LV10954B - Benzimidazole derivatives, process for their production and a pharmaceutical composition containing the same - Google Patents
Benzimidazole derivatives, process for their production and a pharmaceutical composition containing the same Download PDFInfo
- Publication number
- LV10954B LV10954B LVP-93-1371A LV931371A LV10954B LV 10954 B LV10954 B LV 10954B LV 931371 A LV931371 A LV 931371A LV 10954 B LV10954 B LV 10954B
- Authority
- LV
- Latvia
- Prior art keywords
- carbon atoms
- alkyl
- compound
- alkoxy
- methoxy
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 39
- 230000008569 process Effects 0.000 title claims description 10
- 238000004519 manufacturing process Methods 0.000 title claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 8
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 title claims description 4
- 229940058303 antinematodal benzimidazole derivative Drugs 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 216
- 239000003814 drug Substances 0.000 claims abstract description 6
- 239000004480 active ingredient Substances 0.000 claims abstract description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 129
- 125000000217 alkyl group Chemical group 0.000 claims description 93
- 125000003545 alkoxy group Chemical group 0.000 claims description 73
- -1 cationic cation Chemical class 0.000 claims description 55
- 150000003839 salts Chemical class 0.000 claims description 43
- 150000002367 halogens Chemical class 0.000 claims description 40
- 229910052736 halogen Inorganic materials 0.000 claims description 34
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 238000002360 preparation method Methods 0.000 claims description 24
- 125000001424 substituent group Chemical group 0.000 claims description 21
- 125000006239 protecting group Chemical group 0.000 claims description 13
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
- 125000005843 halogen group Chemical group 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 229910052794 bromium Inorganic materials 0.000 claims description 10
- 239000000460 chlorine Substances 0.000 claims description 10
- 229910052740 iodine Inorganic materials 0.000 claims description 10
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 10
- 241000124008 Mammalia Species 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
- 230000027119 gastric acid secretion Effects 0.000 claims description 8
- 125000002071 phenylalkoxy group Chemical group 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 7
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 7
- 125000004414 alkyl thio group Chemical group 0.000 claims description 7
- 150000001768 cations Chemical class 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 7
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 6
- 125000004660 phenylalkylthio group Chemical group 0.000 claims description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 5
- 230000003287 optical effect Effects 0.000 claims description 5
- 230000001590 oxidative effect Effects 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- 125000001589 carboacyl group Chemical group 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- YKYIFUROKBDHCY-ONEGZZNKSA-N (e)-4-ethoxy-1,1,1-trifluorobut-3-en-2-one Chemical group CCO\C=C\C(=O)C(F)(F)F YKYIFUROKBDHCY-ONEGZZNKSA-N 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 claims description 3
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000001453 quaternary ammonium group Chemical group 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 7
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims 5
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims 4
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims 3
- 241000282414 Homo sapiens Species 0.000 claims 3
- 229910052783 alkali metal Inorganic materials 0.000 claims 3
- 210000001035 gastrointestinal tract Anatomy 0.000 claims 2
- 208000027866 inflammatory disease Diseases 0.000 claims 2
- 241000282412 Homo Species 0.000 claims 1
- 150000001340 alkali metals Chemical class 0.000 claims 1
- 150000004703 alkoxides Chemical class 0.000 claims 1
- 229910052751 metal Inorganic materials 0.000 claims 1
- 239000002184 metal Substances 0.000 claims 1
- 150000002829 nitrogen Chemical class 0.000 claims 1
- 239000011593 sulfur Substances 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 53
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 78
- 239000000243 solution Substances 0.000 description 39
- 239000002253 acid Substances 0.000 description 37
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- 229940073584 methylene chloride Drugs 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 20
- 239000002904 solvent Substances 0.000 description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 14
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- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 159000000000 sodium salts Chemical class 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 8
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- 235000000346 sugar Nutrition 0.000 description 8
- 241000282472 Canis lupus familiaris Species 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 239000013543 active substance Substances 0.000 description 7
- 239000004615 ingredient Substances 0.000 description 7
- 150000004702 methyl esters Chemical class 0.000 description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 6
- 238000001990 intravenous administration Methods 0.000 description 6
- 239000008101 lactose Substances 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 150000003254 radicals Chemical class 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 229940083608 sodium hydroxide Drugs 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 6
- 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 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 5
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- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
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- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 4
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- 229940086542 triethylamine Drugs 0.000 description 4
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 3
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
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Claims (29)
- LV 10954 PATENTA FORMULA 1. Savienojums ar formuluun tā fizioloģiski saderīgi sāļi, kur X ir -S-vai-SO-; R1, R2, R3 un R4, kuri ir vienādi vai dažādi, ir (a) H (b) alkilgrupa, kas satur 1-8 oglekļa atomus (c) alkoksigrupa, kas satur 1-8 oglekļa atomus (d) alkoksialkilgrupa, kas satur 1-3 oglekļa atomus katrā alkildaļā (e) alkoksialkoksigrupa, kas satur 1-3 oglekļa atomus katrā alkildaļā (f) halogēns (g) -COR10 (h) alkiltiogrupa, kas satur 1 -6 oglekļa atomus katrā alkildaļā (i) alkilsulfinilgrupa, kas satur 1-7 oglekļa atomus katrā alkildaļā (j) feni laikiIgrupa vai fenilalkoksigrupa, kas satur 1-6 oglekļa atomus alkildaļā un alkoksidaļā (k) fenilgrupa vai fenoksigrupa, pie kam katra fenilgrupa neobligāti ir aizvietota ar 1-3 aizvietotājiem, kas ir vienādi vai dažādi un izvēlēti no halogēna, CF3, (1-5C)alkilgrupas un (1-5C)alkoksi-grupas (l) halogēnalkoksigrupa, kas satur 1-6 oglekļa atomus un 1-11 halogēna atomus 2 D ir O II -0P-0-R6 , (b) alkilgrupa, kas satur 1-8 oglekļa atomus (c) alkoksigrupa, kas satur 1-8 oglekļa atomus (d) halogēns R8 ir (a) H (b) alkilgrupa, kas satur 1-8 oglekļa atomus (c) alkoksigrupa, kas satur 1-8 oglekļa atomus (d) halogēns (e) fenilalkilgrupa, kas satur 1 -4 oglekļa atomus alkildaļā R7 ir (a) H (b) alkilgrupa, kas satur 1-7 oglekļa atomus (c) alkoksigrupa, kas satur 1-7 oglekļa atomus (d) alkoksialkilgrupa, kas satur 1-3 oglekļa atomus katrā alkildaļā (e) alkoksialkoksigrupa, kas satur 1-3 oglekļa atomus katrā alkildaļā I (f) fenoksigrupa, pie kam fenilgrupa neobligāti ir aizvietota ar 1 vai 2 aizvietotājiem, kas ir vienādi vai dažādi un izvēlēti no halogēna, CF3, (1-3C)alkilgrupas vai (1-3C)alkoksigrupas (g) fenilalkilgrupa vai fenilalkoksigrupa, kas satur 1-7 oglekļa atomus alkildaļā, attiecīgi alkoksidaļā, pie kam fenildaļa neobligāti ir aizvietota ar 1 vai 2 aizvietotājiem, kas ir vienādi vai dažādi un izvēlēti no halogēna, CF3, (1-3C)al-kilgrupas un (1-3C)alkoksigrupas (h) alkeniloksigrupa, kas satur līdz 7 oglekļa atomiem alkenil-dalā I (i) alkiniloksigrupa, kas satur līdz 7 oglekļa atomiem alkinildaļā (j) alkiltiogrupa, kas satur 1 -7 oglekļa atomus alkildaļā (k) feniltiogrupa vai fenilalkiItiogrupa, kas satur 1-3 oglekļa atomus alkildaļā 3 LV 10954 (l) dialkilaminogrupa, kas satur 1-7 oglekļa atomus katrā alkil-dalā I (m) morfolīngrupa (n) piperidīngrupa (o) N-metilpiperazīngrupa (p) pirolidīngrupa (q) fluoralkoksigrupa, kas satur 2-5 oglekļa atomus un 1-9 fluora atomus vai R6 un R7, vai R7 un R8 kopā ar blakus esošo oglekļa atomu piridīna ciklā veido 5- vai 6-locekļu piesātinātu vai nepiesātinātu ciklu, kurš var neobligāti saturēt skābekli, sēru vai neobligāti alkilētu slāpekļa atomu; R9 ir (a) H (b) alkilgrupa, kas satur 1-4 oglekļa atomus; R10 ir (a) alkilgrupa, kas satur 1 -6 oglekļa atomus (b) alkoksigrupa, kas satur 1-6 oglekļa atomus (c) fenilgrupa R8 ir (a) H (b) (1-6C)alkilgrupa (c) fenil(0-3C)alkilgrupa; un pie tam grupa D labāk ir mono- vai di-jonogēna sāls formā, kas satur fizioloģiski saderīgu pretkatjonu ar nosacījumu, ka viens no abiem vai abi R6 un R8 ir halogēns, ja R7 ir dialkilaminogrupa, morfolīngrupa, piperidīngrupa, N-metil-piperazīngrupa vai pirolidīngrupa.
- 2. Savienojums saskaņā ar 1. punktu, kur X ir SO.
- 3. Savienojums saskaņā ar 1. punktu, kur X ir S.
- 4. Savienojums saskaņā ar 1. punktu, kur R1, R2, R3 un R4 ir vienādi vai dažādi un izvēlēti no ūdeņraža, (1-4C)alkilgrupas, (5-6C)ciklo-alkilgrupas, (1 -4C)alkoksigrupas, (1-2C)alkoksi(1-2C)alkilgrupas, (1 -2C)alkoksi(1 -2C)alkoksigrupas, halogēna, (2-4C)alkanoilgrupas, fenilkarbonilgrupas, (1 -2C)alkoksikarbonilgrupas, fenil(1 -3C)alk-oksigrupas, fenilgrupas vai halogēn(1-4C)alkoksigrupas. 4
- 5. Savienojums saskaņā ar 1. punktu, kur R1, R2, R3 un R4 ir (b) alkilgrupa, kas satur 1 -6 oglekļa atomus (c) alkoksigrupa, kas satur 1 -6 oglekļa atomus (I) halogēnalkoksigrupa, kas satur 1-6 oglekļa atomus un 1-6 halogēna atomus; un/vai R6 ir (b) alkilgrupa, kas satur 1 -6 oglekļa atomus (c) alkoksigrupa, kas satur 1 -6 oglekļa atomus; un/vai R8 ir (b) alkilgrupa, kas satur 1 -6 oglekļa atomus (c) alkoksigrupa, kas satur 1 -6 oglekļa atomus; un/vai R7 ir (j) alkiltiogrupa, kas satur 1-3 oglekļa atomus alkildaļā (k) fenilalkiltiogrupa, kas satur 1 oglekļa atomu alkildaļā (l) dialkilaminogrupa, kas satur 1-3 oglekļa atomus katrā alkildaļā.
- 6. Savienojums saskaņā ar 1. punktu, kur R1, R2, R3 un R4 ir H, alkilgrupa, kas satur 1-6 oglekļa atomus, vai alkoksigrupa, kas satur 1-6 oglekļa atomus.
- 7. Savienojums saskaņā ar 1. punktu, kur R\ R2, R3 un R4 visi ir H.
- 8. Savienojums saskaņā ar 1. punktu, kur R1, R3 un R4 ir H un R2 ir OCH3 vai R\ R2 un R4 ir ūdeņradis un R3 ir OCH3.
- 9. Savienojums saskaņā ar 1. punktu, kur R7 ir alkilgrupa, kas satur 1-6 oglekļa atomus, vai alkoksigrupa, kas satur 1 -6 oglekļa atomus.
- 10. Savienojums saskaņā ar 1. punktu, kur R9 ir H.
- 11. Savienojums saskaņā ar 1. punktu, kur D ir 0 II -0P-0-R6 I OH 5 LV 10954 un ta sarmu metālu sāļi, kur Re ir, ka noradīts 1. punktā.
- 12. Savienojums saskaņā ar 1. punktu, kur aizvietotājs benzimidazola cikla 1. pozīcijā ir 0 II -ch2op-oh 1 OH un tā sārmu metālu sāļi.
- 13. Savienojums saskaņā ar 1. punktu, kur aizvietotājs benzimidazola cikla 1. pozīcijā ir O II -CKOP-OCpI-U 2 I 25 OH un tā sārmu metālu sāļi.
- 14. Savienojums saskaņā ar 1. punktu, kur R9 ir H un D ir izvēlēts no 0 II -O-P-OH 1 OCH2-C6H5
- 15. Savienojums saskaņā ar 1. punktu, kur piridina fragments ir aizvietots ar 3,5-dimetil-4-metoksigrupu, 3-metil-4-metoksigrupu-, 5-etil-4-met-oksigrupu, 4-metoksigrupu, 4-etoksigrupu, 4-izopropoksigrupu, 3,5-di-metilgrupu, 3,4-dimetilgrupu, 4,5-dimetilgrupu, 3-metil-4(2,2,2-tri-fluor)etoksigrupu, 3,4-dimetoksigrupu, 4,5-dimetoksigrupu, 3-metil-4--etiltiogrupu, 3-metil-4,5-dimetoksigrupu, 3,4,5-trimetilgrupu, 3-etil-4--metoksigrupu, 3-n-propiM-metoksigrupu, 3-izopropil-4-metoksigrupu vai 3-t-butil-4-metoksigrupu.
- 16. Savienojums saskaņā ar 1. punktu, kur piridina fragments ir aizvietots ar 3,5-dimetil-4-metoksigrupu, 3-metil-4-metoksigrupu-, 3-etil-4-met-oksigrupu, 3-izopropil-4-metoksigrupu, 4-metoksigrupu, 4-etoksigrupu vai 4-izopropoksigrupu. 6
- 17. Savienojums saskaņa ar 1. punktu, kur X ir SO R\ R2, R3 un R4 ir, kā aprakstīts 4. punktā, D ir, kā aprakstīts 11. punktā, un R6 un R8 ir CH3, un R7 ir OCH3.
- 18. Savienojums saskaņā ar 1. punktu, kur piridinilmetilsulfinilbenzimid-azola puses ir7 LV 10954
- 19. Savienojums ar formuluCH.OP-oh ‘ i OH vai tā mono- vai di-jonogēns sāls, kas satur fizioloģiski saderīgu pretkatjonu, kur R2 un R3 ir kombinēti sekojoši: w & H och3 OCH3 H
- 20. Farmaceitiska kompozīcija, kas kā aktīvo sastāvdaļu satur savienojumu saskaņā ar jebkuru no 1. līdz 19. punktiem.
- 21. Savienojums, kā noteikts jebkurā no 1. līdz 19. punktiem, izmantošanai terapijā.
- 22. Savienojums, kā noteikts jebkurā no 1. līdz 19. punktiem, izmantošanai kuņģa skābes sekrēcijas inhibēšanai zīdītājiem un cilvēkam.
- 23. Savienojums, kā norādīts jebkurā no 1. līdz 19. punktiem, izmantošanai zīdītāju un cilvēka gremošanas trakta iekaisuma slimību ārstēšanā.
- 24. Savienojums saskaņā ar jebkuru no 1. līdz 19. punktiem izmantošanai medikamentu ražošanā kuņģa skābes sekrēcijas inhibēšanai zīdītājiem un cilvēkam. 8
- 25. Savienojums saskaņā ar jebkuru no 1. līdz 19. punktiem izmantošanai medikamentu ražošanā zīdītāju un cilvēka gremošanas trakta iekaisuma slimību ārstēšanai.
- 26. Metode savienojuma ar formulu I saskaņā ar 1. punktu izgatavošanai, C. oksidējot savienojumu ar formulu Ikur X ir S un R1, R2, R3, R4, R6, R7, R8, R9 un D ir nozīmes, kas dotas 1. punktā, lai iegūtu savienojumu arto pašu formulu I, kurX irSO; D. liekot reaģēt savienojumam ar formulu IIAIIA kur R1, R2, R3, R4, R6, R7, R8 un X ir, kā norādīts formulai I un Ma ir viens no metāla katjoniem, tāds, kā Na+, K+, Li+ vai Ag+, vai četrvērtīgs amonija jons, tāds, kā tetrabutilamonijs, ar savienojumu ar formulu D-CH-Y I R9 XII 9 LV 10954 kur D un R9 ir, kā norādīts formulai I un Y ir halogēns, tāds, kā Cl, Br vai I, vai funkcionāli līdzvērtīga grupa; vai E. noņemot aizsarggrupu aizvietotājā D; pēc tam, ja vajadzīgs, aizsarggrupas tiek noņemtas un šādi iegūtais savienojums ar formulu I, ja vēlams, tiek pārvērsts sālī vai optiskā izomērā.
- 27. Metode savienojuma ar formulu I saskaņa ar 1. punktu izgatavošanai, liekot reaģēt savienojumam ar formulu IVkur R1, R2, R3, R4, R6, R7, R8 un X ir, kā norādīts formulai I 1. punktā un Z ir halogēns, tāds, kā Cl, vai funkcionāli līdzvērtīga grupa, ar savienojumu ar formulu VI, VII, VIII vai IX 0 II Rp0-P-0-Re 1 OM VI 0 II MO-P-O-R9 I OM VII 0 II MO-P-OM 1 OM VIII 0 II RpO-P-OM I OM IX kur R® ir, kā norādīts iepriekš formulai I, Rp ir aizsarggrupa un M ir pretjons, pēc tam, ja vajadzīgs, aizsarggrupas tiek noņemtas un šādi iegūtais savienojums ar formulu I, ja vēlams, tiek pārvērsts sālī vai optiskā izomērā. 10
- 28. Metode saskaņa ar jebkuru no 26. un 27. punktiem savienojuma saskaņā ar 2.-19. punktiem izgatavošanai.
- 29. Savienojums ar formulu 1015 kur R1, R2, R3, R\ R6, R7, R8 un X ir, ka noradīts 1. punkta, un Z ir halogēns, tāds, kā Cl, Br vai I.
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| SE8604998A SE8604998D0 (sv) | 1986-11-21 | 1986-11-21 | Novel pharmacological compounds |
| SE8605551A SE8605551D0 (sv) | 1986-12-23 | 1986-12-23 | Novel pharmacological compounds |
| SE8704049A SE8704049D0 (sv) | 1987-10-16 | 1987-10-16 | Novel pharmacological compounds |
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| SE8801907D0 (sv) * | 1988-05-20 | 1988-05-20 | Haessle Ab | Novel pharmacological compounds |
| US5175286A (en) * | 1988-09-20 | 1992-12-29 | Hisamitsu Pharmaceutical Co., Inc. | Dibenz[b,e]oxepin derivatives |
| SE8804629D0 (sv) * | 1988-12-22 | 1988-12-22 | Ab Haessle | New therapeutically active compounds |
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| US5274099A (en) * | 1989-12-20 | 1993-12-28 | Aktiebolaget Hassle | Therapeutically active fluoro substituted benzimidazoles |
| US4965269A (en) * | 1989-12-20 | 1990-10-23 | Ab Hassle | Therapeutically active chloro substituted benzimidazoles |
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| DE69132082T2 (de) * | 1990-10-17 | 2000-08-31 | Takeda Chemical Industries Ltd | Pyridin-Derivate, Verfahren zu deren Herstellung und Anwendung |
| SE9103776D0 (sv) * | 1991-12-19 | 1991-12-19 | Astra Ab | New compounds |
| WO1993023409A1 (en) * | 1992-05-21 | 1993-11-25 | Otsuka Pharmaceutical Factory, Inc. | Phosphonic diester derivative |
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| US6051570A (en) * | 1997-05-30 | 2000-04-18 | Dr. Reddy's Research Foundation | Benzimidazole derivatives as antiulcer agents, process for their preparation and pharmaceutical compositions containing them |
| KR20010033811A (ko) * | 1997-12-31 | 2001-04-25 | 토마스 안 빅토리아 | 2차 및 3차 아민을 함유하는 약제의 물에 용해가능한프로드럭 및 그것의 제조방법 |
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| JPS5687818A (en) * | 1979-12-19 | 1981-07-16 | Ishikawajima Harima Heavy Ind Co Ltd | Reflex type position detector |
| US4359465A (en) * | 1980-07-28 | 1982-11-16 | The Upjohn Company | Methods for treating gastrointestinal inflammation |
| CH644116A5 (de) | 1980-08-21 | 1984-07-13 | Hoffmann La Roche | Imidazolderivate. |
| JPS57137860A (en) * | 1981-02-20 | 1982-08-25 | Sumitomo Electric Ind Ltd | Optical tachometer |
| JPS5999597A (ja) * | 1982-11-30 | 1984-06-08 | 株式会社東芝 | 光学測定装置 |
| SE8300736D0 (sv) * | 1983-02-11 | 1983-02-11 | Haessle Ab | Novel pharmacologically active compounds |
| JPS6020051U (ja) * | 1983-07-19 | 1985-02-12 | 三洋電機株式会社 | カセツト収納装置 |
| AU568441B2 (en) | 1984-09-24 | 1987-12-24 | Upjohn Company, The | 2-(pyridylalkenesulfinyl) benzimidazole derivatives |
| IL76839A (en) * | 1984-10-31 | 1988-08-31 | Byk Gulden Lomberg Chem Fab | Picoline derivatives,processes for the preparation thereof and pharmaceutical compositions containing the same |
| SE8505112D0 (sv) * | 1985-10-29 | 1985-10-29 | Haessle Ab | Novel pharmacological compounds |
-
1987
- 1987-11-10 NZ NZ222495A patent/NZ222495A/en unknown
- 1987-11-10 NZ NZ234564A patent/NZ234564A/en unknown
- 1987-11-17 IL IL8450487A patent/IL84504A/en not_active IP Right Cessation
- 1987-11-19 IE IE312587A patent/IE61178B1/en not_active IP Right Cessation
- 1987-11-19 EG EG669/87A patent/EG18379A/xx active
- 1987-11-19 IE IE940326A patent/IE940326L/xx unknown
- 1987-11-19 IS IS3284A patent/IS1565B/is unknown
- 1987-11-20 JP JP63500255A patent/JPH02500744A/ja active Pending
- 1987-11-20 AT AT87850362T patent/ATE84032T1/de not_active IP Right Cessation
- 1987-11-20 RU SU874614294A patent/RU2062778C1/ru active
- 1987-11-20 EP EP87908006A patent/EP0332647A1/en active Pending
- 1987-11-20 AU AU83302/87A patent/AU612129B2/en not_active Ceased
- 1987-11-20 HU HU876196A patent/HU204814B/hu not_active IP Right Cessation
- 1987-11-20 YU YU211087A patent/YU47116B/sh unknown
- 1987-11-20 PT PT86186A patent/PT86186B/pt not_active IP Right Cessation
- 1987-11-20 EP EP92108817A patent/EP0510719A1/en not_active Withdrawn
- 1987-11-20 WO PCT/SE1987/000546 patent/WO1988003921A1/en not_active Application Discontinuation
- 1987-11-20 MY MYPI87003072A patent/MY101784A/en unknown
- 1987-11-20 ES ES87850362T patent/ES2052603T3/es not_active Expired - Lifetime
- 1987-11-20 DE DE8787850362T patent/DE3783356T2/de not_active Expired - Fee Related
- 1987-11-20 EP EP87850362A patent/EP0279149B1/en not_active Expired - Lifetime
- 1987-11-21 PL PL1987268927A patent/PL157655B1/pl unknown
-
1988
- 1988-07-01 DK DK365488A patent/DK365488A/da not_active Application Discontinuation
- 1988-07-20 KR KR1019880700859A patent/KR890700125A/ko not_active Application Discontinuation
- 1988-07-20 NO NO883229A patent/NO173998C/no unknown
-
1989
- 1989-05-19 FI FI892454A patent/FI892454A/fi not_active Application Discontinuation
-
1993
- 1993-03-16 GR GR930400598T patent/GR3007385T3/el unknown
- 1993-12-23 LV LVP-93-1371A patent/LV10954B/en unknown
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