Morpholine derivatives and their use as therapeutic agents

Details Morpholine derivatives and their use as therapeutic agents Morpholine derivatives and their use as therapeutic agents

1997-02-27

1998-02-17

Ramsuer, Robert W.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Heterocyclic carbon compounds containing a hetero ring...

5142353, 544 70, 544 87, 544129, 544141, A61K 31535, C07D26532, C07D41306

Patent

active

057191492

DESCRIPTION:

BRIEF SUMMARY
This application is a 371 of PCT/GB95/02039 filed Aug. 30, 1995.
This invention relates to a class of morpholine derivatives which are useful as tachykinin antagonists.
The tachykinins are a group of naturally occurring peptides found widely distributed throughout mammalian tissues, both within the central nervous system and in peripheral nervous and circulatory systems.
At present, there are three known mammalian tachykinins referred to as substance P, neurokinin A (NKA, substance K, neuromedin L) and neurokinin B (NKB, neuromedin K (for review see J. E. Maggio, Peptides (1985) 6(suppl. 3), 237-242). The current nomenclature designates the three tachykinin receptors mediating the biological actions of substance P, NKA and NKB as the NK.sub.1, NK.sub.2 and NK.sub.3 receptors, respectively.
Evidence for the usefulness of tachykinin receptor antagonists in pain, headache, especially migraine, Alzheimer's disease, multiple sclerosis, attenuation of morphine withdrawal, cardiovascular changes, oedema, such as oedema caused by thermal injury, chronic inflammatory diseases such as rheumatoid arthritis, asthma/bronchial hyperreactivity and other respiratory diseases including allergic rhinitis, inflammatory diseases of the gut including ulcerative colitis and Crohn's disease, ocular injury and ocular inflammatory diseases, proliferative vitreoretinopathy, irritable bowel syndrome and disorders of bladder function including cystitis and bladder detruser hyper-reflexia is reviewed in "Tachykinin Receptors and Tachykinin Receptor Antagonists", C. A. Maggi, R. Patacchini, P. Rovero and A. Giachetti, J. Auton. Pharmacol. (1993) 13, 23-93.
For instance, substance P is believed inter alia to be involved in the neurotransmission of pain sensations (Otsuka et al, "Role of Substance P as a Sensory Transmitter in Spinal Cord and Sympathetic Ganglia" in 1982 Substance P in the Nervous System, Ciba Foundation Symposium 91, 13-34 (published by Pitman) and Otsuka and Yanagisawa, "Does Substance P Act as a Pain Transmitter?" TIPS (1987) 8, 506-510), specifically in the transmission of pain in migraine (Sandberg et al, J. Med. Chem., (1982) 25, 1009) and in arthritis (Levine et al in Science (1984) 226, 547-549). Tachykinins have also been implicated in gastrointestinal (GI) disorders and diseases of the GI tract such as inflammatory bowel disease (Mantyh et al in Neuroscience (1988) 25(3), 817-837 and D. Regoli in "Trends in Cluster Headache" Ed. Sicuteri et al, Elsevier Scientific Publishers, Amsterdam (1987) page 85-95) and emesis (F. D. Tattersall et al, Eur. J. Pharmacol., (1993) 250, R5-R6). It is also hypothesised that there is a neurogenic mechanism for arthritis in which substance P may play a role (Kidd et al "A Neurogenic Mechanism for Symmetrical Arthritis" in The Lancet, Nov. 11, 1989 and Gronblad et al, "Neuropeptides in Synovium of Patients with Rheumatoid Arthritis and Osteoarthritis" in J. Rheumatol. (1988) 15(12), 1807-1810). Therefore, substance P is believed to be involved in the inflammatory response in diseases such as rheumatoid arthritis and osteoarthritis, and fibrositis (O'Byrne et al, Arthritis and Rheumatism (1990) 33, 1023-1028). Substance P antagonists alone or in combination with bradykinin receptor antagonists may also be useful in the prevention and treatment of inflammatory conditions in the lower urinary tract, especially cystitis (Giuliani et al, J. Urology (1993) 150, 1014-1017). Other disease areas where tachykinin antagonists are believed to be useful are allergic conditions (Hamelet et al, Can. J. Pharmacol. Physiol. (1988) 66, 1361-1367), immunoregulation (Lotz et al, Science (1988) 241, 1218-1221; Kimball et al, J. Immunol. (1988) 141(10), 3564-3569 and Perianin et al, Biochem. Biophys. Res. Commun. (1989) 161, 520), post-operative pain and nausea (Bountra et al, Eur. J. Pharmacol. (1993) 249, R3-R4 and Tattersall et al, Neuropharmacology (1994) 33, 259-260), vasodilation, bronchospasm, reflex or neuronal control of the viscera (Mantyh et al, PNAS (1988) 85, 3235-3239) and, possibly by ar

REFERENCES:
patent: 5612337 (1997-03-01), Baker et al.

Affiliated with

Also associated with

Rating

Morpholine derivatives and their use as therapeutic agents does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Morpholine derivatives and their use as therapeutic agents, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Morpholine derivatives and their use as therapeutic agents will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1784171