DE68911773T2 - Benzimidazol-Derivate mit pharmakologischer Aktivität. - Google Patents
Benzimidazol-Derivate mit pharmakologischer Aktivität.Info
- Publication number
- DE68911773T2 DE68911773T2 DE68911773T DE68911773T DE68911773T2 DE 68911773 T2 DE68911773 T2 DE 68911773T2 DE 68911773 T DE68911773 T DE 68911773T DE 68911773 T DE68911773 T DE 68911773T DE 68911773 T2 DE68911773 T2 DE 68911773T2
- Authority
- DE
- Germany
- Prior art keywords
- benzimidazole
- ethoxyethyl
- inclusive
- integer
- dimethylaminopropyl
- Prior art date
- 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.)
- Expired - Fee Related
Links
- 229940058303 antinematodal benzimidazole derivative Drugs 0.000 title claims abstract description 7
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 title abstract 2
- 230000000144 pharmacologic effect Effects 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 25
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000002253 acid Substances 0.000 claims abstract description 7
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical group C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims abstract description 6
- 150000003839 salts Chemical class 0.000 claims abstract description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 5
- 231100000252 nontoxic Toxicity 0.000 claims abstract description 5
- 230000003000 nontoxic effect Effects 0.000 claims abstract description 5
- -1 tetrahydrofurfuryl Chemical group 0.000 claims abstract description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 3
- 125000004175 fluorobenzyl group Chemical group 0.000 claims abstract description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims abstract 2
- 150000001556 benzimidazoles Chemical class 0.000 claims description 5
- GNJKPQRRYZIZHK-UHFFFAOYSA-N 3-[1-(2-ethoxyethyl)benzimidazol-2-yl]-n,n-dimethylpropan-1-amine Chemical compound C1=CC=C2N(CCOCC)C(CCCN(C)C)=NC2=C1 GNJKPQRRYZIZHK-UHFFFAOYSA-N 0.000 claims description 3
- UJIKKHVSQJIORR-UHFFFAOYSA-N 2-[1-(2-ethoxyethyl)benzimidazol-2-yl]-n,n-dimethylethanamine Chemical compound C1=CC=C2N(CCOCC)C(CCN(C)C)=NC2=C1 UJIKKHVSQJIORR-UHFFFAOYSA-N 0.000 claims description 2
- GPADADODFARFSV-UHFFFAOYSA-N 3-(1-benzylbenzimidazol-2-yl)-n,n-dimethylpropan-1-amine Chemical compound CN(C)CCCC1=NC2=CC=CC=C2N1CC1=CC=CC=C1 GPADADODFARFSV-UHFFFAOYSA-N 0.000 claims description 2
- KMHNYWITWKFNQW-UHFFFAOYSA-N 3-[1-[(4-fluorophenyl)methyl]benzimidazol-2-yl]-n,n-dimethylpropan-1-amine Chemical compound CN(C)CCCC1=NC2=CC=CC=C2N1CC1=CC=C(F)C=C1 KMHNYWITWKFNQW-UHFFFAOYSA-N 0.000 claims description 2
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
- 150000003254 radicals Chemical group 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims 1
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 230000001387 anti-histamine Effects 0.000 abstract description 4
- 125000004183 alkoxy alkyl group Chemical group 0.000 abstract 1
- 229920006395 saturated elastomer Polymers 0.000 abstract 1
- 241001465754 Metazoa Species 0.000 description 12
- 238000000921 elemental analysis Methods 0.000 description 12
- GPTVQTPMFOLLOA-UHFFFAOYSA-N 1-chloro-2-ethoxyethane Chemical compound CCOCCCl GPTVQTPMFOLLOA-UHFFFAOYSA-N 0.000 description 10
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 10
- 238000000034 method Methods 0.000 description 10
- 229960001340 histamine Drugs 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- JSADNMQUCMCSBS-UHFFFAOYSA-N 3-(1h-benzimidazol-2-yl)-n,n-dimethylpropan-1-amine Chemical compound C1=CC=C2NC(CCCN(C)C)=NC2=C1 JSADNMQUCMCSBS-UHFFFAOYSA-N 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 5
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
- 229960001412 pentobarbital Drugs 0.000 description 4
- 230000004622 sleep time Effects 0.000 description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 4
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Natural products OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 239000000739 antihistaminic agent Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 210000002784 stomach Anatomy 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 2
- QISOBCMNUJQOJU-UHFFFAOYSA-N 4-bromo-1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1NN=CC=1Br QISOBCMNUJQOJU-UHFFFAOYSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229920002873 Polyethylenimine Polymers 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- YECBIJXISLIIDS-UHFFFAOYSA-N mepyramine Chemical compound C1=CC(OC)=CC=C1CN(CCN(C)C)C1=CC=CC=N1 YECBIJXISLIIDS-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 230000011514 reflex Effects 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000001384 succinic acid Substances 0.000 description 2
- 229960000351 terfenadine Drugs 0.000 description 2
- UGLCXJFGJZTCBU-UHFFFAOYSA-N 1-(1h-benzimidazol-2-yl)-5-(dimethylamino)pentan-1-one Chemical compound C1=CC=C2NC(C(=O)CCCCN(C)C)=NC2=C1 UGLCXJFGJZTCBU-UHFFFAOYSA-N 0.000 description 1
- MSRIVCVWSYCUJR-UHFFFAOYSA-N 1-(2-ethoxyethyl)-2-(3-piperidin-1-ylpropyl)benzimidazole Chemical compound N=1C2=CC=CC=C2N(CCOCC)C=1CCCN1CCCCC1 MSRIVCVWSYCUJR-UHFFFAOYSA-N 0.000 description 1
- AVFBCYKITFNXPW-UHFFFAOYSA-N 1-(2-ethoxyethyl)-2-(3-pyrrolidin-1-ylpropyl)benzimidazole Chemical compound N=1C2=CC=CC=C2N(CCOCC)C=1CCCN1CCCC1 AVFBCYKITFNXPW-UHFFFAOYSA-N 0.000 description 1
- IJXVXBFIGJLHPE-UHFFFAOYSA-N 1-(2-ethoxyethyl)-2-(4-piperidin-1-ylbutyl)benzimidazole Chemical compound N=1C2=CC=CC=C2N(CCOCC)C=1CCCCN1CCCCC1 IJXVXBFIGJLHPE-UHFFFAOYSA-N 0.000 description 1
- IZXWCDITFDNEBY-UHFFFAOYSA-N 1-(chloromethyl)-4-fluorobenzene Chemical compound FC1=CC=C(CCl)C=C1 IZXWCDITFDNEBY-UHFFFAOYSA-N 0.000 description 1
- DCRYNQTXGUTACA-UHFFFAOYSA-N 1-ethenylpiperazine Chemical group C=CN1CCNCC1 DCRYNQTXGUTACA-UHFFFAOYSA-N 0.000 description 1
- XLLWSAGWPIQRIC-UHFFFAOYSA-N 2-(1-benzylbenzimidazol-2-yl)-n,n-dimethylethanamine Chemical compound CN(C)CCC1=NC2=CC=CC=C2N1CC1=CC=CC=C1 XLLWSAGWPIQRIC-UHFFFAOYSA-N 0.000 description 1
- HLELOHQPJDTUAB-UHFFFAOYSA-N 2-(1h-benzimidazol-2-yl)-n,n-dimethylethanamine Chemical compound C1=CC=C2NC(CCN(C)C)=NC2=C1 HLELOHQPJDTUAB-UHFFFAOYSA-N 0.000 description 1
- YBZNZLVTLMDPQU-UHFFFAOYSA-N 2-(1h-benzimidazol-2-yl)-n,n-dimethylpropan-1-amine Chemical compound C1=CC=C2NC(C(CN(C)C)C)=NC2=C1 YBZNZLVTLMDPQU-UHFFFAOYSA-N 0.000 description 1
- HYGBHJLTBPTDMR-UHFFFAOYSA-N 2-(3-piperidin-1-ylpropyl)-1h-benzimidazole Chemical compound N=1C2=CC=CC=C2NC=1CCCN1CCCCC1 HYGBHJLTBPTDMR-UHFFFAOYSA-N 0.000 description 1
- WOKMJKFPEQOVSI-UHFFFAOYSA-N 2-(3-pyrrolidin-1-ylpropyl)-1h-benzimidazole Chemical compound N=1C2=CC=CC=C2NC=1CCCN1CCCC1 WOKMJKFPEQOVSI-UHFFFAOYSA-N 0.000 description 1
- RBNYBBQAGXRBCO-UHFFFAOYSA-N 2-(4-piperidin-1-ylbutyl)-1h-benzimidazole Chemical compound N=1C2=CC=CC=C2NC=1CCCCN1CCCCC1 RBNYBBQAGXRBCO-UHFFFAOYSA-N 0.000 description 1
- VOHILFSOWRNVJJ-UHFFFAOYSA-N 2-(bromomethyl)oxolane Chemical compound BrCC1CCCO1 VOHILFSOWRNVJJ-UHFFFAOYSA-N 0.000 description 1
- IVHCSWUKMZEVQR-UHFFFAOYSA-N 2-[1-(2-ethoxyethyl)benzimidazol-2-yl]-n,n-dimethylpropan-1-amine Chemical compound C1=CC=C2N(CCOCC)C(C(C)CN(C)C)=NC2=C1 IVHCSWUKMZEVQR-UHFFFAOYSA-N 0.000 description 1
- GYLPLYCCGIITSG-UHFFFAOYSA-N 3-(1h-benzimidazol-2-yl)-n,n-diethylpropan-1-amine Chemical compound C1=CC=C2NC(CCCN(CC)CC)=NC2=C1 GYLPLYCCGIITSG-UHFFFAOYSA-N 0.000 description 1
- FWTAQZLVKZAMPD-UHFFFAOYSA-N 3-[1-(2-ethoxyethyl)benzimidazol-2-yl]-n,n-diethylpropan-1-amine Chemical compound C1=CC=C2N(CCOCC)C(CCCN(CC)CC)=NC2=C1 FWTAQZLVKZAMPD-UHFFFAOYSA-N 0.000 description 1
- RROHDPSQLOVWIP-UHFFFAOYSA-N 4-(1h-benzimidazol-2-yl)-n,n-dimethylbutan-1-amine Chemical compound C1=CC=C2NC(CCCCN(C)C)=NC2=C1 RROHDPSQLOVWIP-UHFFFAOYSA-N 0.000 description 1
- OXOWTLDONRGYOT-UHFFFAOYSA-N 4-(dimethylamino)butanoic acid Chemical compound CN(C)CCCC(O)=O OXOWTLDONRGYOT-UHFFFAOYSA-N 0.000 description 1
- RIHLZJNHVIZCNO-UHFFFAOYSA-N 4-[1-(2-ethoxyethyl)benzimidazol-2-yl]-n,n-dimethylbutan-1-amine Chemical compound C1=CC=C2N(CCOCC)C(CCCCN(C)C)=NC2=C1 RIHLZJNHVIZCNO-UHFFFAOYSA-N 0.000 description 1
- UYEVTXJVVAHRFL-UHFFFAOYSA-N 5-(dimethylamino)-1-[1-(2-ethoxyethyl)benzimidazol-2-yl]pentan-1-one Chemical compound C1=CC=C2N(CCOCC)C(C(=O)CCCCN(C)C)=NC2=C1 UYEVTXJVVAHRFL-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 102000003834 Histamine H1 Receptors Human genes 0.000 description 1
- 108090000110 Histamine H1 Receptors Proteins 0.000 description 1
- ICFQVBLKMFUCBQ-UHFFFAOYSA-N LSM-31955 Chemical compound C1N(CC)CC(C2=N3)CCCC21C(=O)NC13CCCCC1 ICFQVBLKMFUCBQ-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- ZDIGNSYAACHWNL-UHFFFAOYSA-N brompheniramine Chemical compound C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Br)C=C1 ZDIGNSYAACHWNL-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000000517 effect on sleep Effects 0.000 description 1
- 230000000674 effect on sodium Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 150000002366 halogen compounds Chemical class 0.000 description 1
- 229960004931 histamine dihydrochloride Drugs 0.000 description 1
- PPZMYIBUHIPZOS-UHFFFAOYSA-N histamine dihydrochloride Chemical compound Cl.Cl.NCCC1=CN=CN1 PPZMYIBUHIPZOS-UHFFFAOYSA-N 0.000 description 1
- 229910003480 inorganic solid Inorganic materials 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- UZQMSNUXJVDCHF-UHFFFAOYSA-N n,n-dimethyl-3-[1-(oxolan-2-ylmethyl)benzimidazol-2-yl]propan-1-amine Chemical compound CN(C)CCCC1=NC2=CC=CC=C2N1CC1CCCO1 UZQMSNUXJVDCHF-UHFFFAOYSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/14—Radicals substituted by nitrogen atoms
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S165/00—Heat exchange
- Y10S165/009—Heat exchange having a solid heat storage mass for absorbing heat from one fluid and releasing it to another, i.e. regenerator
- Y10S165/013—Movable heat storage mass with enclosure
- Y10S165/016—Rotary storage mass
- Y10S165/02—Seal and seal-engaging surface are relatively movable
- Y10S165/024—Circumferential seal
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT8821271A IT1226100B (it) | 1988-07-07 | 1988-07-07 | Derivati benzimidazolici farmacologicamente attivi. |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE68911773D1 DE68911773D1 (de) | 1994-02-10 |
| DE68911773T2 true DE68911773T2 (de) | 1994-07-07 |
Family
ID=11179331
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE68911773T Expired - Fee Related DE68911773T2 (de) | 1988-07-07 | 1989-07-06 | Benzimidazol-Derivate mit pharmakologischer Aktivität. |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US4971980A (forum.php) |
| EP (1) | EP0350467B1 (forum.php) |
| JP (1) | JPH0267272A (forum.php) |
| AT (1) | ATE99295T1 (forum.php) |
| DE (1) | DE68911773T2 (forum.php) |
| ES (1) | ES2062098T3 (forum.php) |
| IT (1) | IT1226100B (forum.php) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2665161B1 (fr) * | 1990-07-26 | 1992-11-27 | Esteve Labor Dr | Nouveaux derives de benzimidazole, leur preparation et leur application en tant que medicaments. |
| JP3112290B2 (ja) * | 1990-12-14 | 2000-11-27 | メレルダウファーマスーティカルズ インコーポレイテッド | 抗アレルギー化合物 |
| TW263504B (forum.php) | 1991-10-03 | 1995-11-21 | Pfizer | |
| IT1264456B1 (it) * | 1993-05-14 | 1996-09-23 | Dompe Farmaceutici Spa | Derivati del 2-(benzimidazol-2-il)-1,3-diaminopropano farmacologicamente attivi. |
| GB9413724D0 (en) * | 1994-07-07 | 1994-08-24 | Wellcome Found | Therapeutic nucleosides |
| GB9600143D0 (en) | 1996-01-05 | 1996-03-06 | Wellcome Found | Therapeutic compounds |
| KR100494448B1 (ko) * | 1996-06-04 | 2005-12-02 | 화브리까 에스파놀라 데 프로둑또스 뀌미꼬스 이 화르마세우띠꼬스 쏘시에떼 아노님 | 항히스타민활성을가지는신규한벤조이미다졸유도체 |
| EP0970100B1 (en) | 1997-02-13 | 2003-11-12 | Glaxo Group Limited | Benzimidazole derivatives |
| KR20010020465A (ko) | 1997-06-10 | 2001-03-15 | 그레이엄 브레레톤, 레슬리 에드워즈 | 벤즈이미다졸 유도체 |
| US6455506B1 (en) | 1997-07-30 | 2002-09-24 | Smithkline Beecham Corporation | Lyxofuranosyl benzimidazoles as antiviral agents |
| EP1197487B1 (en) * | 1999-06-28 | 2004-01-14 | Fuji Photo Film Co., Ltd. | Benzimidazole compounds and drugs containing the same |
| HK1046141B (zh) * | 1999-06-28 | 2006-09-22 | 詹森药业有限公司 | 呼吸系统的合胞体病毒复制抑制剂 |
| EP1201664B1 (en) | 1999-06-30 | 2004-09-08 | Fuji Photo Film Co., Ltd. | Benzimidazole compounds and drugs containing the same |
| CA2378007C (en) | 1999-07-07 | 2006-11-28 | Fuji Photo Film Co., Ltd. | Benzimidazole compounds |
| US6349662B1 (en) * | 2000-12-29 | 2002-02-26 | Taco Metals, Inc. | Rub rail |
| CN101374829A (zh) * | 2005-12-19 | 2009-02-25 | 健泰科生物技术公司 | Iap的抑制剂 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1023792A (en) * | 1963-04-17 | 1966-03-23 | Smith & Nephew | Benzimidazole derivatives and processes for making them |
| US3362956A (en) * | 1965-08-19 | 1968-01-09 | Sterling Drug Inc | 1-[(heterocyclyl)-lower-alkyl]-4-substituted-piperazines |
| US4462992A (en) * | 1982-02-08 | 1984-07-31 | Research Corporation | Nitroimidazole radiosensitizers for hypoxic tumor cells and compositions thereof |
| JPS59199679A (ja) * | 1983-04-27 | 1984-11-12 | Kanebo Ltd | 新規なベンズイミダゾ−ル誘導体、その製造法およびその医薬組成物 |
| US4728741A (en) * | 1985-01-08 | 1988-03-01 | Smithkline Beckman Corporation | 1-substituted-2-mercapto benzimidazole compounds and intermediates |
-
1988
- 1988-07-07 IT IT8821271A patent/IT1226100B/it active
-
1989
- 1989-07-06 US US07/376,075 patent/US4971980A/en not_active Expired - Fee Related
- 1989-07-06 JP JP1173174A patent/JPH0267272A/ja active Granted
- 1989-07-06 ES ES89830312T patent/ES2062098T3/es not_active Expired - Lifetime
- 1989-07-06 EP EP89830312A patent/EP0350467B1/en not_active Expired - Lifetime
- 1989-07-06 AT AT89830312T patent/ATE99295T1/de active
- 1989-07-06 DE DE68911773T patent/DE68911773T2/de not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| ATE99295T1 (de) | 1994-01-15 |
| JPH0267272A (ja) | 1990-03-07 |
| EP0350467A1 (en) | 1990-01-10 |
| EP0350467B1 (en) | 1993-12-29 |
| DE68911773D1 (de) | 1994-02-10 |
| US4971980A (en) | 1990-11-20 |
| IT1226100B (it) | 1990-12-10 |
| JPH0567624B2 (forum.php) | 1993-09-27 |
| IT8821271A0 (it) | 1988-07-07 |
| ES2062098T3 (es) | 1994-12-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE68911773T2 (de) | Benzimidazol-Derivate mit pharmakologischer Aktivität. | |
| DE69429717T2 (de) | Heterocyclische verbindungen und ihre herstellung und verwendung | |
| DE69128145T2 (de) | 1,2,5,6-tetrahydro-1-methylpyridine, ihre herstellung und anwendung | |
| DE69326650T2 (de) | Piperidinderivate von Benzimidazole als antihistaminische und antiallergische Mittel | |
| DE69114848T2 (de) | Heterozyklische verbindungen, ihre herstellung und anwendung. | |
| DE69210875T2 (de) | Piperidinderivate, Verfahren zu deren Herstellung und deren therapeutische Anwendung | |
| DE2203373A1 (de) | Neue Imidazolinderivate,Verfahren zu deren Herstellung und diese enthaltende pharmazeutische Praeparate | |
| EP0670318A2 (de) | Acetamide mit analgetischer und neuroprotektiver Wirkung | |
| DE1117584B (de) | Verfahren zur Herstellung von Phentiazinderivaten | |
| DE69722281T2 (de) | 3-Aza-piperidon- (Tetrahydropyrimidin-2-on) und 3-Oxa-piperidon (1,3-Oxazin-2-on) Derivate, deren Herstellung und deren Verwendung als Tachykinin/Neurokinin Antagonisten | |
| DE69013602T2 (de) | Arzneimittel. | |
| DE2854308A1 (de) | Anticholinergische substanzen mit antisekretorischer wirkung, ihre herstellung und verwendung | |
| DE69021355T2 (de) | Pyridon-Derivate, Herstellungsprozess, neu erhaltene Zwischenprodukte und ihre Verwendung als Arzneimittel sowie Arzneimittelzusammensetzungen, die diese enthalten. | |
| DE69302087T2 (de) | Trazodone alkyl derivate mit zns wirkung | |
| DE69120438T2 (de) | 20-21-Dinoreburnamenin-Derivate, Verfahren zu ihrer Herstellung und Zwischenverbindungen, ihre Anwendung als Arzneimittel und diese enthaltende Zusammenstellungen | |
| DE19602505A1 (de) | 1-(Pyrazol-4-Indol-3-yl)-Piperidine | |
| DE2724478C2 (de) | 5,11-Dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-on-derivate, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel | |
| DE68905363T2 (de) | Heterotetracyclische laktamderivate, verfahren zu ihrer herstellung und pharmazeutische zubereitungen, die sie enthalten. | |
| DE3028064C2 (forum.php) | ||
| DE69617001T2 (de) | (2-morpholinylmethyl)benzamid-derivate | |
| DE2425767A1 (de) | 3-alkyl-9-aminoalkyl-1,2,3,4-tetrahydrocarbazole und ihre verwendung in arzneimitteln | |
| DE4019080A1 (de) | Neue 3,7-diazabicycolo (3,3,1)nonan-verbindungen enthaltende arzneimittel | |
| DE69131353T2 (de) | Indolderivate | |
| DE68913167T2 (de) | Indol-Derivate, Verfahren zu ihrer Herstellung und sie enthaltende pharmazeutische Präparate. | |
| DE69101740T2 (de) | (1-Phenylpyrrolidin-2-yl)methylpiperazinderivate, Verfahren zur Herstellung und therapeutische Anwendung. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |