.	(1,2,4)-TRIAZOLO(1,5-c)PYRIMIDINE DERIVATIVE
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US20070010522A1 (en) *	2003-04-09	2007-01-11	Chi Vu	Triazolo[1,5-c]pyrimidines and pyrazolo[1,5-c]pyrimidines useful as a2a adenosine receptor antagonists
US7674791B2 (en)	2003-04-09	2010-03-09	Biogen Idec Ma Inc.	Triazolopyrazines and methods of making and using the same
DE602004018637D1 (de)	2003-04-09	2009-02-05	Biogen Idec Inc	A2a-adenosinrezeptorantagonisten
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
WO2006076706A1 (fr)	2005-01-14	2006-07-20	Millennium Pharmaceuticals, Inc.	Derives de cinnamide et d'hydrocinnamide presentant une activite inhibitrice de raf-kinase
BR112015013195A2 (pt)	2012-12-06	2017-08-29	Siemens Ag	Disposição e método para introduzir calor em uma formação geológica por meio de indução eletromagnética
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
CA3089159A1 (fr) *	2018-02-06	2019-08-15	Jiangsu Hengrui Medicine Co., Ltd.	Derive de pyrazolo[1,5-a][1,3,5]triazine-2-amine, son procede de preparation et son utilisation medicale
WO2020002969A1 (fr) *	2018-06-26	2020-01-02	Zhejiang Vimgreen Pharmaceuticals, Ltd	Dérivés de triazolotriazine en tant qu'antagonistes du récepteur a2a
KR102633145B1 (ko) *	2018-06-26	2024-02-05	쩌지앙 빔그린 파머슈티컬스, 엘티디	A2a 수용체 길항제로서의 트리아졸로 트리아진 유도체
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
CN112608316B (zh) *	2019-07-30	2022-10-21	厦门宝太生物科技股份有限公司	一种吡唑并三嗪类腺苷受体拮抗剂
WO2021105916A1 (fr) *	2019-11-26	2021-06-03	Aurigene Discovery Technologies Limited	Composés de sulfonamide ciblant cd73 et les récepteurs d'adénosine
CN114901665B (zh) *	2019-12-26	2025-02-18	浙江春禾医药科技有限公司	三唑并三嗪衍生物在治疗疾病中的用途
US20240217978A1 (en) *	2021-04-23	2024-07-04	Chong Kun Dang Pharmaceutical Corp.	COMPOUND AS ADENOSINE A2a RECEPTOR ANTAGONIST AND PHARMACEUTICAL COMPOSITION COMPRISING SAME

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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

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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.
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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 CS CS911595A patent/CS159591A3/cs unknown
- 1991-05-28 AU AU77348/91A patent/AU642494B2/en not_active Ceased
- 1991-05-28 CA CA002043424A patent/CA2043424A1/fr not_active Abandoned
- 1991-05-28 FI FI912563A patent/FI912563A7/fi not_active Application Discontinuation
- 1991-05-28 IE IE181891A patent/IE911818A1/en unknown
- 1991-05-28 RO RO147639A patent/RO109542B1/ro unknown
- 1991-05-28 YU YU94791A patent/YU47812B/sh unknown
- 1991-05-28 NO NO912051A patent/NO178401C/no unknown
- 1991-05-28 US US07/708,265 patent/US5270311A/en not_active Expired - Lifetime
- 1991-05-28 NZ NZ238288A patent/NZ238288A/xx unknown
- 1991-05-28 AP APAP/P/1991/000266A patent/AP248A/en active
- 1991-05-28 KR KR1019910008926A patent/KR910020012A/ko not_active Withdrawn
- 1991-05-28 PT PT97776A patent/PT97776A/pt not_active Application Discontinuation
- 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

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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
JPH0597855A (ja)	1993-04-20
HU911789D0 (en)	1991-12-30
CS159591A3 (en)	1992-01-15
EP0459702A1 (fr)	1991-12-04
OA09358A (fr)	1992-09-15
HUT61311A (en)	1992-12-28
YU94791A (sh)	1994-06-24
FI912563A0 (fi)	1991-05-28
AU7734891A (en)	1991-12-05
GB9111132D0 (en)	1991-07-17
KR910020012A (ko)	1991-12-19
NO178401C (no)	1996-03-20
AU642494B2 (en)	1993-10-21
CA2043424A1 (fr)	1991-11-30
IL98316A (en)	1995-05-26
GB2244487A (en)	1991-12-04
NO178401B (no)	1995-12-11
NZ238288A (en)	1993-07-27
IE911818A1 (en)	1991-12-04
JP2504879B2 (ja)	1996-06-05
NO912051L (no)	1991-12-02
NO912051D0 (no)	1991-05-28
AP9100266A0 (en)	1991-07-31
US5270311A (en)	1993-12-14
FI912563A7 (fi)	1991-11-30
GB2244487B (en)	1994-02-02
YU47812B (sr)	1996-01-09
PT97776A (pt)	1992-03-31
CN1056879A (zh)	1991-12-11
IL98316A0 (en)	1992-06-21
RO109542B1 (ro)	1995-03-30

Publication	Publication Date	Title
AP248A (en)	1993-03-16	Azole derivatives.
US5356894A (en)	1994-10-18	Morpholinyl substituted [1,2,4]-triazolo[1,5-a]triazine as antagonist
US5300509A (en)	1994-04-05	2-furyl-oxazolo[5,4-d]-pyrimidines
EP1363910B1 (fr)	2006-03-01	Methodes de traitement des pathologies liees a la kinase p38 et composes de pyrrolotiazine utilises en tant qu'inhibiteurs de la kinase
RU2258705C2 (ru)	2005-08-20	ПРОИЗВОДНЫЕ 8-ФЕНИЛ-6,9-ДИГИДРО[1,2,4]-ТРИАЗОЛО[3,4-i]ПУРИН-5-ОНА, СПОСОБЫ ИХ ПОЛУЧЕНИЯ, ПРОМЕЖУТОЧНЫЕ СОЕДИНЕНИЯ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И СПОСОБ ЛЕЧЕНИЯ
US5290776A (en)	1994-03-01	Azole derivatives
US20040254183A1 (en)	2004-12-16	Pyrazolo[3,4-d]pyrimidines inhibiting h. pylori infections
TW202436303A (zh)	2024-09-16	含有咪唑之alk2激酶抑制劑
BG106568A (bg)	2002-12-29	5-(2-заместени-5-хетероциклилсулфонилпирид-3-ил)-дихидропиразоло[4,3-d]пиримидин-7-они като фосфодиестеразни инхибитори
JPWO2005095419A1 (ja)	2008-02-21	チアゾロピリミジン誘導体
AU2008208801A1 (en)	2008-07-31	Purine derivatives
US20220064163A1 (en)	2022-03-03	PYRIDO[2,3-d]PYRIMIDIN-7-ONES AND RELATED COMPOUNDS AS INHIBITORS OF PROTEIN KINASES
US5246932A (en)	1993-09-21	Heterocyclic compounds
US5380714A (en)	1995-01-10	2-furyl-triazalo [1,5-a]-[1,3,5]triazines and pyrazolo [2,3-a][1,3,5]triazines
WO1994014812A1 (fr)	1994-07-07	Derives d'azole utilises comme antagonistes de l'adenosine
PL167014B1 (pl)	1995-07-31	Sposób wytwarzania nowych pochodnych azolu
HK1057555B (en)	2006-09-15	Methods of treating p38 kinase-associated conditions and pyrrolotriazine compounds useful as kinase inhibitors