WO1995011227B1 - Novel spin trap nitronyl hindered phenols - Google Patents
Novel spin trap nitronyl hindered phenolsInfo
- Publication number
- WO1995011227B1 WO1995011227B1 PCT/US1994/012107 US9412107W WO9511227B1 WO 1995011227 B1 WO1995011227 B1 WO 1995011227B1 US 9412107 W US9412107 W US 9412107W WO 9511227 B1 WO9511227 B1 WO 9511227B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- compound
- alkyl
- tert
- nitronyl
- butyl
- Prior art date
Links
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 title claims abstract 10
- 150000002989 phenols Chemical class 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract 36
- 125000000217 alkyl group Chemical group 0.000 claims abstract 16
- 125000003118 aryl group Chemical group 0.000 claims abstract 5
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract 4
- 239000001257 hydrogen Substances 0.000 claims abstract 4
- DCNIQKYXZZLGFL-UHFFFAOYSA-N 1-phenyl-N-(2,4,4-trimethylpentan-2-yl)methanimine oxide Chemical compound CC(C)(C)CC(C)(C)[N+]([O-])=CC1=CC=CC=C1 DCNIQKYXZZLGFL-UHFFFAOYSA-N 0.000 claims abstract 2
- 230000037396 body weight Effects 0.000 claims 4
- 150000001298 alcohols Chemical class 0.000 claims 2
- 150000001299 aldehydes Chemical class 0.000 claims 2
- 150000001413 amino acids Chemical group 0.000 claims 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims 2
- 150000003857 carboxamides Chemical class 0.000 claims 2
- 150000001735 carboxylic acids Chemical class 0.000 claims 2
- 150000002148 esters Chemical class 0.000 claims 2
- 150000004820 halides Chemical class 0.000 claims 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
- 230000003859 lipid peroxidation Effects 0.000 claims 2
- 150000007523 nucleic acids Chemical class 0.000 claims 2
- 108020004707 nucleic acids Proteins 0.000 claims 2
- 230000002265 prevention Effects 0.000 claims 2
- 125000001424 substituent group Chemical group 0.000 claims 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 230000000111 anti-oxidant Effects 0.000 abstract 2
- 239000003963 antioxidant agent Substances 0.000 abstract 2
- 239000000203 mixture Substances 0.000 abstract 2
- 125000004435 hydrogen atoms Chemical group [H]* 0.000 abstract 1
- 230000001225 therapeutic Effects 0.000 abstract 1
Abstract
The invention is the use of nitronyl substituted hindered phenols as antioxidants in therapeutic applications. In the preferred embodiment the compositions have general formula (I), wherein R1 is hydrogen, an alkyl or an aryl and R2 is an alkyl or an aryl; R3 is an alkyl; and R4 is an alkyl. Further, the invention relates to novel compositions useful as antioxidants. The novel compounds include: 2,6-di-tert-butyl-4-(N-tert-octyl) nitronyl phenol (DBONP); 2,6-dimethyl-4-(N-tert-octyl) nitronyl phenol (DMONP); N-tert-octyl-C-phenyl nitrone (OPN).
Claims
AMENDED CLAIMS
[received by the International Bureau on 24 April 1995 (24.04.95); original claim 16 cancelled; remaining claims amended (5 pages]
1. A compound having the formula:
wherein Rl is a hydrogen, an aryl, or an alkyl;
R2 is an alkyl or an aryl;
R3 is an alkyl from 1 to 4 carbons in length; and R4 is an alkyl of 1 to 4 carbons in length; for use in the in vivo treatment or prevention of lipid peroxidation.
2. The compound of Claim 1 wherein Rl is hydrogen and R2 is an alkyl.
3. The compound of Claim 1 wherein Rl is an alkyl ,
4. The compound of Claim 1 wherein Rl includes polar substituents selected from the group comprising esters, alcohols, halides, carboxylic acids, aldehydes, carboxamides, aralkyl, amino or nucleic acids.
5. The compound of Claim 1 wherein R2 includes polar substituents selected from the group comprising esters, alcohols, halides, carboxylic acids, aldehydes, carboxamides, aralkyl, amino or nucleic acids.
6. The compound of Claim 1 wherein R3 and R4 are methyl groups.
7. The compound of Claim 1 wherein R3 and R4 are butyl groups.
8. The compound of Claim 1 wherein the compound is provided in a dosage of between about 25 and about 250 mg compound/kg body weight.
9. The compound of Claim 1 wherein the compound is 2 , 6-di-tert-butyl-4- (N-tert-octyl) nitronyl phenol.
10. The compound of Claim 1 wherein the compound is 2, 6-dimethvl-4- (N-tert-octyl) nitronyl phenol.
11. The compound of Claim 1 wherein the compound is 2 , 6-di-tert-butyl-4- (N-tert-butyl) nitronyl phenol.
12. The compound of Claim 1 wherein the compound is 2, 6-dimethyl-4- (N-tert-butyl) nitronyl phenol.
13. The compound of Claim 1 wherein the compound is N-tert-octyl C-phenyl nitrone.
14. The compound of Claim 1 wherein Rl is hydrogen and R2 is an aryl .
15. The compound of Claim 1 wherein the compound is provided in a dosage of between about 25 to about 125 mg compound/kg body weight .
17. A compound of a formula:
18. A compound of a formula:
19. A compound having the formula
wherein R5 is an alkyl; R6 is an alkyl R7 is an alkyl R8 is an alkyl and R9 is an alkyl for use in the in vivo treatment or prevention of lipid peroxidation.
20. The compound of Claim 19 wherein the compound is provided in a dosage of between about 25 mg to about 250 mg compound/kg body weight.
21. The compound of Claim 19 wherein the compound is provided in a dosage of between about 25 mg to about 125 mg compound/kg body weight.
22. A compound according to the formula:
0
wherein R10 is an alkyl of 9 or more carbons.
23. The compound of claim 1 wherein the dosage is from about 25 to about 50 g/kg.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA002174628A CA2174628C (en) | 1993-10-22 | 1994-10-20 | Novel spin trap nitronyl hindered phenols |
| AU80869/94A AU696451B2 (en) | 1993-10-22 | 1994-10-20 | Novel spin trap nitronyl hindered phenols |
| DE69420146T DE69420146T2 (en) | 1993-10-22 | 1994-10-20 | NEW STERICALLY HIDDEN NITRONYLPHENOLS AS RADICAL CATCHERS ("SPINTRAPS") |
| EP94931977A EP0724565B1 (en) | 1993-10-22 | 1994-10-20 | Novel spin trap nitronyl hindered phenols |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/141,241 | 1993-10-22 | ||
| US08/141,241 US5455272A (en) | 1993-10-22 | 1993-10-22 | Spin trap nitronyl hindered phenols |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO1995011227A1 WO1995011227A1 (en) | 1995-04-27 |
| WO1995011227B1 true WO1995011227B1 (en) | 1995-05-18 |
Family
ID=22494820
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1994/012107 WO1995011227A1 (en) | 1993-10-22 | 1994-10-20 | Novel spin trap nitronyl hindered phenols |
Country Status (6)
| Country | Link |
|---|---|
| US (4) | US5455272A (en) |
| EP (1) | EP0724565B1 (en) |
| AU (1) | AU696451B2 (en) |
| DE (1) | DE69420146T2 (en) |
| ES (1) | ES2136209T3 (en) |
| WO (1) | WO1995011227A1 (en) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5723502A (en) * | 1985-07-18 | 1998-03-03 | Proctor; Peter H. | Topical spin trap composition and method |
| DK0863878T3 (en) * | 1995-09-11 | 2003-04-22 | Aventis Pharma Inc | Cyclic nitrons and pharmaceutical preparations containing them |
| ATE263559T1 (en) * | 1996-04-23 | 2004-04-15 | Centaur Pharmaceuticals Inc | PREPARATIONS CONTAINING A NITRONIC COMPOUND FOR USE IN THE TREATMENT OF UVEITIS |
| JP2000514822A (en) * | 1996-07-19 | 2000-11-07 | センター ファーマシューティカルズ，インコーポレイテッド | Furanitron compound |
| TW429241B (en) * | 1996-09-26 | 2001-04-11 | Sumitomo Pharma | Nitrone derivatives |
| MA26553A1 (en) | 1997-10-17 | 2004-12-20 | Centaur Pharmaceuticals Inc | ALPHA-ARYL-N-ALKYLNITRONES AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME |
| AU2226999A (en) * | 1998-01-16 | 1999-08-02 | Renovis, Inc. | Thiophene nitrone compounds |
| CA2318357A1 (en) * | 1998-01-16 | 1999-07-22 | Renovis, Inc. | Thioether furan nitrone compounds |
| AU3985799A (en) * | 1998-05-19 | 1999-12-06 | Centaur Pharmaceuticals, Inc. | Furan nitrone therapeutics for the treatment of inflammatory bowel disease |
| WO1999059569A1 (en) | 1998-05-19 | 1999-11-25 | Centaur Pharmaceuticals, Inc. | Benzamide therapeutics for the treatment of inflammatory bowel disease |
| US6083989A (en) * | 1999-05-18 | 2000-07-04 | Centaur Pharmaceuticals, Inc. | Aryl nitrone therapeutics for the treatment of inflammatory bowel disease |
| ATE271384T1 (en) * | 1998-05-19 | 2004-08-15 | Renovis Inc | ARYLNITRON THERAPEUTIC AGENTS FOR THE TREATMENT OF INFLAMMATORY BOWEL DISEASE |
| FR2780404B1 (en) * | 1998-06-26 | 2001-04-13 | Adir | NOVEL NITRONE DERIVATIVES, THEIR PREPARATION PROCESS AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM |
| WO2000003977A1 (en) * | 1998-07-17 | 2000-01-27 | Centaur Pharmaceuticals, Inc. | Alpha-(2-hydroxyphenyl) nitrone compounds, pharmaceutical compositions containing the same and their use for treating inflammation |
| UA66401C2 (en) * | 1998-12-02 | 2004-05-17 | Sentor Pharmaceuticals Inc | 3,4,5-trisubstituted aryl nitrone compounds and pharmaceutical composition containing the same |
| US6730700B2 (en) | 1998-12-02 | 2004-05-04 | Renovis, Inc. | 3,4,5,-trisubstituted aryl nitrone compounds and pharmaceutical compositions containing the same |
| IT1312537B1 (en) * | 1999-04-16 | 2002-04-22 | Euphar Group Srl | DERIVATIVES OF (-) - VERBENONE. |
| AU2002253857A1 (en) * | 2001-01-08 | 2002-09-04 | Centaur Pharmaceuticals, Inc. | Use of aryl nitrone compounds in methods for treating neuropathic pain |
| FR2846968B1 (en) * | 2002-11-08 | 2005-02-04 | Salles Jean Pierre | NOVEL AMPHIPHILIC DERIVATIVES OF ALPHA-C-PHENYL-N-TERT-BUTYL NITRONE |
| US20050059638A1 (en) * | 2003-08-04 | 2005-03-17 | Kelly Michael G. | Aryl, heteroaromatic and bicyclic aryl nitrone compounds, prodrugs and pharmaceutical compositions of the same to treat human disorders |
| US20050182060A1 (en) * | 2004-02-13 | 2005-08-18 | Kelly Michael G. | 2-Substituted and 4-substituted aryl nitrone compounds |
| WO2005087214A1 (en) * | 2004-03-09 | 2005-09-22 | Renovis, Inc. | Methods for treating multiple sclerosis and pharmaceutical compositions therefor |
| ES2367330T3 (en) * | 2007-11-15 | 2011-11-02 | Rohm And Haas Company | NITRON PREPARATION. |
| JP4996575B2 (en) * | 2007-11-15 | 2012-08-08 | ローム アンド ハース カンパニー | Nitron manufacturing |
| US9034926B2 (en) | 2010-12-30 | 2015-05-19 | Nicholas V. Perricone | Topical nitrone spin trap compositions for psoriasis |
| US8986739B2 (en) | 2011-02-28 | 2015-03-24 | Nicholas V. Perricone | Treatment of urinary incontinence using nitrone spin traps |
| EP2785316B1 (en) * | 2011-11-30 | 2019-06-19 | Dow Global Technologies LLC | Nitrone compounds for use as antioxidant in personal care |
| US9701625B2 (en) | 2014-03-07 | 2017-07-11 | Dow Global Technologies Llc | Nitrone compounds and their use in personal care |
| BR112016025498B1 (en) | 2014-05-12 | 2020-09-01 | Dow Global Technologies Llc | NITRONA COMPOUNDS AND THEIR USE IN PERSONAL CARE |
| WO2016003767A1 (en) | 2014-06-30 | 2016-01-07 | Dow Global Technologies Llc | Polymeric nitrones and their use in personal care |
| US10137071B2 (en) | 2015-03-20 | 2018-11-27 | Dow Global Technologies Llc | Nitrone inhibition of oxidation of unsaturated fats |
| EP3270875B1 (en) * | 2015-03-20 | 2019-05-01 | Dow Global Technologies LLC | Nitrone inhibition of oxidation of unsaturated fats |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3903049A (en) * | 1974-01-30 | 1975-09-02 | Goodyear Tire & Rubber | Oxidation resistant sulfur curable rubbery polymers |
| GB2137619A (en) * | 1983-03-30 | 1984-10-10 | Gerald Scott | Nitrone compounds and stabilised rubber compositions containing them |
| US5036097A (en) * | 1989-10-17 | 1991-07-30 | Oklahoma Medical Research Foundation | Phenylbutyl nitrone compositions and methods for prevention of gastric ulceration |
| US5025032A (en) * | 1989-10-17 | 1991-06-18 | Oklahoma Medical Research Foundation | Phenyl butyl nitrone compositions and methods for treatment of oxidative tissue damage |
| JP2797559B2 (en) * | 1989-11-30 | 1998-09-17 | 住友化学工業株式会社 | Nitrone compound and method for producing the same |
| WO1992022290A1 (en) * | 1991-06-18 | 1992-12-23 | Oklahoma Medical Research Foundation | Use of spin trapping for the treatment of diseases associated with oxidation of lipids and proteins |
-
1993
- 1993-10-22 US US08/141,241 patent/US5455272A/en not_active Ceased
-
1994
- 1994-10-20 EP EP94931977A patent/EP0724565B1/en not_active Expired - Lifetime
- 1994-10-20 DE DE69420146T patent/DE69420146T2/en not_active Expired - Fee Related
- 1994-10-20 ES ES94931977T patent/ES2136209T3/en not_active Expired - Lifetime
- 1994-10-20 WO PCT/US1994/012107 patent/WO1995011227A1/en active IP Right Grant
- 1994-10-20 AU AU80869/94A patent/AU696451B2/en not_active Ceased
-
1995
- 1995-04-10 US US08/419,157 patent/US5527828A/en not_active Expired - Lifetime
- 1995-04-10 US US08/419,159 patent/US5532277A/en not_active Expired - Lifetime
-
1997
- 1997-10-02 US US08/942,494 patent/USRE36594E/en not_active Expired - Lifetime
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