RU2012103757A - DIHYDROLIPOIC ACID DERIVATIVES CONTAINING NITROGEN OXIDE AND THERAPEUTIC APPLICATIONS - Google Patents

DIHYDROLIPOIC ACID DERIVATIVES CONTAINING NITROGEN OXIDE AND THERAPEUTIC APPLICATIONS Download PDF

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RU2012103757A
RU2012103757A RU2012103757/04A RU2012103757A RU2012103757A RU 2012103757 A RU2012103757 A RU 2012103757A RU 2012103757/04 A RU2012103757/04 A RU 2012103757/04A RU 2012103757 A RU2012103757 A RU 2012103757A RU 2012103757 A RU2012103757 A RU 2012103757A
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compound
formula
group
butyl
pharmaceutically acceptable
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RU2012103757/04A
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Сэмпат ПАРТАСАРАТИ
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Инваск Терапьютикс, Инк.
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Priority claimed from PCT/US2010/024772 external-priority patent/WO2010096677A2/en
Publication of RU2012103757A publication Critical patent/RU2012103757A/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C313/00—Sulfinic acids; Sulfenic acids; Halides, esters or anhydrides thereof; Amides of sulfinic or sulfenic acids, i.e. compounds having singly-bound oxygen atoms of sulfinic or sulfenic groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C313/08—Sulfenic acids; Derivatives thereof
    • C07C313/18—Sulfenamides
    • C07C313/36—Sulfenamides having nitrogen atoms of sulfenamide groups further bound to other hetero atoms
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
    • C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to atoms of the carbocyclic ring
    • C07D317/64—Oxygen atoms

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
  • Hydrogenated Pyridines (AREA)
  • Pyrrole Compounds (AREA)

Abstract

1. Соединение, имеющее Формулу (I):,где:m - целое число от 1 до 2;n - целое число от 1 до 10;Rи Rнезависимо выбраны из группы, включающей Н, метил, этил, пропил, бутил, изопропил, изобутил, и трет-бутил; иRвыбран из группы, включающей СООН, СООСН, СООСНСН,,,,,, и,или его фармацевтически приемлемая соль или сольват.2. Соединение по п.1, где соединение имеет Формулу (II):.3. Соединение по п.1, где соединение имеет Формулу (III):.4. Соединение из п.1, где соединение имеет Формулу (IV):.5. Соединение из п.1, где соединение имеет Формулу (V):6. Соединение из п.1, где соединение имеет Формулу (VI):.7. Соединение из п.1, где соединение имеет Формулу (VII):.8. Соединение из п.1, где соединение имеет Формулу (VIII):.9. Соединение из п.1, где соединение имеет Формулу (IX):.10. Соединение из п.1, где соединение имеет Формулу (Х):.11. Соединение из п.1, где соединение имеет Формулу (XI):.12. Соединение из п.1, где соединение имеет Формулу (XII):.13. Соединение из п.1, где соединение имеет Формулу (XIII):.14. Соединение из п.1, где соединение имеет Формулу (XIV):.15. Фармацевтическая композиция, включающая соединение по п.1 и фармацевтически приемлемый наполнитель, носитель или эксципиент.16. Соединение, имеющее формулу (XV):,где:Rи Rнезависимо выбраны из группы, включающей Н, CH, и трет-бутил; иRвыбран из группы, включающей СНСНСНСНСООСН, СНСНСНСНСНСООН, и СНСНСНСНСООСНСН;или его фармацевтически приемлемая соль или сольват.17. Соединение из п.16, где соединение имеет Формулу (XVI):18. Соединение из п.16, где соединение имеет Формулу (XVII):.19. Соединение из п.16, где соединение имеет Формулу (XVIII):.20. Способ увеличения вазодилатации, уменьшения степени окисления липопротеидов низкой плотности, уменьшения воспаления, лечения гиперто�1. A compound having Formula (I): where: m is an integer from 1 to 2; n is an integer from 1 to 10; R and R are independently selected from the group consisting of H, methyl, ethyl, propyl, butyl, isopropyl, isobutyl and tert-butyl; and R is selected from the group consisting of COOH, COOCH, COOCHN ,,,,,, and, or a pharmaceutically acceptable salt or solvate thereof. 2. A compound according to claim 1, wherein the compound has Formula (II): 3. A compound according to claim 1, wherein the compound has Formula (III): 4. A compound of claim 1, wherein the compound has Formula (IV): 5. The compound of claim 1, wherein the compound has Formula (V): 6. A compound of claim 1, wherein the compound has Formula (VI): 7. A compound of claim 1, wherein the compound has Formula (VII): 8. A compound of claim 1, wherein the compound has Formula (VIII): 9. A compound of claim 1, wherein the compound has Formula (IX): 10. A compound of claim 1, wherein the compound has Formula (X): 11. A compound of claim 1, wherein the compound has Formula (XI): 12. A compound of claim 1, wherein the compound has Formula (XII): 13. A compound of claim 1, wherein the compound has Formula (XIII): 14. A compound of claim 1, wherein the compound has Formula (XIV): 15. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable excipient, carrier or excipient. A compound having the formula (XV): where: R and R are independently selected from the group consisting of H, CH, and tert-butyl; and R is selected from the group consisting of CHCCHCHCOOCH, CHCCHCCHCOOCH, and CHCCHCCHCOOCHCH; or a pharmaceutically acceptable salt or solvate thereof. 17. The compound of claim 16, wherein the compound has Formula (XVI): 18. A compound of claim 16, wherein the compound has Formula (XVII): 19. A compound of claim 16, wherein the compound has Formula (XVIII): 20. A way to increase vasodilation, reduce the oxidation state of low density lipoproteins, reduce inflammation, treat hypertension

Claims (22)

1. Соединение, имеющее Формулу (I):1. The compound having the Formula (I):
Figure 00000001
,
Figure 00000001
, где:Where: m - целое число от 1 до 2;m is an integer from 1 to 2; n - целое число от 1 до 10;n is an integer from 1 to 10; R1 и R2 независимо выбраны из группы, включающей Н, метил, этил, пропил, бутил, изопропил, изобутил, и трет-бутил; иR 1 and R 2 are independently selected from the group consisting of H, methyl, ethyl, propyl, butyl, isopropyl, isobutyl, and tert-butyl; and R3 выбран из группы, включающей СООН, СООСН3, СООСН2СН3,R 3 is selected from the group consisting of COOH, SOOCH 3 , SOOCH 2 CH 3 ,
Figure 00000002
,
Figure 00000003
,
Figure 00000004
,
Figure 00000005
,
Figure 00000002
,
Figure 00000003
,
Figure 00000004
,
Figure 00000005
,
Figure 00000006
, и
Figure 00000007
,
Figure 00000006
, and
Figure 00000007
, или его фармацевтически приемлемая соль или сольват.or a pharmaceutically acceptable salt or solvate thereof. 2. Соединение по п.1, где соединение имеет Формулу (II):2. The compound according to claim 1, where the compound has the Formula (II):
Figure 00000008
.
Figure 00000008
. 3. Соединение по п.1, где соединение имеет Формулу (III):3. The compound according to claim 1, where the compound has the Formula (III):
Figure 00000009
.
Figure 00000009
. 4. Соединение из п.1, где соединение имеет Формулу (IV):4. The compound of claim 1, where the compound has the Formula (IV):
Figure 00000010
.
Figure 00000010
. 5. Соединение из п.1, где соединение имеет Формулу (V):5. The compound of claim 1, where the compound has the Formula (V):
Figure 00000011
Figure 00000011
 6. Соединение из п.1, где соединение имеет Формулу (VI):6. The compound of claim 1, where the compound has the Formula (VI):
Figure 00000012
.
Figure 00000012
. 7. Соединение из п.1, где соединение имеет Формулу (VII):7. The compound of claim 1, where the compound has the Formula (VII):
Figure 00000013
.
Figure 00000013
. 8. Соединение из п.1, где соединение имеет Формулу (VIII):8. The compound of claim 1, where the compound has the Formula (VIII):
Figure 00000014
.
Figure 00000014
. 9. Соединение из п.1, где соединение имеет Формулу (IX):9. The compound of claim 1, where the compound has the Formula (IX):
Figure 00000015
.
Figure 00000015
. 10. Соединение из п.1, где соединение имеет Формулу (Х):10. The compound of claim 1, where the compound has the Formula (X):
Figure 00000016
.
Figure 00000016
. 11. Соединение из п.1, где соединение имеет Формулу (XI):11. The compound of claim 1, where the compound has the Formula (XI):
Figure 00000017
.
Figure 00000017
. 12. Соединение из п.1, где соединение имеет Формулу (XII):12. The compound of claim 1, where the compound has the Formula (XII):
Figure 00000018
.
Figure 00000018
. 13. Соединение из п.1, где соединение имеет Формулу (XIII):13. The compound of claim 1, where the compound has the Formula (XIII):
Figure 00000019
.
Figure 00000019
. 14. Соединение из п.1, где соединение имеет Формулу (XIV):14. The compound of claim 1, where the compound has the Formula (XIV):
Figure 00000020
.
Figure 00000020
. 15. Фармацевтическая композиция, включающая соединение по п.1 и фармацевтически приемлемый наполнитель, носитель или эксципиент.15. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable excipient, carrier or excipient. 16. Соединение, имеющее формулу (XV):16. The compound having the formula (XV):
Figure 00000021
,
Figure 00000021
, где:Where: R1 и R2 независимо выбраны из группы, включающей Н, CH3, и трет-бутил; иR 1 and R 2 are independently selected from the group consisting of H, CH 3 , and tert-butyl; and R3 выбран из группы, включающей СН2СНСНСН2СООСН3, СН2СНСНСНСНСООН, и СНСНСНСНСООСН2СН3;R 3 is selected from the group consisting of CH 2 CHCHCH 2 COOCH 3 , CH 2 CHCHCHCH, UNCHS, and CHCHCHCHCHCH 2 CH 3 ; или его фармацевтически приемлемая соль или сольват.or a pharmaceutically acceptable salt or solvate thereof. 17. Соединение из п.16, где соединение имеет Формулу (XVI):17. The compound of clause 16, where the compound has the Formula (XVI):
Figure 00000022
Figure 00000022
 18. Соединение из п.16, где соединение имеет Формулу (XVII):18. The compound of clause 16, where the compound has the Formula (XVII):
Figure 00000023
.
Figure 00000023
. 19. Соединение из п.16, где соединение имеет Формулу (XVIII):19. The compound of clause 16, where the compound has the Formula (XVIII):
Figure 00000024
.
Figure 00000024
. 20. Способ увеличения вазодилатации, уменьшения степени окисления липопротеидов низкой плотности, уменьшения воспаления, лечения гипертонии, лечения дислипидемии нормализации почечной недостаточности или замедления ухудшения функции почек, или уменьшения или предотвращения прогрессии микроальбуминурии у субъекта, нуждающегося в этом, включающий введение субъекту, нуждающемуся в этом, эффективного количества соединения, выбранного из группы, включающей следующие Формулы (I) и (XV), или его фармацевтически приемлемую соль или сольват.20. A method of increasing vasodilation, decreasing the oxidation state of low density lipoproteins, reducing inflammation, treating hypertension, treating dyslipidemia, normalizing renal failure, or slowing down the deterioration of kidney function, or reducing or preventing the progression of microalbuminuria in a subject in need thereof, comprising administering to a subject in need thereof , an effective amount of a compound selected from the group consisting of the following Formulas (I) and (XV), or a pharmaceutically acceptable salt or solvate thereof.
Figure 00000025
,
Figure 00000025
, где:Where: m - целое число от 1 до 2;m is an integer from 1 to 2; n - целое число от 1 до 10;n is an integer from 1 to 10; R1 и R2 независимо выбраны из группы, включающей Н, метил, этил, пропил, бутил, изопропил, изобутил, и трет-бутил; иR 1 and R 2 are independently selected from the group consisting of H, methyl, ethyl, propyl, butyl, isopropyl, isobutyl, and tert-butyl; and R3 выбран из группы, включающей СООН, СООСН3, СООСН2СН3,R 3 is selected from the group consisting of COOH, SOOCH 3 , SOOCH 2 CH 3 ,
Figure 00000002
,
Figure 00000003
,
Figure 00000004
,
Figure 00000005
,
Figure 00000002
,
Figure 00000003
,
Figure 00000004
,
Figure 00000005
,
Figure 00000006
, и
Figure 00000007
;
Figure 00000006
, and
Figure 00000007
;
Figure 00000026
,
Figure 00000026
, где:Where: R1 и R2 независимо выбраны из группы, включающей Н, CH3, и трет-бутил; иR 1 and R 2 are independently selected from the group consisting of H, CH 3 , and tert-butyl; and R3 выбран из группы, включающей СН2СНСН2СН2СООСН3, СН2СНСНСНСНСООН, и СНСНСНСНСООСН2СН3.R 3 is selected from the group consisting of CH 2 CHCH 2 CH 2 COOCH 3 , CH 2 CHCHCHCHNOS, and CHCHCHCHCHCH 2 CH 3 . 21. Способ по п.20, предназначенный для коррекции состояний, выбранных из группы, включающей диабеты или гипертензию.21. The method according to claim 20, intended for the correction of conditions selected from the group including diabetes or hypertension. 22. Способ получения соединения из п.1, включающий:22. A method of obtaining a compound of claim 1, including: получение альфа-липоевой кислоты или ее производного;obtaining alpha lipoic acid or its derivative; восстановление альфа-липоевой кислоты или ее производного до дигидролипоевой кислоты или до производного дигидролипоевой кислоты;reduction of alpha lipoic acid or its derivative to dihydrolipoic acid or to a dihydrolipoic acid derivative; обработку дигидролипоевой кислоты или ее производного оксидом азота в течение временного интервала, достаточного для получения нитрозоформы дигидролипоевой кислоты; иtreating the dihydrolipoic acid or its derivative with nitric oxide for a time period sufficient to obtain the nitrosoform of the dihydrolipoic acid; and очистку нитрозоформы дигидролипоевой кислоты. purification of the nitroso form of dihydrolipoic acid.
RU2012103757/04A 2010-02-19 2010-02-19 DIHYDROLIPOIC ACID DERIVATIVES CONTAINING NITROGEN OXIDE AND THERAPEUTIC APPLICATIONS RU2012103757A (en)

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AU (1) AU2010215871A1 (en)
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KR20120107076A (en) 2012-09-28
AU2010215871A1 (en) 2012-11-15

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