CA2119467A1 - Composes pyridiniques pour le traitement des maladies associees aux leucotrienes - Google Patents

Composes pyridiniques pour le traitement des maladies associees aux leucotrienes

Info

Publication number: CA2119467A1
Authority: CA; Canada
Prior art keywords: phenyl; pyridyl; methoxyphenyl; aliphatic; reaction
Prior art date: 1991-09-19
Legal status (The legal status 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 status listed.): Abandoned

Application number

CA002119467A

Other languages

English (en)

Inventor

Pamela Anne Chambers

Robert A. Daines

Dalia R. Jakas

William D. Kingsbury

Israil Pendrak

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

SmithKline Beecham Corp

Original Assignee

Individual

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.)

1991-09-19

Filing date

1992-09-01

Publication date

1993-04-01

1992-09-01 Application filed by Individual filed Critical Individual

1993-04-01 Publication of CA2119467A1 publication Critical patent/CA2119467A1/fr

Status Abandoned legal-status Critical Current

Links

208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 14
201000010099 disease Diseases 0.000 title description 13
150000002617 leukotrienes Chemical class 0.000 title description 11
150000003222 pyridines Chemical class 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 58
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 124
125000001931 aliphatic group Chemical group 0.000 claims description 83
238000000034 method Methods 0.000 claims description 30
150000003839 salts Chemical class 0.000 claims description 29
150000001204 N-oxides Chemical class 0.000 claims description 22
125000000217 alkyl group Chemical group 0.000 claims description 17
150000003254 radicals Chemical class 0.000 claims description 11
229910052739 hydrogen Inorganic materials 0.000 claims description 10
125000003545 alkoxy group Chemical group 0.000 claims description 9
125000004432 carbon atom Chemical group C* 0.000 claims description 9
239000001257 hydrogen Substances 0.000 claims description 9
150000001408 amides Chemical group 0.000 claims description 7
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
239000008194 pharmaceutical composition Substances 0.000 claims description 7
239000000546 pharmaceutical excipient Substances 0.000 claims description 7
201000004681 Psoriasis Diseases 0.000 claims description 6
125000001475 halogen functional group Chemical group 0.000 claims description 5
125000004953 trihalomethyl group Chemical group 0.000 claims description 4
125000002252 acyl group Chemical group 0.000 claims description 3
125000004093 cyano group Chemical group *C#N 0.000 claims description 3
229910052760 oxygen Inorganic materials 0.000 claims description 3
229940124530 sulfonamide Drugs 0.000 claims description 3
150000003456 sulfonamides Chemical group 0.000 claims description 3
150000001768 cations Chemical class 0.000 claims description 2
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims 1
239000003199 leukotriene receptor blocking agent Substances 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 218
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 148
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 142
238000006243 chemical reaction Methods 0.000 description 129
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 123
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 103
150000001336 alkenes Chemical class 0.000 description 95
125000003118 aryl group Chemical group 0.000 description 94
JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 94
235000019439 ethyl acetate Nutrition 0.000 description 92
238000005481 NMR spectroscopy Methods 0.000 description 89
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 87
229910001868 water Inorganic materials 0.000 description 85
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 84
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 78
239000002253 acid Substances 0.000 description 70
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 68
239000000377 silicon dioxide Substances 0.000 description 67
239000007787 solid Substances 0.000 description 66
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 62
239000000243 solution Substances 0.000 description 59
125000001743 benzylic group Chemical group 0.000 description 58
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 58
239000000047 product Substances 0.000 description 57
125000004076 pyridyl group Chemical group 0.000 description 56
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 52
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 52
239000002904 solvent Substances 0.000 description 51
SMBQBQBNOXIFSF-UHFFFAOYSA-N dilithium Chemical class [Li][Li] SMBQBQBNOXIFSF-UHFFFAOYSA-N 0.000 description 50
229910052943 magnesium sulfate Inorganic materials 0.000 description 50
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 48
239000012300 argon atmosphere Substances 0.000 description 47
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 46
239000012267 brine Substances 0.000 description 45
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 45
229910003002 lithium salt Inorganic materials 0.000 description 42
159000000002 lithium salts Chemical class 0.000 description 42
-1 LTB4 Chemical class 0.000 description 40
238000003818 flash chromatography Methods 0.000 description 40
235000019341 magnesium sulphate Nutrition 0.000 description 39
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 38
239000005711 Benzoic acid Substances 0.000 description 37
101150041968 CDC13 gene Proteins 0.000 description 37
235000010233 benzoic acid Nutrition 0.000 description 37
229960004365 benzoic acid Drugs 0.000 description 37
238000001816 cooling Methods 0.000 description 37
125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 description 36
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 36
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 34
229940093499 ethyl acetate Drugs 0.000 description 34
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
125000005447 octyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 33
238000000746 purification Methods 0.000 description 33
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 32
150000004702 methyl esters Chemical class 0.000 description 31
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 29
239000000203 mixture Substances 0.000 description 29
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
238000004458 analytical method Methods 0.000 description 26
229910052786 argon Inorganic materials 0.000 description 26
210000004027 cell Anatomy 0.000 description 26
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 25
150000002500 ions Chemical class 0.000 description 25
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 23
101100073357 Streptomyces halstedii sch2 gene Proteins 0.000 description 22
239000003921 oil Substances 0.000 description 22
235000019198 oils Nutrition 0.000 description 22
235000019441 ethanol Nutrition 0.000 description 21
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 19
238000003820 Medium-pressure liquid chromatography Methods 0.000 description 19
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 16
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
239000011734 sodium Substances 0.000 description 16
229910052708 sodium Inorganic materials 0.000 description 16
229910000030 sodium bicarbonate Inorganic materials 0.000 description 16
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
238000007792 addition Methods 0.000 description 15
150000002148 esters Chemical class 0.000 description 15
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
230000000694 effects Effects 0.000 description 14
239000000284 extract Substances 0.000 description 14
VNYSSYRCGWBHLG-AMOLWHMGSA-N leukotriene B4 Chemical compound CCCCC\C=C/C[C@@H](O)\C=C\C=C\C=C/[C@@H](O)CCCC(O)=O VNYSSYRCGWBHLG-AMOLWHMGSA-N 0.000 description 14
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 13
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 12
229940050390 benzoate Drugs 0.000 description 12
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 12
239000012298 atmosphere Substances 0.000 description 11
239000012230 colorless oil Substances 0.000 description 11
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 11
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
150000001299 aldehydes Chemical class 0.000 description 10
238000004108 freeze drying Methods 0.000 description 10
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 10
229920006395 saturated elastomer Polymers 0.000 description 10
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 10
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
239000012044 organic layer Substances 0.000 description 9
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
239000005557 antagonist Substances 0.000 description 8
239000000872 buffer Substances 0.000 description 8
229910000024 caesium carbonate Inorganic materials 0.000 description 8
239000003054 catalyst Substances 0.000 description 8
229910052744 lithium Inorganic materials 0.000 description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
235000017557 sodium bicarbonate Nutrition 0.000 description 8
238000003756 stirring Methods 0.000 description 8
239000004615 ingredient Substances 0.000 description 7
238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 7
229910000027 potassium carbonate Inorganic materials 0.000 description 7
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
239000004480 active ingredient Substances 0.000 description 6
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 6
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 6
239000000543 intermediate Substances 0.000 description 6
239000007788 liquid Substances 0.000 description 6
GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 6
238000002360 preparation method Methods 0.000 description 6
239000011541 reaction mixture Substances 0.000 description 6
238000003786 synthesis reaction Methods 0.000 description 6
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 6
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 6
150000001412 amines Chemical class 0.000 description 5
230000027455 binding Effects 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
125000001309 chloro group Chemical group Cl* 0.000 description 5
KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 5
238000001704 evaporation Methods 0.000 description 5
230000008020 evaporation Effects 0.000 description 5
238000002474 experimental method Methods 0.000 description 5
238000009472 formulation Methods 0.000 description 5
YFHXZQPUBCBNIP-UHFFFAOYSA-N fura-2 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=3OC(=CC=3C=2)C=2OC(=CN=2)C(O)=O)N(CC(O)=O)CC(O)=O)=C1 YFHXZQPUBCBNIP-UHFFFAOYSA-N 0.000 description 5
125000005843 halogen group Chemical group 0.000 description 5
GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 5
230000008569 process Effects 0.000 description 5
150000003462 sulfoxides Chemical class 0.000 description 5
239000003826 tablet Substances 0.000 description 5
SYSZENVIJHPFNL-UHFFFAOYSA-N (alpha-D-mannosyl)7-beta-D-mannosyl-diacetylchitobiosyl-L-asparagine, isoform B (protein) Chemical compound COC1=CC=C(I)C=C1 SYSZENVIJHPFNL-UHFFFAOYSA-N 0.000 description 4
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-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
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
239000000443 aerosol Substances 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
239000012043 crude product Substances 0.000 description 4
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 4
239000008187 granular material Substances 0.000 description 4
125000004029 hydroxymethyl group Chemical class [H]OC([H])([H])* 0.000 description 4
239000000463 material Substances 0.000 description 4
239000012528 membrane Substances 0.000 description 4
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 4
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 4
LRZGRGVRZSDRTK-UHFFFAOYSA-N oct-3-yn-1-ol Chemical compound CCCCC#CCCO LRZGRGVRZSDRTK-UHFFFAOYSA-N 0.000 description 4
TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 4
239000007800 oxidant agent Substances 0.000 description 4
230000001590 oxidative effect Effects 0.000 description 4
235000015320 potassium carbonate Nutrition 0.000 description 4
229910000029 sodium carbonate Inorganic materials 0.000 description 4
150000003457 sulfones Chemical class 0.000 description 4
SOKBUAQWSPPGGI-UHFFFAOYSA-N trifluoromethanesulfonamide Chemical compound NS(=O)(=O)C(F)(F)F.NS(=O)(=O)C(F)(F)F SOKBUAQWSPPGGI-UHFFFAOYSA-N 0.000 description 4
XFNJVJPLKCPIBV-UHFFFAOYSA-N trimethylenediamine Chemical compound NCCCN XFNJVJPLKCPIBV-UHFFFAOYSA-N 0.000 description 4
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 4
229920002554 vinyl polymer Polymers 0.000 description 4
238000005160 1H NMR spectroscopy Methods 0.000 description 3
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
229910006124 SOCl2 Inorganic materials 0.000 description 3
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
239000000556 agonist Substances 0.000 description 3
125000000746 allylic group Chemical group 0.000 description 3
150000008064 anhydrides Chemical class 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
210000000170 cell membrane Anatomy 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
239000002024 ethyl acetate extract Substances 0.000 description 3
238000011534 incubation Methods 0.000 description 3
238000005259 measurement Methods 0.000 description 3
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 3
239000002480 mineral oil Substances 0.000 description 3
235000010446 mineral oil Nutrition 0.000 description 3
238000002156 mixing Methods 0.000 description 3
GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 3
ATCNYMVVGBLQMQ-UHFFFAOYSA-N oct-7-yn-1-ol Chemical compound OCCCCCCC#C ATCNYMVVGBLQMQ-UHFFFAOYSA-N 0.000 description 3
239000002674 ointment Substances 0.000 description 3
239000008188 pellet Substances 0.000 description 3
239000003208 petroleum Substances 0.000 description 3
229940049953 phenylacetate Drugs 0.000 description 3
230000002685 pulmonary effect Effects 0.000 description 3
125000001424 substituent group Chemical group 0.000 description 3
239000000725 suspension Substances 0.000 description 3
150000003536 tetrazoles Chemical class 0.000 description 3
150000003568 thioethers Chemical class 0.000 description 3
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
230000000699 topical effect Effects 0.000 description 3
XASXKSQAAHFMNH-UEIGIMKUSA-N (e)-4-[6-(chloromethyl)-3-dodecoxypyridin-2-yl]but-3-enoic acid;hydrochloride Chemical compound Cl.CCCCCCCCCCCCOC1=CC=C(CCl)N=C1\C=C\CC(O)=O XASXKSQAAHFMNH-UEIGIMKUSA-N 0.000 description 2
LUBJCRLGQSPQNN-UHFFFAOYSA-N 1-Phenylurea Chemical compound NC(=O)NC1=CC=CC=C1 LUBJCRLGQSPQNN-UHFFFAOYSA-N 0.000 description 2
WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 2
ASCWVQXSKGOWHV-UHFFFAOYSA-N 3-(sulfanylmethyl)benzoic acid Chemical compound OC(=O)C1=CC=CC(CS)=C1 ASCWVQXSKGOWHV-UHFFFAOYSA-N 0.000 description 2
CWLKGDAVCFYWJK-UHFFFAOYSA-N 3-aminophenol Chemical compound NC1=CC=CC(O)=C1 CWLKGDAVCFYWJK-UHFFFAOYSA-N 0.000 description 2
229940018563 3-aminophenol Drugs 0.000 description 2
ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
206010002198 Anaphylactic reaction Diseases 0.000 description 2
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic 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
- 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5

Landscapes

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)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Engineering & Computer Science (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
Pulmonology (AREA)
Immunology (AREA)
Dermatology (AREA)
Pyridine Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Thiazole And Isothizaole Compounds (AREA)
Discharge Lamps And Accessories Thereof (AREA)
Cathode-Ray Tubes And Fluorescent Screens For Display (AREA)

CA002119467A 1991-09-19 1992-09-01 Composes pyridiniques pour le traitement des maladies associees aux leucotrienes Abandoned CA2119467A1 (fr)

Applications Claiming Priority (9)

Application Number	Priority Date	Filing Date	Title
US76271091A	1991-09-19	1991-09-19
US07/762,710		1991-09-19
US79093191A	1991-11-12	1991-11-12
US07/790,931		1991-11-12
US80959391A	1991-12-18	1991-12-18
US07/809,593		1991-12-18
US93286992A	1992-08-20	1992-08-20
US07/932,869		1992-08-20
CN93103596A CN1092409A (zh)	1991-09-19	1993-03-19	用于治疗白三烯有关的疾病的化合物

Publications (1)

Publication Number	Publication Date
CA2119467A1 true CA2119467A1 (fr)	1993-04-01

Family

ID=36809157

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002119467A Abandoned CA2119467A1 (fr)	1991-09-19	1992-09-01	Composes pyridiniques pour le traitement des maladies associees aux leucotrienes

Country Status (12)

Country	Link
EP (1)	EP0604529A1 (fr)
JP (1)	JPH06510786A (fr)
CN (1)	CN1092409A (fr)
AP (1)	AP333A (fr)
AU (1)	AU2573592A (fr)
CA (1)	CA2119467A1 (fr)
IL (1)	IL103205A0 (fr)
MA (1)	MA22649A1 (fr)
MX (1)	MX9205358A (fr)
NZ (1)	NZ244371A (fr)
PT (1)	PT100881A (fr)
WO (1)	WO1993006085A1 (fr)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
NZ254473A (en) *	1992-06-30	1996-11-26	Smithkline Beecham Corp	Preparation of phenylthiomethylpyridinylalkenoates
GB9313145D0 (en) *	1993-06-25	1993-08-11	Smithkline Beecham Plc	Process
IL115420A0 (en)	1994-09-26	1995-12-31	Zeneca Ltd	Aminoheterocyclic derivatives
DK0812194T3 (da) *	1995-03-02	2000-12-18	Smithkline Beecham Corp	Fremgangsmåde til behandling af atopisk dermatitis og kontaktdermatitis
GB9508137D0 (en) *	1995-04-21	1995-06-07	Smithkline Beecham Plc	Formulation
GB9602166D0 (en)	1996-02-02	1996-04-03	Zeneca Ltd	Aminoheterocyclic derivatives
US6313127B1 (en)	1996-02-02	2001-11-06	Zeneca Limited	Heterocyclic compounds useful as pharmaceutical agents
US5929096A (en) *	1996-02-29	1999-07-27	Smithkline Beecham Corporation	Method for treating atopic dermatitis and contact dermatitis
CN1228087A (zh) *	1996-08-14	1999-09-08	曾尼卡有限公司	取代的嘧啶衍生物和它们的药物用途
AU4557397A (en) *	1996-09-26	1998-04-17	Novartis Ag	Aryl-substituted acrylamides with leukotriene b4 (ltb-4) receptor antagonist activity
UA56197C2 (uk)	1996-11-08	2003-05-15	Зенека Лімітед	Гетероциклічні похідні
JP2001511798A (ja)	1997-02-13	2001-08-14	ゼネカ・リミテッド	オキシド−スクアレンシクラーゼ抑制剤として有用な複素環化合物
DE69815509T2 (de)	1997-02-13	2004-05-13	Astrazeneca Ab	Heterozyklische verbindungen die als oxido-squalen-zyklase-inhibitoren anwendung finden
GB9715895D0 (en)	1997-07-29	1997-10-01	Zeneca Ltd	Heterocyclic compounds
GB9902989D0 (en)	1999-02-11	1999-03-31	Zeneca Ltd	Heterocyclic derivatives

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4056619A (en) *	1975-09-08	1977-11-01	Warner-Lambert Company	1-Substituted-2-(2-pyridinyl)ethanone N-oxides
US5004743A (en) *	1987-11-25	1991-04-02	Merck Frosst Canada, Inc.	Pyridyl styrene dialkanoic acids as anti-leukotriene agents
JPH07116150B2 (ja) *	1990-06-07	1995-12-13	スミスクライン・ビーチャム・コーポレイション	安息香酸誘導体

1992
- 1992-09-01 JP JP5506069A patent/JPH06510786A/ja active Pending
- 1992-09-01 AU AU25735/92A patent/AU2573592A/en not_active Abandoned
- 1992-09-01 WO PCT/US1992/007466 patent/WO1993006085A1/fr not_active Ceased
- 1992-09-01 CA CA002119467A patent/CA2119467A1/fr not_active Abandoned
- 1992-09-01 EP EP92920043A patent/EP0604529A1/fr not_active Withdrawn
- 1992-09-08 MA MA22940A patent/MA22649A1/fr unknown
- 1992-09-17 AP APAP/P/1992/000428A patent/AP333A/en active
- 1992-09-17 NZ NZ244371A patent/NZ244371A/en unknown
- 1992-09-17 IL IL103205A patent/IL103205A0/xx unknown
- 1992-09-18 PT PT100881A patent/PT100881A/pt not_active Application Discontinuation
- 1992-09-21 MX MX9205358A patent/MX9205358A/es unknown
1993
- 1993-03-19 CN CN93103596A patent/CN1092409A/zh active Pending

Also Published As

Publication number	Publication date
IL103205A0 (en)	1993-02-21
AU2573592A (en)	1993-04-27
MX9205358A (es)	1993-07-01
EP0604529A1 (fr)	1994-07-06
MA22649A1 (fr)	1993-04-01
AP333A (en)	1994-04-25
AP9200428A0 (en)	1992-10-31
JPH06510786A (ja)	1994-12-01
PT100881A (pt)	1993-10-29
CN1092409A (zh)	1994-09-21
WO1993006085A1 (fr)	1993-04-01
NZ244371A (en)	1995-11-27

Legal Events

Date	Code	Title	Description
1999-03-30	EEER	Examination request
2003-08-04	FZDE	Discontinued

Publication	Publication Date	Title
CA2119467A1 (fr)	1993-04-01	Composes pyridiniques pour le traitement des maladies associees aux leucotrienes
JP2002534415A (ja)	2002-10-15	新規化合物
AU655428B2 (en)	1994-12-22	Benzoic acid derivatives
IE911912A1 (en)	1991-12-18	Pyridyl-benzoic acid derivatives for treating¹leukotriene-related diseases
EP0649412B1 (fr)	2003-01-15	Composes pharmaceutiques a base de pyridine
US5643914A (en)	1997-07-01	Pharmaceutical pyridine compounds
CA2083956A1 (fr)	1991-12-08	Derives pyridylbenzoiques lies a des amines, pour le traitement de maladies associees aux leucotrienes
US5633258A (en)	1997-05-27	Pyridine compounds for treating leukotriene-related diseases
WO1993022285A1 (fr)	1993-11-11	Antagonistes de leucotrienes
JPH08175994A (ja)	1996-07-09	脂質代謝改善剤
EP0532634A1 (fr)	1993-03-24	Derives d'acide phtalamique utilises dans le traitement de maladies associees aux leucotrienes
JPH07309837A (ja)	1995-11-28	ピリジン誘導体、その製造法および剤
EP0639975A1 (fr)	1995-03-01	Composes de pyridine heterocyclique substituee et leurs utilisations
WO1995015950A1 (fr)	1995-06-15	Composes
JP2005519951A (ja)	2005-07-07	β３アドレナリン性受容体作動薬としてのアミノアルコール誘導体
WO1994014442A1 (fr)	1994-07-07	Composes de pyridyle a substitution utiles comme antagonistes des leucotrienes
SI9200314A (sl)	1993-06-30	Spojine za zdravuanje bolezni, ki so v zvezi z levkotrieni