RU2012112461A - Конъюгаты жирных кислот и ниацина и их применение - Google Patents
Конъюгаты жирных кислот и ниацина и их применение Download PDFInfo
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Abstract
1. Молекулярный конъюгат, содержащий ниацин и жирную кислоту, выбранную из омега-3 жирных кислот или жирных кислот, которые метаболизируются in vivo до омега-3 жирных кислот, где конъюгат содержит по меньшей мере один амид.2. Соединение Формулы Iили его фармацевтически приемлемая соль, гидрат, сольват, пролекарство, энантиомер или стереоизомер;где каждый из R, Rи Rнезависимо выбран из группы, состоящей из -Н, -D, -Cl, -F, -CN, -NH, -NH(C-Салкил), -N(C-Салкил), -NH(C(O)C-Cалкил), -N(C(O)C-Cалкил), -С(O)Н, -С(O)С-Салкила, -С(O)ОС-Салкила, -C(O)NH, -C(O)NH(C-Cалкил), -C(O)N(C-Cалкил), -C-Салкила, -O-C-Салкила, -S(O)С-Салкила и -S(O)С-Салкила;каждый из Wи Wнезависимо представляет собой ноль, О, S, NH, NR или Wи Wвместе могут образовывать имидазолидиновую или пиперазиновую группу при условии, что Wи Wне могут одновременно представлять собой О;каждый а, b, с и d независимо представляет собой -Н, -D, -СН, -ОСН, -ОСНСНили -C(O)OR, -O-Z или бензил или два из а, b, с и d, вместе с одинарным атомом углерода, к которому они присоединены, могут образовывать циклоалкил или гетероцикл;каждый n, о, р и q независимо равно 0 или 1;каждый L независимо представляет собой -O-, -S-, -S(O) -, -S(O)-, -S-S-,иликаждый g независимо равен 2, 3 или 4;каждый h независимо равен 1, 2, 3 или 4;каждый Rнезависимо представляет собой Н или C-Салкил или обе группы Rвместе с атомом азота, к которому они присоединены, могут образовывать гетероцикл;каждый Rнезависимо представляет собой е, В или неразветвленный или разветвленный C-Салкил, который может быть необязательно замещен ОН, NH, COR, CONH, фенилом, CHOH, имидазолом или аргинином;каждый е независимо представляет собой Н или любую из боковых цепей природных аминокислот;каждый Z независимо представляет собой -Н илиилипри усл
Claims (35)
1. Молекулярный конъюгат, содержащий ниацин и жирную кислоту, выбранную из омега-3 жирных кислот или жирных кислот, которые метаболизируются in vivo до омега-3 жирных кислот, где конъюгат содержит по меньшей мере один амид.
2. Соединение Формулы I
или его фармацевтически приемлемая соль, гидрат, сольват, пролекарство, энантиомер или стереоизомер;
где каждый из R1, R2 и R3 независимо выбран из группы, состоящей из -Н, -D, -Cl, -F, -CN, -NH2, -NH(C1-С3 алкил), -N(C1-С3 алкил)2, -NH(C(O)C1-C3 алкил), -N(C(O)C1-C3 алкил)2, -С(O)Н, -С(O)С1-С3 алкила, -С(O)ОС1-С3 алкила, -C(O)NH2, -C(O)NH(C1-C3 алкил), -C(O)N(C1-C3 алкил)2, -C1-С3 алкила, -O-C1-С3 алкила, -S(O)С1-С3 алкила и -S(O)2С1-С3 алкила;
каждый из W1 и W2 независимо представляет собой ноль, О, S, NH, NR или W1 и W2 вместе могут образовывать имидазолидиновую или пиперазиновую группу при условии, что W1 и W2 не могут одновременно представлять собой О;
каждый а, b, с и d независимо представляет собой -Н, -D, -СН3, -ОСН3, -ОСН2СН3 или -C(O)OR, -O-Z или бензил или два из а, b, с и d, вместе с одинарным атомом углерода, к которому они присоединены, могут образовывать циклоалкил или гетероцикл;
каждый n, о, р и q независимо равно 0 или 1;
каждый L независимо представляет собой -O-, -S-, -S(O) -, -S(O)2-, -S-S-,
или
каждый g независимо равен 2, 3 или 4;
каждый h независимо равен 1, 2, 3 или 4;
каждый R6 независимо представляет собой Н или C1-С6 алкил или обе группы R6 вместе с атомом азота, к которому они присоединены, могут образовывать гетероцикл;
каждый R7 независимо представляет собой е, В или неразветвленный или разветвленный C1-С10 алкил, который может быть необязательно замещен ОН, NH2, CO2R, CONH2, фенилом, C6H4OH, имидазолом или аргинином;
каждый е независимо представляет собой Н или любую из боковых цепей природных аминокислот;
каждый Z независимо представляет собой -Н или
при условии, что в соединении присутствует по меньшей мере один из
каждый r независимо равен 2, 3 или 7;
каждый s независимо равен 3, 5 или 6;
каждый t независимо равен 0 или 1;
каждый v независимо равен 1, 2 или 6;
каждый из R4 и R5 независимо представляет собой водород, дейтерий, -C1-C4 алкил, -галоген, -ОН, -С(O)С1-С4 алкил, -O-арил, -O-бензил, -OC(O)C1-C4 алкил, -C1-С3 алкен, -C1-С3 алкин, -С(O)С1-С4 алкил, -NH2, -NH(C1-C3 алкил), -N(C1-C3 алкил)2, -NH(С(O)С1-С3 алкил), -N(С(O)С1-С3 алкил)2, -SH, -S(C1-С3 алкил), -S(O)С1-С3 алкил, -S(O)2C1-C3 алкил; и
каждый R независимо представляет собой -Н или -С1-С3 алкил;
при условии, что
если каждый из m, n, о, p и q равен 0, каждый из W1 и W2 равен нулю и Z представляет собой
то t должен равняться 0; и
если каждый из m, n, о, p и q равен 0 и каждый из W1 и W2 равен нулю, то Z не может представлять собой
4. Соединение по п.3, отличающееся тем, что t равно 1.
5. Соединение по п.4, отличающееся тем, что r равно 2, и s равно 6.
6. Соединение по п.4, отличающееся тем, что r равно 3, и s равно 5.
7. Соединение по п.4, отличающееся тем, что r равно 7, и s равно 3.
8. Соединение по п.5, отличающееся тем, что L представляет собой -S-S-
9. Соединение по п.5, отличающееся тем, что L представляет собой -O-.
14. Соединение по п.5, отличающееся тем, что каждый из n, о, p и q равен 1.
15. Соединение по п.5, отличающееся тем, что два из n, о, p и q равны 1.
16. Соединение по п.5, отличающееся тем, что каждый из Wi и Wz представляет собой NH.
17. Соединение по п.5, отличающееся тем, что m равно 1, каждый из n, о, р и q равен 1 и L представляет собой О.
18. Соединение по п.5, отличающееся тем, что m равно 1, каждый из n, о, р и q равен 1 и L представляет собой -S-S-.
21. Соединение по п.5, отличающееся тем, что каждый из m, n и о равен 0 и каждый из р и q равен 1.
25. Соединение по п.5, отличающееся тем, что m равно 1, каждый из n, о, р и q равен 1 и L представляет собой NR6.
26. Соединение по п.5, отличающееся тем, что каждый из m, n и о равен 0 и каждый из р и q равен 1, а один из с представляет собой -СН3 и второй из с представляет собой -СН3.
28. Соединение по п.2, отличающееся тем, что соединение выбрано из группы, состоящей из N-(2-(2-(4Z,7Z,10Z,13Z,16Z,19Z)-докоза-4,7,10,13,16,19-гексаенамидоэтокси)этил)никотинамида; N-(2-(2-(2-(4Z,7Z,10Z,13Z,16Z,19Z)-докоза-4,7,10,13,16,19-гексаенамидоэтил)дисульфанил)этил)никотинамида; и N-(2-(2-(4Z,7Z,10Z,13Z,16Z,19Z)-докоза-4,7,10,13,16,19-гексаенамидоэтиламино)этил)никотинамида.
29. Соединение по п.2, отличающееся тем, что соединение выбрано из группы, состоящей из 1,3-дигидроксипропан-2-ил-6-(4Z,7Z,10Z,13Z,16Z,19Z)-докоза-4,7,10,13,16,19-гексаенамидо-2-(никотинамидо)гексаноата; и 1,3-дигидроксипропан-2-ил-4-(4Z,7Z,10Z,13Z,16Z,19Z)-докоза-4,7,10,13,16,19-гексаенамидо-2-(никотинамидо)бутаноата.
30. Соединение по п.2, отличающееся тем, что соединение выбрано из группы, состоящей из N-(2-(4Z,7Z,10Z,13Z,16Z,19Z)-докоза-4,7,10,13,16,19-гексаенамидоэтил)никотинамида; N-(2-(5Z,8Z,11Z,14Z,17Z)-эйкоза-5,8,11,14,17-пентаенамидоэтил)никотинамида; и N-(1-(4Z,7Z,10Z,13Z,16Z,19Z)-докоза-4,7,10,13,16,19-гексаенамидо-2-метилпропан-2-ил)никотинамида.
31. Соединение по п.2, отличающееся тем, что соединение выбрано из группы, состоящей из (S)-6-((4Z,7Z,10Z,13Z,16Z,19Z)-докоза-4,7,10,13,16,19-гексаенамидо)-2-(никотинамидо)гексановой кислоты; (S)-2-((4Z,7Z,10Z,13Z,16Z,19Z)-докоза-4,7,10,13,16,19-гексаенамидо)-6-(никотинамидо)гексановой кислоты; (S)-6-((5Z,8Z,11Z,14Z,17Z)-эйкоза-5,8,11,14,17-пентаенамидо)-2-(никотинамидо)гексановой кислоты; (S)-2-((5Z,8Z,11Z,14Z,17Z)-эйкоза-5,8,11,14,17-пентаенамидо)-6-(никотинамидо)гексановой кислоты; и 2-(2-(4Z,7Z,10Z,13Z,16Z,19Z)-докоза-4,7,10,13,16,19-гексаенамидоэтил)-4-(никотинамидо)бутановой кислоты.
32. Соединение по п.2, отличающееся тем, что соединение выбрано из группы, состоящей из (S)-((R)-1-(никотинамидо)пропан-2-ил)-2-((5Z,8Z,11Z,14Z,17Z)-эйкоза-5,8,11,14,17-пентаенамидо)пропаноата; и (S)-((R)-1-(никотинамид)пропан-2-ил)-2-((5Z,8Z,11Z,14Z,17Z)-эйкоза-5,8,11,14,17-пентаенамидо)-3-мэтилбутаноата.
33. Фармацевтическая композиция, содержащая соединение по п.2 и фармацевтически приемлемый носитель.
34. Способ лечения метаболического расстройства, включающий введение пациенту, который нуждается в таком лечении, эффективного количества соединения по п.2.
35. Способ по п.34, отличающийся тем, что метаболическое расстройство выбрано из гипертриглицеридемии, гиперхолестеринемии, жирового заболевания печенки, атеросклероза, заболевания коронарных сосудов сердца, диабета 2 типа, диабетической нефропатии, диабетической невропатии, диабетической ретинопатии, метаболического синдрома или сердечнососудистого заболевания.
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Families Citing this family (63)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2733353T3 (es) | 2007-11-09 | 2019-11-28 | Basf As | Compuestos lípidos para uso en productos cosméticos, como suplemento alimenticio o como un medicamento |
EP2147910A1 (en) * | 2008-07-15 | 2010-01-27 | Pronova BioPharma Norge AS | Novel lipid compounds |
EP2424521A4 (en) | 2009-04-29 | 2015-03-04 | Amarin Pharmaceuticals Ie Ltd | PHARMACEUTICAL COMPOSITIONS COMPRISING EPA AND CARDIOVASCULAR AGENT AND METHODS OF USE |
CN102458109B (zh) | 2009-04-29 | 2015-02-11 | 阿马里纳制药公司 | 稳定的药物组合物和使用其的方法 |
CA2760877C (en) | 2009-05-08 | 2020-09-08 | Pronova Biopharma Norge As | Polyunsaturated fatty acids for the treatment of diseases related to cardiovascular, metabolic and inflammatory disease areas |
KR102012111B1 (ko) | 2009-06-15 | 2019-08-19 | 아마린 파마, 인크. | 병용 스타틴 요법을 받는 대상체에서 ldl-c 수준을 상승시키지 않으면서 트리글리세리드를 저하시키기 위한 조성물 및 방법 |
USRE46608E1 (en) | 2009-09-01 | 2017-11-14 | Catabasis Pharmaceuticals, Inc. | Fatty acid niacin conjugates and their uses |
CN102724877B (zh) | 2009-09-01 | 2015-05-13 | 凯特贝希制药公司 | 脂肪酸烟酸缀合物及其用途 |
SG10201405994UA (en) | 2009-09-23 | 2014-10-30 | Amarin Pharmaceuticals Ie Ltd | Pharmaceutical Composition Comprising Omega-3 Fatty Acid And Hydroxy-derivative Of A Statin And Methods Of Using Same |
ES2618604T3 (es) | 2010-11-05 | 2017-06-21 | Pronova Biopharma Norge As | Métodos de tratamiento usando compuestos lipídicos |
US11712429B2 (en) | 2010-11-29 | 2023-08-01 | Amarin Pharmaceuticals Ireland Limited | Low eructation composition and methods for treating and/or preventing cardiovascular disease in a subject with fish allergy/hypersensitivity |
NZ712068A (en) | 2010-11-29 | 2017-03-31 | Amarin Pharmaceuticals Ie Ltd | Low eructation composition and methods for treating and/or preventing cardiovascular disease in a subject with fish allergy/hypersensitivity |
US20140315786A1 (en) | 2011-03-18 | 2014-10-23 | Catabasis Pharmaceuticals, Inc. | Use of intracellular enzymes for the release of covalently linked bioactives |
EP2751071B1 (en) * | 2011-08-31 | 2019-11-27 | Jill C. Milne | Fatty acid amides, compositions and methods of use |
US11291643B2 (en) | 2011-11-07 | 2022-04-05 | Amarin Pharmaceuticals Ireland Limited | Methods of treating hypertriglyceridemia |
EP2775837A4 (en) | 2011-11-07 | 2015-10-28 | Amarin Pharmaceuticals Ie Ltd | METHODS OF TREATING HYPERTRIGLYCERIDEMIA |
PL2800563T3 (pl) | 2012-01-06 | 2018-12-31 | Omthera Pharmaceuticals Inc. | Wzbogacone w DPA kompozycje wielonienasyconych kwasów tłuszczowych omega-3 w postaci wolnego kwasu |
WO2013103958A1 (en) | 2012-01-06 | 2013-07-11 | Amarin Pharmaceuticals Ireland Limited | Compositions and methods for lowering levels of high-sensitivity (hs-crp) in a subject |
AU2013256362A1 (en) * | 2012-05-01 | 2014-11-13 | Catabasis Pharmaceuticals, Inc. | Fatty acid conjugates of statin and FXR agonists: compositions and methods of use |
JP6173437B2 (ja) | 2012-05-07 | 2017-08-02 | オムセラ・ファーマシューティカルズ・インコーポレイテッド | スタチン及びω−3脂肪酸の組成物 |
CN107243078A (zh) * | 2012-05-25 | 2017-10-13 | 克塔巴西斯制药有限公司 | 使前蛋白转化酶枯草溶菌素/kexin 9型(pcsk9)减少的方法 |
KR101520653B1 (ko) | 2012-06-11 | 2015-05-15 | 주식회사 휴메딕스 | 복합 비타민 컨쥬게이트 및 그를 포함하는 항산화제 |
SG11201408769QA (en) | 2012-06-29 | 2015-01-29 | Amarin Pharmaceuticals Ie Ltd | Methods of reducing the risk of a cardiovascular event in a subject on statin therapy |
CN104780915A (zh) | 2012-07-11 | 2015-07-15 | 埃尔舍利克斯治疗公司 | 包含他汀、双胍和用于减小心脏代谢风险的其它药剂的组合物 |
WO2014068463A2 (en) * | 2012-11-03 | 2014-05-08 | Mahesh Kandula | Compositions and methods for the treatment of inflammation and metabolic disorders |
US20150265566A1 (en) | 2012-11-06 | 2015-09-24 | Amarin Pharmaceuticals Ireland Limited | Compositions and Methods for Lowering Triglycerides without Raising LDL-C Levels in a Subject on Concomitant Statin Therapy |
WO2014083476A2 (en) * | 2012-11-27 | 2014-06-05 | Mahesh Kandula | Compositions and methods for the treatment of metabolic and lipid disorders |
CN103007081B (zh) * | 2012-11-27 | 2013-12-04 | 鞠法红 | 一种治疗非酒精性脂肪肝的中药组合物 |
WO2014087307A2 (en) * | 2012-12-04 | 2014-06-12 | Mahesh Kandula | Compositions and methods for the treatment of metabolic syndrome and diabetes |
CN103012419B (zh) * | 2012-12-20 | 2015-01-07 | 中国科学院深圳先进技术研究院 | 一种罗丹明b衍生物的合成方法 |
US20140187633A1 (en) | 2012-12-31 | 2014-07-03 | Amarin Pharmaceuticals Ireland Limited | Methods of treating or preventing nonalcoholic steatohepatitis and/or primary biliary cirrhosis |
WO2014106804A2 (en) * | 2013-01-04 | 2014-07-10 | Mahesh Kandula | Compositions and methods for the treatment of metabolic syndrome and diabetes |
WO2014106805A2 (en) * | 2013-01-05 | 2014-07-10 | Mahesh Kandula | Fatty acid conjugates and their uses |
WO2014107730A2 (en) * | 2013-01-07 | 2014-07-10 | Catabasis Pharmaceuticals, Inc. | Use of fatty acid niacin conjugates for treating diseases |
US9452151B2 (en) | 2013-02-06 | 2016-09-27 | Amarin Pharmaceuticals Ireland Limited | Methods of reducing apolipoprotein C-III |
WO2014122575A2 (en) * | 2013-02-08 | 2014-08-14 | Mahesh Kandula | Fatty acid conjugates for the treatment of inflammation and metabolic diseases |
US9624492B2 (en) | 2013-02-13 | 2017-04-18 | Amarin Pharmaceuticals Ireland Limited | Compositions comprising eicosapentaenoic acid and mipomersen and methods of use thereof |
WO2014132134A1 (en) | 2013-02-28 | 2014-09-04 | Pronova Biopharma Norge As | A composition comprising a lipid compound, a triglyceride, and a surfactant, and methods of using the same |
US20140271841A1 (en) | 2013-03-15 | 2014-09-18 | Amarin Pharmaceuticals Ireland Limited | Pharmaceutical composition comprising eicosapentaenoic acid and derivatives thereof and a statin |
US10966968B2 (en) | 2013-06-06 | 2021-04-06 | Amarin Pharmaceuticals Ireland Limited | Co-administration of rosiglitazone and eicosapentaenoic acid or a derivative thereof |
US20150065572A1 (en) | 2013-09-04 | 2015-03-05 | Amarin Pharmaceuticals Ireland Limited | Methods of treating or preventing prostate cancer |
US9585859B2 (en) | 2013-10-10 | 2017-03-07 | Amarin Pharmaceuticals Ireland Limited | Compositions and methods for lowering triglycerides without raising LDL-C levels in a subject on concomitant statin therapy |
WO2015073901A1 (en) * | 2013-11-15 | 2015-05-21 | Catabasis Pharmaceuticals, Inc. | Fatty acid niacin conjugates |
US10561631B2 (en) | 2014-06-11 | 2020-02-18 | Amarin Pharmaceuticals Ireland Limited | Methods of reducing RLP-C |
US10172818B2 (en) | 2014-06-16 | 2019-01-08 | Amarin Pharmaceuticals Ireland Limited | Methods of reducing or preventing oxidation of small dense LDL or membrane polyunsaturated fatty acids |
MA41031A (fr) | 2014-11-26 | 2017-10-03 | Catabasis Pharmaceuticals Inc | Conjugués cystéamine-acide gras et leur utilisation comme activateurs de l'autophagie |
WO2016130417A1 (en) * | 2015-02-11 | 2016-08-18 | Omthera Pharmaceuticals Inc | Omega-3 fatty acid prodrug compounds and uses thereof |
AU2016256552B2 (en) | 2015-04-28 | 2021-04-01 | Pronova Biopharma Norge As | Use of structurally enhanced fatty acids containing sulphur for preventing and/or treating non-alcoholic steatohepatitis |
US10406130B2 (en) | 2016-03-15 | 2019-09-10 | Amarin Pharmaceuticals Ireland Limited | Methods of reducing or preventing oxidation of small dense LDL or membrane polyunsaturated fatty acids |
WO2018081167A1 (en) | 2016-10-24 | 2018-05-03 | Yumanity Therapeutics | Compounds and uses thereof |
EP3566055A4 (en) | 2017-01-06 | 2020-12-02 | Yumanity Therapeutics, Inc. | TREATMENT METHODS FOR NEUROLOGICAL DISORDERS |
TW201900160A (zh) | 2017-05-19 | 2019-01-01 | 愛爾蘭商艾瑪琳製藥愛爾蘭有限公司 | 用於降低腎功能下降之個體中的三酸甘油酯之組合物及方法 |
CA3068254A1 (en) | 2017-06-20 | 2018-12-27 | Imbria Pharmaceuticals, Inc. | Compositions and methods for increasing efficiency of cardiac metabolism |
CA3083000A1 (en) | 2017-10-24 | 2019-05-02 | Yumanity Therapeutics, Inc. | Compounds and uses thereof |
KR20200096791A (ko) | 2017-12-06 | 2020-08-13 | 바스프 에이에스 | 비알콜성 지방간염 치료용 지방산 유도체 |
US11058661B2 (en) | 2018-03-02 | 2021-07-13 | Amarin Pharmaceuticals Ireland Limited | Compositions and methods for lowering triglycerides in a subject on concomitant statin therapy and having hsCRP levels of at least about 2 mg/L |
CA3102404A1 (en) | 2018-06-05 | 2019-12-12 | Flagship Pioneering Innovations V, Inc. | Active agents and methods of their use for the treatment of metabolic disorders and nonalcoholic fatty liver disease |
KR102296068B1 (ko) | 2018-09-24 | 2021-09-02 | 애머린 파마슈티칼스 아일랜드 리미티드 | 대상체에서 심혈관 사건의 위험도를 감소시키는 방법 |
US11767314B2 (en) | 2018-11-02 | 2023-09-26 | Conopco, Inc. | Bioenergetic nicotinic acid glycerol esters, compositions and methods of using same |
US11530184B2 (en) | 2020-06-30 | 2022-12-20 | Imbria Pharmaceuticals, Inc. | Crystal forms of 2-[4-[(2,3,4-trimethoxyphenyl)methyl]piperazin-1-yl]ethyl pyridine-3-carboxylate |
US11780811B2 (en) | 2020-06-30 | 2023-10-10 | Imbria Pharmaceuticals, Inc. | Methods of synthesizing 2-[4-[(2,3,4-trimethoxyphenyl)methyl]piperazin-1-yl]ethyl pyridine-3-carboxylate |
KR20240012390A (ko) | 2021-04-21 | 2024-01-29 | 애머린 파마슈티칼스 아일랜드 리미티드 | 심부전의 위험을 감소시키는 방법 |
US11883396B2 (en) | 2021-05-03 | 2024-01-30 | Imbria Pharmaceuticals, Inc. | Methods of treating kidney conditions using modified forms of trimetazidine |
Family Cites Families (53)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4036951A (en) | 1973-03-12 | 1977-07-19 | Synergistics, Inc. | Ultra-violet filtration with certain aminosalicylic acid esters |
US4169923A (en) * | 1974-10-15 | 1979-10-02 | Paolo Ferruti | High polymers containing nicotinic acid, process for their preparation and their use |
CA1113486A (en) | 1977-04-01 | 1981-12-01 | Alfred Halpern | Ultra-violet filtration with certain aminosalicylic acid esters |
US4264517A (en) | 1978-12-11 | 1981-04-28 | G.D. Searle & Co. | Alkylphenyl 5Z,8Z,11Z,14Z,17Z-eicosapentaenoates |
US4619938A (en) * | 1984-03-21 | 1986-10-28 | Terumo Kabushiki Kaisha | Fatty acid derivatives of aminoalkyl nicotinic acid esters and platelet aggregation inhibitors |
IT1196348B (it) | 1984-11-29 | 1988-11-16 | Italfarmaco Spa | Composti ad attivita'antiinfiammatoria |
JPS61204171A (ja) | 1985-03-06 | 1986-09-10 | Terumo Corp | 5−フルオロウラシル誘導体およびこれを含有する医薬製剤 |
JPH0248545B2 (ja) | 1985-10-30 | 1990-10-25 | Terumo Corp | 33pirijinkarubonsann11okishidojudotaioyobikoreoganjusuruketsushobangyoshuyokuseizai |
JPS62106080A (ja) | 1985-11-01 | 1987-05-16 | Terumo Corp | エタノ−ルアミン誘導体およびこれを含有する抗高脂血症剤 |
JPS62106019A (ja) * | 1985-11-01 | 1987-05-16 | Terumo Corp | 抗高脂血症剤 |
JPS62258362A (ja) * | 1986-05-02 | 1987-11-10 | Terumo Corp | アミド誘導体およびこれを含有する5−リポキシゲナ−ゼ作用阻害剤 |
US4670465A (en) | 1986-05-21 | 1987-06-02 | Syntex (U.S.A.) Inc. | Arachidonic acid analogs |
JPH01121253A (ja) | 1987-11-05 | 1989-05-12 | Terumo Corp | エタノールアミン誘導体包接化合物およびその製法 |
US5760261A (en) | 1990-02-28 | 1998-06-02 | Guttag; Alvin | Higher fatty acid derivatives of salicylic acid and salts thereof |
US5262564A (en) | 1992-10-30 | 1993-11-16 | Octamer, Inc. | Sulfinic acid adducts of organo nitroso compounds useful as retroviral inactivating agents anti-retroviral agents and anti-tumor agents |
GB9403857D0 (en) | 1994-03-01 | 1994-04-20 | Scotia Holdings Plc | Fatty acid derivatives |
GB9508023D0 (en) | 1995-04-20 | 1995-06-07 | Scotia Holdings Plc | Fatty acid derivatives |
MY118354A (en) | 1995-05-01 | 2004-10-30 | Scarista Ltd | 1,3-propane diol derivatives as bioactive compounds |
WO1996034858A1 (en) | 1995-05-01 | 1996-11-07 | Scotia Holdings Plc | Nicotinic acid esters and pharmaceutical compositions containing them |
US6576636B2 (en) | 1996-05-22 | 2003-06-10 | Protarga, Inc. | Method of treating a liver disorder with fatty acid-antiviral agent conjugates |
GB9622636D0 (en) | 1996-10-30 | 1997-01-08 | Scotia Holdings Plc | Presentation of bioactives |
US5728732A (en) | 1996-11-27 | 1998-03-17 | Elizabeth Arden Company, Division Of Conopco, Inc. | Skin treatment with salicylic acid esters and retinoids |
NZ337698A (en) | 1997-04-04 | 2001-07-27 | Pfizer Prod Inc | Nicotinamide derivatives for selective inhibition of phosphodiesterase type 4 (PDE4) and the production of tumour necrosis factor (TNF) useful for the treatment of respiratory, rheumatoid and allergic diseases |
ATE329911T1 (de) | 1998-08-07 | 2006-07-15 | Applied Research Systems | Fsh mimetika zur behandlung von infertilität |
DE60021855T2 (de) * | 1999-01-29 | 2006-05-18 | Amersham Biosciences K.K. | Temperatursensitives polymer und verfahren zu seiner herstellung |
GB9930026D0 (en) | 1999-12-21 | 2000-02-09 | Univ Sheffield | Novel compounds of unsaturated fatty acids |
AU2700201A (en) | 2000-01-31 | 2001-08-14 | Pfizer Products Inc. | Nicotinamide benzofused-heterocyclyl derivatives useful as selective inhibitors of pde4 isozymes |
US6562995B1 (en) * | 2000-12-21 | 2003-05-13 | Beacon Laboratories, Inc. | Delta dicarbonyl compounds and methods for using the same |
KR20090028654A (ko) * | 2001-01-19 | 2009-03-18 | 인스티튜트 오브 파마콜로지 앤드 톡시콜로지 아캐더미 오브 밀리터리 메디칼 사이언시스 피.엘.에이. 차이나 | 포타슘 채널의 기능을 조절하는 아민 유도체, 그의 제조방법 및 용도 |
IL156413A0 (en) * | 2001-01-31 | 2004-01-04 | Pfizer Prod Inc | Nicotinamide biaryl derivatives useful as inhibitors of pde4 isozymes |
EP1461014B1 (en) * | 2001-12-04 | 2021-07-14 | Ben Gurion University Of The Negev Research And Development Authority | Amphiphilic compounds and vesicles/liposomes for organ-specific drug targeting |
US6756392B2 (en) | 2002-02-11 | 2004-06-29 | Pfizer Inc | Nicotinamide derivatives useful as PDE4 inhibitors |
US20040254357A1 (en) | 2002-12-19 | 2004-12-16 | Zaloga Gary P. | Fatty acid phenolic conjugates |
US20040191278A1 (en) | 2003-03-31 | 2004-09-30 | Christensen Flemming Kjaergaar | Topical agent for application to the skin prior to luminous treatment |
RU2379292C2 (ru) * | 2003-04-18 | 2010-01-20 | Мемори Фармасьютиклз Корпорейшн | Производные пиразола в качестве ингибиторов фосфодиэстеразы 4 |
US20050267091A1 (en) | 2004-05-25 | 2005-12-01 | Roger Berlin | Compositions containing policosanol and niacin and/or niacin derivatives and their pharmaceutical uses |
US20060105021A1 (en) * | 2004-09-24 | 2006-05-18 | Remington Direct Lp | Cholesterol-reducing liquid |
CN101102988B (zh) | 2004-11-19 | 2011-12-14 | 马泰克生物科学公司 | 来自长链多不饱和脂肪酸的氧脂素及其制备和使用方法 |
US20090054423A1 (en) | 2005-04-13 | 2009-02-26 | Imbriglio Jason E | Niacin receptor agonists, compositions containing such compounds and methods of treatment |
ES2391305T3 (es) | 2006-04-12 | 2012-11-23 | Unilever N.V. | Composición oral que comprende un ácido graso poliinsaturado y ácido salicílico para obtener un efecto antiinflamatorio en la piel |
BRPI0913425A2 (pt) | 2008-06-02 | 2015-11-24 | Reddys Lab Ltd Dr | formulações de niacina com liberação modificada |
US9085527B2 (en) | 2008-07-08 | 2015-07-21 | Catabasis Pharmaceuticals, Inc. | Fatty acid acylated salicylates and their uses |
SG192488A1 (en) | 2008-07-08 | 2013-08-30 | Catabasis Pharmaceuticals Inc | Fatty acid acetylated salicylates and their uses |
WO2011006000A1 (en) | 2009-07-08 | 2011-01-13 | Haiyan Liu | Berberine derivatives useful for modulating lipid levels and their methods of synthesis |
CN102724877B (zh) | 2009-09-01 | 2015-05-13 | 凯特贝希制药公司 | 脂肪酸烟酸缀合物及其用途 |
US9216224B2 (en) | 2010-03-05 | 2015-12-22 | Catabasis Pharmaceuticals, Inc. | Fatty acid COX inhibitor derivatives and their uses |
WO2011116312A1 (en) | 2010-03-19 | 2011-09-22 | Catabasis Pharmaceuticals, Inc. | Fatty acid macrolide derivatives and their uses |
US20140315786A1 (en) | 2011-03-18 | 2014-10-23 | Catabasis Pharmaceuticals, Inc. | Use of intracellular enzymes for the release of covalently linked bioactives |
US20120252810A1 (en) | 2011-04-04 | 2012-10-04 | Catabasis Pharmaceuticals, Inc. | Fatty acid non-flushing niacin derivatives and their uses |
AU2013256362A1 (en) | 2012-05-01 | 2014-11-13 | Catabasis Pharmaceuticals, Inc. | Fatty acid conjugates of statin and FXR agonists: compositions and methods of use |
CN107243078A (zh) | 2012-05-25 | 2017-10-13 | 克塔巴西斯制药有限公司 | 使前蛋白转化酶枯草溶菌素/kexin 9型(pcsk9)减少的方法 |
WO2014107730A2 (en) | 2013-01-07 | 2014-07-10 | Catabasis Pharmaceuticals, Inc. | Use of fatty acid niacin conjugates for treating diseases |
WO2015073901A1 (en) | 2013-11-15 | 2015-05-21 | Catabasis Pharmaceuticals, Inc. | Fatty acid niacin conjugates |
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