IE44397B1 - Imidazoles - Google Patents

Description

This invention relates to substituted imidazole compounds which are useful intermediates in the preparation of compounds having pharmacological activity.

According to the present invention there are provided compounds of the formula 4 wnere R is hydrogen or lower alkyl, and R is lower alkyl, phenyl, benzyl or chlorobenzyl. 4 R is preferably methyl. R is preferably methyl.

As used herein, lower alkyl refers to alkyl groups containing from one to four carbon atoms.

The compounds of formula I can be prepared as described and claimed in Acceptance No. 2379/76 Reference is made throughout the present Specification to the compounds of formula I in the form of the free bases. However, it will be appreciated that these compounds can exist in the form of acid addition salts. For example salts with hydrochloric acid, and reference to the free base is intended herein to include reference to the acid addition salts.

The imidazole compounds of formula I are useful as. intermediates for the production of pharmacologically active compounds, in particular histamine ^-antagonists, for example N-cy ano-N'-me thy 1-N-/S-fS-R^-imidazolylmethylthio)44397 ethyi7suani6ine and N-methyl-N’ r/'2-(.5'-R^-imidaaolylmethylthio)ethyljbhiourea compounds, Histamine ^^antagonists act as histamine Hg-receptqrs which a3 described by Black et al. /Nature 236:385 (1972)7 defined as those histamine receptors which are not blocked by antihistamines such as mepyramine but are blocked by burimamide. Blockade of histamine Hg-receptors is of utility in inhibiting the biological actions of histamine which are not inhibited by antihistamines. Histamine Hg-antagonists are useful, for example, as inhibitors of gastric acid secretion.

Conversion of the compounds of formula Z into pharmacologically active guanidine and thiourea products can be accomplished in a variety of ways, as described in , Acceptance No. 2379/76 In particular, the compounds of 15 formula 1 can be treated with a reducing agent, for example with Raney nickel, to give the corresponding 4-(2-aminoethyl) thiomethylimidazoles. These compounds can then be converted into guanidine and thiourea products by reaction with methyl isothiocyanate to give the corresponding N-methyl-N*-(2-(.520 R1-imidazolylmethylthio)ethyVthioureas, or by reaction with N-cyano-N’-5-dimethylisothiourea to give the corresponding N-cyano-N *-methyl-N-Ci-(5~R1imidazolyImethylthio)ethyV guanidines. The guanidines can also be prepared by reaction of an imidazole of the present invention with dimethyl-N25 cyanoimidodithiocarbonate with subsequent reaction of the N-cyano-N*-/2-(S-R^imidazolylmethylthioJethylJ-S-methylisothiourea with methylamine.

These thiourea and cyanoguanidine products prepared from the compounds of formula I are described in Patent Specification 36050.

Claims (6)

1. A compound of the formula Z CH 2 SCH 2 CH 2 NH 2 Ν 8H SR 1 4 where R is hydrogen or lower alkyl, and R is lower alkyl, phenyl, benzyl or chlorobenzyl.

2. A compound according to claim 1, where R^ is methyl.

3. A compound according to claim 1 or claim 2, where R is methyl.

4. 4-(2-Aminoethyl)thIomethyl-

5. -methyl-2-methylthioimidazole.

6. A compound according to any of the preceding claims in the form of an acid addition salt thereof.