2,4-disulfo phenyl butyl nitrone, its salts and their use as pha

Details 2,4-disulfo phenyl butyl nitrone, its salts and their use as pha 2,4-disulfo phenyl butyl nitrone, its salts and their use as pha

1997-06-19

1998-07-14

Reamer, James H.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Radical -xh acid, or anhydride, acid halide or salt thereof...

514658, 562 62, 564282, A61K 31185

Patent

active

057805105

DESCRIPTION:

BRIEF SUMMARY
BACKGROUND OF THE INVENTION

This invention relates to a particular nitrone compound and its salts and their advantageous use as pharmaceutical nitrone free radical trapping agents.
Alpha-phenyl tert butyl nitrone ##STR1## or "PBN") was identified in the 1970s as a useful analytical reagent to be used in conjunction with electron spin resonance ("ESR") to aid in the detection of free radicals. PBN was found to react with certain free radicals and generate a chemical species yielding a characteristic ESR spectrum and thus making it possible to determine the presence or absence of free radicals.
In the late 1970s and early 1980s the medical community began to focus on the roles played by free radicals in diseases such as heart attacks, strokes and the like. PBN was used increasingly in vitro to provide analytical evidence of the presence of free radicals in these settings. It was also later administered in vivo in animal models, again as an analytical adjunct in attempts to observe free radicals during ischemia simulations and the like.
In the mid 1980s, the first possible therapeutic effects of PBN were implied when severe trauma ischemia animal tests showed that PBN-treated animals were more likely to survive than controls.
On May 2, 1991, PCT patent application WO-91-05552 was published. This patent application, which in part corresponds to now-issued U.S. Pat. Nos. 5,825,032 and 5,036,097, described PBN and a family of PBN derivatives defined by the formula ##STR2## wherein X is phenyl or ##STR3## where R is H, ##STR4## or Z; or ##STR5## and n is a whole integer from 1 to 5 or ##STR6## and Y is tert-butyl or a hydroxylated or acetylated tert-butyl or a substituted phenyl. These compounds were proposed as pharmaceutical agents to treat the aftermath of stroke and other conditions reported to be associated with free radical damage.
In 1992 a second PCT patent application was filed directed to PBN and related compounds and their medical use. This application, based on prior U.S. patent application Ser. No. 716,952 (filed Jun. 18, 1991), was published on Dec. 23, 1992 as WO 92/22290. This 1992 publication provided two extremely broad and general disclosures. First, it attempted to describe as many disease states as possible which were associated with free radicals. These ranged from CNS conditions (including stroke, aging, migraine, etc.) through peripheral organ disease (including atherosclerosis, bed sores, wounds, and muscle overexertion) through UV exposure, to mention but a few highlights. Second, it attempted to list as many potential spin traps as possible.
In addition to a whole range of non-PBN materials, this application greatly expanded the definition of potentially useful PBN compounds to include PBN, and derivatives thereof of the formula ##STR7## wherein X is phenyl, imidazolyl, phenothiazinyl or ##STR8## n=1-5, preferably 1-3; R.sup.2 =independently (can vary within the molecule) halogen, alkyl, oxyalkyl, alkenyl, oxyalkenyl, OH, NH.sub.2, NHZ, NZ.sub.2, NO, ##STR9## --SO.sub.3 H, --OSO.sub.3 H, SH, --S(alkyl), --S(alkenyl, and haloalkyl, specifically including --CF.sub.3 ; more positions; phenyl or ##STR10##
PBN was stated to be the most preferred compound at that time, being said to have no measurable effect on normal or uninjured cells, and a number of derivatives were also stated to be useful, including hydroxy derivatives, especially 2-, 3- or 4-hydroxyphenyl t-butyl nitrone and phenyl (mono-, di- or trihydroxy) tert-butyl nitrone; PBN esters, especially esters which release 2-, 3-, or 4-hydroxyphenyl t-butyl nitrone such as acetoxy derivative; 2-, 3-, or 4-carboxyphenyl t-butyl nitrone; phenyl hydroxybutyl nitrone; alkoxyl derivatives, especially alkoxyl derivatives which release 2-, 3-, or 4-hydroxyphenyl t-butyl nitrone, for example, the 2-, 3-, or 4-methoxyphenyl derivatives of PBN; and acetamide derivatives, especially acetamide derivatives which release 2-, 3-, or 4-aminophenyl t-butyl nitrone; diphenyl nitrone (PPN) and the analogous diphenyl nitrone derivatives; N-tert-butyl-.alph

REFERENCES:
patent: 5475032 (1995-12-01), Carney
patent: 5488145 (1996-01-01), Carney
patent: 5508305 (1996-04-01), Carney

Affiliated with

Also associated with

Rating

2,4-disulfo phenyl butyl nitrone, its salts and their use as pha does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with 2,4-disulfo phenyl butyl nitrone, its salts and their use as pha, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and 2,4-disulfo phenyl butyl nitrone, its salts and their use as pha will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1882256