Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1998-08-18
2000-09-12
Ford, John M.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
544 8, A61K 31549, C07D41712
Patent
active
061178675
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This invention relates to novel 6-R-1,3,4-thiadiazin-2-amine derivatives, to the use of them in medicine and veterinary as anaesthetics, cardiovascular and hypometabolic agents and to pharmaceutical compositions containing them.
BACKGROUND OF THE INVENTION
Anaesthesia may generally be described as a state in which noxious events such as surgical procedures are rendered imperceptible by the body, the state being accompanied either by loss of consciousness (general anaesthesia) or no loss of consciousness (local anaesthesia). A complete or general anaesthetic given by inhalation or intravenous route produces a state of profound sleep and loss of motor activity (hypnosis), analgesia, muscle relaxation and protection against the increase in blood pressure and heart rate resulting from surgical stress. Anaesthetics generally display hypometabolic activity and frequently act as respiratory or cardiovascular depressants. Certain anaesthetics may be used to produce deliberate hypotensive effects which are very valuable in intracranial and other surgical procedures. Although a large number of agents having anaesthetic and cardiovascular activity have been identified and/or commercialised, there is a continuing need for now materials having hypometabolic activity, which are valuable for inducing sleep, reduction in motor activity, hypotension, bradycardiac, hypocoagulative, anti-aggregant and other hypobiosis effects such as reduced oxygen consumption and reduced body temperature, which would be valuable for use in complex surgical procedures or in the treatment of life threatening and/or traumatic situations such as brain stroke and myocardial infarction, and which have excellent potency, duration and CNS and cardiovascular toxicity profiles with absence of side effects such as tremor, convulsions and irregular breathing and heart beat.
There is considerable body of data concerning 6-R-1,3,4-thiadiazin-2-amines (for reviews see [1-3]). Also patent literature provides data on myo-relaxant [4-7], sedative [8,9], spasmolytic [10-12] and other types of biological activity [3]. A number of 5-aryl derivatives of 1,3,4-thiadiazines have been specifically described in the art [14-20] as well as 6-alkyl and 6-phenyl analogs thereof [13 and 21]. The value of 6-R-1,3,4-thiadiazin-2-amines as hypometabolic anaesthetics and cardiovascular agents has not hitherto been recognised however. Moreover, many of the5e compounds are apparently novel and have not been previously described in the literature.
The prior art on 6-R-1,3,4-thiadiazin-2-amines includes: Geterotsikl. Soedin., No 4, 435, (1991). Soedin., No 11, 1443, (1991). 30(2), 162-165 (1990).
SUMMARY OF THE INVENTION
According to one aspect off the invention, there is provxided the use off the substituted 6-R,-1,3,4-thiadiazin-2-amines of the following general formula as anaesthetic or cardiovascular agents: ##STR2## wherein Ar is phenyl or phenyl substituted with one or more atoms of chloro, bromo, C.sub.1 -C.sub.4 alkcoxy or C.sub.1 -C.sub.4 alkyl groups; R.sup.1 and R.sup.2 are each independently hydrogen atom or C.sub.1 -C.sub.4 alkyl moiety; and R.sup.3 and R.sup.4 are each independently selected from C.sub.1 -C.sub.4 alkyl groups; and pharmaceutically acceptable salts thereof.
According to a further aspect of the invention, there is provided novel substituted 6-R-1,3,4-thiadiazin-2-amines of the general formula set out above.
According to a still further .aspect of the invention, there is provided pharmaceutical compositions comprising one or more substituted 6-R-1,3,4-thiadiazin-2-amines as an active compound or pharmaceutically acceptable salts thereof.
DISCLOSURE OF THE INVENTION
1,3,4-Thiadiazines suitable for use herein contain at the 5 position of the thiadiazine ring unsubstituted phenyl or phenyl substituted with one or more straight or branched chain C.sub.1 -C.sub.4 alkyl, alkenyl, alkoxy or acyloxy groups, one or more hydroxy groups or halogen atoms. In preferred compounds of this formula Ar represents unsubstituted phenol or phenyl
REFERENCES:
patent: 3956311 (1976-05-01), Kuffner et al.
patent: 4272532 (1981-06-01), Jones et al.
patent: 4309426 (1982-01-01), Jones, Jr. et al.
patent: 4558045 (1985-12-01), Hargreaves et al.
patent: 4645528 (1987-02-01), Diehr et al.
patent: 4940790 (1990-07-01), Thorwart et al.
patent: 5021413 (1991-06-01), Terada et al.
patent: 5411955 (1995-05-01), Strasser et al.
Beyer,H. "Desulfurization Reactions with the Formation of Pyrazoles." Z. Chem.9 JG. (1969) p. 369 (with English Translation) with English Translation of DD 288824 Dated Apr. 1991.
Pfieffer, W.D. et al. "About Contraction of the Ring of 6H 1,3,4-Thiadiazines . . . " Synthesis, No. 7 (1977) pp. 485-486 (with English Translation).
"Evaluation of the Effect of Narcotic, Analgetic and Psychotropic Agents in Clinical Anesthesiology." N. A. Psipova, The Meditsina Publishers, Leningrad, Chapter 2 (1988) pp. 14-16 (in English and Russian).
Textbook of Anesthesiology. Moscow, the Meditsina Publishers (1994) pp. 10-13 (in English and Russian).
"Side Effects of Drugs." The Meditsina Publishers, Moscow (1983) pp. 1-6 (in English and Russian).
Usoltseva S.V., et al., "1,3,4-Thiadiazines: Method of Synthesis and Reactivity." Khim. Geterotsikl. Soedin No. 4 (1991) pp. 435-448 And English comments thereon.
Novikova A.P., et al. "Synthesis and Properties of Functional Derivatives of 1,3,4. Thiadiazines . . . " Khim. Geterotsikl. Soedin No: 11 (1991) pp. 1443-1457 And English comments thereon.
Rasina L.N., et al. "On Some Mechanisms of Action of Radioprotectors of Various Chemical Classes In Intestinal Syndrome" Radiobiologiya, 30(2) (1990) pp. 162-165 And English comments thereon.
Belik A.V. et al., "Prediction of A Class of Strong Toxicity of 1,3,4-Thiadiazine Derivatives" Khim-Farm. Zh., 26(3), (1992) pp. 62-64 And English comments thereon.
Perova N.M. et al., "Transformation of 2-Cycloalkylimino-6H-1-3-4-Thiadiazines under UV Irradiation" Khim. Geterotsikl. Soedin., No. 4, (1993) pp. 565-600 And English comments thereon.
Patent Abstracts of Japan of JP 06253976 Dated Sep. 13, 1994.
Chupakhin Oleg Nikolaevich
Novikova Antonina Petrovna
Perova Natalya Mikhailovna
Sidorova Larisa Petrovna
Tarakhty Emma Afanasievna
Ford John M.
Nauchno-Tekhnologicheskoepredpriyatie "Ligand"(Tovarischestvo S
Procter & Gamble Company
LandOfFree
Substituted 6-R-1,3,4-thiadiazine-2-amines, the use thereof as a does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Substituted 6-R-1,3,4-thiadiazine-2-amines, the use thereof as a, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Substituted 6-R-1,3,4-thiadiazine-2-amines, the use thereof as a will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-96362