Patent GB-1190268-A (GB)
Title: Pyridine Derivatives
IPC: C07D213/81
Filed: 1966-05-12
Abstract: 1,190,268. Pyridine derivatives. NYEGAARD & CO. A.S. 11 May, 1967 [12 May, 1966], No. 21078/66. Heading C2C. Novel compounds of Formulµ I or II and acid addition and quaternary ammonium salts thereof and zwitterions thereof, wherein R is OH, O- or an ether or a cycloxy group ;R<SP>1</SP> is a mercapto group; or an aliphatic, araliphatic or aromatic thioether group which may carry one or more halogen atoms or carboxyl, esterified carboxyl, carbamoyl, N-substituted carbamoyl, cyano, hydroxy, ether, acyloxy, thioether, acylthio, secondary or tertiary amino or N-acylamino groups as substituents; an acylthio group or an isothiouronium group; R<SP>2</SP> is H or an aliphatic group which may carry one of the substituents given above for R<SP>1</SP> when a thioether group, and the 4-, 5-, and 6-positions of the pyridine ring may optionally be substituted by halogen atoms, NO 2 , ether, acyloxy, thioether, acylthio, primary, secondary or tertiary amino, N-acylamino, carboxylic ester or carbamoyl groups or aliphatic, araliphatic or aromatic hydrocarbon groups, are prepared by one of the following methods: (a) a pyridine derivative of Formula IV or an N-R<SP>2</SP> quaternary derivative thereof, wherein Z is a reactive ester group, R and R<SP>2</SP> have the above meanings and the 4,- 5- and 6- positions may be substituted as above, are reacted with a sulphur derivative R<SP>1</SP>H or a metal salt thereof; (b) those falling within the 'formula are prepared -by reacting the corresponding lactam with phosphorus pentasulphide, optionally reducing to give the corresponding amino compounds and optionally acylating or alkylating the amino compounds; (c) a compound containing a cation of formula wherein R<SP>3</SP> is an alkyl or aralkyl group and R<SP>4</SP> is an ether or acyloxy group is reacted with hydrogen sulphide or a thiol or a salt thereof; (d) compounds substituted at the 4-position may be prepared by reaction of a quaternary salt with an appropriate electrophilic reagent optionally followed by hydrogenolysis; (e) compounds wherein R<SP>1</SP> is a thioether group are prepared by reaction of the corresponding compound wherein R<SP>1</SP> is mercapto or a thioketo compound of .Formula II above with a reagent R<SP>1</SP>Z; and (f) acid addition and quaternary salts may be prepared by conventional methods. Compounds containing a cation of formula wherein R is as above and the 2, 3, 5, 6 and 7 positions may carry any of 'the substituents defined for the 4, 5 and 6 position of the pyridine ring in the above novel compounds, are prepared from those novel compounds above which fall within the formula wherein Z<SP>1</SP> is a mercapto group or a thioether, acylthio or isothiouronium group by reaction with a quaternizing or etherifying agent to add on to the nitrogen atom, or the sulphur atom when Z<SP>1</SP> is mercapto, an ethyl group carrying a reactive substituent in the #- position, followed by cyclization to complete the dihydrothiazole ring. Compounds of Formula IV -above wherein Z is halogen are prepared by halogenation of the corresponding 2-unsubstituted-3-R-pyridine. 2 - Bromo - 3 - hydroxy - 4 - nitro - 6 - methyl - pyridine is prepared by nitration of the corresponding 4-unsubstituted compound. 2-methyl-5-hydroxy-pyridine is prepared by fusion of KOH and 2-methylpyridine-5-sulphonic acid. Pharmaceutical compositions in conventional forms for oral and parenteral administration and having anti-viral and anti-cancer activity comprise an above novel compound and a pharmaceutical carrier or excipient.