Naphthothiopyranone derivatives

Details Naphthothiopyranone derivatives Naphthothiopyranone derivatives

1992-12-11

1994-09-13

Morris, Patricia L.

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C07D40906

Patent

active

053470125

DESCRIPTION:

BRIEF SUMMARY
DESCRIPTION

1. Technical Field
The present invention relates to naphthothiopyranone derivatives, and more particularly relates to naphthothiopyranone derivatives having the antagonist effect of 5-HT (serotonin) at 5-HT.sub.3 (serotonin 3) receptors.
Background Art
Compounds described in EP-A-364274 have heretofore been known as having the structure and effect similar to those of the compounds of the present invention, but they do not have a satisfactory degree of the drug effect.
An object of the present invention is to provide compounds having more excellent anti-vomiting effect, gastrointestinal movement regulating effect and anti-anxiety effect based on the antagonist effect at serotonin 3 receptors than the prior art compounds.


DISCLOSURE OF THE INVENTION

The present invention is a naphthothiopyranone derivative represented by the formula: ##STR2## (wherein R.sup.1 is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms) or an acid addition salt thereof, and further a compound represented by the formula: ##STR3## which is an intermediate of the compound of Formula (I).
In the present invention, the alkyl group having 1 to 4 carbon atoms means a straight or branched chain alkyl group. The acid addition salt of the compound of Formula (I) means an addition salt of a pharmacologically acceptable acid, for example, hydrochloride, hydrobromide, hydroiodide, sulfate, acetate, citrate, maloate, maleate, tartarate and succinate.
The compound of Formula (I) of the present invention can be prepared, for example, by the following processes.
A compound of Formula (II) is first reacted with a halogenating agent of common use (e.g. hydrobromic acid, thionyl chloride, phosphorus pentachloride, thionyl bromide and phosphorus tribromide) in an organic solvent or without solvent to give a compound represented by the formula: ##STR4## (wherein X is a halogen atom). The halogen atom herein means a chlorine atom, a bromine atom or an iodine atom. Examples of the organic solvent to be used are tetrahydrofuran, dioxane, ether, benzene, toluene, chloroform, dichloromethane, carbon tetrachloride, pyridine and a mixture of these solvents with hexamethylphosphorus triamide. A base such as triethylamine can also be added.
The compound obtained above is reacted with a compound represented by the formula: ##STR5## (wherein R.sup.1 is as defined above) or an acid addition salt thereof in an organic solvent in the presence or absence of a base to give a compound of Formula (I). Examples of the base to be used in the reaction are triethylamine, pyridine, potassium carbonate, sodium carbonate, lithium carbonate, cesium carbonate, sodium bicarbonate, sodiumshydride, sodium hydroxide, potassium hydroxide, sodium ethoxide and potassium t-butoxide ("base" used hereinafter in the term of the disclosure of the invention is the same as defined herein). Examples of the organic solvent to be used are dichloromethane, chloroform, carbon tetrachloride, tetrahydrofuran, diethyl ether, dioxane, N,N-dimethylformamide, benzene, toluene and alcohols. In addition, iodides (e.g. potassium iodide) or phase-transfer catalysts (e.g. tetrabutylammonium bromide) can be used as a catalyst to accelerate the reaction.
On the other hand, the compound of Formula (II) of the intermediate is a novel compound and can be prepared, for example, by the following processes.
A known compound represented by the formula: ##STR6## which can be prepared by the method described in Journal of Chemical Society, Parkin Trans. I, vol. 6, pp. 787-792 (1972), is reacted with formaldehyde in the presence of a base in an organic solvent at from room temperature to the boiling point of the solvent to give the compound of Formula (II). Examples of the organic solvent to be used in the reaction are tetrahydrofuran, dioxane, methanol, ethanol, isopropanol and N,N-dimethylformamide.
On the other hand, the compound of Formula (III) is reacted with formamide in the presence of a base in an organic solvent at from a temperature under ice-cooling to room temperature, and then the

REFERENCES:
patent: 5006544 (1991-04-01), North et al.
Chemical Abstracts, vol. 94, No. 7, abstract no. 47079p, (J. Org. Chem., 45(23), 4611-15 1980.
Chemical Abstracts, vol. 93, No.23, abstract no. 220537r, (Bull. Chem. Soc., Japan. 53(7), 2046-9 1980.

Affiliated with

Also associated with

Rating

Naphthothiopyranone derivatives does not yet have a rating. At this time, there are no reviews or comments for this patent.

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

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1121457