Medicinal Chemistry - Volume 3, Issue 6, 2007

Bioisosterism represents one approach used by the medicinal chemist for the rational modification of lead compounds into safer and more clinically effective agents. Bioisosteres are substituents or groups that have chemical or physical similarities and that produce broadly similar biological effects. The sulfone moiety is recognized as a nonclassical bioisostere for replacement of the carbonyl group. When sulfonyl derivatives Read More

A series of thioamides were designed as bio-isosteres to the non-nucleoside reverse transcriptase inhibitor trovirdine by replacement of the thiourea NH groups with methylene groups. Eight thioamides were synthesized and in vitro tested for inhibitory effects on the activity of HIV-1 reverse transcriptase wild and mutant types. Three of the 8- thioamides exhibited enzyme inhibitory activities with IC50 values below 10 Read More

A series N,N'-bis[4-(1H(2H)-benzotriazol-1(2)-yl)phenyl]alkyldicarboxamides (3a-f and 5a-j) were prepared starting from their already known (1a-d) and (4a-c) or new (4d) amine parents. Because of the antiviral activity of several N-[4-(1H(2H)-benzotriazol-1(2)-yl)phenyl]alkylcarboxamides previously reported, title compounds were evaluated in vitro for cytotoxicity and antiviral activity against viruses representative of Picor Read More

The design, synthesis and anti HIV-1 replication inhibition of 3-(cyclopropylethynyl)-3-hydroxy-indolin-2- ones, analogues of efavirenz (Sustiva™), are described. Different substituted isatins were used to generate final products that contain pharmacophoric features for RT inhibition, such as the oxoindole and cyclopropylethynyl groups. The suitability of the indolin-2-one ring in the planned compounds in replacement to the benzo Read More

Oxybutynin (1) is a non-selective muscarinic receptor antagonist that is used clinically for the treatment of urinary incontinence. The major metabolite of oxybutynin in humans is desethyloxybutynin (2). We have prepared the enantiomers of 1 and 2 and evaluated their ability to displace N-CT3-scopolamine chloride (3H-NMS) binding on human cloned muscarinic m1-5 receptors. Compounds 1 and 2 potently displaced 3H- Read More

20α-hydroxysteroid dehydrogenase (AKR1C1) plays a key role in the metabolism of progesterone and other steroid hormones, thereby regulating their action at the pre-receptor level. AKR1C1 is implicated in neurological and psychiatric conditions such as catamenial epilepsy and depressive disorders. Increased activity of AKR1C1 is associated with termination of pregnancy and the development of breast cancer, endometrios Read More

In the present study we describe the synthesis of a new series of 1,2,4-triazoles: [3-(arylmethyl)thio-5-aryl-4H- [1,2,4]triazol-4-yl]acetic acids 5a-g, [5-(arylmethyl)thio-3-aryl-1H-[1,2,4]triazol-1-yl]acetic acids 8a-d, and [3-(arylmethyl) thio-5-aryl-1H-[1,2,4]triazol-1-yl] acetic acids 9a-d. These compounds were tested in binding assays to evaluate their ability as ligands for human ETA and ETB receptors stably expressed in CHO Read More

The synthesis of a series of new N-OMe fluoro-indoles with melatoninergic activity in the Xenopus melanophore assay is described. All of the 4-F substituted compounds, 22a-e and 25a,b, were antagonists on the clonal Xenopus melanophore line. Conversely, the 5-F substituted analogs (15a-e) did not share the same pharmacological profile, as two of them, compounds 15d (R=c-C3H5) and 15e (R=c-C4H7), exhibited a weak Read More

Antedrug approach of the corticosteroids has been described as a fundamentally sound approach for the development of safer anti-inflammatory steroids devoid of systemic side effects. In our continued efforts under the antedrug paradigm, we have recently extended this effort to synthesize the 21-thioalkylether derivatives of methyl 16- prednisolonecarboxylates. The 21-mesylate of the methyl-16-perdnisolonecarboxylates a Read More

A three dimensional Quantitative Structure Activity Relationship (3D-QSAR) model for a series of (S)-3-Aryl- 5-substituted oxazolidinones was developed to gain insights into the design for potential new antibacterial agents. It was found that the Comparative Molecular Field Analysis (CoMFA) method yielded good results while the Comparative Molecular Similarity Indices Analysis (CoMSIA) was less satisfactory. The CoMFA met Read More

Opioidmimetics containing 3-[H-Dmt-NH-(CH2)m]-6-[H-Dmt-NH-(CH2)n]-2(1H)-pyrazinone symmetric (m = n, 1-4) (1 - 4) and asymmetric (m, n = 1 - 4) aliphatic chains (5 - 16) were synthesized using dipeptidyl chloromethylketone intermediates. They had high μ-affinity (Kiμ = 0.021 - 2.94 nM), δ-affinity (Kiδ = 1.06 - 152.6 nM), and μ selectivity (Kiδ/Kiμ = 14 - 3,126). The opioidmimetics (1 - 16) exhibited μ agonism in proportion to Read More

In this work we examined the affinity and the selectivity of V. adscendens, Iresine herbstii Hook. (Amaranthaceae) and Brugmansia arborea (L.) Lagerheim (Solanaceae) towards 5-HT1A, 5-HT2A, 5-HT2C serotononergic, D1 and D2 dopaminergic, α1 and α2 adrenergic receptors by radioligand assays. The results show weak affinity to 5-HT1A only for the aqueous extract of V. adscendens and no affinity for 5-HT2A, 5- Read More

Emerging concepts in the construction of nanostructures hold immense potential in the areas of drug delivery and targeting. Such nanoscopic assemblies/structures, similar to natural proteins and self-associating systems, may lead to the formation of programmable soft structures with expanded drug delivery options and the capability to circumvent firstpass metabolism. This article aims to illustrate key recent develop Read More