BG63777B1 - Ароматни съединения и фармацевтични състави, които ги съдържат - Google Patents

Ароматни съединения и фармацевтични състави, които ги съдържат Download PDF

Info

Publication number: BG63777B1
Authority: BG; Bulgaria
Prior art keywords: alkyl; formula; compound; group; optionally substituted
Prior art date: 1995-06-20

Application number

BG102173A

Other languages

Bulgarian (bg)

English (en)

Other versions

BG102173A (en

Inventor

Gloria Breault

Original Assignee

Zeneca Limited

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.)

1995-06-20

Filing date

1998-01-09

Publication date

2002-12-29

1995-06-20 Priority claimed from GBGB9512476.4A external-priority patent/GB9512476D0/en

1996-01-25 Priority claimed from GBGB9601462.6A external-priority patent/GB9601462D0/en

1996-03-30 Priority claimed from GBGB9606831.7A external-priority patent/GB9606831D0/en

1998-01-09 Application filed by Zeneca Limited filed Critical Zeneca Limited

1998-09-30 Publication of BG102173A publication Critical patent/BG102173A/xx

2002-12-29 Publication of BG63777B1 publication Critical patent/BG63777B1/bg

Links

239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 7
150000001491 aromatic compounds Chemical class 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims abstract description 196
238000000034 method Methods 0.000 claims abstract description 58
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 31
239000001257 hydrogen Substances 0.000 claims abstract description 30
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 29
150000002148 esters Chemical class 0.000 claims abstract description 27
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 22
150000003839 salts Chemical class 0.000 claims abstract description 21
238000001727 in vivo Methods 0.000 claims abstract description 19
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 18
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 17
150000001408 amides Chemical class 0.000 claims abstract description 14
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 13
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 11
125000004076 pyridyl group Chemical group 0.000 claims abstract description 11
238000002360 preparation method Methods 0.000 claims abstract description 9
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 7
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 7
229910052799 carbon Inorganic materials 0.000 claims abstract description 6
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 6
-1 pyazinyl Chemical group 0.000 claims description 146
125000000217 alkyl group Chemical group 0.000 claims description 107
229910052736 halogen Inorganic materials 0.000 claims description 22
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
125000006239 protecting group Chemical group 0.000 claims description 18
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
208000002193 Pain Diseases 0.000 claims description 17
125000003545 alkoxy group Chemical group 0.000 claims description 15
239000002253 acid Substances 0.000 claims description 14
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 14
125000000623 heterocyclic group Chemical group 0.000 claims description 14
125000001424 substituent group Chemical group 0.000 claims description 14
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 12
125000001589 carboacyl group Chemical group 0.000 claims description 12
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
125000003342 alkenyl group Chemical group 0.000 claims description 10
125000000304 alkynyl group Chemical group 0.000 claims description 10
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
229910052757 nitrogen Inorganic materials 0.000 claims description 10
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
229910052760 oxygen Inorganic materials 0.000 claims description 10
239000001301 oxygen Substances 0.000 claims description 10
125000002098 pyridazinyl group Chemical group 0.000 claims description 10
125000001544 thienyl group Chemical group 0.000 claims description 10
150000002431 hydrogen Chemical class 0.000 claims description 9
125000000335 thiazolyl group Chemical group 0.000 claims description 9
125000003282 alkyl amino group Chemical group 0.000 claims description 8
125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 8
125000005843 halogen group Chemical group 0.000 claims description 8
125000001113 thiadiazolyl group Chemical group 0.000 claims description 8
241001465754 Metazoa Species 0.000 claims description 7
125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 6
230000003213 activating effect Effects 0.000 claims description 6
125000005647 linker group Chemical group 0.000 claims description 6
125000002971 oxazolyl group Chemical group 0.000 claims description 6
125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
229910052717 sulfur Chemical group 0.000 claims description 6
239000011593 sulfur Chemical group 0.000 claims description 6
125000005236 alkanoylamino group Chemical group 0.000 claims description 5
125000001072 heteroaryl group Chemical group 0.000 claims description 5
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
125000003831 tetrazolyl group Chemical group 0.000 claims description 5
125000004423 acyloxy group Chemical group 0.000 claims description 4
125000003373 pyrazinyl group Chemical group 0.000 claims description 4
125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 3
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
FBEXNBDUERYLOP-UHFFFAOYSA-N 4-[(2-methoxyphenyl)methylamino]benzoic acid Chemical compound COC1=CC=CC=C1CNC1=CC=C(C(O)=O)C=C1 FBEXNBDUERYLOP-UHFFFAOYSA-N 0.000 claims description 3
DEQLKIKNMOLOGX-UHFFFAOYSA-N 4-chloro-3-[(2-methoxyphenyl)methylamino]-5-sulfamoylbenzoic acid Chemical compound COC1=CC=CC=C1CNC1=CC(C(O)=O)=CC(S(N)(=O)=O)=C1Cl DEQLKIKNMOLOGX-UHFFFAOYSA-N 0.000 claims description 3
JJLIONLDXUJJOW-UHFFFAOYSA-N 5-[(2,5-dimethoxyphenyl)methylamino]-2-hydroxybenzoic acid Chemical compound COC1=CC=C(OC)C(CNC=2C=C(C(O)=CC=2)C(O)=O)=C1 JJLIONLDXUJJOW-UHFFFAOYSA-N 0.000 claims description 3
GMMBETCEGBXFIY-UHFFFAOYSA-N 6-[(2-methoxyphenyl)methylamino]pyridine-3-carboxylic acid Chemical compound COC1=CC=CC=C1CNC1=CC=C(C(O)=O)C=N1 GMMBETCEGBXFIY-UHFFFAOYSA-N 0.000 claims description 3
125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 3
125000000539 amino acid group Chemical group 0.000 claims description 3
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 3
125000004981 cycloalkylmethyl group Chemical group 0.000 claims description 3
239000003814 drug Substances 0.000 claims description 3
125000002883 imidazolyl group Chemical group 0.000 claims description 3
125000005322 morpholin-1-yl group Chemical group 0.000 claims description 3
125000001624 naphthyl group Chemical group 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
239000002243 precursor Substances 0.000 claims description 3
125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 3
NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 claims description 2
IKNZBNHVVQIRTO-UHFFFAOYSA-N 2h-tetrazole-5-carboxylic acid Chemical compound OC(=O)C=1N=NNN=1 IKNZBNHVVQIRTO-UHFFFAOYSA-N 0.000 claims description 2
DIDWQBYXIYMULL-UHFFFAOYSA-N 4-chloro-3-[(2,3-dimethoxyphenyl)methylamino]-5-sulfamoylbenzoic acid Chemical compound COC1=CC=CC(CNC=2C(=C(C=C(C=2)C(O)=O)S(N)(=O)=O)Cl)=C1OC DIDWQBYXIYMULL-UHFFFAOYSA-N 0.000 claims description 2
150000001204 N-oxides Chemical class 0.000 claims description 2
125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 2
PGRHXDWITVMQBC-UHFFFAOYSA-N dehydroacetic acid Natural products CC(=O)C1C(=O)OC(C)=CC1=O PGRHXDWITVMQBC-UHFFFAOYSA-N 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
125000005842 heteroatom Chemical group 0.000 claims description 2
230000003993 interaction Effects 0.000 claims description 2
PEQJBOMPGWYIRO-UHFFFAOYSA-N n-ethyl-3,4-dimethoxyaniline Chemical compound CCNC1=CC=C(OC)C(OC)=C1 PEQJBOMPGWYIRO-UHFFFAOYSA-N 0.000 claims description 2
230000008569 process Effects 0.000 claims description 2
BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 claims description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
125000004122 cyclic group Chemical group 0.000 abstract description 5
230000001225 therapeutic effect Effects 0.000 abstract description 4
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 3
125000006273 (C1-C3) alkyl group Chemical group 0.000 abstract 1
125000003601 C2-C6 alkynyl group Chemical group 0.000 abstract 1
239000005864 Sulphur Substances 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 135
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 126
239000000243 solution Substances 0.000 description 81
230000000052 comparative effect Effects 0.000 description 78
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 76
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 72
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 71
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 62
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 53
239000011541 reaction mixture Substances 0.000 description 53
239000000203 mixture Substances 0.000 description 52
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 49
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 46
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 45
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 42
239000007787 solid Substances 0.000 description 38
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 28
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 28
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
238000006243 chemical reaction Methods 0.000 description 23
239000012044 organic layer Substances 0.000 description 19
RUUOPSRRIKJHNH-UHFFFAOYSA-N pyridazine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=N1 RUUOPSRRIKJHNH-UHFFFAOYSA-N 0.000 description 19
229920006395 saturated elastomer Polymers 0.000 description 19
229910052943 magnesium sulfate Inorganic materials 0.000 description 18
235000019341 magnesium sulphate Nutrition 0.000 description 18
239000000047 product Substances 0.000 description 18
238000000921 elemental analysis Methods 0.000 description 17
150000002367 halogens Chemical group 0.000 description 17
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 16
229960000583 acetic acid Drugs 0.000 description 16
239000012267 brine Substances 0.000 description 16
XIUVRDRLZYFQCI-UHFFFAOYSA-N 6-[[5-bromo-2-(cyclopropylmethoxy)phenyl]methyl-ethylamino]pyridazine-3-carboxylic acid Chemical compound C=1C=C(C(O)=O)N=NC=1N(CC)CC1=CC(Br)=CC=C1OCC1CC1 XIUVRDRLZYFQCI-UHFFFAOYSA-N 0.000 description 15
239000002904 solvent Substances 0.000 description 15
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
229910052786 argon Inorganic materials 0.000 description 14
229910000027 potassium carbonate Inorganic materials 0.000 description 14
230000002829 reductive effect Effects 0.000 description 14
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
239000003921 oil Substances 0.000 description 12
235000019198 oils Nutrition 0.000 description 12
229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
235000017557 sodium bicarbonate Nutrition 0.000 description 12
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 11
239000002585 base Substances 0.000 description 11
DMYLUKNFEYWGCH-UHFFFAOYSA-N pyridazine-3-carboxamide Chemical compound NC(=O)C1=CC=CN=N1 DMYLUKNFEYWGCH-UHFFFAOYSA-N 0.000 description 11
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 10
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 10
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 10
125000002252 acyl group Chemical group 0.000 description 10
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 10
239000000460 chlorine Substances 0.000 description 10
239000002244 precipitate Substances 0.000 description 10
239000000725 suspension Substances 0.000 description 10
NBXDNBXAUOSKHT-UHFFFAOYSA-N 6-[(5-bromo-2-propoxyphenyl)methyl-ethylamino]pyridazine-3-carbonitrile Chemical compound CCCOC1=CC=C(Br)C=C1CN(CC)C1=CC=C(C#N)N=N1 NBXDNBXAUOSKHT-UHFFFAOYSA-N 0.000 description 9
239000000284 extract Substances 0.000 description 9
239000006260 foam Substances 0.000 description 9
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 9
239000011347 resin Substances 0.000 description 9
229920005989 resin Polymers 0.000 description 9
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
235000019270 ammonium chloride Nutrition 0.000 description 8
125000001246 bromo group Chemical group Br* 0.000 description 8
230000000694 effects Effects 0.000 description 8
239000010410 layer Substances 0.000 description 8
229910052938 sodium sulfate Inorganic materials 0.000 description 8
235000011152 sodium sulphate Nutrition 0.000 description 8
238000004809 thin layer chromatography Methods 0.000 description 8
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 7
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
238000002474 experimental method Methods 0.000 description 7
210000003405 ileum Anatomy 0.000 description 7
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
238000010992 reflux Methods 0.000 description 7
239000012279 sodium borohydride Substances 0.000 description 7
229910000033 sodium borohydride Inorganic materials 0.000 description 7
238000003786 synthesis reaction Methods 0.000 description 7
238000012360 testing method Methods 0.000 description 7
AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 6
NMCKZYHQHAZHIO-UHFFFAOYSA-N 6-chloropyridazine-3-carboxamide Chemical compound NC(=O)C1=CC=C(Cl)N=N1 NMCKZYHQHAZHIO-UHFFFAOYSA-N 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
230000000202 analgesic effect Effects 0.000 description 6
239000005557 antagonist Substances 0.000 description 6
230000015572 biosynthetic process Effects 0.000 description 6
WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
238000003756 stirring Methods 0.000 description 6
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
MKKSTJKBKNCMRV-UHFFFAOYSA-N 5-bromo-2-hydroxybenzaldehyde Chemical compound OC1=CC=C(Br)C=C1C=O MKKSTJKBKNCMRV-UHFFFAOYSA-N 0.000 description 5
YMUOLGNUZURDEW-UHFFFAOYSA-N 6-chloropyridazine-3-carbonitrile Chemical compound ClC1=CC=C(C#N)N=N1 YMUOLGNUZURDEW-UHFFFAOYSA-N 0.000 description 5
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
241000282412 Homo Species 0.000 description 5
239000000010 aprotic solvent Substances 0.000 description 5
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
229910052794 bromium Inorganic materials 0.000 description 5
AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
229910052801 chlorine Inorganic materials 0.000 description 5
125000001309 chloro group Chemical group Cl* 0.000 description 5
238000004587 chromatography analysis Methods 0.000 description 5
239000007789 gas Substances 0.000 description 5
230000007062 hydrolysis Effects 0.000 description 5
238000006460 hydrolysis reaction Methods 0.000 description 5
239000012074 organic phase Substances 0.000 description 5
201000008482 osteoarthritis Diseases 0.000 description 5
238000000746 purification Methods 0.000 description 5
239000007858 starting material Substances 0.000 description 5
150000003536 tetrazoles Chemical group 0.000 description 5
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 5
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 4
QTYSIKBFSFIFOD-UHFFFAOYSA-N 6-[[5-chloro-2-(2-methylpropoxy)phenyl]methyl-ethylamino]pyridazine-3-carboxylic acid Chemical compound C=1C=C(C(O)=O)N=NC=1N(CC)CC1=CC(Cl)=CC=C1OCC(C)C QTYSIKBFSFIFOD-UHFFFAOYSA-N 0.000 description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
239000012359 Methanesulfonyl chloride Substances 0.000 description 4
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-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
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
125000003435 aroyl group Chemical group 0.000 description 4
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 4
QGEIXOVZBMCRHR-UHFFFAOYSA-N butyl 6-[(5-bromo-2-hydroxyphenyl)methyl-ethylamino]pyridazine-3-carboxylate Chemical compound N1=NC(C(=O)OCCCC)=CC=C1N(CC)CC1=CC(Br)=CC=C1O QGEIXOVZBMCRHR-UHFFFAOYSA-N 0.000 description 4
238000004440 column chromatography Methods 0.000 description 4
238000001816 cooling Methods 0.000 description 4
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
XWBDWHCCBGMXKG-UHFFFAOYSA-N ethanamine;hydron;chloride Chemical compound Cl.CCN XWBDWHCCBGMXKG-UHFFFAOYSA-N 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D237/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Pain & Pain Management (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Rheumatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Pyridine Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)

BG102173A 1995-06-20 1998-01-09 Ароматни съединения и фармацевтични състави, които ги съдържат BG63777B1 (bg)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
GBGB9512476.4A GB9512476D0 (en)	1995-06-20	1995-06-20	Aromatic compounds
GBGB9601462.6A GB9601462D0 (en)	1996-01-25	1996-01-25	Aromatic compounds
GBGB9606831.7A GB9606831D0 (en)	1996-03-30	1996-03-30	Aromatic compounds
PCT/GB1996/001442 WO1997000863A1 (en)	1995-06-20	1996-06-17	Aromatic compounds and pharmaceutical compositions containing them

Publications (2)

Publication Number	Publication Date
BG102173A BG102173A (en)	1998-09-30
BG63777B1 true BG63777B1 (bg)	2002-12-29

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ID=27267781

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BG102173A BG63777B1 (bg)	1995-06-20	1998-01-09	Ароматни съединения и фармацевтични състави, които ги съдържат

Country Status (29)

Country	Link
US (2)	US5994353A (es)
EP (1)	EP0835246B1 (es)
JP (1)	JP3949166B2 (es)
KR (1)	KR19990023006A (es)
CN (1)	CN1193963A (es)
AR (1)	AR004495A1 (es)
AT (1)	ATE207468T1 (es)
AU (1)	AU700337B2 (es)
BG (1)	BG63777B1 (es)
BR (1)	BR9608956A (es)
CA (1)	CA2220925A1 (es)
CZ (1)	CZ290923B6 (es)
DE (1)	DE69616323T2 (es)
DK (1)	DK0835246T3 (es)
EE (1)	EE9700341A (es)
ES (1)	ES2165505T3 (es)
HR (1)	HRP960288B1 (es)
HU (1)	HUP9802317A3 (es)
IL (1)	IL118664A (es)
MX (1)	MX9710218A (es)
MY (1)	MY116531A (es)
NO (1)	NO311129B1 (es)
NZ (1)	NZ311082A (es)
PL (1)	PL324205A1 (es)
PT (1)	PT835246E (es)
RO (1)	RO119945B1 (es)
SK (1)	SK282450B6 (es)
TW (1)	TW434240B (es)
WO (1)	WO1997000863A1 (es)

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1996
- 1996-06-12 TW TW085107056A patent/TW434240B/zh not_active IP Right Cessation
- 1996-06-16 IL IL11866496A patent/IL118664A/en not_active IP Right Cessation
- 1996-06-17 ES ES96920936T patent/ES2165505T3/es not_active Expired - Lifetime
- 1996-06-17 JP JP50365397A patent/JP3949166B2/ja not_active Expired - Fee Related
- 1996-06-17 HU HU9802317A patent/HUP9802317A3/hu unknown
- 1996-06-17 EE EE9700341A patent/EE9700341A/xx unknown
- 1996-06-17 BR BR9608956A patent/BR9608956A/pt not_active Application Discontinuation
- 1996-06-17 EP EP96920936A patent/EP0835246B1/en not_active Expired - Lifetime
- 1996-06-17 RO RO97-02367A patent/RO119945B1/ro unknown
- 1996-06-17 CZ CZ19974109A patent/CZ290923B6/cs not_active IP Right Cessation
- 1996-06-17 NZ NZ311082A patent/NZ311082A/xx unknown
- 1996-06-17 PT PT96920936T patent/PT835246E/pt unknown
- 1996-06-17 MX MX9710218A patent/MX9710218A/es not_active IP Right Cessation
- 1996-06-17 CN CN96196398A patent/CN1193963A/zh active Pending
- 1996-06-17 KR KR1019970709476A patent/KR19990023006A/ko not_active Ceased
- 1996-06-17 US US08/973,887 patent/US5994353A/en not_active Expired - Fee Related
- 1996-06-17 DK DK96920936T patent/DK0835246T3/da active
- 1996-06-17 AU AU62320/96A patent/AU700337B2/en not_active Ceased
- 1996-06-17 SK SK1732-97A patent/SK282450B6/sk unknown
- 1996-06-17 PL PL96324205A patent/PL324205A1/xx unknown
- 1996-06-17 CA CA002220925A patent/CA2220925A1/en not_active Abandoned
- 1996-06-17 DE DE69616323T patent/DE69616323T2/de not_active Expired - Fee Related
- 1996-06-17 WO PCT/GB1996/001442 patent/WO1997000863A1/en not_active Ceased
- 1996-06-17 AT AT96920936T patent/ATE207468T1/de not_active IP Right Cessation
- 1996-06-18 MY MYPI96002451A patent/MY116531A/en unknown
- 1996-06-18 HR HR960288A patent/HRP960288B1/xx not_active IP Right Cessation
- 1996-06-20 AR ARP960103226A patent/AR004495A1/es not_active Application Discontinuation
1997
- 1997-12-19 NO NO19975985A patent/NO311129B1/no unknown
1998
- 1998-01-09 BG BG102173A patent/BG63777B1/bg unknown
1999
- 1999-09-13 US US09/395,229 patent/US6365603B1/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
CN1193963A (zh)	1998-09-23
DE69616323T2 (de)	2002-07-25
AU700337B2 (en)	1998-12-24
JP3949166B2 (ja)	2007-07-25
HRP960288A2 (en)	1998-02-28
IL118664A0 (en)	1996-10-31
NO975985L (no)	1997-12-19
MX9710218A (es)	1998-03-31
WO1997000863A1 (en)	1997-01-09
IL118664A (en)	2001-12-23
CZ290923B6 (cs)	2002-11-13
EP0835246A1 (en)	1998-04-15
US5994353A (en)	1999-11-30
RO119945B1 (ro)	2005-06-30
BG102173A (en)	1998-09-30
SK173297A3 (en)	1998-07-08
EE9700341A (et)	1998-06-15
NO311129B1 (no)	2001-10-15
US6365603B1 (en)	2002-04-02
DK0835246T3 (da)	2002-01-21
DE69616323D1 (de)	2001-11-29
BR9608956A (pt)	1999-03-02
NZ311082A (en)	2000-01-28
HUP9802317A3 (en)	2001-11-28
AR004495A1 (es)	1998-12-16
ES2165505T3 (es)	2002-03-16
TW434240B (en)	2001-05-16
CA2220925A1 (en)	1997-01-09
PT835246E (pt)	2002-04-29
ATE207468T1 (de)	2001-11-15
HRP960288B1 (en)	2003-02-28
MY116531A (en)	2004-02-28
EP0835246B1 (en)	2001-10-24
PL324205A1 (en)	1998-05-11
KR19990023006A (ko)	1999-03-25
SK282450B6 (sk)	2002-02-05
CZ410997A3 (cs)	1998-03-18
JPH11508878A (ja)	1999-08-03
AU6232096A (en)	1997-01-22
HUP9802317A2 (hu)	1999-03-29
NO975985D0 (no)	1997-12-19

Publication	Publication Date	Title
BG63777B1 (bg)	2002-12-29	Ароматни съединения и фармацевтични състави, които ги съдържат
EP0773930B1 (en)	2000-10-11	Aromatic amino ethers as pain relieving agents
RU2198878C2 (ru)	2003-02-20	Ароматические соединения и содержащие их фармацевтические композиции
US6787562B2 (en)	2004-09-07	Substituted aryl and heteroaryl compounds as E-type prostaglandin antagonists
JP2006525984A (ja)	2006-11-16	Ｖｒ−１アンタゴニストとしての置換−１−フタラジナミン
RU2182574C2 (ru)	2002-05-20	Ароматические соединения и содержащие их фармацевтические композиции