CZ289278B6 - Benzimidazolové deriváty s antihistaminickou aktivitou - Google Patents
Benzimidazolové deriváty s antihistaminickou aktivitou Download PDFInfo
- Publication number
- CZ289278B6 CZ289278B6 CZ19971723A CZ172397A CZ289278B6 CZ 289278 B6 CZ289278 B6 CZ 289278B6 CZ 19971723 A CZ19971723 A CZ 19971723A CZ 172397 A CZ172397 A CZ 172397A CZ 289278 B6 CZ289278 B6 CZ 289278B6
- Authority
- CZ
- Czechia
- Prior art keywords
- ethyl
- phenyl
- piperidin
- dimethyl
- benzimidazole
- Prior art date
Links
- 230000001387 anti-histamine Effects 0.000 title claims abstract description 12
- 229940058303 antinematodal benzimidazole derivative Drugs 0.000 title abstract description 5
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 title abstract description 3
- 230000001747 exhibiting effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 32
- -1 4,4-dimethyl-2- oxazolinyl Chemical group 0.000 claims abstract description 18
- 239000000739 antihistaminic agent Substances 0.000 claims abstract description 16
- 239000002253 acid Substances 0.000 claims abstract description 13
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 11
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 239000001257 hydrogen Substances 0.000 claims abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 6
- 150000007513 acids Chemical class 0.000 claims abstract description 5
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims abstract 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 9
- 150000001556 benzimidazoles Chemical class 0.000 claims description 8
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 4
- 125000004278 2-oxazolin-2-yl group Chemical group [H]C1([H])OC(*)=NC1([H])[H] 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- RMALIQMLRXZLAU-UHFFFAOYSA-N 2-[4-[2-[4-[1-(2-hydroxyethyl)benzimidazol-2-yl]piperidin-1-yl]ethyl]phenyl]-2-methylpropanoic acid Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1CCN1CCC(C=2N(C3=CC=CC=C3N=2)CCO)CC1 RMALIQMLRXZLAU-UHFFFAOYSA-N 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- LGGVQONVCGKZQF-UHFFFAOYSA-N ethyl 2-[4-[2-[4-[1-(2-ethoxyethyl)benzimidazol-2-yl]piperidin-1-yl]ethyl]phenyl]-2-methylpropanoate Chemical compound N=1C2=CC=CC=C2N(CCOCC)C=1C(CC1)CCN1CCC1=CC=C(C(C)(C)C(=O)OCC)C=C1 LGGVQONVCGKZQF-UHFFFAOYSA-N 0.000 claims description 2
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims 1
- ACCMWZWAEFYUGZ-UHFFFAOYSA-N bilastine Chemical compound N=1C2=CC=CC=C2N(CCOCC)C=1C(CC1)CCN1CCC1=CC=C(C(C)(C)C(O)=O)C=C1 ACCMWZWAEFYUGZ-UHFFFAOYSA-N 0.000 claims 1
- 108010011222 cyclo(Arg-Pro) Chemical group 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 8
- 210000003169 central nervous system Anatomy 0.000 abstract description 6
- 230000003266 anti-allergic effect Effects 0.000 abstract description 4
- 210000000748 cardiovascular system Anatomy 0.000 abstract description 4
- 125000000753 cycloalkyl group Chemical group 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract description 2
- 125000004432 carbon atom Chemical group C* 0.000 abstract 4
- 239000013543 active substance Substances 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 229940125715 antihistaminic agent Drugs 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 230000000144 pharmacologic effect Effects 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 230000009471 action Effects 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 4
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 3
- 241000700199 Cavia porcellus Species 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 210000003405 ileum Anatomy 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 229910000103 lithium hydride Inorganic materials 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
- MMHBELNONNBOIY-UHFFFAOYSA-N 2-[4-[2-[4-[1-(2-ethoxyethyl)benzimidazol-2-yl]piperidin-1-yl]ethyl]phenyl]-2-methylpropan-1-ol Chemical compound N=1C2=CC=CC=C2N(CCOCC)C=1C(CC1)CCN1CCC1=CC=C(C(C)(C)CO)C=C1 MMHBELNONNBOIY-UHFFFAOYSA-N 0.000 description 2
- HBOGHPAOOWUTLB-UHFFFAOYSA-N 2-piperidin-4-yl-1h-benzimidazole Chemical compound C1CNCCC1C1=NC2=CC=CC=C2N1 HBOGHPAOOWUTLB-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 238000007126 N-alkylation reaction Methods 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 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 2
- 239000000654 additive Substances 0.000 description 2
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 2
- 150000008046 alkali metal hydrides Chemical class 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- 230000004856 capillary permeability Effects 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 229960001340 histamine Drugs 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 239000012053 oil suspension Substances 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 229920002554 vinyl polymer Polymers 0.000 description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- UOUIKYFLNQXAFR-UHFFFAOYSA-N 1h-benzimidazole;piperidine Chemical class C1CCNCC1.C1=CC=C2NC=NC2=C1 UOUIKYFLNQXAFR-UHFFFAOYSA-N 0.000 description 1
- 206010027654 Allergic conditions Diseases 0.000 description 1
- ZNSMNVMLTJELDZ-UHFFFAOYSA-N Bis(2-chloroethyl)ether Chemical compound ClCCOCCCl ZNSMNVMLTJELDZ-UHFFFAOYSA-N 0.000 description 1
- 208000020446 Cardiac disease Diseases 0.000 description 1
- 206010010744 Conjunctivitis allergic Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229940122236 Histamine receptor antagonist Drugs 0.000 description 1
- 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 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 206010047281 Ventricular arrhythmia Diseases 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 201000009961 allergic asthma Diseases 0.000 description 1
- 208000002205 allergic conjunctivitis Diseases 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 201000010435 allergic urticaria Diseases 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- 230000003126 arrythmogenic effect Effects 0.000 description 1
- GXDALQBWZGODGZ-UHFFFAOYSA-N astemizole Chemical compound C1=CC(OC)=CC=C1CCN1CCC(NC=2N(C3=CC=CC=C3N=2)CC=2C=CC(F)=CC=2)CC1 GXDALQBWZGODGZ-UHFFFAOYSA-N 0.000 description 1
- 229960004754 astemizole Drugs 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 208000024998 atopic conjunctivitis Diseases 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000001451 cardiotoxic effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 206010013781 dry mouth Diseases 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- VEUUMBGHMNQHGO-UHFFFAOYSA-N ethyl chloroacetate Chemical compound CCOC(=O)CCl VEUUMBGHMNQHGO-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000037023 motor activity Effects 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 102220240796 rs553605556 Human genes 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229960000351 terfenadine Drugs 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
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
- C07D401/04—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 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES09601236A ES2124167B1 (es) | 1996-06-04 | 1996-06-04 | Nuevos derivados del bencimidazol con actividad antihistaminica. |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CZ172397A3 CZ172397A3 (en) | 1997-12-17 |
| CZ289278B6 true CZ289278B6 (cs) | 2001-12-12 |
Family
ID=8295035
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CZ19971723A CZ289278B6 (cs) | 1996-06-04 | 1997-06-04 | Benzimidazolové deriváty s antihistaminickou aktivitou |
Country Status (27)
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6545009B1 (en) | 1998-07-01 | 2003-04-08 | Takeda Chemical Industries, Ltd. | Retinoid-related receptor function regulating agent |
| HUP0200749A3 (en) | 1998-11-27 | 2003-03-28 | Basf Ag | Substituted benzimidazoles and their use as parp inhibitors and process for their preparation |
| ES2151442B1 (es) * | 1999-01-11 | 2001-07-01 | Espanola Prod Quimicos | Nuevo derivado del bencenoetanol. |
| US6826561B2 (en) | 2000-05-22 | 2004-11-30 | Broadcom Corporation | Method and apparatus for performing a binary search on an expanded tree |
| RU2288917C2 (ru) * | 2002-04-19 | 2006-12-10 | Фаэс Фарма, С.А. | Полиморф 4-[2-[4-[1-(2-этоксиэтил)-1h-бензимидазол-2-ил]-1-пиперидинил]этил]-альфа, альфа-диметилбензолуксусной кислоты, способ его получения, фармацевтический препарат на его основе и его применение |
| HU230032B1 (hu) * | 2002-04-19 | 2015-05-28 | Faes Farma, S.A | Polimorf 4-{2-[4-[1-(2-etoxietil)-1H-benzimidazol-2-il]-1-piperidinil]etil}-alfa,alfa-dimetil-benzenoecetsav |
| CA2489128C (en) * | 2002-06-13 | 2012-01-03 | Vertex Pharmaceuticals Incorporated | 2-ureido-6-heteroaryl-3h-benzoimidazole-4-carboxylic acid derivatives and related compounds as gyrase and/or topoisomerase iv inhibitors for the treatment of bacterial infections |
| US20070188330A1 (en) * | 2006-01-24 | 2007-08-16 | Morhard Robert C | System and method for detecting, monitoring, tracking and identifying explosive materials using ID marks |
| US7247623B2 (en) * | 2005-08-19 | 2007-07-24 | Inspire Pharmaceuticals, Inc. | Method of treating dry eye disease with non-drying antihistamines |
| KR101123903B1 (ko) * | 2008-02-12 | 2012-03-23 | 주식회사유한양행 | 2-메틸-2'-페닐프로피온산 유도체의 제조 방법 및 이에 사용되는 신규한 중간체 화합물 |
| JP2010013472A (ja) * | 2009-09-09 | 2010-01-21 | Faes Farma Sa | ４−［２−［１−（２−エトキシエチル）−１Ｈ−ベンズイミダゾール−２−イル］−１−ピペリジニル］エチル］−α，α−ジメチルベンゼノ酢酸の多形体 |
| CN102675101B (zh) * | 2012-05-16 | 2014-01-29 | 王蕾 | 2-(4-卤乙基)苯基-2-甲基丙酸酯的制备方法及合成比拉斯汀的方法 |
| CZ307500B6 (cs) | 2012-08-15 | 2018-10-24 | Zentiva, K.S. | Způsob přípravy derivátu 2-methyl-2´-fenylpropionové kyseliny využívající nové intermediáty |
| CN105209122B (zh) * | 2013-03-15 | 2018-07-17 | 赫尔克里士公司 | 组合物和制备具有提高的沉积性能的个人护理组合物的方法 |
| CN103214455B (zh) * | 2013-03-30 | 2018-08-31 | 北京万全德众医药生物技术有限公司 | 一种比拉斯汀的制备方法 |
| CN103214454A (zh) * | 2013-03-30 | 2013-07-24 | 北京万全德众医药生物技术有限公司 | 一种比拉斯汀晶型及制备方法 |
| WO2014188453A2 (en) * | 2013-05-24 | 2014-11-27 | Msn Laboratories Private Limited | Novel process for the preparation of 2-[4-(2-{4-[1-(2-ethoxyethyl)-1h-benzimidazol-2-yl]-1-piperidinyl}ethyl) phenyl]-2-methylpropanoic acid |
| CN103351380B (zh) * | 2013-06-30 | 2019-01-22 | 北京万全德众医药生物技术有限公司 | 一种制备比拉斯汀的方法 |
| CN104447683A (zh) * | 2013-09-12 | 2015-03-25 | 天津市汉康医药生物技术有限公司 | 一种稳定的比拉斯汀化合物 |
| CN103896915A (zh) * | 2014-04-01 | 2014-07-02 | 中国药科大学 | 苯并咪唑类衍生物、其制备方法及其在医药上的应用 |
| EP3040334A1 (en) | 2014-12-29 | 2016-07-06 | Faes Farma, S.A. | New benzimidazole derivatives as antihistamine agents |
| CN106349214B (zh) * | 2015-07-13 | 2020-11-03 | 南京长澳医药科技有限公司 | 一种比拉斯汀杂质的制备方法 |
| WO2017017301A1 (es) * | 2015-07-24 | 2017-02-02 | Urquima, S.A | Formas cristalinas de bilastina y procedimientos para su preparación |
| CN105272977A (zh) * | 2015-09-19 | 2016-01-27 | 万全万特制药江苏有限公司 | 一种制备比拉斯汀中间体的方法 |
| EP3170816A1 (en) | 2015-11-20 | 2017-05-24 | Faes Farma, S.A. | Supersaturated compositions of benzimidazole compounds |
| EP3170817A1 (en) | 2015-11-20 | 2017-05-24 | Faes Farma, S.A. | Co-crystals of benzimidazole compounds |
| WO2017167949A1 (en) | 2016-04-01 | 2017-10-05 | Krka, D.D., Novo Mesto | Crystalline forms of bilastine |
| EP3452462A4 (en) * | 2016-05-05 | 2019-10-23 | MSN Laboratories Private Limited, R&D Center | Solid state forms of 2-[4-(2-{4-[1-(2-ethoxyethyl)-1h-benzimidazol-2-yl]-1-piperidinyl}ethyl)phenyl]-2-methylpropanoic acid and process for preparation thereof |
| CN107365298A (zh) * | 2017-03-14 | 2017-11-21 | 罗欣生物科技（上海）有限公司 | 一种2‑甲基‑2’‑苯基丙酸衍生物的制备方法 |
| CN109456316A (zh) * | 2017-09-06 | 2019-03-12 | 万全万特制药江苏有限公司 | 一种比拉斯汀杂质的制备方法 |
| ES2813561T3 (es) | 2017-09-07 | 2021-03-24 | Tiefenbacher Alfred E Gmbh & Co Kg | Composición farmacéutica en comprimido que comprende bilastina |
| HUE053233T2 (hu) | 2017-10-16 | 2021-06-28 | Faes Farma Sa | Bilasztint és mometanzont tartalmazó vizes készítmények |
| ES2864176T3 (es) | 2017-12-18 | 2021-10-13 | Tiefenbacher Alfred E Gmbh & Co Kg | Composición farmacéutica en comprimido que comprende la forma 3 de bilastina y una carga soluble en agua |
| EP3470062B1 (en) | 2017-12-18 | 2020-10-28 | Alfred E. Tiefenbacher (GmbH & Co. KG) | Pharmaceutical tablet composition comprising bilastine polymorphic form 3 and magnesium aluminometasilicate |
| MA51612B1 (fr) | 2018-01-18 | 2021-06-30 | Faes Farma Sa | Compositions ophtalmiques comprenant de la bilastine, une bêta-cyclodextrine et au moins un agent gélifiant |
| CN109081827A (zh) * | 2018-11-06 | 2018-12-25 | 北京天弘天达医药科技股份有限公司 | 一种比拉斯汀的制备方法及应用 |
| EP3725298A1 (en) | 2019-04-16 | 2020-10-21 | Faes Farma, S.A. | Stable and preserved pharmaceutical compositions of bilastine |
| EP4188339A1 (en) | 2020-07-30 | 2023-06-07 | Faes Farma, S.A. | Decongestant drug delivery system |
| CN112110893A (zh) * | 2020-10-28 | 2020-12-22 | 山东齐环医药科技有限公司 | 一种比拉斯汀的制备方法 |
| EP4247331A1 (en) | 2020-11-18 | 2023-09-27 | BioPharma Synergies, S. L. | Orodispersible powder composition comprising an antihistamine compound |
| EP4267109A1 (en) | 2020-12-23 | 2023-11-01 | Noucor Health S.A. | A non-micronized bilastine composition |
| WO2023156559A1 (en) | 2022-02-17 | 2023-08-24 | Faes Farma, S.A. | Bilastine composition for once-daily parenteral administration |
| WO2024224308A1 (en) * | 2023-04-27 | 2024-10-31 | Leiutis Pharmaceuticals Llp | Liquid parenteral formulations of bilastine free of cyclodextrins |
| WO2024224326A1 (en) * | 2023-04-27 | 2024-10-31 | Leiutis Pharmaceuticals Llp | Liquid parenteral formulations of bilastine |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8904174D0 (en) * | 1989-02-23 | 1989-04-05 | British Bio Technology | Compounds |
| CA2077897A1 (en) * | 1990-04-13 | 1991-10-14 | Robert G. Franz | Substituted benzimidazoles |
| ES2048109B1 (es) * | 1992-07-20 | 1994-12-16 | Espanola Prod Quimicos | Procedimiento de preparacion de nuevos derivados piperidicos del bencimidazol. |
| DK0701443T4 (da) * | 1992-08-03 | 2000-12-18 | Sepracor Inc | Terfenadinmetabolitter og deres optisk rene isomerer til behandling af allergiske lidelser |
| AU699559B2 (en) * | 1993-06-25 | 1998-12-10 | Aventisub Ii Inc. | Novel intermediates for the preparation of antihistaminic piperidine derivatives |
-
1996
- 1996-06-04 ES ES09601236A patent/ES2124167B1/es not_active Expired - Fee Related
-
1997
- 1997-06-03 PT PT97500099T patent/PT818454E/pt unknown
- 1997-06-03 RU RU97108980/04A patent/RU2182150C2/ru active
- 1997-06-03 AT AT97500099T patent/ATE264317T1/de active
- 1997-06-03 DE DE69728608T patent/DE69728608T2/de not_active Expired - Lifetime
- 1997-06-03 NO NO19972525A patent/NO313195B1/no not_active IP Right Cessation
- 1997-06-03 EP EP97500099A patent/EP0818454B1/en not_active Expired - Lifetime
- 1997-06-03 ZA ZA9704893A patent/ZA974893B/xx unknown
- 1997-06-03 AU AU24672/97A patent/AU725700B2/en not_active Expired
- 1997-06-03 DE DE122011000006C patent/DE122011000006I1/de active Pending
- 1997-06-03 CA CA002206754A patent/CA2206754C/en not_active Expired - Lifetime
- 1997-06-03 DK DK97500099T patent/DK0818454T3/da active
- 1997-06-03 HR HR970307A patent/HRP970307B1/xx not_active IP Right Cessation
- 1997-06-03 SI SI9730652T patent/SI0818454T1/xx unknown
- 1997-06-04 HU HU9700997A patent/HU227598B1/hu active Protection Beyond IP Right Term
- 1997-06-04 MX MXPA97004127A patent/MXPA97004127A/es active IP Right Grant
- 1997-06-04 TR TR97/00464A patent/TR199700464A2/xx unknown
- 1997-06-04 CN CN97114905A patent/CN1105716C/zh not_active Expired - Lifetime
- 1997-06-04 PL PL97320358A patent/PL188908B1/pl unknown
- 1997-06-04 BR BR9703276-0A patent/BR9703276A/pt not_active IP Right Cessation
- 1997-06-04 JP JP16201097A patent/JP4218991B2/ja not_active Expired - Lifetime
- 1997-06-04 CZ CZ19971723A patent/CZ289278B6/cs not_active IP Right Cessation
- 1997-06-04 US US08/868,743 patent/US5877187A/en not_active Expired - Lifetime
- 1997-06-04 IN IN1498DE1997 patent/IN186319B/en unknown
- 1997-06-05 AR ARP970102441A patent/AR008386A1/es active IP Right Grant
- 1997-07-22 TW TW086110371A patent/TW438794B/zh not_active IP Right Cessation
-
2011
- 2011-03-22 LU LU91798C patent/LU91798I2/fr unknown
- 2011-05-24 NO NO2011008C patent/NO2011008I2/no unknown
- 2011-07-08 FR FR11C0023C patent/FR11C0023I2/fr active Active
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CZ289278B6 (cs) | Benzimidazolové deriváty s antihistaminickou aktivitou | |
| CA2100503C (en) | Piperidine derivatives of benzimidazole | |
| US6130235A (en) | Compounds and methods to treat cardiac failure and other disorders | |
| JP3048067B2 (ja) | 新規方法 | |
| EP1513826B1 (en) | New indolylpiperidine derivatives as potent antihistaminic and antiallergic agents | |
| US5019583A (en) | N-phenyl-N-(4-piperidinyl)amides useful as analgesics | |
| JP2944221B2 (ja) | 新規複素環式化合物 | |
| US20030073699A1 (en) | Compounds and methods to treat cardiac failure and other disorders | |
| JP2000512646A (ja) | ５ｈｔ７受容体アンタゴニストとしてのスルホンアミド誘導体 | |
| JP3060054B2 (ja) | ベンゾイミダゾールから誘導される非鎮静性抗ヒスタミン作用を有する新規化合物 | |
| KR100683454B1 (ko) | 항히스타민제 그리고 항알레르기제로서의 인돌일피페리딘유도체 | |
| JP2002541104A (ja) | ピロリジン系ケモカイン受容体活性調節剤 | |
| CZ316497A3 (cs) | Nové heterocyklické sloučeniny | |
| US6054458A (en) | Heterocyclic compounds | |
| FI91748B (fi) | Menetelmä terapeuttisesti käyttökelpoisten kinolinonijohdannaisten valmistamiseksi | |
| DK167118B1 (da) | Substituerede benzylphthalazinonderivater, fremgangsmaade til fremstilling deraf, laegemidler indeholdende derivaterne, samt anvendelse af derivaterne til fremstilling af laegemidler | |
| JP6585718B2 (ja) | 抗ヒスタミン剤としての新規ベンゾイミダゾール誘導体 | |
| RU2418794C2 (ru) | ПРОИЗВОДНЫЕ ИЗОХИНОЛИНА И БЕНЗО[h]ИЗОХИНОЛИНА, ИХ ПОЛУЧЕНИЕ И ИХ ПРИМЕНЕНИЕ В ТЕРАПИИ В КАЧЕСТВЕ АНТАГОНИСТОВ РЕЦЕПТОРА ГИСТАМИНА H3 | |
| CZ46896A3 (en) | Anti-migraine 1,2,5-thiadiazole derivatives of indolylalkyl-pyridinyl and -pyrimidinyl piperazines | |
| JPH08151377A (ja) | キナゾリン誘導体 | |
| KR100494448B1 (ko) | 항히스타민활성을가지는신규한벤조이미다졸유도체 | |
| JP2573195B2 (ja) | 環状アミン誘導体 | |
| WO1991000275A1 (en) | Butane compounds or salts thereof and their medical uses |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PD00 | Pending as of 2000-06-30 in czech republic | ||
| MK4A | Patent expired |
Effective date: 20170604 |
|
| MK4A | Patent expired |
Effective date: 20220604 |