ES2687420T3 - Profármacos de éster de [3-(1-(1H-imidazol-4-il)etil)-2-metilfenil]-metanol para tratar enfermedades y afecciones de la piel - Google Patents
Profármacos de éster de [3-(1-(1H-imidazol-4-il)etil)-2-metilfenil]-metanol para tratar enfermedades y afecciones de la piel Download PDFInfo
- Publication number
- ES2687420T3 ES2687420T3 ES16161920.0T ES16161920T ES2687420T3 ES 2687420 T3 ES2687420 T3 ES 2687420T3 ES 16161920 T ES16161920 T ES 16161920T ES 2687420 T3 ES2687420 T3 ES 2687420T3
- Authority
- ES
- Spain
- Prior art keywords
- methyl
- ethyl
- imidazol
- acid
- ester
- 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.)
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- -1 [3- (1- (1 H -imidazol-4-yl) ethyl) -2-methylphenyl] -methanol ester Chemical class 0.000 title claims abstract description 93
- 208000017520 skin disease Diseases 0.000 title claims abstract description 36
- 229940002612 prodrug Drugs 0.000 title description 49
- 239000000651 prodrug Substances 0.000 title description 49
- 150000001875 compounds Chemical class 0.000 claims abstract description 78
- 239000000203 mixture Substances 0.000 claims abstract description 59
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 34
- 150000003839 salts Chemical class 0.000 claims abstract description 33
- 238000011282 treatment Methods 0.000 claims abstract description 25
- 201000008937 atopic dermatitis Diseases 0.000 claims abstract description 24
- 125000003118 aryl group Chemical group 0.000 claims abstract description 23
- 201000004700 rosacea Diseases 0.000 claims abstract description 22
- 241001303601 Rosacea Species 0.000 claims abstract description 17
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 17
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 16
- 206010012438 Dermatitis atopic Diseases 0.000 claims abstract description 16
- 208000033830 Hot Flashes Diseases 0.000 claims abstract description 16
- 206010060800 Hot flush Diseases 0.000 claims abstract description 16
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims abstract description 14
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 14
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 10
- 150000002367 halogens Chemical group 0.000 claims abstract description 10
- 208000002874 Acne Vulgaris Diseases 0.000 claims abstract description 9
- 206010015150 Erythema Diseases 0.000 claims abstract description 9
- 206010000496 acne Diseases 0.000 claims abstract description 9
- 206010012434 Dermatitis allergic Diseases 0.000 claims abstract description 8
- 206010051246 Photodermatosis Diseases 0.000 claims abstract description 8
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- 206010039793 Seborrhoeic dermatitis Diseases 0.000 claims abstract description 8
- 206010042496 Sunburn Diseases 0.000 claims abstract description 8
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- 230000001684 chronic effect Effects 0.000 claims abstract description 8
- 231100000321 erythema Toxicity 0.000 claims abstract description 8
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- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 8
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- 150000004677 hydrates Chemical class 0.000 claims abstract description 7
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 7
- 239000012453 solvate Substances 0.000 claims abstract description 7
- 150000001335 aliphatic alkanes Chemical group 0.000 claims abstract description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract 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 claims abstract description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
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- 150000001408 amides Chemical group 0.000 claims abstract description 4
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- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 4
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 4
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000003277 amino group Chemical group 0.000 claims abstract description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 3
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- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims description 59
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- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 19
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 claims description 16
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 claims description 14
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- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Chemical compound OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 5
- ZYJPUMXJBDHSIF-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoic acid Chemical compound CC(C)(C)OC(=O)NC(C(O)=O)CC1=CC=CC=C1 ZYJPUMXJBDHSIF-UHFFFAOYSA-N 0.000 claims description 4
- 239000008177 pharmaceutical agent Substances 0.000 claims 8
- 239000005022 packaging material Substances 0.000 claims 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 125000004429 atom Chemical group 0.000 abstract description 4
- 125000002619 bicyclic group Chemical group 0.000 abstract 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract 1
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- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 58
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 48
- 238000000034 method Methods 0.000 description 44
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- HTQCEFAVROSRIW-UHFFFAOYSA-N [3-[1-(1h-imidazol-5-yl)ethyl]-2-methylphenyl]methanol Chemical compound C=1C=CC(CO)=C(C)C=1C(C)C1=CNC=N1 HTQCEFAVROSRIW-UHFFFAOYSA-N 0.000 description 22
- HTQCEFAVROSRIW-JTQLQIEISA-N [3-[(1s)-1-(1h-imidazol-5-yl)ethyl]-2-methylphenyl]methanol Chemical group C1([C@@H](C)C=2C(=C(CO)C=CC=2)C)=CNC=N1 HTQCEFAVROSRIW-JTQLQIEISA-N 0.000 description 18
- 239000000543 intermediate Substances 0.000 description 17
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 16
- 239000003795 chemical substances by application Substances 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
- 239000002085 irritant Substances 0.000 description 14
- 231100000021 irritant Toxicity 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- HTQCEFAVROSRIW-SNVBAGLBSA-N [3-[(1r)-1-(1h-imidazol-5-yl)ethyl]-2-methylphenyl]methanol Chemical compound C1([C@H](C)C=2C(=C(CO)C=CC=2)C)=CNC=N1 HTQCEFAVROSRIW-SNVBAGLBSA-N 0.000 description 12
- 235000013334 alcoholic beverage Nutrition 0.000 description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 235000019439 ethyl acetate Nutrition 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
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- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- 229960004295 valine Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4174—Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Ophthalmology & Optometry (AREA)
- Dermatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
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| US383370P | 2010-09-16 |
Publications (1)
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Family
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| ES18160174T Active ES2781681T3 (es) | 2010-09-16 | 2011-09-16 | Profármacos de ésteres de [3-(1-(1H-imidazol-4-il)etil)-2-metilfenil]-metanol para reducir la presión intraocular |
| ES16161922.6T Active ES2684055T3 (es) | 2010-09-16 | 2011-09-16 | Profármacos de éster de [3-(1-(1H-imidazol-4-il)etil)-2-metilfenil]-metanol para reducir la presión intraocular |
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| WO2010093930A1 (en) | 2009-02-13 | 2010-08-19 | Allergan, Inc. | Pharmaceutical compositions comprising (3-(1-(1h-imidazol-4-yl)ethyl)-2-methylphenyl)methanol |
| JP6196041B2 (ja) | 2010-01-11 | 2017-09-13 | オレキシジェン・セラピューティクス・インコーポレーテッド | 大うつ病を有する患者において減量療法を提供する方法 |
| US8492557B2 (en) * | 2010-09-16 | 2013-07-23 | Allergan, Inc. | Ester pro-drugs of [3-(1-(1H-imidazol-4-yl)ethyl)-2-methylphenyl] methanol |
| CA2842866A1 (en) * | 2011-07-22 | 2013-01-31 | Allergan, Inc. | Alpha-2 adrenergic modulators for treating visual disorders mediated by central visual projections from the eye |
| WO2013078151A1 (en) | 2011-11-21 | 2013-05-30 | Allergan, Inc. | Pharmaceutical compositions comprising 4-[1-(2,3-dimethylphenyl)ethyl]-3h-imidazole derivatives for treating retinal diseases |
| USD794650S1 (en) | 2014-11-28 | 2017-08-15 | Samsung Electronics Co., Ltd. | Display screen or portion thereof with a graphical user interface |
| CN108310442B (zh) * | 2017-01-17 | 2021-08-27 | 台北科技大学 | 眼科用组合物 |
| KR102050506B1 (ko) | 2017-06-20 | 2019-11-29 | 한국식품연구원 | 망막 질환 예방, 개선, 완화 또는 치료용 조성물 |
| CN108872431B (zh) * | 2018-07-09 | 2021-03-23 | 成都倍特药业股份有限公司 | 一种检测4-(1-(2,5-二甲基苯基)乙基)-1h-咪唑或/和其盐酸盐的方法 |
| CN111386275B (zh) * | 2018-08-24 | 2023-03-10 | 杭州阿诺生物医药科技有限公司 | 高活性sting蛋白激动剂 |
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| SG45449A1 (en) | 1992-05-13 | 1998-01-16 | Sandoz Ltd | Ophthalmic compositions |
| US5459133A (en) * | 1992-06-05 | 1995-10-17 | Telor Ophthalmic Pharmaceuticals, Inc. | Methods and products for treating presbyopia |
| ES2188649T3 (es) | 1993-11-15 | 2003-07-01 | Schering Corp | Fenil-alquil-imidazoles como antagonistas del receptor h3. |
| US5474979A (en) | 1994-05-17 | 1995-12-12 | Allergan, Inc. | Nonirritating emulsions for sensitive tissue |
| EP0957073A1 (en) * | 1998-05-12 | 1999-11-17 | Schwarz Pharma Ag | Novel derivatives of 3,3-diphenylpropylamines |
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| US20020198209A1 (en) | 2001-05-03 | 2002-12-26 | Allergan Sales Inc. | Compositions having enhanced pharmacokinetic characteristics |
| US7439241B2 (en) * | 2003-05-27 | 2008-10-21 | Galderma Laboratories, Inc. | Compounds, formulations, and methods for treating or preventing rosacea |
| WO2004106307A2 (fr) * | 2003-05-27 | 2004-12-09 | Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R.A.S.) | Nouveaux derives d’imidazoles, leur preparation et leur utilisation en tant que medicament |
| WO2005006720A1 (en) * | 2003-07-14 | 2005-01-20 | Koninklijke Philips Electronics N.V. | Projection device |
| CA2538445A1 (en) * | 2003-09-12 | 2005-04-21 | Allergan, Inc. | Methods and compositions for the treatment of pain and other alpha 2 adrenergic-mediated conditions |
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| DK1761266T3 (da) * | 2004-05-25 | 2013-08-05 | Galderma Pharma Sa | Forbindelser, formuleringer og fremgangsmåder til at behandle eller forebygge inflammatoriske hudsygdomme |
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| JP2008514601A (ja) * | 2004-09-24 | 2008-05-08 | アラーガン、インコーポレイテッド | 特異的α２アドレナリン作動剤としての４−（フェニルメチルおよび置換フェニルメチル）−イミダゾール−２−チオン |
| US7931909B2 (en) | 2005-05-10 | 2011-04-26 | Allergan, Inc. | Ocular therapy using alpha-2 adrenergic receptor compounds having enhanced anterior clearance rates |
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| US20070082070A1 (en) * | 2005-10-11 | 2007-04-12 | Stookey Evangeline L | Treating skin disorders |
| US7902247B2 (en) | 2008-01-09 | 2011-03-08 | Allergan, Inc. | Substituted-aryl-2-phenylethyl-1H-imidazole compounds as subtype selective modulators of alpha 2B and/or alpha 2C adrenergic receptors |
| AU2010210513A1 (en) | 2009-02-06 | 2011-09-01 | Allergan, Inc. | Pyridine compounds as subtype selective modulators of alpha2B and/or alpha 2C adrenergic receptors |
| WO2010093930A1 (en) | 2009-02-13 | 2010-08-19 | Allergan, Inc. | Pharmaceutical compositions comprising (3-(1-(1h-imidazol-4-yl)ethyl)-2-methylphenyl)methanol |
| US8394800B2 (en) * | 2009-11-19 | 2013-03-12 | Galderma Laboratories, L.P. | Method for treating psoriasis |
| US8492557B2 (en) * | 2010-09-16 | 2013-07-23 | Allergan, Inc. | Ester pro-drugs of [3-(1-(1H-imidazol-4-yl)ethyl)-2-methylphenyl] methanol |
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2011
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