4-Hydroxy-2-quinolones 126. 1-Hydroxy-3-oxo-5,6-dihydro-3H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic acid hydrazide and its derivatives

Abstract

A preparative method has been developed for the synthesis of 1-hydroxy-3-oxo-5,6-dihydro-3H pyrrolo[3,2,1-ij]quinoline-2-carboxylic acid hydrazide and its derivatives. The results of a study of the antitubercular activity of the synthesized compounds are presented.Hydrazine derivatives occupy a special place in the chemotherapy of tuberculosis which is one of the most dangerous contemporary infectious illnesses. Thus isonicotinic acid hydrazide has been used in medical practice for more than half a century under the name of isoniazid and it has not lost its value to the present day [2]. Further, on its basis it has given rise to phthivazid, saluzid, metazid [3] and there continue to be discovered modified analogs with improved pharmacological properties (e.g. flurenizid [4]). Rifampicin and rifapentin are amongst the most effective semi-synthetic antitubercular agents and they also contain a hydrazine fragment in their structure [2].In continuing our systematic search for potential agents amongst amidated 1-R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids we repeatedly noted the high activity of the corresponding hydrazides [5], in particular the benzylidenehydrazides [6][7][8], in relation to the stimulation of tubercular and non-tubercular micobacteria. Following on in this area and with the aim of revealing a structure biological activity relationship in the studied series this report concerns tricyclic analogs of 4-hydroxy-2-quinolones and particularly the 1-hydroxy-3-oxo-5,6-dihydro-3H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic acid derivative.Ethyl 1-hydroxy-3-oxo-5,6-dihydro-3H-pyrrolo[3,2,1-ij]quinoline-2-carboxylate (1) reacts with hydrazine hydrate in alcohol solution at room temperature to give the hydrazine 2 in virtually quantitative yield. An attempt to purify this material by crystallization from DMF led to a very unexpected result. Immediately _______ * For Communication 125 see [1].

Acid Hydrazides, Potent Reagents for Synthesis of Oxygen-, Nitrogen-, and/or Sulfur-Containing Heterocyclic Rings

“…21 It appears that INH, like numerous other compounds, has physiological potency in the inhibition of root growth development of levels substantially lower than those that elicit any morphological responses in the tops of established plants. 22 It is perhaps from the ranks of such compounds that materials suitable for preemergence weed control should be sought. Thus, isonicotinic acid hydrazide has been used in medical practice for more than half a century under the name of isoniazid, and it has not lost its value to the present day.…”

“…Isonicotinic acid hydrazide, commercially known as (INH, isoniazid) (Figure ), has been one of the most effective agents in tuberculosis therapy since 1952, when its action against Mycobacterium tuberculosis was first discovered . It appears that INH, like numerous other compounds, has physiological potency in the inhibition of root growth development of levels substantially lower than those that elicit any morphological responses in the tops of established plants …”

Pharmacophore modeling, docking and the integrated use of a ligand- and structure-based virtual screening approach for novel DNA gyrase inhibitors: synthetic and biological evaluation studies

“…A set of 27 structurally diverse quinolones, spanning 5 log activities, were chosen to form the training set. Their structures and biological activity [38][39][40][41] are shown in Fig. 1.…”

4-Hydroxy-2-quinolones. 152*. 3-acetyl-4-hydroxy-2-oxo-1,2-dihydroquinoline and its biologically active derivatives

“…In the synthesis of the acylhydrazones 4a-h presented in this study both methods proved of approximately equal value although for other 4-hydroxyquinol-2-ones specific limitations can certainly appear. One such example concerns the hydrazide of 1-hydroxy-3-oxo-5,6-dihydro-3H-pyrrolo[3,2,1-if]quinoline-2-carboxylic acid, the use of which for preparation of the corresponding acylhydrazone via method A is known to be impossible due to its instability in refluxing DMF [9].…”