CA1075703A - Process for preparing amidinosulphinic acid derivatives - Google Patents
Process for preparing amidinosulphinic acid derivativesInfo
- Publication number
- CA1075703A CA1075703A CA320,456A CA320456A CA1075703A CA 1075703 A CA1075703 A CA 1075703A CA 320456 A CA320456 A CA 320456A CA 1075703 A CA1075703 A CA 1075703A
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- thiourea
- histamine
- ethyl
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
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Abstract
ABSTRACT OF THE DISCLOSURE
Compounds of the formula wherein R is hydrogen or lower alkyl are disclosed.
The compounds have histamine H2- receptor antagonist activity and have been found to inhibit the basal secretion of gastric acid.
Compounds of the formula wherein R is hydrogen or lower alkyl are disclosed.
The compounds have histamine H2- receptor antagonist activity and have been found to inhibit the basal secretion of gastric acid.
Description
~o75703 This invention relates to a process for preparing amidino-sulphinic acid derivatives and to pharmaceutical compositions containing these compounds.
Many physiologically active substances elicit their biological actions by interaction with specific sites known as receptors.
Histamine is such a substance and it has a number of biological actions. Those biological actions of histamine which are ~
inhibited by drugs commonly called "antihistamines" of which -mepyramine, diphenyhydramine and chloropheniramine are examples, are mediated through histamine Hl-receptors, and drugs with this activity are hereinafter referred to as histamine Hl-receptor antagonists. However, other of the biological actions of histamine are not inhibited by histamine Hl-receptor --antagonists and actions of this type which are inhibited by a compound called burimamide are mediated through receptors which -are defined as histamine H2-receptors. Thus histamine H2-receptors are defined as those histamine receptors which are not blocked by mepyramine but are blocked by burimamide. Compounds which --~
block histamine H2-receptors are referred to as histamine H2-receptor antagonists.
. ~ , -;i Blockade of histamine H2-receptors is of utility in inhibiting the biological actions of histamine which are not inhibited by histamine Hl-receptor antagonists. Histamine H2-receptor ~ antagonists are therefore useful, for example, as inhibitors ,! of gastric acid secretion, as anti-inflammatory agents and as ~agents which act on the cardiovascular system, for e~ample as ., .i . q~
' ' ' .
.. ~ . : -10757(~
inhibitors of the effects of histamine on blood pressure. In the treatment of certain conditions, for example inflammation, and in inhibiting the actions of histamine on blood pressure, a combination of histamine Hl- and H2-receptor antagonists is useful.
The compounds of this invention have histamine H2-receptor antagonist activity and can be used in the treatment of conditions wherein histamine H2-receptor antagonists are useful.
The present invention provides a process for preparing amidinosulphonic acid derivatives of the formula:
R CH2 S C~2 C~I2 N~ - C ~ 2 ~ 3 .', . ' ' - ' .
where R is a lower alkyl group or hydrogen atom.
-; Compounds of formula I are particularly useful as inhi~itors of histamine stimulated gastric acid secretion.
Thr~ughout this specification by the term "lower alkyl" wemean an alkyl group containing from 1 to 4 carbon atoms.
.
The compounds of formula I can be re~resented by many tautomeric structures, and can also be referred to as t~iourea S,S-dioxides as sho~n by for~ulae II and TII.
- . . . .
S102H l2 Z - .~'H - C = NR ~ - ~ Z - .~H - C - N~R
II III
Also certain of the heterocyclyl groups represented by Het can exist in several tautomeric forms, and it will be understood that all of the alternatiYe representations of these forms are within the scope of the present invention. The compounds of the invention can exist as acid addition salts but, for convenience reference will be made throughout this specification to the compounds as shown in formula I. Hydrates of compounds of formula I and pharmaceutically acceptable hydrated salts of compounds of formula I are also ~ithin the scope of this invention. ~-Compounds of formula 1 can be prepared by reacting a thiourea -of the formula:
_ S
~ ~ CH2 S CH2 CH2 - N~ - C~
., i -- ~where R ls as defined for formula I) with hydrogen peroxide.
Preferably this reaction is carried out under neutral conditions ~, at a temperature in the range -5C to +10C in a solvent such as ~3~ a lower alcohol.
~ Thioureas of formula IV are described and claimed inter alia -- ~; in British Patent Specifications 1307539, 1338169, and 1395929 ~ ~, :``:` "` ` `
~ . ~
, ; . .
iO~5703 : 4:
The compounds of formula I block histamine H2-receptors, that is they inhibit biological actions of histamine which are not inhibited by histamine Hl-receptor antagonists surh as mepyramine but aTe inhibited by burimamide. For example, the compounds produced in accordance with this invention have been found to inhibit histamine-stimulated secretion of gastric acid from the lumen-perfused stomachs or rats anaesthetised with urethane, at doses of from 0.5 to 256 micromoles per kilograme intravenously.
The activity of these compounds as histamine H2-receptor antagonists is also demonstrated by their ability to inhibit other actions of histamine which are not mediated by histamine -Hl-receptors. For example, they inhibit the àctions of histamine on the isolated guinea pig atrium and isolated rat uterus.
Compounds produced in accordance with this invention have been found to inhibit the basal secretion of gastric acid and also that stimulated by pentagastrin or by food.
In addition, in a conventional test such as the measurement of blood pressure in the anaesthetised cat, the actlon of the compounds produced in accordance with this invention can inhibit the vasodilator action of histamine when administered intravenously at doses of from 0.5 to 256 micromoles per Xilogram.
The level of activity of the compounds produced in accordance wi-th this invention is illustrated by the effective dose . .
: 5:
producing 50~ inhibition of gastric acid secretion in the anaesthetised rat and the dose producing 50~ inhibition of histamine-induced tachycardia in the isolated guinea pig atrium ~less than 10 4 Molar).
For therapeutic use, the pharmacologically active compounds produced in accordance with this present invention will normally be administered as a pharmaceutical composition comprising as the or an essential active ingredient at least one such compound in the neutral form or in the form of a pharmaceutically acceptable addition salt with an acid and in association with a pharmaceutical carrier therefore. Such addition salts include those with hydrochloric, hydrobromic, hydriodic, sulphuric and maleic acids and can conveniently be formed from the corresponding compound of Formula I by standard procedures, for example by treating the compound with an acid in a lower alkanol or by use of ion exchange resins to form the required salt either directly from the neutral compound or from a different addition salt.
The invention also provides ph-armaceutical compositions comprising a pharmaceutical carrier and a compound of formula I or a pharmaceutically acceptable acid addition salt thereof.
The pharmaceutical carrier employed can be solid or liquid.
Examples of solid carriers are lactose, terra alba, sucrose, i -` talc, gelatin, agar, pectin, acacia, magnesium stearate, ' stearic acid and the like. Examples of liquid carriers are . syrup, peanut oil, olive oil, water and the like.
, ... ...
A wide variety of pharmaceutical forms can be employed. Thus, if a solid carrier is used, the compositions can be tableted in a hard gelatin capsule in powder or pellet form, or in the form of a troche or lozenge. The amount of solid carrier can be varied widely but preferably it is from 25 mg to 300 mg. If a liquid carrier is used, the preparation can be in the form of a syrup, emulsion, in a soft gelatin capsule, or as a sterile injectable liquid contained for example in an ampoule, or as an aqueous or non-aqueous li~uid suspension.
:
The pharmaceutical compositions can be prepared by conventional techniques involving procedures such as mixing, granulating and compressing or dissolving the ingredients as appropriate to the desired preparation.
' The active ingredient will be present in the compositions in an ~` effective amount to block histamine H2-receptors. The route of administration can be oral or parenteral. - --'.' - Preferably, each dosage unit will contain the active ingredient in an amount of from about 50 mg to about 250 mg.
:~, ~-- The active ingredient will preferably be administered one to six ; , - . .
times per day. The daily dosage regimen will preferably be from 150 mg to l500 mg.
.
i l .
,. ~ .
.
.
- . -` . - -: 7 :
Advantageously the composition will be made up in a dosa~c form appropriate to the desired mode of administration for example as a tablet, capsule injectable solution or as a cream or ointment for topical application.
In our co-pending Canadian Patent application No.
Z73,246 we describe and claim processes for preparing corresponding amidinoformic acid derivatives.
`:
This invention is illustrated by the following Examples wherein all temperatures are in degrees Centigrade.
.:' ' .
... .
EXAMPLE i ~' .
~ Z N-Methyl-N'[2-~5-methyl-4-imidazolylmethylthio)ethyl]-.:
~ amidinosulphinic acid s N-Methyl-N'-[2-(5-methyl-4-imidazolylmethylthio)ethyl]- -thiourea ~2.93 g) was stirred in methanol (12 ml) with cooling, in an ice bath. 30~ Hydrogen peroxide (2.72 g) was added dropwise over 30 min. to give a clear solution which was stored overnight at 0 to yield a white, crystalline solid which was filtered off and dried to give ''~ the title product m.p. 120-121.
':
' ., ~:: .
~' -: ~
, - ~ . ,, :; - ~. - . .
: 8 :
tFound: C 39.0; Il, 5.8; N, 20~0; S, 22.8; C~ 6N402S2 requires: C, 39.1; Il, 5.8; N, 20.3; S, 23.2~) . . EXA~PLE 2 Substitution of the follo~ing thioureas (a). N-Methyl-N'-[2-(5-ethyl-4-imidazolyl)methylthio)-ethyl]thiourea (b) N-Methyl-N'-[2-(S-bromo-4-imidazolyl)metllylthio)ethyl]-thiourea ~c) N-Methyl-N'-C2-(5-trifluoromethyl-4-imidazolyl)methyl-thio)ethyl]thiourea (dj N-hlethyl-N'-[2-(5-hydroxymethyl-4-imidazolyl)methylthio)-ethyl]thiourea (e) N-Methyl-N'-[2-(2-pyridylmethylthio)ethyl]thiourea (f) N-Methyl-N'-[2-(3-methyl-2-pyridylmethylthio)ethy-1] ~
thiourea - :
g).' N-Methyl-N'-E2-(3-hydroxy-2-pyridylmethylthio)ethyl]-thiourea (h) N-Methyl-N'-[2-(2-thiazolylmethylthio)ethyl]thiourea - :--(i} N-Methyl-N'- [2-(3-isothiazolylmethylthio)ethyl]-thiourea (j) N-Methyl-N'- [2-(4-bromo-3-isothiazolylmethylthio)-ethyl]thiourea (k) N-Methyl-N'-[2-~3-isoxaazolylmethylthio)ethyl]thiourea .
(1) N-Methyl-N'-[2-(5-amino-2-(1,3,4)thiadiazolylmethylthio)-ethyl]thiourea (m) N-Methyl-N'-[2-~2-imidazolyl)ethylthio)et}lyl]thiourea (n) N-Methyl-N'[3-(2-imidazolylthio)propyl]thiourea (o) N-Methyl-N'-a2-pyridylthio)propyl]thiourea ''' . ' ' - .
~075703 . : 9: , (p) N-Methyl-N'-~-(2-thiazolvlthio)propyl]thiourea (q) N-Metllyl-N'-~3(2-oxazolylthio)pro~yl]thiourca (r~ N-Methyl-N'-~3-(5-amino-2-(1,3,4)thiadiazolyltllio)-. propyl]thiourea (s) N-Methyl-N'-[2-(4-imidazolylmethyoxy)ethyl]thiourea ~t) N-Methyl-N'-[3-(4-imidazolylmethoxy)pro~yl]thiourea for N-methyl-N'-[2-(5-methyl-4-imidazolylthio)ethyl]-- thiourea in th2procedure of Example~leads to the production of the corresponding amidinosulphinic acids. --. Substitution of the following,thioureas:-' . (a) . N-Methyl-N'-[4-(4-imidazolyl)butyl]thiourea :,~ (bj N-Butyl-N'-~4-t4-imidazolyl)butyl]thiourea . . (c) N-Methyl-N'-[4-(5-bromo-4-imidazolyl)butyl]thiourea ,, (d) N-Methyl-N'-[4-(5-methyl-4-imidazolyl)butyl]thiourea (e) N-Methyl-N'-[5-(4-imidazolyl)pentyl]thiourea tf) N-Methyl-N'-[4-~2-pyridyl)butyl]thiourea - (g) N-Methyl-N'-~4-~2-thiazolyl)butyl]thiourea (h) N-Methyl-N'-[4-(3-(1,2~4)triazolyl)butyl]thiourea ~, . .
for N-methyl-N'-[2-(5-methyl-4-imidazolylmethyltllio)ethvl]-. thiourea in the procedure of Example 1 leads to the production , of th: Forrespondin5 amidinosulphiAic acids ` 1 .
. ' ' .
` 1075703 -- .
: 10:
. EXAM~L~. 4 Substitution of the following thioureas:- -(a) N-[2-t4-Imidazolylmethvlthio)ethyl]thiourea (b) N-[2-(5-Methyl-4-imidazolylmethylthio)ethyl~thiourea ~c) N-[4-(4-Imidazolyl)butyl3thiourea for N-methyl-N'-[2-(.5-methyl-4-imidazolylmethylthio)ethyl]-thiourea ln the procedure of Example 1 leads to the production of the corresponding amidinosulphinic acids.
- , :
. EXA~lPLE 5 Substituion of the following thioureas:-(a) N,N'-bist2-(5-methyl-4-imidazolylmethylthio)ethyl]thiourea (b) N-[2-(2-Pyridylmethylthio)ethyl]-N'-[2-~5-methyl-4-imidazolylmethylthio)ethyl]thiourea (c? N,N'-bis[4-(4-imidazolyl)butyl]thiourea . : -~ '-for N-methyl-N'-[2-(5-methyl-4-imidazolylmethylthio~ethy~ - ~
thiourea in the procedure of Example 1 leads to the production .-of the corresponding amidinosulphinic acids.
~ ! :
. I . .
,~
,i, , ' ' '1 ~ _ ,.' .`~ ' , .
` .
.
_. . . . . .
Many physiologically active substances elicit their biological actions by interaction with specific sites known as receptors.
Histamine is such a substance and it has a number of biological actions. Those biological actions of histamine which are ~
inhibited by drugs commonly called "antihistamines" of which -mepyramine, diphenyhydramine and chloropheniramine are examples, are mediated through histamine Hl-receptors, and drugs with this activity are hereinafter referred to as histamine Hl-receptor antagonists. However, other of the biological actions of histamine are not inhibited by histamine Hl-receptor --antagonists and actions of this type which are inhibited by a compound called burimamide are mediated through receptors which -are defined as histamine H2-receptors. Thus histamine H2-receptors are defined as those histamine receptors which are not blocked by mepyramine but are blocked by burimamide. Compounds which --~
block histamine H2-receptors are referred to as histamine H2-receptor antagonists.
. ~ , -;i Blockade of histamine H2-receptors is of utility in inhibiting the biological actions of histamine which are not inhibited by histamine Hl-receptor antagonists. Histamine H2-receptor ~ antagonists are therefore useful, for example, as inhibitors ,! of gastric acid secretion, as anti-inflammatory agents and as ~agents which act on the cardiovascular system, for e~ample as ., .i . q~
' ' ' .
.. ~ . : -10757(~
inhibitors of the effects of histamine on blood pressure. In the treatment of certain conditions, for example inflammation, and in inhibiting the actions of histamine on blood pressure, a combination of histamine Hl- and H2-receptor antagonists is useful.
The compounds of this invention have histamine H2-receptor antagonist activity and can be used in the treatment of conditions wherein histamine H2-receptor antagonists are useful.
The present invention provides a process for preparing amidinosulphonic acid derivatives of the formula:
R CH2 S C~2 C~I2 N~ - C ~ 2 ~ 3 .', . ' ' - ' .
where R is a lower alkyl group or hydrogen atom.
-; Compounds of formula I are particularly useful as inhi~itors of histamine stimulated gastric acid secretion.
Thr~ughout this specification by the term "lower alkyl" wemean an alkyl group containing from 1 to 4 carbon atoms.
.
The compounds of formula I can be re~resented by many tautomeric structures, and can also be referred to as t~iourea S,S-dioxides as sho~n by for~ulae II and TII.
- . . . .
S102H l2 Z - .~'H - C = NR ~ - ~ Z - .~H - C - N~R
II III
Also certain of the heterocyclyl groups represented by Het can exist in several tautomeric forms, and it will be understood that all of the alternatiYe representations of these forms are within the scope of the present invention. The compounds of the invention can exist as acid addition salts but, for convenience reference will be made throughout this specification to the compounds as shown in formula I. Hydrates of compounds of formula I and pharmaceutically acceptable hydrated salts of compounds of formula I are also ~ithin the scope of this invention. ~-Compounds of formula 1 can be prepared by reacting a thiourea -of the formula:
_ S
~ ~ CH2 S CH2 CH2 - N~ - C~
., i -- ~where R ls as defined for formula I) with hydrogen peroxide.
Preferably this reaction is carried out under neutral conditions ~, at a temperature in the range -5C to +10C in a solvent such as ~3~ a lower alcohol.
~ Thioureas of formula IV are described and claimed inter alia -- ~; in British Patent Specifications 1307539, 1338169, and 1395929 ~ ~, :``:` "` ` `
~ . ~
, ; . .
iO~5703 : 4:
The compounds of formula I block histamine H2-receptors, that is they inhibit biological actions of histamine which are not inhibited by histamine Hl-receptor antagonists surh as mepyramine but aTe inhibited by burimamide. For example, the compounds produced in accordance with this invention have been found to inhibit histamine-stimulated secretion of gastric acid from the lumen-perfused stomachs or rats anaesthetised with urethane, at doses of from 0.5 to 256 micromoles per kilograme intravenously.
The activity of these compounds as histamine H2-receptor antagonists is also demonstrated by their ability to inhibit other actions of histamine which are not mediated by histamine -Hl-receptors. For example, they inhibit the àctions of histamine on the isolated guinea pig atrium and isolated rat uterus.
Compounds produced in accordance with this invention have been found to inhibit the basal secretion of gastric acid and also that stimulated by pentagastrin or by food.
In addition, in a conventional test such as the measurement of blood pressure in the anaesthetised cat, the actlon of the compounds produced in accordance with this invention can inhibit the vasodilator action of histamine when administered intravenously at doses of from 0.5 to 256 micromoles per Xilogram.
The level of activity of the compounds produced in accordance wi-th this invention is illustrated by the effective dose . .
: 5:
producing 50~ inhibition of gastric acid secretion in the anaesthetised rat and the dose producing 50~ inhibition of histamine-induced tachycardia in the isolated guinea pig atrium ~less than 10 4 Molar).
For therapeutic use, the pharmacologically active compounds produced in accordance with this present invention will normally be administered as a pharmaceutical composition comprising as the or an essential active ingredient at least one such compound in the neutral form or in the form of a pharmaceutically acceptable addition salt with an acid and in association with a pharmaceutical carrier therefore. Such addition salts include those with hydrochloric, hydrobromic, hydriodic, sulphuric and maleic acids and can conveniently be formed from the corresponding compound of Formula I by standard procedures, for example by treating the compound with an acid in a lower alkanol or by use of ion exchange resins to form the required salt either directly from the neutral compound or from a different addition salt.
The invention also provides ph-armaceutical compositions comprising a pharmaceutical carrier and a compound of formula I or a pharmaceutically acceptable acid addition salt thereof.
The pharmaceutical carrier employed can be solid or liquid.
Examples of solid carriers are lactose, terra alba, sucrose, i -` talc, gelatin, agar, pectin, acacia, magnesium stearate, ' stearic acid and the like. Examples of liquid carriers are . syrup, peanut oil, olive oil, water and the like.
, ... ...
A wide variety of pharmaceutical forms can be employed. Thus, if a solid carrier is used, the compositions can be tableted in a hard gelatin capsule in powder or pellet form, or in the form of a troche or lozenge. The amount of solid carrier can be varied widely but preferably it is from 25 mg to 300 mg. If a liquid carrier is used, the preparation can be in the form of a syrup, emulsion, in a soft gelatin capsule, or as a sterile injectable liquid contained for example in an ampoule, or as an aqueous or non-aqueous li~uid suspension.
:
The pharmaceutical compositions can be prepared by conventional techniques involving procedures such as mixing, granulating and compressing or dissolving the ingredients as appropriate to the desired preparation.
' The active ingredient will be present in the compositions in an ~` effective amount to block histamine H2-receptors. The route of administration can be oral or parenteral. - --'.' - Preferably, each dosage unit will contain the active ingredient in an amount of from about 50 mg to about 250 mg.
:~, ~-- The active ingredient will preferably be administered one to six ; , - . .
times per day. The daily dosage regimen will preferably be from 150 mg to l500 mg.
.
i l .
,. ~ .
.
.
- . -` . - -: 7 :
Advantageously the composition will be made up in a dosa~c form appropriate to the desired mode of administration for example as a tablet, capsule injectable solution or as a cream or ointment for topical application.
In our co-pending Canadian Patent application No.
Z73,246 we describe and claim processes for preparing corresponding amidinoformic acid derivatives.
`:
This invention is illustrated by the following Examples wherein all temperatures are in degrees Centigrade.
.:' ' .
... .
EXAMPLE i ~' .
~ Z N-Methyl-N'[2-~5-methyl-4-imidazolylmethylthio)ethyl]-.:
~ amidinosulphinic acid s N-Methyl-N'-[2-(5-methyl-4-imidazolylmethylthio)ethyl]- -thiourea ~2.93 g) was stirred in methanol (12 ml) with cooling, in an ice bath. 30~ Hydrogen peroxide (2.72 g) was added dropwise over 30 min. to give a clear solution which was stored overnight at 0 to yield a white, crystalline solid which was filtered off and dried to give ''~ the title product m.p. 120-121.
':
' ., ~:: .
~' -: ~
, - ~ . ,, :; - ~. - . .
: 8 :
tFound: C 39.0; Il, 5.8; N, 20~0; S, 22.8; C~ 6N402S2 requires: C, 39.1; Il, 5.8; N, 20.3; S, 23.2~) . . EXA~PLE 2 Substitution of the follo~ing thioureas (a). N-Methyl-N'-[2-(5-ethyl-4-imidazolyl)methylthio)-ethyl]thiourea (b) N-Methyl-N'-[2-(S-bromo-4-imidazolyl)metllylthio)ethyl]-thiourea ~c) N-Methyl-N'-C2-(5-trifluoromethyl-4-imidazolyl)methyl-thio)ethyl]thiourea (dj N-hlethyl-N'-[2-(5-hydroxymethyl-4-imidazolyl)methylthio)-ethyl]thiourea (e) N-Methyl-N'-[2-(2-pyridylmethylthio)ethyl]thiourea (f) N-Methyl-N'-[2-(3-methyl-2-pyridylmethylthio)ethy-1] ~
thiourea - :
g).' N-Methyl-N'-E2-(3-hydroxy-2-pyridylmethylthio)ethyl]-thiourea (h) N-Methyl-N'-[2-(2-thiazolylmethylthio)ethyl]thiourea - :--(i} N-Methyl-N'- [2-(3-isothiazolylmethylthio)ethyl]-thiourea (j) N-Methyl-N'- [2-(4-bromo-3-isothiazolylmethylthio)-ethyl]thiourea (k) N-Methyl-N'-[2-~3-isoxaazolylmethylthio)ethyl]thiourea .
(1) N-Methyl-N'-[2-(5-amino-2-(1,3,4)thiadiazolylmethylthio)-ethyl]thiourea (m) N-Methyl-N'-[2-~2-imidazolyl)ethylthio)et}lyl]thiourea (n) N-Methyl-N'[3-(2-imidazolylthio)propyl]thiourea (o) N-Methyl-N'-a2-pyridylthio)propyl]thiourea ''' . ' ' - .
~075703 . : 9: , (p) N-Methyl-N'-~-(2-thiazolvlthio)propyl]thiourea (q) N-Metllyl-N'-~3(2-oxazolylthio)pro~yl]thiourca (r~ N-Methyl-N'-~3-(5-amino-2-(1,3,4)thiadiazolyltllio)-. propyl]thiourea (s) N-Methyl-N'-[2-(4-imidazolylmethyoxy)ethyl]thiourea ~t) N-Methyl-N'-[3-(4-imidazolylmethoxy)pro~yl]thiourea for N-methyl-N'-[2-(5-methyl-4-imidazolylthio)ethyl]-- thiourea in th2procedure of Example~leads to the production of the corresponding amidinosulphinic acids. --. Substitution of the following,thioureas:-' . (a) . N-Methyl-N'-[4-(4-imidazolyl)butyl]thiourea :,~ (bj N-Butyl-N'-~4-t4-imidazolyl)butyl]thiourea . . (c) N-Methyl-N'-[4-(5-bromo-4-imidazolyl)butyl]thiourea ,, (d) N-Methyl-N'-[4-(5-methyl-4-imidazolyl)butyl]thiourea (e) N-Methyl-N'-[5-(4-imidazolyl)pentyl]thiourea tf) N-Methyl-N'-[4-~2-pyridyl)butyl]thiourea - (g) N-Methyl-N'-~4-~2-thiazolyl)butyl]thiourea (h) N-Methyl-N'-[4-(3-(1,2~4)triazolyl)butyl]thiourea ~, . .
for N-methyl-N'-[2-(5-methyl-4-imidazolylmethyltllio)ethvl]-. thiourea in the procedure of Example 1 leads to the production , of th: Forrespondin5 amidinosulphiAic acids ` 1 .
. ' ' .
` 1075703 -- .
: 10:
. EXAM~L~. 4 Substitution of the following thioureas:- -(a) N-[2-t4-Imidazolylmethvlthio)ethyl]thiourea (b) N-[2-(5-Methyl-4-imidazolylmethylthio)ethyl~thiourea ~c) N-[4-(4-Imidazolyl)butyl3thiourea for N-methyl-N'-[2-(.5-methyl-4-imidazolylmethylthio)ethyl]-thiourea ln the procedure of Example 1 leads to the production of the corresponding amidinosulphinic acids.
- , :
. EXA~lPLE 5 Substituion of the following thioureas:-(a) N,N'-bist2-(5-methyl-4-imidazolylmethylthio)ethyl]thiourea (b) N-[2-(2-Pyridylmethylthio)ethyl]-N'-[2-~5-methyl-4-imidazolylmethylthio)ethyl]thiourea (c? N,N'-bis[4-(4-imidazolyl)butyl]thiourea . : -~ '-for N-methyl-N'-[2-(5-methyl-4-imidazolylmethylthio~ethy~ - ~
thiourea in the procedure of Example 1 leads to the production .-of the corresponding amidinosulphinic acids.
~ ! :
. I . .
,~
,i, , ' ' '1 ~ _ ,.' .`~ ' , .
` .
.
_. . . . . .
Claims (4)
1. A process for preparing compounds of the formula:
I
where R is a hydrogen atom or lower alkyl group, characterized in that a compound of the formula:
II
(where R is as defined above) is reacted with hydrogen peroxide.
I
where R is a hydrogen atom or lower alkyl group, characterized in that a compound of the formula:
II
(where R is as defined above) is reacted with hydrogen peroxide.
2. A compound of the formula where R is a hydrogen atom or a lower alkyl group whenever prepared by the process claimed in claim 1 or by any obvious chemical equivalents thereof.
3. A process for preparing N-methyl-N'[2-(5-methyl-4-imidazolylmethylthio) ethyl] amidinosulphinic acid which comprises reacting N-methyl-N'-[2-(5-methyl-4-imidazolylmethylthio) ethyl ] thiourea with hydrogen peroxide.
4. N-methyl-N'[2-(5-methyl-4-imidazolylmethyl-thio)ethyl ] amidinosulphinic acid whenever prepared or produced by the process of claim 4 or by an obvious chemical equivalent thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA320,456A CA1075703A (en) | 1976-03-11 | 1979-01-30 | Process for preparing amidinosulphinic acid derivatives |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9750/76A GB1574214A (en) | 1976-03-11 | 1976-03-11 | Amidines |
| CA273,246A CA1075700A (en) | 1976-03-11 | 1977-03-04 | Process for preparing amidinoformic acid derivatives |
| CA320,456A CA1075703A (en) | 1976-03-11 | 1979-01-30 | Process for preparing amidinosulphinic acid derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1075703A true CA1075703A (en) | 1980-04-15 |
Family
ID=27164949
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA320,456A Expired CA1075703A (en) | 1976-03-11 | 1979-01-30 | Process for preparing amidinosulphinic acid derivatives |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1075703A (en) |
-
1979
- 1979-01-30 CA CA320,456A patent/CA1075703A/en not_active Expired
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