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IDO inhibitors

Presently provided are methods for (a) modulating an activity of indoleamine 2,3-dioxygenase comprising contacting an indoleamine 2,3-dioxygenase with a modulation effective amount of a compound as described in one of the aspects described herein; (b) treating indoleamine 2,3-dioxygenase (IDO) mediated immunosuppression in a subject in need thereof, comprising administering an effective indoleamine 2,3-dioxygenase inhibiting amount of a compound as described in one of the aspects described herein; (c) treating a medical conditions that benefit from the inhibition of enzymatic activity of indoleamine-2,3-dioxygenase comprising administering an effective indoleamine 2,3-dioxygenase inhibiting amount of a compound as described in one of the aspects described herein; (d) enhancing the effectiveness of an anti-cancer treatment comprising administering an anti-cancer agent and a compound as described in one of the aspects described herein; (e) treating tumor-specific immunosuppression associated with cancer comprising administering an effective indoleamine 2,3-dioxygenase inhibiting amount of a compound as described in one of the aspects described herein; and (f) treating immunosuppression associated with an infectious disease, e.g., HIV-I infection, comprising administering an effective indoleamine 2,3-dioxygenase inhibiting amount a compound as described in one of the aspects described herein.

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Reference£º
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

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Adeninic and ureidic cytokinins: Primary response events in in vitro tomato caulogenesis

Among the molecules showing cytokinin activity, phenylurea derivatives have been long discussed as regards their direct or indirect action in cytokinin-mediated processes. This paper considers the activity of three cytokinins, an adenine and two phenylurea derivatives, on the caulogenesis onset. Caulogenesis is composed of sequential stages involving peculiar hormonal requirements and the differential activation of genes that can be considered markers of the steps leading to shoot production. Our study shows that the expression of LESK1, marker of caulogenic competence acquisition, is induced by both adeninic and ureidic derivatives, indicating that morphogenesis is induced by these molecules through the activation of common components of response pathway. The detailed analysis on morphogenesis in a system deprived of endogenous cytokinins strengthen the hypothesis of a proper cytokinin activity for the two phenylurea derivatives, 1-phenyl-3-(1,2,3-thiadiazol-5-yl)urea (thidiazuron TDZ) and N-phenyl-N?-benzothiazol-6-ylurea (PBU). A different behaviour of zeatin riboside (ZR), TDZ and PBU, emerges when the growth regulator supply is preceded by a 3-day pre-culture which positively affects the caulogenesis obtained with TDZ, while it strongly inhibits the action of ZR. PBU activity instead resulted more similar to that of the cytokinin/auxin treatment, supporting the idea of an interaction of diphenylurea derivatives with auxin metabolism. The synergistic effect of auxin on shoot production emerges from both the higher rate of caulogenic competence acquisition, marked by a sharper peak of LESK1 expression, which leads to a strong increase in shoot number produced per explant when cytokinin and auxin are supplied together.

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Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

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1,2-Benzisoxazole-3-acetamide derivatives as dual agents for DPP-IV inhibition and anticancer activity

Herein, we have designed various benzisoxazole acetamide derivatives with and without glycine spacer as DPP-IV inhibitors. Compounds 9a?d and 11a?e were synthesized and screened for their in vitro DPP-IV inhibition. Compounds 11a and 11c showed moderate activity for DPP-IV inhibition, whereas other remained inactive at 25?200 muM concentrations. DPP-IV inhibition can be a good strategy for modulating diabetes and cancer; hence, we have screened compounds 9a?d and 11a?e for their anticancer activity using MTT assay against A549 and MCF7 cell lines. Compounds 9a?d without glycine spacer have shown good anticancer activity compared to compounds 11a?e with glycine spacer. Compound 9b has shown moderate activity with IC50 values 4.72 ¡À 0.72 and 4.39 ¡À 0.809 muM against A549 and MCF7 cell lines, respectively. Interestingly, compound 9c with cyano group has shown very good anticancer activity with IC50 2.36 ¡À 0.34 muM against MCF7 cell line as compared to fluorouracil with IC50 45.04 ¡À 1.02 muM.

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Reference£º
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

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Synthesis, anti-bacterial, anti-asthmatic and anti-diabetic activities of novel N-substituted-2-(benzo[d]isoxazol-3-ylmethyl)-1H-benzimidazoles

(Chemical Equation Presented) Synthesis of a series of novel class of N-substituted-2-(benzo[d]isoxazol-3-ylmethyl)-1H-benzimidazoles (4) by the condensation of o-phenylenediamine (1) with benzo[d]isoxazol-3-yl-acetic acid (2) and subsequent reactions with different types of electrophiles have been reported. Some compounds exhibited promising anti-bacterial activity against Salmonella typhimurium, however poor activity against Staphylococcus aureus. The compound 4t was found to have high activity even at 1 mug/ml compared to Cephalexin against S. aureus. The biological activity against PDE-IV for potential anti-asthmatic effect and against DP-IV and PTP-1B for potential anti-diabetic effects was disappointing.

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Reference£º
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics

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Substituted benzisoxazole and benzisothiazole herbicidal agents

There are provided substituted benzisoxazole and benzisothiazole compounds having the structural formula I STR1 Further provided are compositions and methods comprising those compounds for the control of undesirable plant species.

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Benzisoxazole – Wikipedia,
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1H-PYRROLE-2,5-DIONE COMPOUNDS AND METHODS OF USING THEM TO INDUCE SELF-RENEWAL OF STEM/PROGENITOR SUPPORTING CELLS

The present invention relates to 1H-pyrrole-2,5-dione compounds and methods of using them to induce self-renewal of stem/progenitor supporting cells, including inducing the stem/progenitor cells to proliferate while maintaining, in the daughter cells, the capacity to differentiate into tissue cells.

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NOVEL OXABISPIDINE COMPOUNDS AND THEIR USE IN THE TREATMENT OF CARDIAC ARRHYTHMIAS

There is provided compounds of formula (I), wherein R1, R2, R3, R4, R 41 to R46, A, B and G have meanings given in the description, which are useful in the prophylaxis and in the treatment of arrhythmias, in particular atrial and ventricular arrhythmias.

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METHOD FOR SULFONATION OF 1,2-BENZISOXAZOLE-3-ACETIC ACID

An efficient method for the preparation of 1,2-benzisoxazole-3-methanesulfonic acid involves a reaction of 1,2-benzisoxazole-3-acetic acid in toluene with chlorosulfonic acid optionally mixed with an inert solvent in the presence of a particular Lewis base (ester or a nitrile).

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A PROCESS FOR THE MANUFACTURE OF ZONISAMIDE

The present invention describes an improved process for the preparation of 1,2Benzisoxazole-3-methanesulphonamide (Zonisamide), a well known anti-epileptic agent which possesses anti-convulsant and anti-neurotoxic effects. Other aspect of this invention are isolation of a key intermediate, viz., crystalline sodium chloride associated 1,2Benzisoxazole-3-methane sodium sulfonate (BOS-Na:NaCl). The isolated crude BOSNa:NaCl is directly converted to Zonisamide using controlled molar ratio of chlorosulfonic acid to avoid the disulfonated side products. The analytical characteristics like IR and XRD data of the BOS-Na:NaCl are also reported to confirm its nature.

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Benzisoxazole – Wikipedia,
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The expression of LESK1 morphogenetic marker along the tomato hypocotyl axis is linked to a position-dependent competence for shoot regeneration

Somatic morphogenesis is an important process whose mechanisms are still not completely understood. This is partially due to the lack of reliable morphogenetic markers that identify the different stages of the process. In the present work, a fragment of LESK1 gene (Lycopersicon esculentum shoot kinase 1) has been utilized as a marker of somatic caulogenesis. The expression of this marker pointed out a particular abundance of the corresponding transcript in tomato hypocotyls from 8-day-old plantlets. This elevated expression underlines the particular attitude to regeneration of this organ. Hypocotyl explants can in fact regenerate in the absence of exogenous growth regulators giving rise to shoot and root production at the apical and basal ends, respectively. The polarization observed in morphogenesis is always associated with polarized expression of LESK1 gene, which is elevated at the top of the explants, where shoot production occurs, and low at the basal pole, where roots were observed. A non-homogeneous LESK1 expression was also found along the hypocotyl axis where apparently marks cell populations with different competence to caulogenesis. These different levels of competence may be due to a variation in cell sensitivity to growth regulators, or the reaching of a well determined hormonal ratio required by the cells to be driven toward caulogenesis. LESK1 represents a reliable marker probably linked to the acquisition of competence for somatic caulogenesis.

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Reference£º
Benzisoxazole – Wikipedia,
Benzisoxazole – an overview | ScienceDirect Topics