Anesthetic chlorocyclopropanes

Abstract

The following chlorocyclopropanes have been found to possess utility as general inhalation anesthetics: 1,1-dichloro-2-methyl-2,3,3-trifluorocyclopropane, 1,2-dichloro-1-fluoro-2-methylcyclopropane, 1,1,2-trichloro-2,3,3-trifluorocyclopropane, 1,1-dichloro-2-trifluoromethyl-2,3,3-trifluorocyclopropane, 1,2-dichloro-1,2,3,3-tetrafluorocyclopropane, 1,1,2,2-tetrachloro-3,3-difluorocyclopropane and 1,1-dichloro-2,3,3-trifluorocyclopropane.THE PRIOR ARTIn the continuing search for general inhalation anesthetics, there has been recently discovered a few halocyclopropanes and methylhalocyclopropanes and some methyl halocycloproyl ethers. These compounds are disclosed in U.S. Pat. Nos. 3,865,950, 3,839,589 and 3,769,429 as well as in pending applications Ser. No. 499,761 (filed Aug. 22, 1974) for the methylcyclopropanes, and Ser. No. 451,677 (filed Mar. 15, 1974) for the methyl ethers. Prior to these current developments, which have been contributed to the art by the present applicants, the only known cyclopropane compounds with a claim to anesthetic utility were cyclopropane itself and the 1-methyl-1-trifluoromethylcyclopropane reported by Krantz and Rudo [Handbuch of Experimental Pharmakologie 20 (1), at page 525 (1966)]. On assessing the progress reported in the art, as just reviewed, one must agree with these authors who, after an extensive compilation of the results of a few hundred tests on fluorinated compounds, conclude that cyclic halogenated compounds tend to be toxic. In fact, it has been the applicants' experience generally that for each useful compound discovered, there has been found one or more other structurally closely related compounds which are either useless or deleterious.In the case of chlorinated cycloalkanes specifically, the only compound mentioned in the literature in an anesthetic context is the 1,2-dichlorohexafluorocyclobutane, a compound which is said to be toxic, in contrast to its 1,2-dihydro-analog to which anesthetic properties have been ascribed [Burns et al, Anaesthesia 16 No. 1, page 14 (January 1961)].Thus, despite the disclosures in recent years, it can be reasonably said that little has been added to the understanding of the mode of action of chemical compounds in this physiological role and, because of this, the relationship of the similarities and differences between fairly similar compounds with either their toxic or therapeutic properties remains substantially unidentified. The discovery of additional substances possessing a desirable combination of properties for anesthetic purposes still lies, therefore, beyond the scope of routine expertise.SUMMARY OF THE INVENTIONSeveral dichlorocyclopropane compounds have now been found to possess useful anesthetic activity. This is rather surprising in view of the toxicity of the only dichlorocycloalkane reported upon before the contributions of the present inventors and also, in the case of many of the compounds of the present invention, the absence of the ring hydrogen which is believed to be necessary for anesthetic action. The compounds which form the basis of this invention are the following ones: 1,1-dichloro-2-methyl-2,3,3-trifluorocyclopropane, 1,2-dichloro-1-fluoro-2-methylcyclopropane, 1,1,2-trichloro-2,3,3-trifluorocyclopropane, 1,1-dichloro-2-trifluoromethyl-2,3,3-trifluorocyclopropane, 1,2dichloro1,2,3,3-tetrafluorocyclopropane, 1,1,2,2-tetrachloro-3,3-difluorocyclopropane and 1,1-dichloro-2,3,3-trifluorocyclopropane.DETAILED DESCRIPTIONThe chlorocyclopropanes of this invention may be synthesized by any several methods depending on the availability of starting materials and on the yield considered acceptable under the circumstances. The methods actually used in the preparation of the instant compounds are illustrated in the following examples.

Description

Claims

1. The process of inducing anesthesia in a mammal, which comprises administering by inhalation to said mammal an effective quantity for inducing anesthesia, of a cyclopropane selected from the group consisting of:

1,1-dichloro-2-methyl-2,3,3-trifluorocyclopropane, 1,2-dichloro-1-fluoro-2-methylcyclopropane, 1,1,2-trichloro-2,3,3-trifluorocyclopropane, 1,1-dichloro-2-trifluoromethyl-2,3,3-trifluorocyclopropane, 1,2-dichloro-1,2,3,3-tetrafluorocyclopropane, 1,1,2,2-tetrachloro-3,3-difluorocyclopropane and

2. The process of claim 1 wherein the cyclopropane employed is

3. The process of claim 1 wherein the cyclopropane employed is

4. The process of claim 1 wherein the cyclopropane employed is

5. The process of claim 1 wherein the cyclopropane employed is

6. The process of claim 1 wherein the cyclopropane employed is

7. The process of claim 1 wherein the cyclopropane employed is

8. The process of claim 1 wherein the cyclopropane employed is 1,1-dichloro-2,3,3-trifluorocyclopropane.