- Novel derivatives of urea and use thereof
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The present invention relates to a novel urea derivative compound and 5HT thereof. 2A The present invention relates to the use of antagonists as antagonists for the prevention or treatment of neuropsychiatric disorders, degenerative brain diseases, propagated disorders and/or metabolic diseases.
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Paragraph 0241-0243
(2021/10/27)
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- Design, Synthesis, and Biological Evaluation of New Peripheral 5HT2A Antagonists for Nonalcoholic Fatty Liver Disease
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Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent worldwide, causing serious liver complications, including nonalcoholic steatohepatitis. Recent findings suggest that peripheral serotonin (5-hydroxytryptamine, 5HT) regulates energy homeostasis, including hepatic lipid metabolism. More specifically, liver-specific 5HT2A knockout mice exhibit alleviated hepatic lipid accumulation and hepatic steatosis. Here, structural modifications of pimavanserin (CNS drug), a 5HT2A antagonist approved for Parkinson's disease, led us to synthesize new peripherally acting 5HT2A antagonists. Among the synthesized compounds, compound 14a showed good in vitro activity, good liver microsomal stability, 5HT subtype selectivity, and no significant inhibition of CYP and hERG. The in vitro and in vivo blood-brain barrier permeability study proved that 14a acts peripherally. Compound 14a decreased the liver weight and hepatic lipid accumulation in high-fat-diet-induced obesity mice. Our study suggests new therapeutic possibilities for peripheral 5HT2A antagonists in NAFLD.
- Kim, Minhee,Hwang, Inseon,Pagire, Haushabhau S.,Pagire, Suvarna H.,Choi, Wonsuk,Choi, Won Gun,Yoon, Jihyeon,Lee, Won Mi,Song, Jin Sook,Yoo, Eun Kyung,Lee, Seung Mi,Kim, Mi-Jin,Bae, Myung Ae,Kim, Dooseop,Lee, Heejong,Lee, Eun-Young,Jeon, Jae-Han,Lee, In-Kyu,Kim, Hail,Ahn, Jin Hee
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supporting information
p. 4171 - 4182
(2020/04/30)
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- COMPOSITIONS FOR PROMOTING READTHROUGH OF PREMATURE TERMINATION CODONS, AND METHODS OF USING THE SAME
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Disclosed are compounds of general formula (I) that promote readthrough of a premature termination codon (PTC) of an RNA molecule in a translation system, and their use, alone or in combination with other compounds, such as aminoglycoside, to treat diseases or disorders ameliorated by modulation of a premature termination codon (PTC) of an RNA molecule in a translation system. The disorder or disease may be Dystrophic epidermolysis bullosa, Batten disease, Duchenne muscular dystrophy, cancer, and spinal muscular atrophy. Ar-L-B (I)
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Page/Page column 214; 216; 217; 224
(2017/04/11)
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- Design, synthesis, and conformational dynamics of a gated molecular basket
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We have developed a synthesis and examined the conformational behavior and recognition properties of dynamic molecular containers 1-3. As follows from the 1H NMR dilution, diffusion NMR, and vapor pressure osmometry measurements, compound 1 has a low affinity for intermolecular aggregation and is mostly present in monomeric form in dilute chloroform solutions. Inspecting the O-H chemical shift resonances of 1, 3, and model compound 4 as a function of temperature afforded the Δδ/ΔT coefficients of 17.0, 17.3, and 4.7 ppb K-1, respectively. In combination with the results from variable temperature 1H NMR and IR measurements, the existence of conformers of 1 and 3 in equilibrium, each having a different extent of hydrogen bonding, was confirmed. Molecular mechanics calculations suggested 1 a as the most favorable conformation, with three additional conformers, 1b, 1C, and 1d, populating local energy minima. Further optimization of each of the four conformers using semiempirical PM3 and ab initio (HF/6-31G*) methods allowed a determination of their relative free energies and the corresponding Boltzmann population distributions which were heavily weighted toward 1a. A computed composite IR spectrum of a fraction-weighted mixture of the conformers of 1 reproduced the experimentally observed IR spectrum in its structural features, leading to a conclusion that conformer 1a indeed dominates the equilibrium. The egg-shaped cavity of 1 (136.6 A3) is complementary in size, shape, and electrostatic potential to chloroform (74.9 A3). A single-crystal X-ray study of 2 revealed a disordered chloroform molecule positioned inside the cavitand along its C3, axis.
- Maslak, Veselin,Yan, Zhiqing,Xia, Shijing,Gallucci, Judith,Hadad, Christopher M.,Badjic, Jovica D.
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p. 5887 - 5894
(2007/10/03)
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- Synthesis and opioid activities of some naltrexone oxime ethers
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A series of alkyl, cycloalkyl, aryl, and aralkyl ethers of naltrexone oxime was prepared.The compounds were examined in binding assays for μ, δ, and κ opioid receptor affinity.In addition, the naltrexone oxime ethers were studied in animal models that measure opioid agonist and antagonist activity.These studies led to the discovery of several compounds, notably phenethyl 3e and phenylpropyl 3f ethers of naltrexone, which have a 10-fold increase in potency at the κ opioid receptor with potent μ and κ agonist properties in vivo.naltrexone / oxime ether / opioid receptor / analgesia / receptor binding / kappa
- Mavunkel, B. J.,Rzeszotarski, W. J.,Kaplita, P. V.,DeHaven-Hudkins, D. L.
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p. 659 - 666
(2007/10/02)
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