4 H -Thieno[3,2- b ]pyrrole-5-carbohydrazides and Their Derivatives
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hieno[3,2-b]pyrrole-5-carbohydrazides and Their Derivatives S. A. Torosyana, Z. F. Nuriakhmetovaa, F. A. Gimalovaa,*, V. A. Egorova, and M. S. Miftakhova a
Ufa Institute of Chemistry, Ufa Federal Research Center, Russian Academy of Sciences, Ufa, 450054 Russia *e-mail: [email protected] Received April 10, 2020; revised April 18, 2020; accepted April 24, 2020
Abstract—Acylation of 4-substituted 4H-thieno[3,2-b]pyrrole-5-carbohydrazides with chloroacetyl chloride, dichloroacetyl chloride, and methacryloyl chloride afforded the corresponding mixed bis-acylhydrazines. Likewise, the reaction of 4-benzyl-4H-thieno[3,2-b]pyrrole-5-carbonyl chloride with ethyl 5-(hydrazinocarbonyl)pyridine-2-carboxylate gave ethyl 5-[2-(4-benzyl-4H-thieno[3,2-b]pyrrole-5-carbonyl)hydrazine-1-carbonyl]pyridine-2-carboxylate. Keywords: 4H-thieno[3,2-b]pyrrole-5-carboxylic acid, hydrazides, acylation
DOI: 10.1134/S1070428020090079 Compounds with a thieno[3,2-b]pyrrole skeleton have found diverse applications in medicinal chemistry. For example, thieno[3,2-b]pyrrole-5-carboxamides (e.g., compound 1) inhibit alphaviruses (such as chikungunya virus) and exhibit a broad spectrum of antiviral activity [1]. Some carboxamides were reported to inhibit neurotropic alphaviruses [2] and reversibly inhibit lysine-specific demethylases (e.g., compound 2) which regulate histon methylation; this opens prospects of using them in oncology [3] (Scheme 1).
reacted with hydrazine hydrate in boiling ethanol. Hydrazides 5a–5d thus obtained were acylated with chloro- and dichloroacetyl chlorides and methacryloyl chloride to produce building blocks 6c, 7a–7d, 8b, and 8c containing a terminal functionality convenient for further modification (Scheme 2). The oxidation of hydrazide 7c with lead tetraacetate afforded diazene 9. Mixed hydrazide 12 was synthesized by reaction of acid chloride 10 with hydrazide 11 derived from pyridine-2,5-dicarboxylic acid (Scheme 3).
Thieno[3,2-b]pyrroles without a carboxamide functionality behaved as allosteric inhibitors of hepatitis C virus NS5B polymerase [4]. In continuation of our studies on thienopyrrolecarboxylate derivatives [5–8], herein we report the synthesis of their hydrazide ana logs from acids 3a–3d [5, 9] with a view to obtaining new antituberculostatic agents (Scheme 2).
Compounds 5c, 7c, and 8c were tested for antitubercular activity at the Republican Clinical Antitubercular Dispensary; compound 7c showed a moderate antitubercular activity. Thus, we have synthesized a series of functionalized 1,2-diacyl hydrazine derivatives as starting materials for further enlargement and complication of their molecules with the goal of searching for biologically active compounds.
The carboxy group of 3a–3d was initially activated via conversion to imidazolides 4a–4d [5] which were
Scheme 1. MeO
O
Pr NH
NH HN
S N
N
N
O
O
Me S
O 1
2
1545
O
1546
TOROSYAN et al. Scheme 2. S
CDI, CH2Cl2 r.t., 3–4 h
COOH N
O
S N
82–84%
O
S
N2H4·H2O EtOH, Δ
N
N
R
R
3a–3d
4a–4d
HN
NH2
R N
O
S
ClCH2COCl or Cl2CHCOCl pyr
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