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Abstract: A practical and metal free method for methylthiolation of imidazo[1,2-a]pyridines and other imidazo-fused heterocycles using DMSO–POCl3 complex is reported. The reactions are carried out at room temperature that give the corresponding methylthiolated products in good to excellent yield. Further, its application to indole has been demonstrated. [Copyright &y& Elsevier]

The article presents chemical equations related to synthesis of thioethers where from methylthiolation of Imidazo-fused heterocycles such as Imidazo [1,2-a] pyridines a reagent is obtained, published in the volume 38 of 2013 issue of the journal "Tetrahedron."

This data article presents a description of a benchmark dataset for the multiple depot vehicle scheduling problem (MDVSP). The MDVSP is to assign vehicles from different depots to timetabled trips to minimize the total cost of empty travel and waiting. The dataset has been developed to evaluate the heuristics of the MDVSP that are presented in "A new formulation and a column generation-based heuristic for the multiple depot vehicle scheduling problem" (Kulkarni et al., 2018). The dataset contains 60 problem instances of varying size. Researchers can use the dataset to evaluate the future algorithms for the MDVSP and compare the performance with the existing algorithms. The dataset includes a program that can be used to generate new problem instances of the MDVSP.

Natural products with macrocyclic structural features often display intriguing biological properties. Molecular design incorporating macrocycles may lead to molecules with unique protein-ligand interactions. We generated novel human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs) containing a macrocycle and bis-tetrahydrofuranylurethane. Four such compounds exerted potent activity against HIV-1LAI and had 50% effective concentrations (EC50s) of as low as 0.002 microM with minimal cytotoxicity. GRL-216 and GRL-286 blocked the replication of HIV-1NL4-3 variants selected by up to 5 microM saquinavir, ritonavir, nelfinavir, lopinavir, or atazanavir; they had EC50s of 0.020 to 0.046 microM and potent activities against six multi-PI-resistant clinical HIV-1 (HIVmPIr) variants with EC50s of 0.027 to 0.089 microM. GRL-216 and -286 also blocked HIV-1 protease dimerization as efficiently as darunavir. When HIV-1NL4-3 was selected by GRL-216, it replicated progressively more poorly and failed to replicate in the presence of >0.26 microM GRL-216, suggesting that the emergence of GRL-216-resistant HIV-1 variants is substantially delayed. At passage 50 with GRL-216 (the HIV isolate selected with GRL-216 at up to 0.16 microM [HIV216-0.16 microM]), HIV-1NL4-3 containing the L10I, L24I, M46L, V82I, and I84V mutations remained relatively sensitive to PIs, including darunavir, with the EC50s being 3- to 8-fold-greater than the EC50 of each drug for HIV-1NL4-3. Interestingly, HIV216-0.16 microM had 10-fold increased sensitivity to tipranavir. Analysis of the protein-ligand X-ray structures of GRL-216 revealed that the macrocycle occupied a greater volume of the binding cavity of protease and formed greater van der Waals interactions with V82 and I84 than darunavir. The present data warrant the further development of GRL-216 as a potential antiviral agent for treating individuals harboring wild-type and/or HIVmPIr.

We present a new type of non-contact sensor for use in ambulatory cardiac monitoring. The sensor operation is based on a microwave Doppler technique; however, instead of detecting the heart activity from a distance, the sensor is placed on the patient's chest over the clothing. The microwave sensor directly measures heart movement rather than electrical activity, and is thus complementary to ECG. The primary advantages of the microwave sensor includes small size, light weight, low power, low-cost, and the ability to operate through clothing. We present a sample sensor design that incorporates a 2.4 GHz Doppler circuit, integrated microstrip patch antenna, and microntroller with 12-bit ADC data sampling. The prototype sensor also includes a wireless data link for sending data to a remote PC or mobile phone. Sample data is shown for several subjects and compared to data from a commercial portable ECG device. Data collected from the microwave sensor exhibits a significant amount of features, indicating possible use as a tool for monitoring heart mechanics and detection of abnormalities such as fibrillation and akinesia.

The structure-based design, synthesis, and biological evaluation of a series of nonpeptidic macrocyclic HIV protease inhibitors are described. The inhibitors are designed to effectively fill in the hydrophobic pocket in the S1'-S2' subsites and retain all major hydrogen bonding interactions with the protein backbone similar to darunavir (1) or inhibitor 2. The ring size, the effect of methyl substitution, and unsaturation within the macrocyclic ring structure were assessed. In general, cyclic inhibitors were significantly more potent than their acyclic homologues, saturated rings were less active than their unsaturated analogues and a preference for 10- and 13-membered macrocylic rings was revealed. The addition of methyl substituents resulted in a reduction of potency. Both inhibitors 14b and 14c exhibited marked enzyme inhibitory and antiviral activity, and they exerted potent activity against multidrug-resistant HIV-1 variants. Protein-ligand X-ray structures of inhibitors 2 and 14c provided critical molecular insights into the ligand-binding site interactions.

Structure-based design and synthesis of a number of potent and selective memapsin 2 inhibitors are described. These inhibitors were designed based upon the X-ray structure of memapsin 2-bound inhibitor 3 that incorporates methylsulfonyl alanine as the P2-ligand and a substituted pyrazole as the P3-ligand. Of particular importance, we examined the ability of the substituted isophthalic acid amide derivative to mimic the key interactions in the S2-S3 regions of the enzyme active sites of 3-bound memapsin 2. We investigated various substituted phenylethyl, alpha-methylbenzyl, and oxazolylmethyl groups as the P3-ligands. A number of inhibitors exhibited very potent inhibitory activity against mempasin 2 and good selectivity against memapsin 1. Inhibitor 5d has shown low nanomolar enzyme inhibitory potency (Ki=1.1 nM) and very good cellular inhibitory activity (IC50=39 nM). Furthermore, in a preliminary study, inhibitor 5d has shown 30% reduction of Abeta40 production in transgenic mice after a single intraperitoneal administration (8 mg/kg). A protein-ligand X-ray crystal structure of 5d-bound memapsin 2 provided vital molecular insight that can serve as an important guide to further design of novel inhibitors.

TiCl(4)-promoted multicomponent reactions involving N-tosyl imino ester, cyclic enol ether, and silane reagents in a single one-pot operation provide functionalized alpha-amino acids with multiple stereogenic centers in good to excellent yields. Cis/trans selectivities with optically active substituted dihydrofurans have been investigated.