Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...
Reexamination Certificate
2002-01-25
2004-08-31
Jiang, Shaojia Anna (Department: 1617)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Radical -xh acid, or anhydride, acid halide or salt thereof...
C514S553000, C514S554000, C514S577000, C514S578000
Reexamination Certificate
active
06784208
ABSTRACT:
This application claims the benefit of European Patent Application No. 01 400 214.1 filed Jan. 26, 2001.
FIELD OF THE INVENTION
This invention relates to a method for preventing and treating visceral pain, and gastrointestinal disorders such as functional bowel disorders and inflammatory bowel diseases, through the use of effective amounts of bicyclic amino acids.
BACKGROUND OF THE INVENTION
The viscera encompasses the organs of the abdominal cavity. These organs include the sex organs, spleen and part of the digestive system. Pain associated with the viscera can be divided into digestive visceral pain and non digestive visceral pain.
Commonly encountered gastrointestinal (GI) disorders include the functional bowel disorders (FBD) and the inflammatory bowel diseases (IBD). These GI disorders include a wide range of disease states that are currently only moderately controlled, including—for FBD, gastro-esophageal reflux, dyspepsia, the irritable bowel syndrome (IBS) and functional abdominal pain syndrome (FAPS), and—for IBD, Crohn's disease, ileitis, and ulcerative colitis, and all regularly produce visceral pain. It has been shown recently in these pathologies, in particular the irritable bowel syndrome and dyspepsia, that the visceral pain threshold is decreased, indicating a visceral hypersensitivity. Other types of visceral pain include the pain associated with dysmenorrhea, pelvic pain, cystitis and pancreatitis.
Few drugs are known to act selectively upon GI disorder-associated hypersensitivity (Farthing M. J. (1998)
Drugs
56:11-21).
Available treatments of pain fall into two main categories: 1) nonsteroidal anti-inflammatory drugs, used to treat mild pain, but whose therapeutic use is limited by GI adverse effects (gastric erosion, peptic ulcer formation, inflammation of the duodenum and colon); 2) morphine and related opioids, used to treat moderate to severe pain but whose therapeutic use is limited by undesirable side effects including constipation, respiratory depression, tolerance, and abuse potential.
International patent publication WO 99/21824 disclose the use of cyclic amino acids and derivatives thereof for use in treating gastrointestinal disorders such as irritable bowel syndrome.
There is a need for drugs that can alleviate visceral pain without undesirable side effects.
SUMMARY OF THE INVENTION
It has now been found that compounds of formula I-IV (outlined below) are useful for the treatment of disorders such as visceral pain, FBD such as gastro-esophageal reflux, dyspepsia, IBS and FAPS, and IBD such as Crohn's disease, ileitis, and ulcerative colitis, and other types of visceral pain associated with dysmenorrhea, pelvic pain, cystitis and pancreatitis. The inventors have unexpectedly found that the compounds of formula I-IV have the capacity to prevent or treat disorders associated with visceral pain such as:
FBD, including gastro-esophageal reflux, dyspepsia, IBS and FAPS, and
IBD including Crohn's disease, ileitis, and ulcerative colitis, and
other types of visceral pain associated with dysmenorrhea, pelvic pain, cystitis and pancreatitis.
This invention provides a method for preventing and treating visceral pain and GI disorders, including FBS and IBD, comprising administering to a subject in need of treatment an effective amount of a compound of formula I-IV:
or a pharmaceutically acceptable salt thereof, wherein n is an integer of from 1 to 4. Where there are stereocenters, each center may be independently R or S.
Preferred compounds of the invention are those of formulae I-IV above wherein n is an integer of from 2 to 4.
Other preferred compounds are those of Formula I above.
Especially preferred compounds are:
(1&agr;,6&agr;,8&bgr;)(2-Aminomethyl-octahydro-inden-2-yl)-acetic acid,
(2-Aminomethyl-octahydro-inden-2-yl)-acetic acid,
(2-Aminomethyl-octahydro-pentalen-2-yl)-acetic acid, and
(3-Aminomethyl-bicyclo[3.2.0]hept-3-yl)-acetic acid.
A most preferred compound is (1&agr;,3&agr;,5&agr;)-3-aminomethyl-bicyclo[3.2.0]heptane-3-acetic acid, of formula Ia:
Other preferred compounds are those selected from
(1&agr;,5&bgr;)(3-Aminomethyl-bicyclo[3.1.0]hex-3-yl)-acetic acid,
(1&agr;,5&bgr;)(3-Aminomethyl-bicyclo[3.2.0]hept-3-yl)-acetic acid,
(1&agr;,5&bgr;)(2-Aminomethyl-octahydro-pentalen-2-yl)-acetic acid,
(1&agr;,6&bgr;)(2-Aminomethyl-octahydro-inden-2-yl)-acetic acid,
(1&agr;,7&bgr;)(2-Aminomethyl-decahydro-azulen-2-yl)-acetic acid,
(1&agr;,5&bgr;)(3-Aminomethyl-bicyclo[3.1.0]hex-3-yl)-acetic acid,
(1&agr;,5&bgr;)(3-Aminomethyl-bicyclo[3.2.0]hept-3-yl)-acetic acid,
(1&agr;,5&bgr;)(2-Aminomethyl-octahydro-pentalen-2-yl)-acetic acid,
(1&agr;,6&bgr;)(2-Aminomethyl-octahydro-inden-2-yl)-acetic acid,
(1&agr;,7&bgr;)(2-Aminomethyl-decahydro-azulen-2-yl)-acetic acid,
(1&agr;,3&agr;,5&agr;)(3-Aminomethyl-bicyclo[3.1.0]hex-3-yl)-acetic acid,
(1&agr;,3&agr;,5&agr;)(2-Aminomethyl-octahydro-pentalen-2-yl)-acetic acid,
(1&agr;,6&agr;,8&agr;)(2-Aminomethyl-octahydro-inden-2-yl)-acetic acid,
(1&agr;,7&agr;,9&agr;)(2-Aminomethyl-decahydro-azulen-2-yl)-acetic acid,
(1&agr;,3&agr;,5&agr;)(3-Aminomethyl-bicyclo[3.1.0]hex-3-yl)-acetic acid,
(1&agr;,3 &bgr;,5&agr;)(3-Aminomethyl-bicyclo[3.2.0]hept-3-yl)-acetic acid,
(1&agr;,3&bgr;,5&agr;)(2-Aminomethyl-octahydro-pentalen-2-yl)-acetic acid,
(1&agr;,6&agr;,8&bgr;)(2-Aminomethyl-octahydro-inden-2-yl)-acetic acid,
(1&agr;,7&agr;,9&bgr;)(2-Aminomethyl-decahydro-azulen-2-yl)-acetic acid,
((1R,3R,6R)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,
((1R,3S,6R)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,
((1S,3S,6S)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,
((1S,3R,6S)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,
((1R,3R,6S)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,
((1R,3S,6S)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,
((1S,3S,6R)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,
((1S,3R,6R)-3-Aminomethyl-bicyelo[4.2.0]oct-3-yl)-acetic acid,
((3&agr;R,5R,7&agr;S)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,
((3&agr;R,5S,7&agr;S)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,
((3&agr;S,5S,7&agr;R)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,
((3&agr;S,5R,7&agr;R)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,
((2R,4&agr;S,8&agr;R)-2-Aminomethyl-decahydro-naphthalen-2-yl)-acetic acid,
((2S,4&agr;S,8&agr;R)-2-Aminomethyl-decahydro-naphthalen-2-yl)-acetic acid,
((2S,4&agr;R,8&agr;S)-2-Aminomethyl-decahydro-naphthalen-2-yl)-acetic acid, ((2R,4&agr;R,8&agr;S)-2-Aminomethyl-decahydro-naphthalen-2-yl)-acetic acid,
((2R,4&agr;S,9&agr;R)-2-Aminomethyl-decahydro-benzocyclophepten-2-yl)-acetic acid,
((2S,4&agr;S,9&agr;R)-2-Aminomethyl-decahydro-benzocyclophepten-2-yl)-acetic acid,
((2S,4&agr;R,9&agr;S)-2-Aminomethyl-decahydro-benzocyclophepten-2-yl)-acetic acid,
((2R,4&agr;R,9&agr;S)-2-Aminomethyl-decahydro-benzocyclophepten-2-yl)-acetic acid,
((1R,3R,6S)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,
((1R,3S,6S)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,
((1S,3S,6R)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,
((1S,3R,6R)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,
((1R,3R,6R)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,
((1R,3S,6R)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,
((1S,3S,68)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,
((1S,3R,6S)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,
((3&agr;,5R,7&agr;R)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,
((3&agr;R,5S,7&agr;R)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,
((3&agr;S,5S,7&agr;S)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,
((3&agr;S,5R,7&agr;S)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,
((2R,4&agr;R,8&agr;R)-2-Aminomethyl-dctahydro-naphthalen-2-yl)-acetic acid,
((2S,4&agr;S,8&agr;R)-2-Aminomethyl-decahydro-naphthalen-5-2-yl)-acetic acid,
((2S,4&agr;R,8&agr;S)-2-Aminomethyl-decahydro-nap
Chovet Maria
Diop Laurent
Ashbrook Charles W.
Jiang Shaojia Anna
Kurlandsky David R.
Warner-Lambert & Company
LandOfFree
Method for preventing and treating visceral pain and... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method for preventing and treating visceral pain and..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for preventing and treating visceral pain and... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3337248