Chemotherapie der experimentellen Tuberkulose IV. Aminosäure‐Derivate des Isonicotinsäurehydrazids und des 2‐Methyl‐isonicotinsäurehydrazids

Some 27 N-acyl derivatives of isonicotinic acid hydrazide and 2-methylisonicotinic acid hydrazide with amino acids and acylamino acids have been synthesized. The synthesis of the acylamino acyl compounds was carried out according to three different methods: (1) condensation of an acylated amino acid hydrazide with isonicotinic acid chloride hydrochloride or 2-methylisonicotinic acid chloride hydrochloride, resp., (2) condensation of an acylated amino acid chloride with isonicotinic acid hydrazide or 2-methylisonicotinic acid hydrazide, resp., and (3) condensation of an acylated amino acid thiol ester with isonicotinic acid hydrazide. The synthesis of the amino acid compounds with a free amino group was carried out in all cases by condensation of a carbobenzoxy amino acid with isonicotinic acid hydrazide according to the peptide synthesis of Boissonnas-Wieland with subsequent hydrogenolysis of the carbobenzoxy group. These substances have been isolated either as free bases or as the respective chlorohydrates. Biological tests revealed that, as a rule, derivatives of α-amino acids possess an activity comparable to that of unsubstituted isonicotinic acid hydrazide or 2-methylisonicotinic acid hydrazide, resp., derivatives of β- and γ-amino acids being almost inactive. All the derivatives exhibit lower acute toxicity than isoniazide. Some of them are practically non-toxic. The optical configuration of the amino acids frequently has a pronounced influence on the activity of the condensation products.

[1]  R. Schwyzer,et al.  Über aktivierte Ester V. Verwendung der Cyanmethylester‐Methode zur Herstellung von (N‐Carbobenzoxy‐S‐benzyl‐L‐cysteinyl)‐L‐tyrosyl‐L‐isoleucin auf verschiedenen Wegen , 1955 .

[2]  H. Gutmann,et al.  Chemotherapie der experimentellen Tuberkulose III. Derivate des 2-Methyl-isonicotinsäurehydrazids , 1955 .

[3]  H. Gutmann,et al.  Chemotherapie der experimentellen Tuberkulose II. Kernsubstituierte Isonicotinsäurehydrazide , 1955 .

[4]  T. Wieland.  Peptidsynthesen II. 9. Mitteilung , 1954 .

[5]  C. Jutz,et al.  Über Peptid‐Synthesen, III. Mitteil.: Eine neue Synthese des Glutathions , 1953 .

[6]  K. P. Link,et al.  Interaction of 1,3,4,6-Tetraacetyl-β-D-glucosamine with Acyl Amino Acid Azides1 , 1953 .

[7]  R. Schwyzer.  Coenzym A. Modellversuche zur biologischen Acylierungsreaktion. Über die Reaktionsfähigkeit von Thiolcarbonsäuren und ihren Estern , 1953 .

[8]  G. P. Wheeler,et al.  The Resolution of Amino Acids. III. Methionine1 , 1951 .

[9]  T. Wieland,et al.  Über Peptidsynthesen V. Über eine bequeme Darstellungsweise von Acylthiophenolen und ihre Verwendung zu Amid‐ und Peptid‐Synthesen , 1951 .

[10]  R. A. Boissonnas.  Une nouvelle méthode de synthèse peptidique , 1951 .

[11]  A. Mclaren,et al.  Several Derivatives of Acetyl-dl-phenylalanine1 , 1950 .

[12]  S. Fox,et al.  New Compounds. Crystalline Carbobenzoxy Derivatives of DL-Valine and DL-Leucine , 1950 .

[13]  C. Harington,et al.  Synthesis of peptides containing cystine and glutamine, with remarks on their possible bearing on the structure of insulin and a note on the amide nitrogen of insulin. , 1936, The Biochemical journal.

[14]  M. Bergmann,et al.  Über ein allgemeines Verfahren der Peptid‐Synthese , 1932 .

[15]  E. Cherbuliez,et al.  Sur le dosage des acides aminés formés par l'hydrolyse de protides. II. Les éthers acétylés des amino-acides , 2022 .

[16]  E. Späth,et al.  Zur Kenntnis der Chloride einiger einfacher Pyridin‐ und Chinolin‐carbonsäuren , 1926 .