Demet Astley

Synthesis and biological activity of novel thiourea derivatives as carbonic anhydrase inhibitors

Abstract A new series of chiral thiourea derivatives (5a–5c) and thiourea containing benzimidazole moieties (9b–9e) were synthesized from different amino acids (l-valine, l-isoleucine, l-methionine, l-phenylalanine, and d-phenylglycine). The compounds were characterized and tested against the two most studied members of the pH regulatory enzyme family, carbonic anhydrase (CA, EC 4.2.1.1). KI values of the novel compounds were measured in the range of 3.4–73.6 μM for hCA I isozyme and 8.7–1.44.2 μM for hCA II isozyme, respectively. Phenol was also tested as standard in order to understand the structure activity relationship and the clinically used sulfonamide acetazolamide was tested for comparison reasons. All of the compounds exhibited competitive inhibition with 4-nitrophenylacetate as substrate.

A beneficial effect of ortho-substituents in the arylation of (benzene)tricarbonylmanganese(1+) hexafluorophosphate(1−)

Abstract ortho -Substituted aryllithium and aryl Grignard reagents react with (benzene)manganesetricarbonyl cation ( 1 ) to give good yields of the expected ring adducts. The presence of the ortho substituent(s) appears to be necessary for the satisfactory outcome of the reaction with aryllithiums. This reactivity opens up the possibility of preparing novel heterocyclic structures via the initial reaction of 1 with functionalised metallated arenes.

trans-Diaqua­{5,5′-[(E,E)-pyridine-2,6-diylbis(methyl­idynenitrilo)]bis­[pyrimi­dine-2,4(1H,3H)-dione]}zinc(II) nitrate hexa­fluorophosphate trihydrate

The title compound, [Zn(C(15)H(11)N(7)O(4))(H(2)O)(2)](NO(3))(PF(6)).3H(2)O, contains a mononuclear zinc(II) complex. The Zn(2+) centre is seven-coordinated in a slightly distorted pentagonal-bipyramidal geometry, with the two water O atoms located in the apical positions, and the pyridine N atom, the two imine N atoms and two carbonyl O atoms of the uracil groups located in the equatorial plane. The charge is balanced by PF(6)(-) and NO(3)(-) anions.

STEREOCONTROLLED ORGANOMANGANESE SYNTHESIS OF CIS-4A, 10B-DIHYDROPHENANTHRIDINE DERIVATIVES

Abstract Cis-4a,10b-dihydrophenanthridine derivatives have been prepared in high yield via nucleophilic addition of a functionalised metalated arene to (benzene)tricarbonylmanganese(1+) hexafluorophosphate(1−) followed by reactivation, and intramolecular nucleophile addition.

Preparation of o-bromobenzophenone derivatives from lithium diarylcuprate(I) reagents

The reaction of lithium diarylcuprate(I) reagents with o-bromobenzoyl chloride has been investigated. In general, the reaction proceeds well to give synthetically useful o-bromobenzophenone derivatives as the major product. It is suggested that a minor substituent effect, whereby diarylcuprate reagents containing an ortho or meta substituent react more favourably, may be attributed to small changes in the structure of the organometallic reagent. Copyright

Kinetic and docking studies of cytosolic/tumor-associated carbonic anhydrase isozymes I, II and IX with some hydroxylic compounds

Abstract A series of hydroxylic compounds (1–10, NK-154 and NK-168) have been assayed for the inhibition of three physiologically relevant carbonic anhydrase isozymes, the cytosolic isozymes I, II and tumor-associated isozyme IX. The investigated compounds showed inhibition constants in the range of 0.068–4003, 0.012–9.9 and 0.025–115 μm at the hCA I, hCA II and hCA IX enzymes, respectively. In order to investigate the binding mechanisms of these inhibitors, in silico studies were also applied. Molecular docking scores of the studied compounds are calculated using scoring algorithms, namely Glide/induced fit docking. The inhibitory potencies of the novel compounds were analyzed at the human isoforms hCA I, hCA II and hCA IX as targets and the KI values were calculated.

Synthesis of Stable Acyclic Aminals Derived from L-(+)-Aspartic Acid and Their Application in Asymmetric Henry Reactions

A series of stable acyclic aminals derived from L-(+)-aspartic acid were synthesized in excellent yields (up to 96%) and characterized by spectroscopic methods. They were applied as enantioselective catalysts in Henry reactions of nitromethane with various aldehydes in the presence of Cu(II) ions, affording the corresponding adducts in high yields (up to 90%) and enantioselectivities (up to 92% ee). Graphical Abstract Synthesis of Stable Acyclic Aminals Derived from L-(+)-Aspartic Acid and Their Application in Asymmetric Henry Reactions