Synthesis and pharmacological evaluation of a new class of 2-(2-aminothiazol-4-yl)-2-hydrazonoacetamido cephalosporins

Brandt, A.; M, Cerquetti; Gb, Corsi; Pascucci, G; Simeoni, A.; Martelli, Paolo; Valcavi, U

doi:10.1021/jm00388a003

Cited by 13 publications

(3 citation statements)

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“…After the desiccant was filtered off, the filtrate was evaporated to obtain crude product, which was purified by column chromatography on silica gel (petroleum ether:ethyl acetate 3:1 as the eluent) to afford a light yellow oil (9.5 g, 56% yield). 1 …”

Section: Methodsmentioning

confidence: 99%

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A One-Pot Domino Synthesis of 5-(Trifluoromethyl)-2-thiazolamine

Bao¹,

Qiao²,

Hou³

et al. 2016

Journal of the Brazilian Chemical Society

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5-(Trifluoromethyl)-2-thiazolamine is a key intermediate for manufacturing numerous pharmaceuticals and chemicals. Here, a low-cost, one-pot multicomponent domino synthetic route has been reported for the synthesis of 5-(trifluoromethyl)-2-thiazolamine, which was successfully prepared from 3-bromo-1,1,1-trifluoro-2-propanone, phosphorus pentasulfide and cyanamide in the presence of sodium carbonate with the yield of 56%.

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Section: Methodsmentioning

confidence: 99%

“…[1][2][3][4] In general, fluoroalkylsubstituted 2-aminothiazoles are regarded as privileged structure motifs in medicinal chemistry due to its presence in antimicrobial or antiviral agents, anticancer agents, etc. (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

A One-Pot Domino Synthesis of 5-(Trifluoromethyl)-2-thiazolamine

Bao¹,

Qiao²,

Hou³

et al. 2016

Journal of the Brazilian Chemical Society

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“…This isomerization phenomenon observed in a wide range of hydrazones of different nature is extensively documented in the literature. [21] …”

Section: Introductionmentioning

confidence: 99%

3‐Substituted Indazoles as Configurationally Locked 4EGI‐1 Mimetics and Inhibitors of the eIF4E/eIF4G Interaction

Yefidoff-Freedman¹,

Chen²,

Sahoo³

et al. 2014

ChemBioChem

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4EGI-1, the prototypic inhibitor of eIF4E/eIF4G interaction, was identified in a high-throughput screening of small molecule libraries using a fluorescence polarization assay that measures inhibition of binding of an eIF4G-derived peptide to recombinant eIF4E. As such, the molecular probe 4EGI-1 holds a potential for studying molecular mechanisms involved in human disorders characterized by loss of physiologic restrains on translation initiation. A hit-to-lead optimization campaign was carried out to overcome the liability of the configurational instability in 4EGI-1, which stems from the (E)-to-(Z) isomerization of the hydrazone function. We identified compound 1a, in which the labile hydrazone was incorporated into a rigid indazole scaffold as a promising rigidified 4EGI-1 mimetic lead. In a structure-activity relationship study aimed at probing the structural latitude of this new chemotype as an inhibitor of eIF4E/eIF4G interaction and translation initiation we identified 1d, an indazole-based 4EGI-1 mimetic, as a new and improved lead inhibitor of eIF4E/eIF4G interaction and a promising molecular probe candidate for elucidating the role of cap-dependent translation initiation in a host of pathophysiological states.

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Synergism through direct covalent bonding between agents: A strategy for rational design of chemotherapeutic combinations

et al. 1990

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Self-assembling chemotherapeutic agents are mixtures of relatively nontoxic precursors that can combine chemically under physiological conditions to form products with greater cytotoxic and/or antimicrobial activity than either of the precursors. Combinations that form products more rapidly in or near the target (tumor, pathogen, virally infected cell) than in normal tissues will exhibit target-selective synergism, thus exhibiting an antitarget selectivity that is greater than the selectivities of the product (e.g., a hydrazone) and of either precursor (e.g., a hydrazine derivative or ketone) used singly. This paper describes the target-selective cytotoxic synergism of a cationic aldehyde (A) and a cationic acylhydrazine (B) containing a triarylalkylphosphonium moiety against Ehrlich ascites carcinoma cells (ELA) in culture, in addition to reviewing previous work on self-assembling cytotoxins. The synergism between A and B is carcinoma selective when the ELA cells (the target) are compared to CV-1, an untransformed African green monkey kidney epithelial line. Like tetraphenylphosphonium and rhodamine 123, which are selectively concentrated in ELA cells relative to CV-1, A, B and the hydrazone C resulting from their reaction are lipophilic delocalized cations that selectively inhibit ELA growth relative to CV-1 growth. The hydrazone C is more growth inhibitory than either A or B for both cell lines. A combination of A with an unreactive analogue of B and a combination of B with an unreactive analogue of A did not synergistically inhibit ELA proliferation. The degree of synergism is greater against the ELA cells than against the CV-1 cells. These data, together with hydrazone formation kinetics, suggest that A and B are both concentrated together selectively inside the ELA due to the transmembrane potentials, reacting inside the ELA cells at a higher velocity than inside the CV-1 cells to form the more growth-inhibitory hydrazone C.

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Synthesis and pharmacological evaluation of a new class of 2-(2-aminothiazol-4-yl)-2-hydrazonoacetamido cephalosporins

Cited by 13 publications

References 1 publication

A One-Pot Domino Synthesis of 5-(Trifluoromethyl)-2-thiazolamine

A One-Pot Domino Synthesis of 5-(Trifluoromethyl)-2-thiazolamine

3‐Substituted Indazoles as Configurationally Locked 4EGI‐1 Mimetics and Inhibitors of the eIF4E/eIF4G Interaction

Synergism through direct covalent bonding between agents: A strategy for rational design of chemotherapeutic combinations

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