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Synthesis of trimethylsilyl-substituted pentacyclo(5.4.0.0²,⁶.0³,¹º.0⁵,⁹)undecanes and chloro-substituted pentacyclo(5.4.0.0²,⁶.0³,¹º.0⁵,⁹)undecaneHuang, Chunmin 08 1900 (has links)
As part of a continuing study of the synthesis and chemistry of new, substituted pentacyclo(5.4.0.0²,⁶.0³,¹º.0⁵,⁹)undecanes, the following compounds have been synthesized: 1: X=O, Y=SiMe_3; 2: X=CH_2, Y=SiMe_3; 3: X=O, Y=Cl; 6: X=OAc, Y=H; 8: X=OC(O)Ph, Y=H; 9: X=OSO_2Ph, Y=H; 11: X=OH, Y=H; 12: X=OMe, Y=H; 14: X=CHSiMe_3, Y=SiMe_3; 15: X=OH, Y=Cl; 16: X=OAc, Y=Cl; 17: X=OMe, Y=Cl. An important objective of this work is to prepare new polycyclic cage compounds which can be utilized as intermediates for the synthesis of new, substituted tricyclopentanoid natural products (triquinanes) and related systems. Compounds 1-4 were identified as target molecules in this connection.
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Polycyclic compounds as carriers for neuroactive non- steroidal anti-inflammatory drugsAbaniwonda, Modupe January 2017 (has links)
Magister Pharmaceuticae - MPharm / Recent scientific findings have highlighted the beneficial roles of polycyclic cage compounds in neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Further interest into the chemistry of these compounds is stimulated by their remarkable ability to improve the pharmacokinetics profile of known neuroprotective agents. As potent lipophilic scaffolds, they can be employed to target the brain delivery of desired compounds.
Inflammation is a key mediator of neuronal cell's degeneration as activated microglia and other inflammatory mediators propagate oxidative damage and neuronal loss. Epidemiological and clinical evidence suggests that non-steroidal anti-inflammatory drugs (NSAIDs) slow down the progression and onset of neurodegenerative diseases. The beneficial effects of NSAIDs in ND can be attributed to their ability to inhibit cyclooxygenase enzymes thereby halting the biosynthesis of prostaglandins (PG) which are powerful mediators of inflammation. NSAIDs also inhibit the expression of pro- inflammatory genes. Despite their potential neuroprotective activity, NSAIDs are poorly lipophilic due to the presence of polar carboxylic acid groups and will therefore ionise at physiological pH, deterring them from reaching the desired site of action in the central nervous system (CNS).
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Synthesis & biological evaluation of neuroprotective molecules with polycyclic scaffoldsSharma, Rajan January 2017 (has links)
Doctor Pharmaceuticae - Dpharm / Among neurological disorders, many of the most devastating disorders are
neurodegenerative. Modern research associates excitotoxicity to a variety of
neuropathological conditions, suggesting that the neurodegenerative diseases with
distinct etiologies may have excitotoxicity as a common pathway. Excitotoxicity
occurs through over-stimulation of receptors for excitatory neurotransmitters like
the N-methyl-D-aspartate (NMDA) receptors. Due to the relevance of NMDA
receptors and excitotoxic processes, the antagonism or modulation of NMDA
receptors is used as a therapeutic tool against neurodegenerative diseases. NMDA
receptor activity can be modulated by S-nitrosylation and this modulation of
NMDA receptor activity can be utilised in the development of neuroprotective
drugs.
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