Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...
Reissue Patent
2000-03-30
2001-09-04
Lambkin, Deborah C. (Department: 1626)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Nitrogen containing other than solely as a nitrogen in an...
C514S506000, C514S620000, C514S349000, C514S369000, C514S445000, C564S305000, C560S039000, C558S070000, C546S300000, C548S189000, C549S065000
Reissue Patent
active
RE037355
ABSTRACT:
BACKGROUND OF THE INVENTION
6dimethylaminomethyl-1-phenyl-cyclohexane compounds as pharmaceutical active ingredients
This invention relates to 6-dimethylaminomethyl-1-phenyl-cyclohexane compounds, to methods of preparing them and to the use of these compounds in drugs.
The treatment of chronic and non-chronic pain conditions is of great importance in medicine. There is currently a world-wide need for additional pain therapy which is not exclusively opioid but which exhibits good efficacy. The pressing requirement for a target-oriented treatment of chronic and non-chronic pain conditions which is right for the patient, which is to be understood as the successful and satisfactory treatment of pain for the patients, is documented in the large number of scientific works which have recently appeared in the field of applied analgesics or on basic research on nociception.
Opioids have been used for many years for the treatment of pain, even though they give rise to a series of side effects, for example dependency, respiratory depression, gastrointestinal inhibition effects and obstipation. They can therefore only be given over an extended period of time or in high dosages subject to special precautions, for example special prescription regulations (Goodman, Gilman “The Pharmaceutical Basis of Therapeutics” Pergamon Press, New York, 1990).
Tramadol hydrochloride—(1RS,2RS)-2[(dimethylamino) methyl]-1-(3 -methoxyphenyl)cyclohexanol hydrochloride—assumes a special position amongst centrally acting analgesics, since this active ingredient acts as a strong inhibitor of pain without the side effects which are known for opioids (J. Pharmacol. Exp. Ther. 267, 331 (1993)). Tramadol is a racemate and consists of equal amounts of (+) and (−) enantiomers. In vivo, this active ingredient forms the metabolite O-desmethyl-tramadol, which likewise exists as a mixture of enantiomers. Investigations have shown that both the enantiomers of tramadol and the enantiomers of the tramadol metabolite have a part in the analgesic effect (J. Pharmacol. Exp. Ther. 260, 275 (1992)).
Compounds of formula
are known from Chem. Pharm. Bull. 32, 2279 (1984) in which Z represents H or OH These substances have an analgesic effect which is considerably weaker than that of tramadol.
SUMMARY OF THE INVENTION
The underlying object of the present invention was to develop substances with an analgesic effect which are suitable for the treatment of severe pain without giving rise to the side effects which are known for opioids. The object was also that the substances to be developed should not exhibit the side effects which occur in some cases of treatment with tramadol for example nausea and vomiting.
It has now been found that the requirements imposed on the substances to be developed are fulfilled by certain 6-dimethylaminomethyl-1-phenyl-cyclohexane compounds. These compounds are distinguished by a pronounced analgesic effect, which is significantly more intense compared with tramadol and with the compounds of formula
which are known from Arzneim.-Forsch./Drug Res. 28 (IA) 107 (1978), where Z
1
is H, OH or Cl and Z
2
is CH
3
, or Z
1
is OH and Z
2
is H.
REFERENCES:
patent: 3652589 (1972-03-01), Flick et al.
Sauda et al. (I) “Aralkylcyclohexanemethylamines”, CA 88: 22336, 1988.*
Sawa et al (II), “Phenylcyclohexane and Benzylcyclohexane derivatives”, CA 87: 52931, 1987.*
Bundgaard,Drugs of the Future16 443 (1991).
Bundgaard et al.,J. Med. Chem.,32, 2503 (1989).
Craig et al.,J. Am. Chem. Soc.74, 1316 (1952).
D'Amour et al.,J. Pharm. Exp. Ther.72, 74-79 (1941).
Dittert et al.,J. Pharm. Sci.,57, 774 (1968).
Flick et al.,Arzneim.-Forsch./Drug Res.,28 (IA) 107 (1978).
Hudlicky,Org. Reac.,35, 513 (1988).
Jaffe et al., Goodman, Gilman “The Pharmaceutical Basis of Therapeutics” Pergamon Press, New York, 1990, pp. 485-521.
Kato et al.,Chem. Pharm. Bull.32 2279 (1984).
Kim et al.,Angew. Chem.,95 568 (1983).
Litchfield et al.,J. Pharm. Exp. Ther.96, 99-113, (1949).
Olofson et al.,Tetrahedron Lett.,1977, 1571.
Raffa et al.,J. Pharmacol. Exp. Ther.,260, 275 (1992).
Raffa et al.,J. Pharmacol. Exp. Ther.,267, 331 (1993).
Smith et al.,J. Org. Chem.,17, 1116 (1952).
Thornberg et al.,J. Med. Chem.,30, 2008 (1989).
Tietze et al., “Reaktionen und Synthesen im Organisch-Chemischen Praktikum”, [“Reactions and Synthesis in the Practice of Organic Chemistry”], Thieme-Verlag, Stuttgart 1991, p. 189.
Tramontini,Synthesis,1973, 703.
Vogel,J. Chem. Soc.,1943, 636.
Wang et al.,J. Org. Chem.,59, 6895 (1994).
Welch et al.,J. Org. Chem.,43, 4797 (1978).
Winterfeldt,Synthesis,1975, 617.
Buschmann Helmut Heinrich
Friderichs Elmar Josef
Selve Norma
Strassburger Wolfgang Werner Alfred
Evenson, McKeown, Edwards & Lenahan P.L.L.C.
Gruenenthal GmbH
Lambkin Deborah C.
LandOfFree
6-dimethylaminomethyl-1-phenyl-cyclohexane compounds as... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with 6-dimethylaminomethyl-1-phenyl-cyclohexane compounds as..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and 6-dimethylaminomethyl-1-phenyl-cyclohexane compounds as... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2514511