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ANTI-CANCER ACTIVITY OF NOVEL BICYCLIC HETEROCYCLES

The present invention relates to compound of formula I, II, III, or IV, and/or a pharmaceutical acceptable addition salt thereof and/or a stereoisomer thereof and/or a solvate thereof, Formulas (I), (II), (III) and (IV) wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R11, and R12 are as defined in the claim 1 or as described in detail in the description of the invention, and to the use of said compounds to treat or prevent proliferative disorders and their use to manufacture a medicine to treat or prevent proliferative disorders, particularly cancer such as leukemia. The present invention also relates to pharmaceutical compositions of said compounds and the use of said pharmaceutical compositions to treat or prevent proliferative disorders. The present invention further relates to the use of said compounds as biologically active ingredients, more specifically as medicaments for the treatment of proliferative disorders and pathologic conditions such as, but not limited to, cancer such as leukemia.

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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ORTHO SUBSTITUTED ARYL OR HETEROARYL AMIDE COMPOUNDS

This invention provides a compound of the formula (I): wherein X represents a carbon atom or the like: Y represents imino, or the like: Z represents a hydrogen atom or the like: R1 represents an alkyl group having from 1 to 6 carbon atoms or the like: R2 and R3 independently represents a hydrogen atom or the like. These compounds are useful for the treatment of disease conditions mediated by prostaglandin such as pain, or the like in mammalian. This invention also provides a pharmaceutical composition comprising the above compound.

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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6-Benzoyl-3-hydroxypyrimidine-2,4-diones as dual inhibitors of HIV reverse transcriptase and integrase

N-3-Hydroxylation of pyrimidine-2,4-diones was recently found to yield inhibitors of both HIV-1 reverse transcriptase (RT) and integrase (IN). An extended series of analogues featuring a benzoyl group at the C-6 position of the pyrimidine ring was synthesized. Through biochemical studies it was found that these new analogues are dually active against both RT and IN in low micromolar range. Antiviral assays confirmed that these new inhibitors are active against HIV-1 in cell culture at nanomolar to low micromolar range, further validating 3-hydroxypyrimidine-2,4-diones as a viable scaffold for antiviral development.

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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alpha-Amino Diphenyl Phosphonates as Novel Inhibitors of Escherichia coli ClpP Protease

Increased Gram-negative bacteria resistance to antibiotics is becoming a global problem, and new classes of antibiotics with novel mechanisms of action are required. The caseinolytic protease subunit P (ClpP) is a serine protease conserved among bacteria that is considered as an interesting drug target. ClpP function is involved in protein turnover and homeostasis, stress response, and virulence among other processes. The focus of this study was to identify new inhibitors of Escherichia coli ClpP and to understand their mode of action. A focused library of serine protease inhibitors based on diaryl phosphonate warheads was tested for ClpP inhibition, and a chemical exploration around the hit compounds was conducted. Altogether, 14 new potent inhibitors of E. coli ClpP were identified. Compounds 85 and 92 emerged as most interesting compounds from this study due to their potency and, respectively, to its moderate but consistent antibacterial properties as well as the favorable cytotoxicity profile.

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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ANTIVIRAL AGENT

The present invention provides an integrase inhibitor. The inventors have have found the following compound of formula (I) possessing an integrase inhibitory activity. (wherein, R C and R D taken together with the neighboring carbon atoms form a ring which may be a condensed ring, Y is hydroxy, mercapto or amino; Z is O, S or NH ; R A is a group shown by (wherein, C ring is N-containing aromatic heterocycle) or the like)

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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Discovery of 7- N -piperazinylthiazolo[5,4- d ]pyrimidine analogues as a novel class of immunosuppressive agents with in vivo biological activity

Herein we describe the synthesis and in vitro and in vivo activity of thiazolo[5,4-d]pyrimidines as a novel class of immunosuppressive agents, useful for preventing graft rejection after organ transplantation. This research resulted in the discovery of a series of compounds with potent activity in the mixed lymphocyte reaction (MLR) assay, which is well-known as the in vitro model for in vivo rejection after organ transplantation. The most potent congeners displayed IC50 values of less than 50 nM in this MLR assay and hence are equipotent to cyclosporin A, a clinically used immunosuppressive drug. One representative of this series was further evaluated in a preclinical animal model of organ transplantation and showed excellent in vivo efficacy. It validates these compounds as new promising immunosuppressive drugs.

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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A General, Practical Triethylborane-Catalyzed Reduction of Carbonyl Functions to Alcohols

A combination of the abundant and low-cost triethylborane and sodium alkoxide generates a highly efficient catalyst for reduction of esters, as well as ketones and aldehydes, to alcohols using an inexpensive hydrosilane under mild conditions. The catalyst system exhibits excellent chemoselectivity and a high level of functional group tolerance. Mechanistic studies revealed a resting state of sodium triethylalkoxylborate that is the product of the reaction of BEt3 with sodium alkoxide. This borate species reacts with hydrosilane to form NaBEt3H, which rapidly reduces esters.

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Reference£º
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

More research is needed about 5-(Bromomethyl)-2,3-dihydro-1,4-benzodioxine

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Biocatalytic Formal Anti-Markovnikov Hydroamination and Hydration of Aryl Alkenes

Biocatalytic anti-Markovnikov alkene hydroamination and hydration were achieved based on two concepts involving enzyme cascades: epoxidation-isomerization-amination for hydroamination and epoxidation-isomerization-reduction for hydration. An Escherichia coli strain coexpressing styrene monooxygenase (SMO), styrene oxide isomerase (SOI), omega-transaminase (CvTA), and alanine dehydrogenase (AlaDH) catalyzed the hydroamination of 12 aryl alkenes to give the corresponding valuable terminal amines in high conversion (many ?86%) and exclusive anti-Markovnikov selectivity (>99:1). Another E. coli strain coexpressing SMO, SOI, and phenylacetaldehyde reductase (PAR) catalyzed the hydration of 12 aryl alkenes to the corresponding useful terminal alcohols in high conversion (many ?80%) and very high anti-Markovnikov selectivity (>99:1). Importantly, SOI was discovered for stereoselective isomerization of a chiral epoxide to a chiral aldehyde, providing some insights on enzymatic epoxide rearrangement. Harnessing this stereoselective rearrangement, highly enantioselective anti-Markovnikov hydroamination and hydration were demonstrated to convert alpha-methylstyrene to the corresponding (S)-amine and (S)-alcohol in 84-81% conversion with 97-92% ee, respectively. The biocatalytic anti-Markovnikov hydroamination and hydration of alkenes, utilizing cheap and nontoxic chemicals (O2, NH3, and glucose) and cells, provide an environmentally friendly, highly selective, and high-yielding synthesis of terminal amines and alcohols.

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Reference£º
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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Copper-TEMPO-catalyzed synthesis of alpha-ketoamides: Via tandem sp3C-H aerobic oxidation and amination of phenethyl alcohol derivatives

An efficient copper-TEMPO-catalyzed one-pot synthesis of alpha-ketoamides from phenethyl alcohol derivatives was developed firstly. Moreover, molecular oxygen in open air was employed as the oxidant with a broad substrate scope, which makes this methodology more practical. Based on some control experiments, a plausible mechanism was proposed.

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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Temporal separation of catalytic activities allows anti-Markovnikov reductive functionalization of terminal alkynes

There is currently great interest in the development of multistep catalytic processes in which one or several catalysts act sequentially to rapidly build complex molecular structures. Many enzymes – often the inspiration for new synthetic transformations – are capable of processing a single substrate through a chain of discrete, mechanistically distinct catalytic steps. Here, we describe an approach to emulate the efficiency of these natural reaction cascades within a synthetic catalyst by the temporal separation of catalytic activities. In this approach, a single catalyst exhibits multiple catalytic activities sequentially, allowing for the efficient processing of a substrate through a cascade pathway. Application of this design strategy has led to the development of a method to effect the anti-Markovnikov (linear-selective) reductive functionalization of terminal alkynes. The strategy of temporal separation may facilitate the development of other efficient synthetic reaction cascades.

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Reference£º
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem