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The present invention relates to processes for the synthesis of 1-[4-(2-methoxyphenyl)piperazin-1-yl]-3-(2,6-dioxopiperidin-1-yl) propane hydrochloride having protracted uro-selective (alpha1-adrenoceptor antagonistic activity. The compound holds promise for treating benign prostatic hyperplasia (BPH).

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Piperidine – Wikipedia,
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Cocrystals and eutectics are different yet related crystalline multi-component adducts with diverse applications in pharmaceutical and materials fields. Recently, they were shown to be alternate products of cocrystallization experiments. Whereas a cocrystal shows distinct diffraction, spectroscopic and thermal signatures as compared to parent components, the hallmark of a eutectic is its low melting nature. However, in certain cases, there can be a problem when one resorts to design a cocrystal and assess its formation vis-a-vis a eutectic. In the absence of a gold standard method to make a cocrystal, it is often difficult to judge how exhaustive should the cocrystallization trials be to ensure the accomplishment of a desired/putative cocrystal. Further, a cocrystal can manifest with intermolecular interactions and/or crystal structure similar to that of its parent compounds such that the conventional diffraction and spectroscopic techniques will be of little help to conclusively infer the formation of cocrystal in the lack of single crystals. Such situations combined with low melting behavior of a combination brings the complication of resolving the combination as a cocrystal or eutectic since now both the adducts share common features. Based on the curious case of Caffeine-Benzoic acid combination, this study aims to unfold the intricate issues related to the design, formation and characterization of cocrystals and eutectics for a way forward. The utility of heteronuclear seeding methodology in establishing a given combination as a cocrystal-forming one or a eutectic-forming one in four known systems is appraised.

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The dinuclear hydroxo complex [{Pd(mu-OH)(Phox)}2] (I) (Phox = 2-(2-oxazolinyl)phenyl) reacts in a 1:2 molar ratio with several imidate ligands to yield new cyclometallated palladium complexes [{Pd(mu-NCO)(Phox)}2] containing asymmetric imidate -NCO- bridging units. [-NCO- = succinimidate (succ) (1), phtalimidate (phtal) (2), maleimidate (mal) (3), 2,3-dibromomaleimidate (2,3-diBrmal) (4) and glutarimidate (glut) (5)]. The reaction of these complexes with tertiary phosphines provides novel mononuclear N-bonded imidate derivatives of the general formula [Pd(imidate)(Phox)(PR3)] [R = Ph (a), 4-F-C6H4 (b) or CH2CH2CN (c)]. The new complexes were characterized by partial elemental analyses and spectroscopic methods (IR, FAB, 1H, 13C and 31P). The single-crystal structures of compounds 4, 4a and 5a have been established.

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Using N-acyliminium cyclization as a key-step, the total synthesis of (+/-)-lasubine I has been achieved in six steps starting from veratraldehyde.

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Synthesis and preliminary anticancer study of 5-fluorouracil-phthalimide conjugate utilizing molecular hybridization approach

Cancer is still the most challenging disease in the entire world. Molecular hybridization is very interesting approach in design of drug and development depends on the combination of pharmacophoric moieties of two pharmacologically active compounds results in a new hybrid compound with better affinity and efficacy, when compared to the parent drugs. The aim of the present study is to synthesize new 5-fluorouracil derivatives as probable more active anticancer agents than the parent drug. 5-fluoro-4-oxo-1,4-dihydropyrimidin-2-yl2-(1,3-dioxoisoindolin-2-ylamino) acetate [IV] and 2-(2-(5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-oxoethylamino) isoindoline-1,3-dione [V] have been synthesized utilizing hybridization approach from 5-fluorouracil and phthalimide through amino acetate or 2-oxoethylamino linkers. The structures of the newly synthesized compounds and their intermediates were characterized by FT-IR,13C-NMR ESI-MS spectral analysis. A preliminary cytotoxicity study that evaluated by crystal violet assay using a target breast cancer cell, murine mammary adenocarcinoma cell line indicates that the compounds have considerable anticancer activity relative to the lead one.

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DIELS-ALDER REACTIONS OF 2-AZADIENES. DIASTEREOSELECTIVE SYNTHESES OF 2-AZABICYCLO<2.2.2>OCTAN-2-ONES AND OF 2,3,4-SUBSTITUTED CYCLOHEXANONES

Glutarimide is readily disilylated to yield the cyclic 2-azadiene 1 which reacts with open-chain dienophiles with surprisingly high exo-selectivity.The resulting 2-aza-bicyclo<2.2.2>octan-3-ones are stereoselectively transformed into substituted cyclohexanones.

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Design, synthesis and biological assessment of novel N-substituted 3-(phthalimidin-2-yl)-2,6-dioxopiperidines and 3-substituted 2,6-dioxopiperidines for TNF-alpha inhibitory activity

Eight novel 2-(2,6-dioxopiperidin-3-yl)phthalimidine EM-12 dithiocarbamates 9 and 10, N-substituted 3-(phthalimidin-2-yl)-2,6-dioxopiperidines 11-14 and 3-substituted 2,6-dioxopiperidines 16and 18were synthesized as tumor necrosis factor-alpha (TNF-alpha) synthesis inhibitors. Synthesis involved utilization of a novel condensation approach, a one-pot reaction involving addition, iminium rearrangement and elimination, to generate the phthalimidine ring required for the creation of compounds 9-14. Agents were, thereafter, quantitatively assessed for their ability to suppress the synthesis on TNF-alpha in a lipopolysaccharide (LPS)-challenged mouse macrophage-like cellular screen, utilizing cultured RAW 264.7 cells. Whereas compounds 9, 14 and 16 exhibited potent TNF-alpha lowering activity, reducing TNF-alpha by up to 48% at 30 muM, compounds 12, 17and 18 presented moderate TNF-alpha inhibitory action. The TNF-alpha lowering properties of these analogs proved more potent than that of revlimid (3) and thalidomide (1). In particular, N-dithiophthalimidomethyl-3-(phthalimidin-2-yl)-2,6-dioxopiperidine 14 not only possessed the greatest potency of the analogs to reduce TNF-alpha synthesis, but achieved this with minor cellular toxicity at 30 muM. The pharmacological focus of the presented compounds is towards the development of well-tolerated agents to ameliorate the neuroinflammation, that is, commonly associated with neurodegenerative disorders, epitomized by Alzheimer’s disease and Parkinson’s disease.

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Bioactive metabolites from rare actinomycetes

New antibiotics are desperately needed to combat the increasing number of antibiotic resistant strains of pathogenic microorganisms. Natural products remain the most propitious source of novel antibiotics. It is widely accepted that actinobacteria are prolific producers of natural bioactive compounds. We argue that the likelihood of discovering a new compound having a novel chemical structure can be increased with intensive efforts in isolating and screening rare genera of microorganisms. Screening rare actinomycetes and their previously underrepresented genera from unexplored environments in natural product screening collections is one way of achieving this. Rare actinomycetes are usually regarded as the actinomycete strains whose isolation frequency is much lower than that of the streptomycete strains isolated by conventional methods. The relevance of the rare actinomycetes in this regard can also be demonstrated by the fact that many of the successful antimicrobial agents currently available in the market are produced by them. This chapter focuses on the bioactive secondary metabolites from rare actinomycetes with emphasis on their structures, relevant biological activities, source organisms, covering over 150 structures of different bioactive compounds produced by them with 84 citations. Its aim is to give the reader a brief view of the bioactive compounds from the rare actinomycetes and we wish to update our understanding of the potential of the rare actinomycetes by focusing on their biodiscovery potential. The emphasis is placed on new compounds discovered from these microorganims with bioactive potential. Copyright

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Design, synthesis and biological assessment of novel N-substituted 3-(phthalimidin-2-yl)-2,6-dioxopiperidines and 3-substituted 2,6-dioxopiperidines for TNF-alpha inhibitory activity

Eight novel 2-(2,6-dioxopiperidin-3-yl)phthalimidine EM-12 dithiocarbamates 9 and 10, N-substituted 3-(phthalimidin-2-yl)-2,6-dioxopiperidines 11-14 and 3-substituted 2,6-dioxopiperidines 16and 18were synthesized as tumor necrosis factor-alpha (TNF-alpha) synthesis inhibitors. Synthesis involved utilization of a novel condensation approach, a one-pot reaction involving addition, iminium rearrangement and elimination, to generate the phthalimidine ring required for the creation of compounds 9-14. Agents were, thereafter, quantitatively assessed for their ability to suppress the synthesis on TNF-alpha in a lipopolysaccharide (LPS)-challenged mouse macrophage-like cellular screen, utilizing cultured RAW 264.7 cells. Whereas compounds 9, 14 and 16 exhibited potent TNF-alpha lowering activity, reducing TNF-alpha by up to 48% at 30 muM, compounds 12, 17and 18 presented moderate TNF-alpha inhibitory action. The TNF-alpha lowering properties of these analogs proved more potent than that of revlimid (3) and thalidomide (1). In particular, N-dithiophthalimidomethyl-3-(phthalimidin-2-yl)-2,6-dioxopiperidine 14 not only possessed the greatest potency of the analogs to reduce TNF-alpha synthesis, but achieved this with minor cellular toxicity at 30 muM. The pharmacological focus of the presented compounds is towards the development of well-tolerated agents to ameliorate the neuroinflammation, that is, commonly associated with neurodegenerative disorders, epitomized by Alzheimer’s disease and Parkinson’s disease.

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Reference£º
Piperidine – Wikipedia,
Piperidine | C5H1441N – PubChem

 

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Bioactive metabolites from rare actinomycetes

New antibiotics are desperately needed to combat the increasing number of antibiotic resistant strains of pathogenic microorganisms. Natural products remain the most propitious source of novel antibiotics. It is widely accepted that actinobacteria are prolific producers of natural bioactive compounds. We argue that the likelihood of discovering a new compound having a novel chemical structure can be increased with intensive efforts in isolating and screening rare genera of microorganisms. Screening rare actinomycetes and their previously underrepresented genera from unexplored environments in natural product screening collections is one way of achieving this. Rare actinomycetes are usually regarded as the actinomycete strains whose isolation frequency is much lower than that of the streptomycete strains isolated by conventional methods. The relevance of the rare actinomycetes in this regard can also be demonstrated by the fact that many of the successful antimicrobial agents currently available in the market are produced by them. This chapter focuses on the bioactive secondary metabolites from rare actinomycetes with emphasis on their structures, relevant biological activities, source organisms, covering over 150 structures of different bioactive compounds produced by them with 84 citations. Its aim is to give the reader a brief view of the bioactive compounds from the rare actinomycetes and we wish to update our understanding of the potential of the rare actinomycetes by focusing on their biodiscovery potential. The emphasis is placed on new compounds discovered from these microorganims with bioactive potential. Copyright

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Reference£º
Piperidine – Wikipedia,
Piperidine | C5H1377N – PubChem