A one-pot synthesis of 2,3-dihydrobenzofurans, benzofuran-2(3)-ones, and indoles a [4 + 1] annulation reaction of -substituted -quinone methides and bromonitromethane.

Under mild and metal-free reaction conditions, a facile one-pot synthesis of oxygen- and nitrogen-containing benzoheterocycles has been achieved through [4 + 1] annulation of -quinone methides, followed by an oxidation/elimination sequence, efficiently synthesizing functionalized 2,3-dihydrobenzofuran, benzofuran-2(3)-one, and indole derivatives in moderate to good yields (up to 72%). A novel functional group tolerant oxidative Nef reaction utilizes DDQ without a base.

Juvenile Hyaline Fibromatosis.

Syndromes, especially if they occur early in the growth phase can be very debilitating and cause severe restriction of function. Juvenile hyaline fibromatosis is one such disorder. Our case report presents a girl child who was diagnosed with this debilitating condition.

Dandy-Walker Syndrome with Giant Cell Lesions and Cherubism.

It has been very aptly quoted, "Variety is the spice of life"; and so variations exist in all forms and kinds good or bad, and for the worst or the best! Mother nature in all her glory and beauty has been very generous, but what when she fails to provide? It is this very character of nature that gives us variations which sometimes manifest in a cruel way on the human body and gives us the eponym of syndromes. Dandy-Walker malformation is an abnormality of the central nervous system, which leads to hydrocephalus and is associated with other abnormalities. Neurologic symptoms are the norm in afflicted patients due to the inherent nature of the disease in that it affects the very center of human function-the brain.

Alleviating CYP and hERG liabilities by structure optimization of dihydrofuran-fused tricyclic benzo[d]imidazole series - Potent, selective and orally efficacious microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors: Part-2.

In an effort to identify CYP and hERG clean mPGES-1 inhibitors from the dihydrofuran-fused tricyclic benzo[d]imidazole series lead 7, an extensive structure-activity relationship (SAR) studies were performed. Optimization of A, D and E-rings in 7 afforded many potent compounds with human whole blood potency in the range of 160-950 nM. Selected inhibitors 21d, 21j, 21m, 21n, 21p and 22b provided selectivity against COX-enzymes and mPGES-1 isoforms (mPGES-2 and cPGES) along with sufficient selectivity against prostanoid synthases.

Discovery of furan and dihydrofuran-fused tricyclic benzo[d]imidazole derivatives as potent and orally efficacious microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors: Part-1.

This letter describes the synthesis and biological evaluation of furan and dihydrofuran-fused tricyclic benzo[d]imidazole derivatives as novel mPGES-1 inhibitors, capable of inhibiting an increased PGE production in the disease state. Structure-activity optimization afforded many potent mPGES-1 inhibitors having <50 nM potencies in the A549 cellular assay and adequate metabolic stability in liver microsomes. Lead compounds 8l and 8m demonstrated reasonable in vitro pharmacology and pharmacokinetic properties over other compounds.

Design and synthesis of novel xanthine derivatives as potent and selective A adenosine receptor antagonists for the treatment of chronic inflammatory airway diseases.

Adenosine induces bronchial hyperresponsiveness and inflammation in asthmatics through activation of A adenosine receptor (AAdoR). Selective antagonists have been shown to attenuate airway reactivity and improve inflammatory conditions in pre-clinical studies. Hence, the identification of novel, potent and selective AAdoR antagonist may be beneficial for the potential treatment of asthma and Chronic Obstructive Pulmonary Disease (COPD).

Tricyclic 4,4-dimethyl-3,4-dihydrochromeno[3,4-d]imidazole derivatives as microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors: SAR and in vivo efficacy in hyperalgesia pain model.

A series of substituted tricyclic 4,4-dimethyl-3,4-dihydrochromeno[3,4-d]imidazole derivatives have been synthesized and their mPGES-1 biological activity has been disclosed in detail. Structure-activity relationship (SAR) optimization provided inhibitors with excellent mPGES-1 potency and low to moderate PGE release A549 cell potency. Among the mPGES-1 inhibitors studied, 7, 9 and 11l provided excellent selectivity over COX-2 (>200-fold) and >70-fold selectivity for COX-1 except 11l, which exhibited dual mPGES-1/COX-1 activity.

Discovery of 2-((2-chloro-6-fluorophenyl)amino)-N-(3-fluoro-5-(trifluoromethyl)phenyl)-1-methyl-7,8-dihydro-1H-[1,4]dioxino[2',3':3,4]benzo[1,2-d]imidazole-5-carboxamide as potent, selective and efficacious microsomal prostaglandin E synthase-1 (mPGES-1) inhibitor.

The discovery and SAR of potent, selective dioxane-fused tricyclic benz[d]imidazole derivatives as mPGES-1 inhibitor are herein described. Various amide modifications in this series afforded many potent mPGES-1 inhibitors, of which 17d proved to be suitable for further profiling in vivo. Compound 17d {2-((2-chloro-6-fluorophenyl)amino)-N-(3-fluoro-5-(trifluoromethyl)phenyl)-1-methyl-7,8-dihydro-1H-[1,4]dioxino[2',3':3,4]benzo[1,2-d]imidazole-5-carboxamide} exhibited excellent mPGES-1 enzyme (IC: 8nM), cell (A549 IC: 16.

A adenosine receptor antagonists: Design, synthesis and biological evaluation of novel xanthine derivatives.

AdoR is a low affinity adenosine receptor that functions by Gs mediated elevation of cAMP and subsequent downstream signaling. The receptor has been implicated in lung inflammatory disorders like COPD and asthma. Several potent and selective AAdoR antagonists have been reported in literature, however most of the compounds suffer from poor pharmacokinetic profile.

Assessment of temperature-induced hERG channel blockade variation by drugs.

Drug-induced QT prolongation has been reported in humans and animals. This potentially lethal effect can be induced by drugs interacting with a cardiac potassium channel, namely hERG (human ether-a go-go-related gene) leading to arrhythmia or torsade de pointes (TdP). Hence, in vitro evaluation of therapeutics for their effects on the rapid delayed rectifier current (IKr) mediated by the K(+) ion channel encoded by hERG is a valuable tool for identifying potential arrhythmic side effects during drug safety testing.

Evaluation of brimonidine-timolol fixed combination in patients of primary open-angle glaucoma.

The aim of present study was to compare the efficacy and safety of fixed combination of brimonidine and timolol with individual components used as monotherapy in patients of primary open angle glaucoma. Patients were randomly assigned to receive brimonidine or timolol or brimonidine-timolol fixed combination, with 30 patients in each group. The mean reduction in intraocular pressure in brimonidine, timolol, and brimonidine-timolol group were 4.

Antifungal Activity of Leaves of Mangroves Plant Acanthus licifolius Against Aspergillus fumigatus.

The antifungal activity of chloroform extract of leaves of Acanthus ilicifolius was evaluated in Aspergillus fumigatus infected mice. Swiss albino mice (60) were divided into five groups. All the groups were immunosuppressed with cyclophosphamide and cortisone acetate couple of days prior to intranasal inoculation with Aspergillus fumigatus conidia (10(6)) in all the groups, except the first.

Microwave assisted nano (ZnO-TiO2) catalyzed synthesis of some new 4,5,6,7-tetrahydro-6-((5-substituted-1,3,4-oxadiazol-2-yl)methyl)thieno[2,3-c]pyridine as antimicrobial agents.

Combined nano zinc oxide and titanium dioxide [nano (ZnO-TiO(2))] has been reported first time for the synthesis of novel series of 4,5,6,7-tetrahydro-6-((5-substituted-1,3,4-oxadiazol-2-yl)methyl)thieno[2,3-c]pyridine. All the synthesized compounds (7a-7m) are novel and were screened for their antimicrobial activity against four different strains like Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilis and antifungal activity was determined against two strains Candida albicans and Aspergillus niger. SAR for the newly synthesised derivatives has been developed by comparing their MIC values with ampicillin, ciprofloxacin and miconazole for antibacterial and antifungal activities, respectively.

Preparation of nano cellulose fibers and its application in kappa-carrageenan based film.

Bio-based nanocomposite films were successfully developed using nanofibrillated cellulose (NFC) as the reinforcing phase and kappa-carrageenan (KCRG) as the matrix. NFC was successfully synthesis from short stable cotton fibers by chemo-mechanical process. The bionanocomposites were prepared by incorporating 0.

Comparison of the efficacy and tolerability of telmisartan and enalapril in patients of mild to moderate essential hypertension.

Background: Theoretically, angiotensin II receptor blockers (ARBs) have certain advantages over angiotensin-converting enzyme inhibitors, but the contribution of these advantages to the clinical effect of ARBs is not known.

Objective: To compare the efficacy and tolerability of telmisartan with enalapril in patients of essential hypertension.

Materials And Methods: Patients of mild to moderate hypertension were randomized to receive either 40 mg of telmisartan or enalapril 10 mg once a day orally for 12 weeks.

Characterization of active and inactive states of CB1 receptor and the differential binding state modulation by cannabinoid agonists, antagonists and inverse agonists.

Cannabinoid 1 (CB1) receptors have the ability to change conformation between active (R*) and inactive (R) receptor states. Herein, we further characterize these receptor states using series of saturation radioligand binding studies and their differential displacement binding by various CB1 receptor ligands. Binding experiments were carried out in naïve rat/dog whole brain membranes using radioligands [(3)H]CP55,940 (for R* state) & [(3)H]SR141716A (both R* and R states) and various agonist, antagonist & inverse agonist ligands at CB1 receptors.

A prospective randomized controlled trial of preimplantation genetic screening in the "good prognosis" patient.

Objective: To determine whether the routine use of preimplantation genetic screening (PGS) in "good prognosis" women improves in vitro fertilization (IVF) cycle outcome.

Design: Randomized, controlled, prospective clinical study.

Setting: Private infertility clinic.

Impact of EmbryoGlue as the embryo transfer medium.

Routine use of EmbryoGlue did not significantly improve pregnancy or implantation rates in nonselected patients receiving either a day 3 or day 5 embryo transfer compared with standard culture media. Future prospective randomized studies need to be performed to determine whether EmbryoGlue is beneficial in a selected patient population.

Managing and predicting low response to standard in vitro fertilization therapy: a review of the options.

Low responders remain a difficult group of patients to manage in an in vitro fertilization (IVF) program. Such patients have low peak estradiol concentrations (<500 ng/L) and few dominant follicles on the day of human chorionic gonadotropin administration (<5 to <2), and therefore have few retrieved mature oocytes (< or = 4 to < or = 6) with resultant lower pregnancy rates when stimulated with standard IVF therapy (daily gonadotropin dose 150-300IU [2-4 ampoules]). It is difficult to compare the various strategies that have been utilized to manage low responders because the definition of a low responder varies widely.

Administration of recombinant human FSH (solution in cartridge) with a pen device in women undergoing ovarian stimulation.

This study evaluated the first multiple-use pen device for the self-administration of recombinant FSH. The pen device is used for the subcutaneous injection of a pre-mixed ready-to-use solution of follitropin beta from a multiple-dose cartridge, and has flexible dosing capabilities. In the ease-of-use questionnaire, 90% of subjects rated the overall experience of self-injecting follitropin beta using the pen device as 'very good' (on day 6).