Antihypertensive hydrazidones: α-aminoacylated 2-chlorobenzylidene hydrazines

doi:10.1016/0223-5234(94)90064-7

European Journal of Medicinal Chemistry

Volume 29, Issue 5, 1994, Pages 389-392

https://doi.org/10.1016/0223-5234(94)90064-7 Get rights and content

Abstract

Hydrazides of amino acids and acylamino acids were condensed with 2-chlorobenzaldehyde or 2-chloroacetophenone. The hydrazidones obtained exhibited antihypertensive activity. In a few cases the activities were similar or higher than those of the reference compounds.

References (15)

H Galons et al.
Eur J Med Chem
(1990)
Y Mousawa et al.
Jpn Kokai
(1987)
Chem Abstr
(1987)
JFM Smits et al.
J Pharmacol Exp Ther
(1985)
KG Hofbauer et al.
J Hypertension
(1986)
G Palla et al.
Tetrahedron
(1986)
G Palla et al.
Gazz Chim Ital
(1982)
W Holzer et al.
Monat Chem
(1992)

There are more references available in the full text version of this article.

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Azine-Hydrazone Tautomerism of Guanylhydrazones: Evidence for the Preference Toward the Azine Tautomer
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Guanylhydrazones have been known for a long time and have wide applications in organic synthesis, medicinal chemistry, and material science; however, little attention has been paid toward their electronic and structural properties. Quantum chemical analysis on several therapeutically important guanylhydrazones indicated that all of them prefer the azine tautomeric state (by about 3–12 kcal/mol). A set of simple and conjugated azines were designed using quantum chemical methods, whose tautomeric preference toward the azine tautomer is in the range of 3–8 kcal/mol. Twenty new azines were synthesized and isolated in their neutral state. Variable temperature NMR study suggests existence of the azine tautomer even at higher temperatures with no traces of the hydrazone tautomer. The crystal structures of two representative compounds confirmed that the title compounds prefer to exist in their azine tautomeric form.
Studies on the synthesis and some reactions of (S)-proline hydrazides
2012, Tetrahedron Asymmetry
Citation Excerpt :
The molecule had the expected (S)-configuration and the CN bond was (E)-configured. The amide group forms an intramolecular hydrogen bond with the ring N-atom to give a loop with a graph set motif18 of S(5). Reactions of butyl isocyanate and butyl isothiocyanate with 5 occurred smoothly in boiling ethanol to yield the desired semicarbazide 9a and thiosemicarbazide 9b, respectively (Scheme 5).
A convenient synthesis of (S)-proline hydrazide 2a via the reaction of ethyl (S)-N-benzylprolinate with hydrazine hydrate and subsequent deprotection of (S)-N-benzyl proline hydrazide 5 is described. The latter, in methanolic solution, reacted with aromatic aldehydes as well as with cycloaliphatic ketones at room temperature to give the corresponding hydrazones of type 7 in good yields. The structure of the product with furan-2-carbaldehyde 7b, proving the (E)-configuration of the hydrazone, was established by X-ray crystallography. In the case of the unprotected (S)-proline hydrazide 2a, the analogous reaction with aromatic aldehydes led either to the expected hydrazones 7 or the 1H-pyrrolo[1,2-c]imidazol-1-one derivatives 8, depending on the reaction conditions. The latter were formed via a secondary cyclocondensation of the initially formed 7 with a second molecule of the aldehyde. Whereas the reaction of (S)-N-benzyl proline hydrazide 5 with butyl isocyanate and isothiocyanate gave the corresponding semicarbazide and thiosemicarbazide, respectively, of type 9, the unprotected (S)-proline hydrazide 2a yielded the 1:2 adducts 10. Thiosemicarbazide 9b underwent cyclization reactions under basic (NaOH) and acidic (H₂SO₄) conditions to yield (S)-prolinyl-substituted 1,2,4-triazole-3-thione 11 and 1,3,4-thiadiazole-2-amine 12, respectively.
Synthesis and Biological Activity Characterization of Novel 5-Oxopyrrolidine Derivatives with Promising Anticancer and Antimicrobial Activity
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Short communicationAntihypertensive hydrazidones: α-aminoacylated 2-chlorobenzylidene hydrazines

Abstract

Eur J Med Chem

Jpn Kokai

Chem Abstr

J Pharmacol Exp Ther

J Hypertension

Tetrahedron

Gazz Chim Ital

Monat Chem

Short communication
Antihypertensive hydrazidones: α-aminoacylated 2-chlorobenzylidene hydrazines