SK284434B6 - Kondenzované deriváty imidazolu, spôsob a medziprodukty na ich prípravu a farmaceutické kompozície a prostriedky na ich báze - Google Patents

Kondenzované deriváty imidazolu, spôsob a medziprodukty na ich prípravu a farmaceutické kompozície a prostriedky na ich báze Download PDF

Info

Publication number: SK284434B6
Authority: SK; Slovakia
Prior art keywords: alkyl; formula; substituted; halogen; alkoxy
Prior art date: 1996-03-19

Application number

SK662-98A

Other languages

English (en)

Slovak (sk)

Other versions

SK66298A3 (en

Inventor

Frans Eduard Janssens

Joseph Elisabeth Leenaerts

Fran�Ois Maria Sommen

Dominique Louis Nestor Ghislaine Surleraux

Original Assignee

Janssen Pharmaceutica N. V.

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.)

1996-03-19

Filing date

1997-03-11

Publication date

2005-04-01

1997-03-11 Application filed by Janssen Pharmaceutica N. V. filed Critical Janssen Pharmaceutica N. V.

1999-06-11 Publication of SK66298A3 publication Critical patent/SK66298A3/sk

2005-04-01 Publication of SK284434B6 publication Critical patent/SK284434B6/sk

Links

238000000034 method Methods 0.000 title claims abstract description 27
230000008569 process Effects 0.000 title claims abstract description 5
238000002360 preparation method Methods 0.000 title claims description 16
239000008194 pharmaceutical composition Substances 0.000 title claims description 13
150000002460 imidazoles Chemical class 0.000 title claims description 11
229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 title claims description 9
239000013067 intermediate product Substances 0.000 title 1
239000000825 pharmaceutical preparation Substances 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 156
239000000203 mixture Substances 0.000 claims abstract description 91
150000003839 salts Chemical class 0.000 claims abstract description 28
239000003814 drug Substances 0.000 claims abstract description 18
125000000217 alkyl group Chemical group 0.000 claims description 109
239000000543 intermediate Substances 0.000 claims description 65
-1 2-quinolylmethoxy Chemical group 0.000 claims description 63
229910052739 hydrogen Inorganic materials 0.000 claims description 63
239000001257 hydrogen Substances 0.000 claims description 63
229910052736 halogen Inorganic materials 0.000 claims description 50
150000002367 halogens Chemical class 0.000 claims description 50
125000003545 alkoxy group Chemical group 0.000 claims description 45
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 45
150000002431 hydrogen Chemical class 0.000 claims description 43
239000002904 solvent Substances 0.000 claims description 37
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 29
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 27
239000002253 acid Substances 0.000 claims description 27
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 27
238000011282 treatment Methods 0.000 claims description 26
238000006243 chemical reaction Methods 0.000 claims description 23
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
125000001424 substituent group Chemical group 0.000 claims description 19
239000002585 base Substances 0.000 claims description 17
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 14
125000004076 pyridyl group Chemical group 0.000 claims description 14
BKYBFFVPONLJLQ-UHFFFAOYSA-N 3-benzazepine-3-carboxylic acid Chemical compound C1=CN(C(=O)O)C=CC2=CC=CC=C21 BKYBFFVPONLJLQ-UHFFFAOYSA-N 0.000 claims description 13
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
239000004480 active ingredient Substances 0.000 claims description 12
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 12
229910052799 carbon Inorganic materials 0.000 claims description 12
125000001624 naphthyl group Chemical group 0.000 claims description 12
125000005493 quinolyl group Chemical group 0.000 claims description 12
239000003795 chemical substances by application Substances 0.000 claims description 11
239000012442 inert solvent Substances 0.000 claims description 10
125000002971 oxazolyl group Chemical group 0.000 claims description 9
244000052769 pathogen Species 0.000 claims description 9
239000003937 drug carrier Substances 0.000 claims description 8
125000002883 imidazolyl group Chemical group 0.000 claims description 8
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 claims description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
239000008177 pharmaceutical agent Substances 0.000 claims description 7
150000001204 N-oxides Chemical group 0.000 claims description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
238000005804 alkylation reaction Methods 0.000 claims description 5
125000000335 thiazolyl group Chemical group 0.000 claims description 5
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 5
239000003638 chemical reducing agent Substances 0.000 claims description 4
125000002541 furyl group Chemical group 0.000 claims description 4
230000003647 oxidation Effects 0.000 claims description 4
238000007254 oxidation reaction Methods 0.000 claims description 4
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
239000003513 alkali Substances 0.000 claims description 2
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 2
125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 2
239000003153 chemical reaction reagent Substances 0.000 claims description 2
230000032050 esterification Effects 0.000 claims description 2
238000005886 esterification reaction Methods 0.000 claims description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
230000009467 reduction Effects 0.000 claims description 2
238000002560 therapeutic procedure Methods 0.000 claims description 2
230000009466 transformation Effects 0.000 claims description 2
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 3
230000000118 anti-neoplastic effect Effects 0.000 claims 1
KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 claims 1
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 1
RTKPBQOFWIQRSO-UHFFFAOYSA-N ethyl 11-[1-[2-[4-(quinolin-2-ylmethoxy)phenyl]ethyl]piperidin-4-ylidene]-5,6-dihydroimidazo[2,1-b][3]benzazepine-3-carboxylate Chemical compound C12=CC=CC=C2CCN2C(C(=O)OCC)=CN=C2C1=C1CCN(CCC=2C=CC(OCC=3N=C4C=CC=CC4=CC=3)=CC=2)CC1 RTKPBQOFWIQRSO-UHFFFAOYSA-N 0.000 claims 1
239000012458 free base Substances 0.000 claims 1
230000003301 hydrolyzing effect Effects 0.000 claims 1
YGGCJLOLGMGBQM-UHFFFAOYSA-N methyl 11-[1-[[3,5-dimethoxy-4-(quinolin-2-ylmethoxy)phenyl]methyl]piperidin-4-ylidene]-5,6-dihydroimidazo[2,1-b][3]benzazepine-3-carboxylate Chemical compound C12=CC=CC=C2CCN2C(C(=O)OC)=CN=C2C1=C1CCN(CC=2C=C(OC)C(OCC=3N=C4C=CC=CC4=CC=3)=C(OC)C=2)CC1 YGGCJLOLGMGBQM-UHFFFAOYSA-N 0.000 claims 1
239000007800 oxidant agent Substances 0.000 claims 1
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims 1
150000003053 piperidines Chemical group 0.000 claims 1
230000000694 effects Effects 0.000 abstract description 8
238000009472 formulation Methods 0.000 abstract description 5
230000002401 inhibitory effect Effects 0.000 abstract description 5
238000002651 drug therapy Methods 0.000 abstract description 2
125000000815 N-oxide group Chemical group 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 87
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
239000000243 solution Substances 0.000 description 29
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150000003254 radicals Chemical class 0.000 description 24
AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 22
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
239000012044 organic layer Substances 0.000 description 19
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
239000002244 precipitate Substances 0.000 description 18
239000003480 eluent Substances 0.000 description 15
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
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206010059866 Drug resistance Diseases 0.000 description 12
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
239000002246 antineoplastic agent Substances 0.000 description 12
210000004027 cell Anatomy 0.000 description 11
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
229940009456 adriamycin Drugs 0.000 description 10
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239000003826 tablet Substances 0.000 description 9
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
125000004432 carbon atom Chemical group C* 0.000 description 8
239000011521 glass Substances 0.000 description 8
241000699670 Mus sp. Species 0.000 description 7
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
239000003054 catalyst Substances 0.000 description 7
201000010099 disease Diseases 0.000 description 7
150000002148 esters Chemical class 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
241001465754 Metazoa Species 0.000 description 6
JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 6
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125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
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238000003756 stirring Methods 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
150000007513 acids Chemical class 0.000 description 5
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238000010934 O-alkylation reaction Methods 0.000 description 4
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UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
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LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
125000003386 piperidinyl group Chemical group 0.000 description 4
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YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
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OTKFCIVOVKCFHR-UHFFFAOYSA-N (Methylsulfinyl)(methylthio)methane Chemical compound CSCS(C)=O OTKFCIVOVKCFHR-UHFFFAOYSA-N 0.000 description 3
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YGLDQFWPUCURIP-UHFFFAOYSA-N 3h-3-benzazepine Chemical compound C1=CNC=CC2=CC=CC=C21 YGLDQFWPUCURIP-UHFFFAOYSA-N 0.000 description 3
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
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WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
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238000007126 N-alkylation reaction Methods 0.000 description 3
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HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 3
230000010534 mechanism of action Effects 0.000 description 3
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HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 1
UEDZHBJQHGVXQY-UHFFFAOYSA-N ethyl 4-(3-chloro-5,6-dihydroimidazo[2,1-b][3]benzazepin-11-ylidene)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=CC=CC=C2CCN2C(Cl)=CN=C21 UEDZHBJQHGVXQY-UHFFFAOYSA-N 0.000 description 1
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RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
229960005420 etoposide Drugs 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
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229960003180 glutathione Drugs 0.000 description 1
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125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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 description 1
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XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
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BYDXDJKUMAQVNF-UHFFFAOYSA-N methyl 11-[1-[2-[4-(naphthalen-2-ylmethoxy)phenyl]ethyl]piperidin-4-ylidene]-5,6-dihydroimidazo[2,1-b][3]benzazepine-3-carboxylate Chemical compound C12=CC=CC=C2CCN2C(C(=O)OC)=CN=C2C1=C1CCN(CCC=2C=CC(OCC=3C=C4C=CC=CC4=CC=3)=CC=2)CC1 BYDXDJKUMAQVNF-UHFFFAOYSA-N 0.000 description 1
UHTKAUBOWHDYSP-UHFFFAOYSA-N methyl 11-[1-[3-[4-(quinolin-2-ylmethoxy)phenyl]propyl]piperidin-4-ylidene]-5,6-dihydroimidazo[2,1-b][3]benzazepine-3-carboxylate Chemical compound C12=CC=CC=C2CCN2C(C(=O)OC)=CN=C2C1=C1CCN(CCCC=2C=CC(OCC=3N=C4C=CC=CC4=CC=3)=CC=2)CC1 UHTKAUBOWHDYSP-UHFFFAOYSA-N 0.000 description 1
NTNUDYROPUKXNA-UHFFFAOYSA-N methyl 2-(triphenyl-$l^{5}-phosphanylidene)acetate Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OC)C1=CC=CC=C1 NTNUDYROPUKXNA-UHFFFAOYSA-N 0.000 description 1
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150000002826 nitrites Chemical class 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
125000001400 nonyl group Chemical group [H]C([*])([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])[H] 0.000 description 1
239000002777 nucleoside Substances 0.000 description 1
150000003833 nucleoside derivatives Chemical class 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
239000002574 poison Substances 0.000 description 1
231100000614 poison Toxicity 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229940068918 polyethylene glycol 400 Drugs 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
ZLMJMSJWJFRBEC-BKFZFHPZSA-N potassium-44 Chemical compound [44K] ZLMJMSJWJFRBEC-BKFZFHPZSA-N 0.000 description 1
125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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125000006239 protecting group Chemical group 0.000 description 1
239000008213 purified water Substances 0.000 description 1
229960005206 pyrazinamide Drugs 0.000 description 1
IPEHBUMCGVEMRF-UHFFFAOYSA-N pyrazinecarboxamide Chemical compound NC(=O)C1=CN=CC=N1 IPEHBUMCGVEMRF-UHFFFAOYSA-N 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
WKSAUQYGYAYLPV-UHFFFAOYSA-N pyrimethamine Chemical compound CCC1=NC(N)=NC(N)=C1C1=CC=C(Cl)C=C1 WKSAUQYGYAYLPV-UHFFFAOYSA-N 0.000 description 1
229960000611 pyrimethamine Drugs 0.000 description 1
JADFCQKRKICRKI-UHFFFAOYSA-N quinoline;sulfane Chemical compound S.N1=CC=CC2=CC=CC=C21 JADFCQKRKICRKI-UHFFFAOYSA-N 0.000 description 1
239000000376 reactant Substances 0.000 description 1
QEVHRUUCFGRFIF-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C(C5=CC=C(OC)C=C5N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 QEVHRUUCFGRFIF-MDEJGZGSSA-N 0.000 description 1
230000008261 resistance mechanism Effects 0.000 description 1
229960001225 rifampicin Drugs 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
229940081974 saccharin Drugs 0.000 description 1
235000019204 saccharin Nutrition 0.000 description 1
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
230000007017 scission Effects 0.000 description 1
238000010956 selective crystallization Methods 0.000 description 1
230000008313 sensitization Effects 0.000 description 1
ZVCDLGYNFYZZOK-UHFFFAOYSA-M sodium cyanate Chemical compound [Na]OC#N ZVCDLGYNFYZZOK-UHFFFAOYSA-M 0.000 description 1
MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000008137 solubility enhancer Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
239000000126 substance Substances 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
KCDXJAYRVLXPFO-UHFFFAOYSA-N syringaldehyde Chemical compound COC1=CC(C=O)=CC(OC)=C1O KCDXJAYRVLXPFO-UHFFFAOYSA-N 0.000 description 1
COBXDAOIDYGHGK-UHFFFAOYSA-N syringaldehyde Natural products COC1=CC=C(C=O)C(OC)=C1O COBXDAOIDYGHGK-UHFFFAOYSA-N 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
238000007910 systemic administration Methods 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
229940063683 taxotere Drugs 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
150000003626 triacylglycerols Chemical class 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
NOYPYLRCIDNJJB-UHFFFAOYSA-N trimetrexate Chemical compound COC1=C(OC)C(OC)=CC(NCC=2C(=C3C(N)=NC(N)=NC3=CC=2)C)=C1 NOYPYLRCIDNJJB-UHFFFAOYSA-N 0.000 description 1
229960001099 trimetrexate Drugs 0.000 description 1
MDDPTCUZZASZIQ-UHFFFAOYSA-N tris[(2-methylpropan-2-yl)oxy]alumane Chemical compound [Al+3].CC(C)(C)[O-].CC(C)(C)[O-].CC(C)(C)[O-] MDDPTCUZZASZIQ-UHFFFAOYSA-N 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
229960004528 vincristine Drugs 0.000 description 1
239000000080 wetting agent 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
- C07D487/12—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 three hetero rings
- C07D487/14—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A61P31/06—Antibacterial agents for tuberculosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/04—Amoebicides
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/06—Antimalarials
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
- 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
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D495/14—Ortho-condensed systems

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
General Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Tropical Medicine & Parasitology (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Pulmonology (AREA)
Hematology (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Plural Heterocyclic Compounds (AREA)

SK662-98A 1996-03-19 1997-03-11 Kondenzované deriváty imidazolu, spôsob a medziprodukty na ich prípravu a farmaceutické kompozície a prostriedky na ich báze SK284434B6 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP96200755		1996-03-19
PCT/EP1997/001264 WO1997034897A1 (en)	1996-03-19	1997-03-11	Fused imidazole derivatives as multidrug resistance modulators

Publications (2)

Publication Number	Publication Date
SK66298A3 SK66298A3 (en)	1999-06-11
SK284434B6 true SK284434B6 (sk)	2005-04-01

Family

ID=8223797

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK662-98A SK284434B6 (sk)	1996-03-19	1997-03-11	Kondenzované deriváty imidazolu, spôsob a medziprodukty na ich prípravu a farmaceutické kompozície a prostriedky na ich báze

Country Status (29)

Country	Link
US (3)	US6218381B1 (es)
EP (1)	EP0888352B1 (es)
JP (3)	JP3630434B2 (es)
KR (2)	KR100330698B1 (es)
CN (1)	CN1083453C (es)
AR (1)	AR006271A1 (es)
AT (1)	ATE241626T1 (es)
BG (1)	BG62734B1 (es)
BR (1)	BR9708140A (es)
CA (1)	CA2237594C (es)
CZ (1)	CZ294060B6 (es)
DE (1)	DE69722389T2 (es)
EA (1)	EA001004B1 (es)
EE (1)	EE03773B1 (es)
ES (1)	ES2200159T3 (es)
HR (1)	HRP970161B1 (es)
HU (1)	HU224528B1 (es)
ID (1)	ID16375A (es)
IL (1)	IL124572A (es)
MX (1)	MX9804426A (es)
MY (1)	MY118282A (es)
NO (1)	NO310659B1 (es)
NZ (1)	NZ330466A (es)
PL (1)	PL193444B1 (es)
SK (1)	SK284434B6 (es)
TR (1)	TR199801191T2 (es)
TW (1)	TW527186B (es)
WO (1)	WO1997034897A1 (es)
ZA (1)	ZA972351B (es)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP3775780B2 (ja) *	1997-09-18	2006-05-17	ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ	薬剤の経口的バイオアベイラビリテイを向上させるための縮合イミダゾール誘導体
CN100341485C (zh) *	1998-04-01	2007-10-10	斯凯伊药品加拿大公司	抗癌组合物
US6743794B2 (en)	1999-12-22	2004-06-01	Eli Lilly And Company	Methods and compounds for inhibiting MRP1
US6376514B1 (en)	2000-10-17	2002-04-23	The Procter & Gamble Co.	Substituted six-membered heterocyclic compounds useful for treating multidrug resistance and compositions and methods thereof
US6693099B2 (en)	2000-10-17	2004-02-17	The Procter & Gamble Company	Substituted piperazine compounds optionally containing a quinolyl moiety for treating multidrug resistance
AU2002319232B2 (en)	2001-06-12	2007-09-06	Janssen Pharmaceutica N.V.	Novel substituted tetracyclic imidazole derivatives, processes for their preparation, pharmaceutical compositions comprising them and their use as a medicine
AU2002356715B2 (en) *	2001-11-23	2008-05-15	Janssen Pharmaceutica N.V.	The use of anti-histaminics for acute reduction of elevated intracranial pressure
GB0301736D0 (en) *	2003-01-24	2003-02-26	Xenova Ltd	Pharmaceutical compounds
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1997
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Publication number	Publication date
BG62734B1 (bg)	2000-06-30
AR006271A1 (es)	1999-08-11
NO982124L (no)	1998-09-18
AU709683B2 (en)	1999-09-02
ZA972351B (en)	1998-09-18
EE03773B1 (et)	2002-06-17
MX9804426A (es)	1998-09-30
CN1083453C (zh)	2002-04-24
CA2237594A1 (en)	1997-09-25
US20030087895A1 (en)	2003-05-08
HRP970161A2 (en)	1998-04-30
JP2000505477A (ja)	2000-05-09
KR100330698B1 (ko)	2002-10-31
DE69722389T2 (de)	2009-09-24
HU224528B1 (hu)	2005-10-28
TW527186B (en)	2003-04-11
BR9708140A (pt)	1999-07-27
WO1997034897A1 (en)	1997-09-25
JP4205319B2 (ja)	2009-01-07
HK1015769A1 (en)	1999-10-22
IL124572A (en)	2002-03-10
US6476018B1 (en)	2002-11-05
CZ152998A3 (cs)	1999-02-17
JP2004067701A (ja)	2004-03-04
SK66298A3 (en)	1999-06-11
NZ330466A (en)	1999-03-29
EP0888352B1 (en)	2003-05-28
ID16375A (id)	1997-09-25
ATE241626T1 (de)	2003-06-15
HUP9900415A3 (en)	2001-11-28
KR100349500B1 (ko)	2002-08-21
MY118282A (en)	2004-09-30
CA2237594C (en)	2006-05-30
JP2002012594A (ja)	2002-01-15
EA199800586A1 (ru)	1998-12-24
DE69722389D1 (de)	2003-07-03
US6218381B1 (en)	2001-04-17
BG102459A (en)	1999-06-30
PL193444B1 (pl)	2007-02-28
NO982124D0 (no)	1998-05-11
IL124572A0 (en)	1998-12-06
EP0888352A1 (en)	1999-01-07
CN1211985A (zh)	1999-03-24
HRP970161B1 (en)	2002-06-30
EA001004B1 (ru)	2000-08-28
HUP9900415A2 (hu)	1999-05-28
PL327985A1 (en)	1999-01-04
CZ294060B6 (cs)	2004-09-15
JP3630434B2 (ja)	2005-03-16
NO310659B1 (no)	2001-08-06
ES2200159T3 (es)	2004-03-01
JP4251447B2 (ja)	2009-04-08
AU2026997A (en)	1997-10-10
TR199801191T2 (xx)	1998-10-21
EE9800281A (et)	1999-02-15
KR20000064358A (ko)	2000-11-06

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