[Antimycobacterial acting carbazole derivatives]. / Antimycobakteriell wirksame Carbazolderivate.

Carbazoles are synthesized and tested for antimycobacterial properties (M. tuberculosis H 37 Ra, Middlebrook-7H9-broth). The different antimycobacterial properties of diastereomeres are examined using compounds 32 and 33, those of a racemic compound and the (+)-enantiomer are tested with (+/-)-12/(+)-12 and (+/-)-5/(+)-5, respectively. (+)-12 is prepared by enantioselective synthesis.

[Antimycobacterial indole derivatives]. / Antimykobakteriell wirksame Indolderivate.

1,3-Dinitro-2-(indol-3'-yl)-propanes 3 are synthesized by Michael reaction of nitromethane with the indolylnitroethenes 2. Reaction of the aldehydes 4 and 10 with the benzylamines 12 as well as the reaction of the indolylalkylamines 6a and 9a with the benzaldehydes 11 lead to Schiff bases which are reduced to N-benzyl-(indol-3-ylmethyl)-amines 13 and N-benzyl-(indol-3-ylethyl)-amines 14, respectively; tert amines 16 are synthesized via the formamides 15, amines 18 are prepared according to Mannich. Inhibitory effects on Mycobacterium tuberculosis H 37 Ra are investigated, a structure-activity relationship is discussed.

[Antimycobacterial 1-phenyl-1-alkylaminoalkanes]. / Antimykobakterielle 1-phenyl-1-alkylaminoalkane.

Synthesis and testing for antimycobacterial properties (M. tuberculosis H 37 Ra, Middlebrook-7H9-broth) of 1-phenyl-1-alkylaminoalkanes, which differ from antimycobacterial N-alkylbenzylamines by an additional alkyl chain in alpha-position, is described. By variation of both alkyl chains and introduction of one or two Cl-substituents in the aromatic ring the activity increases up to an optimum within the homologous series. Overstepping optimal lipophilicity or ramification of the alkyl chains decrease activity.

In vitro and in vivo effects of N-methyl-3,5-dichloro-benzylamine hydrochloride on Mycobacterium leprae.

The antimicrobial effects of a new benzylamine, ME-93 (N-methyl-3,5-dichloro-benzylamine hydrochloride), alone and in combination with dapsone and rifampicin, have been evaluated in vitro in cell-free culture system and in vivo in mouse foot pad system. Even at 50 micrograms/ml, ME-93 did not completely inhibit the in vitro growth of M. leprae, and the effects were bacteriostatic. However, there was a synergism when ME-93 was combined with rifampicin, and the effects were bactericidal. Similar findings were also obtained in the mouse foot pad system. Thus, there is a new drug that needs further attention in the chemotherapy of leprosy.

[Antimycobacterial acting 2-hydroxyquinolizin-4-ones]. / Antimykobakteriell wirksame 2-Hydroxychinolizin-4-one.

Reaction of ethyl 2-pyridyl acetates and activated malonates (magic malonates) leads to 1-ethoxycarbonyl-2-hydroxy-quinolizin-4-ones, which yield the corresponding C-1 unsubstituted derivatives by hydrolysis and decarboxylation. These compounds are catalytically hydrogenated to afford the corresponding tetrahydro derivatives. Significant inhibitory effects on mycobacterium tuberculosis H 37 Ra are shown, a structure-activity relationship is discussed.

[The effect of agonists and antagonists of histamine H1- and H2-receptors on the growth of Mycobacterium tuberculosis H 37 Ra]. / Einfluss von Agonisten und Antagonisten des Histamin-H1- und H2-Rezeptors auf das Wachstum von Mycobacterium tuberculosis H 37 Ra.

The influence of histamine H1- and H2-agonists and -antagonists on the growth of mycobacteria is described. While compounds which are strongly related to histamine improve the growth, predominantly H1-antagonists inhibit bacterial growth.

[Antimycobacterial antihistaminics]. / Antimykobakterielle Antihistaminika.

The testing of antihistaminic compounds of various chemical classes for antimycobacterial properties is described. A lot of these compounds inhibit the growth of mycobacteria at a concentration of 8-32 micrograms/ml.

[The mode of action of antimycobacterial benzylamines]. / Untersuchungen zum Wirkmechanismus antimykobakterieller Benzylamine.

The antimycobacterial effects of benzylamines are not related to an inhibition of aminoacyl-tRNA synthetases.

[Antimycobacterial properties of phenothiazine type compounds]. / Antimykobakterielle Eigenschaften von Verbindungen des Phenothiazintyps.

Tests for antimycobacterial properties (Mycobacterium tuberculosis H37 Ra, Middlebrook-7H9-broth) of the phenothiazines 1-11 are described. The growth inhibition of these compounds can be blocked by the addition of histamine.

Benzylamines: synthesis and evaluation of antimycobacterial properties.

The synthesis of benzylamines with various N-alkyl chains and substituents in the aromatic system as well as their evaluation on Mycobacterium tuberculosis H 37 Ra are described. The most active compounds in this test, N-methyl-3-chlorobenzylamine (19, MIC 10.2 micrograms/mL), N-methyl-3,5-dichlorobenzylamine (93, MIC 10.2 micrograms/mL), and N-butyl-3,5-difluorobenzylamine (103, MIC 6.4 micrograms/mL), also exhibited a marked inhibitory effect on Mycobacterium marinum and Mycobacterium lufu used for the determination of antileprotic properties. The combinations of 93 with aminosalicylic acid, streptomycin, or dapsone exert marked supra-additive effects on M. tuberculosis H 37 Ra.