Patent GB-1156769-A (GB)
Title: Sulphur-Containing Pyridine Derivatives
IPC: A61K31/54
Filed: 1968-06-05
Abstract: 1,156,769. Sulphur containing pyridine derivatives. E MERCK A.G. 5 June, 1968 [8 June, 1967; 18 April, 1968], No. 26794/68. Heading C2C. Novel compounds (including sulphonium, quaternary and acid addition salts thereof) of the general Formula I wherein R<SP>1</SP> is -S- or -SO-; R<SP>2</SP> is acyl, -CO.NR<SP>3</SP>R<SP>4</SP> or alkyl or an unsaturated aliphatic hydrocarbon group which may be substituted by at least one halogen, -OH, -SH, alkoxy, alkylthio, free and functionally changed carboxyl and/or -NR<SP>3</SP>R<SP>4</SP> with the proviso that R<SP>2</SP> is other than Et, #- chloroethyl or #-hydroxyethyl when R<SP>1</SP> is -S-; and R<SP>3</SP> and R<SP>4</SP> which may be the same or different are H, alkyl or together form a 5- or 6- membered alkylene chain which may be interrupted by N, O or S, are obtained: (a) by liberating functionally changed amino and/or hydroxy groups from a compound of the general Formula II (or a salt thereof) wherein R<SP>5</SP> and R<SP>6</SP> which may be the same or different, are free or functionally changed hydroxyl groups (at least one of R<SP>5</SP> and R<SP>6</SP> is functionally changed) and R<SP>1</SP> and R<SP>2</SP> are the same as defined above but R<SP>2</SP> can contain at least one functionally changed hydroxyl and/or amino group; (b) by acylating or alkylating a compound of the general Formula III (or a salt thereof) wherein X is H or an alkali metal or alkaline earth metal cation, or is an unsubstituted or substituted undesired hydrocarbon group or an undesired acyl radical or a radical of the general Formula IV, wherein R<SP>8</SP> is -CH 2 - or -S-CH 2 -; (c) by reacting a compound of the general Formula V (or a salt thereof) with the compound YS.R<SP>2</SP> wherein Z is a sulphonic acid residue, a halogen atom or a radical of the general Formula VI and Y is H or an alkali metal or alkaline earth metal cation; (d) by reducing or treating with a nucleophilic agent, e.g., a base, a compound of the general Formula VII (or a salt thereof) wherein R‹ is a N-atom or an N-oxide group, R<SP>10</SP> is a -CH 2 R<SP>6</SP> group or a free or functionally changed formyl group and R<SP>11</SP> signifies -S-, -SO- or -SO 2  with the proviso that R<SP>9</SP> is always an N-oxide group when R<SP>10</SP> is -CH 2 R<SP>6</SP> and R<SP>11</SP> is -S-, and that R<SP>10</SP> is always a free or functionally changed formyl group when R<SP>9</SP> is a N-atom and R<SP>11</SP> is -S-, and that R<SP>11</SP> is always -SO- or -SO 2 - when R<SP>9</SP> is a N-atom and R<SP>10</SP> is -CH 2 R<SP>6</SP> (R<SP>2</SP>, R<SP>5</SP> and R<SP>6</SP> are as above defined but R<SP>2</SP> can also contain undesirable substituents which can be split off by reduction or can be converted into desired substituents); (e) by treating a compound of the general Formula VIII or a salt thereof) with nitrous acid wherein R<SP>12</SP> is an amino group which can be substituted by acyl radicals or by a triphenyl-methyl radical; or (f) by adding a compound of the general Formula III to an alkene or alkyne which can be substituted as above defined in connection with R<SP>2</SP> as an alkyl or unsaturated hydrocarbon group; compounds of the general Formula I may also be derived from the corresponding compounds (or a salt thereof) which contains in the radical R<SP>2</SP> undesired substituents especially halogen, CO, NO 2 , NO and/or CO 2 H and/or carbon-carbon multiple bonds or does not contain desired substituents, especially NH 2 , N(CH 3 ) 2 , CO 2 H, SH and/or OH and/or desired carbon-carbon multiple bonds, the undesired substituents being split off or converted into desired substituents and/or the undesired carbon-carbon multiple bonds are hydrogenated or the desired substituents and/or carbon-carbon multiple bonds are introduced. If desired, the compounds of general Formula I in which R<SP>1</SP> is -S- can be oxidized to the corresponding compounds in which R<SP>1</SP> is an -SO- group. Any protective group present in R<SP>5</SP> and R<SP>6</SP> after carrying out the above reactions can be split off. 3,41 - Isopropylidene - 5 - acetylthiomethyl - pyridoxine (and as the hydrochloride) is obtained by the interaction of thioacetic acid and isopropylidene - 5<SP>1</SP>- chloropyridoxine in hydrochloride. 2 - Methyl - 3 - hydroxy - 4 - (1 - adamantyl - oxycarbonylaminomethyl) - 5 - pivalylthiomethylpyridine is obtained by the interaction of the corresponding 5-thiomethyl-pyridine and pivalic acid. Pharmaceutical preparations facilitating, in particular, a resistance to oxygen deficiency, contain as active ingredient the above novel compounds and administration is parenterally, enterally or topically.