Changes in depression status in low socioeconomic perinatal subjects in rural India after supervised physical exercise: A randomized controlled study.

BACKGROUND: Perinatal depression is a major public health problem, affecting up to a quarter of all pregnant women in rural Asean countries and often leads to psychologic symptoms, lower quality of life, and higher health care costs. The purpose of this study was to assess the impact of supervised physical exercise on depression level of perinatal subjects. SUBJECTS/INTERVENTION: 60 subjects who fulfill the selection criteria were randomly assigned to exercise (Group-1, n=30) and control group (Group-2, n=30). Participants completed general screening form and Physical health questionnaire-9 (PHQ-9) before their intervention and again 4 weeks and 8 weeks later. Group-1 underwent aerobic training with 60-65% maximum heart rate and Group-2 was prescribed with handouts for 4 weeks. STATISTICS: Repeated-measures analysis of variance (ANOVA) was use to analyze group differences over time while controlling for baseline differences. RESULTS: Demographic and the baseline values show homogenous population (P>0.05). Patients in both groups experienced significant reduction in depression level. Group A showed reduction of 91.70% (P=0.00) as compared to Group B 69.01% (P=0.00). CONCLUSION: These results suggest that supervised physical exercise provides better improvement in depression status in perinatal subjects than providing handouts alone.

Discovery of pyrazolo[3,4-d]pyrimidine derivatives as GPR119 agonists.

We designed and synthesized a novel series of phenylamino- and phenoxy-substituted pyrazolo[3,4-d]pyrimidine derivatives as GPR119 agonists. SAR studies indicated that electron-withdrawing substituents on the phenyl ring are important for potency and full efficacy. Compound 26 combined good potency with a promising pharmacokinetic profile in mice, and lowered the glucose excursion in mice in an oral glucose-tolerance test.

Straightforward assembly of the octahydroisoquinoline core of morphinan alkaloids.

The octahydroisoquinoline core of morphinan was assembled starting from readily available arylcyclohexadienes. Three different approaches were developed, including a metal- and an acid-mediated Mannich type process and an anionic-mediated cyclization. All provided the desired motif as a single diastereomer having a C9-C13-C14 trans-cis relative configuration.

Birch reductive alkylation of biaryls: scope and limitations.

Birch reductive alkylation of biaryls has been carried out by varying the nature of the substituents on the aromatic rings. Our investigations have focused on electron-rich substituents such as OMe, OH, and NR(2) groups as they are present on the skeleton of targeted alkaloids. The regioselectivity is strongly affected by the electronic nature of these substituents on both rings. The 3,5-dimethoxyphenyl moiety is selectively reduced and then alkylated, while phenols and anilines do not react under these conditions. A biaryl possessing both a 3,5-dimethoxyphenyl moiety and a phenol ring may, however, be reduced and alkylated provided the acidic phenolic proton is removed prior to the treatment with Li in NH(3). Similarly, biaryls possessing a o-sulfonamide group are reduced regioselectively and alkylated with alpha-chloroacetonitrile or N-tosylaziridine to provide the corresponding dienes in reasonable to good yields. A survey of the alkylating agents was also performed showing that various functional groups may be introduced at the benzylic position, including esters, primary and tertiary amides, nitriles, epoxides, and acetals and also unfunctionalized sterically hindered t-Bu groups and cyclopropyl substituents. The introduction of the latter indicates that both a S(N)2 and a SET mechanism may take place during the alkylating step.

Synthesis, reactions and structure-activity relationships of 1-hydroxyspiro[2.5]cyclooct-4-en-3-ones: illudin analogs with in vitro cytotoxic activity.

1-Hydroxyspiro[2.5]cyclooct-4-en-3-ones-analogs of natural illudines--were prepared in good yields by cyclization of 1,3-dicarbonyl dianions or 1,3-bis-silyl enol ethers ('masked dianions') with 1,1-diacylcyclopropanes. Several spirocyclopropanes showed a significant antiproliferative activity against human leukemia HL60 cells in vitro. 1-Hydroxyspiro[2.5]cyclooct-4-en-3-ones represent highly reactive precursors of unstable spiro[5.2]cycloocta-4,7-dien-6-ones and reactions with a number of nucleophiles were studied.

Domino "[3+3]-cyclization-homo-Michael" reactions of 1,3-bissilyl enol ethers with 1,1-diacylcyclopropanes.

The Lewis acid mediated domino "[3+3]-cyclization-homo-Michael" reaction of 1,3-bissilyl enol ethers with 1,1-diacylcyclopropanes allows an efficient one-pot synthesis of functionalized salicylates containing a halogenated side chain. A great variety of substitution patterns could be realized by variation of the starting materials and of the Lewis acid. The mechanism of the domino process was studied.

Synthesis of spiro[5.4]decenones and their transformation into bicyclo[4.4]deca-1,4-dien-3-ones by domino "elimination- double-Wagner-Meerwein-rearrangement" reactions.

The [3+3] cyclization of 1,3-bis-silyl enol ethers with 1,1-diacylcyclopentanes allows a convenient synthesis of spiro[5.4]decenones. Treatment of these compounds with trifluoroacetic acid (TFA) afforded a great variety of bicyclo[4.4.0]deca-1,4-dien-3-ones containing an angular alkyl group. This core structure occurs in a number of pharmacologically relevant natural products.