Tuberculostatic activity

A thioamide of isonicotinic acid has also shown tuberculostatic activity in the clinic. The additional substitution on the pyridine ring precludes its preparation from simple starting materials. Reaction of ethyl methyl ketone with ethyl oxalate leads to the ester-diketone, 12 (shown as its enol). Condensation of this with cyanoacetamide gives the substituted pyridone, 13, which contains both the ethyl and carboxyl groups in the desired position. The nitrile group is then excised by means of decarboxylative hydrolysis. Treatment of the pyridone (14) with phosphorus oxychloride converts that compound (after exposure to ethanol to take the acid chloride to the ester) to the chloro-pyridine, 15. The halogen is then removed by catalytic reduction (16). The ester at the 4 position is converted to the desired functionality by successive conversion to the amide (17), dehydration to the nitrile (18), and finally addition of hydrogen sulfide. There is thus obtained ethionamide (19)... 

In China, tuberculostatic activity has been observed recently with 2-arylpy-ridazinones of type (116, R1 = HO, Cl R2 = F, Cl R3 = aryl) and related compounds [333], In the U.S.S.R., antibacterial 6-chloro-3-hydrazinopyrida-zine derivatives (117, R = aryl) have been described [334],... 

Aminosalicylic acid is a bacteriostatic that inhibits most tuberculous mycobacteria, hi terms of tuberculostatic activity it is inferior to isoniazid and streptomycin. It is nephro-and hepatotoxic, and is rarely used. A synonym of this drug is apacizin. 

Bromo-2-furyl)quinoxaIine and 3-(5-nitro-2-furyl)-2-quin-oxalinone, and numerous substituted derivatives, have been synthesized and found to be active antibacterials and antimicrobials.153 2-[2-(5-Nitro-2-furyl)vinyl]quinoxalines (147) have also been prepared, and some derivatives (6-nitro and 6-amino) were found to have high tuberculostatic activity.134... 

Triphenylphosphine, imidazole mixture as catalyst, 90 Triticum vulgare, 134 Tuberculostatic activity, 141,440, 441. 

A group of l,3,4-oxadiazolin-5-ones and l,3,4-oxadiazoline-5-thiones show antitubercular activity.18,43a 76,84 86,181, 132,157 160 They have been investigated with regard to their mode of action. 2-(4 -Pyridyl)-l,3,4-oxadiazolin-5-one (S 57) has shown itself active against Mycobacterium tuberculosis and Mycobacterium leprae.86-158 It possesses some advantages compared with isonicotinic acid hydrazide. Derivatives of S 57 also have some tuberculostatic activity.159, lfl1,162 Further tuberculostatic compounds are derived from p-aminosalicylic acid, for example WS 127 [2-(4 -amino-2 -hydroxyphenyl)-l,3,4-oxadiazoline-5-thione] and WS 174 [2-(4 -acetamido-2 -hydroxyphenyl)-l,3,4-oxadiazolin-5-one].85 2-Cyano-methyl-l,3,4-oxadiazolin-5-one shows a tuberculostatic activity comparable with that of Reazid. 18 Oxadiazolin-5-ones and oxa-... 

An attempt to reduce the toxicity of streptomycin by attaching it to soluble polymers has been reported recently The formyl group of streptomycin has been condensed with methacrylic acid hydrazide in order to form a polymerizable derivative of streptomycin. The resulting hydrazone has been copolymerized with methacrylamide and 2-methyIsulfinylethyl methacrylate to form water-soluble polymers. These copolymers show an increasing tuberculostatic activity. 

Amino-6-[(5-nitro-2-furyl)vinyl]-l,2,4-triazine (505) (Panfuran) shows antibacterial and tuberculostatic activity. 

Phenylflavazoles have found little application in chemotherapeutics, however certain 1-unsubstituted compounds show tuberculostatic activity 7.47 Compounds 49 and 50 show analgesic activity at 100 mg/kg orally in the mouse acetic acid antiwrithing test but are inactive in the rat paw volume test. The quinone 29 has been patented as having antiinflammatory and diuretic activity. ... 

Salinazid. [(2-Hydroxyphenyl)methy ene]hydra-zide 4-pyridinecarboxyllc acid 1 -isonicotinoyl-2-salicylid-enehydrazine isonicotinic acid salicyltdenehydrazide sali-niazid JV -o-hydroxybenzylidenepyridine -4 car boxy hydra -zide o-hydroxybenzal isonicotinylhydrazone Salizid Nupa-sal At-ozid Nupasal-2 3. CuH.,N302 mol wt 241.24. C 64.72%, H 4.60%, N 17.42%, O 13.26%. Prepd by the interaction of isoniazid and salicylaldebyde in water Hart ei at, Antibiot. Chemother. 4, 803 (1954) cf. Yale r at, J, Am. Chem. Soc. 75, 1933 (1953). Tuberculostatic activity and toxicity Bavin et at, J. Pharm. Pharmacol. 7, 1032 (1955). 

As synthesis intermediates are chemically connected to final products, and as they often present some common groupings with them, it is not inconceivable that they share some pharmacological properties. For this reason, it is always prudent also to submit these compounds to a pharmacological evaluation. Among drugs discovered in this way are the tuberculostatic semicarbazones they were initially used in the synthesis of antibacterial sulfathiazoles. Subsequent testing of isonicotinic acid hydrazide, destined for the synthesis of a particular thiosemicarbazone, revealed the powerful tuberculostatic activity of the precursor which has since become a major antitubercular drug (isoniazide). 

CijHjftNjO, Mr 258.36, yellow oil, [ajp +38.4° (CjHjOH). Azoxy compound with tuberculostatic activity from cultures of Streptomyces hepaticus. E. is an experimental carcinogen and exhibits in mice a subcutaneous LD30 of 63 mg/kg. 

C10H12N4O4, Mr 252.23, cryst., mp. 182-183 °C, [a] -46.8° (H2O). A nucleoside antibiotic from the fungus Clitocybe nebularis, an agaric frequently found in Central European woods in autumn. N. has also been found in a Streptomyces species. N. has antimitotic and tuberculostatic activities, LD50 (rat/guinea-pig s.c.) 220/15 mg/kg. 

Since aminocoumarins have been found to exert some antibacterial activity [377], investigations were started to explore tuberculostatic activity of various coumarins related to p-aminosalicylic acid (55). 7-Amino-4-methylcoumarin (56) was found to be about one-half, and ffa s-p-aminocinnamic acid (57) one-fourth, as active as p-aminosalicylic acid [392]. The tuberculostatic action of 7-amino-4-methylcoumarin is probably dependent on the opening of the lactone... 

Tuberculostatic tests found that AG and modified eompoimds of AG, AG and AGlm possess tuberculostatic activity in vitro against pathogenic mycobacteria of the same level as free INAH. Partial growth inhibition of mycobacteria tuberculosis was noted for AG and AG. ... 

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