82628-68-0Relevant articles and documents
Application of conjugate of polyethylene glycol and local anesthetic to non-narcotic analgesia
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Paragraph 0196; 0197; 0199, (2018/03/25)
The invention discloses application of a conjugate of polyethylene glycol and local anesthetic to non-narcotic analgesia. The local anesthetic is made into a prodrug or a sustained release preparation, wherein high-molecular polymers such as polyethylene glycol in the prodrug are covalently bonded with local anesthetic, and auxiliary materials with a sustained release function in the sustained release preparation are covalently bonded with the local anesthetic. After application of the conjugate, anesthesia and analgesia effects are not achieved until release of free local anesthetic, and an analgesia effect is achieved after release of the free local anesthetic. Due to low release speed of the prodrug or the sustained release preparation of the local anesthetic, drug concentration can bestably and enduringly kept in an effective concentration range of non-narcotic analgesia, long-acting non-narcotic analgesia effects can be achieved while remarkable reduction of clinical untoward effects of the local anesthetic and reduction of dosing frequency are realized, drug effectiveness is improved, and a clinical application range of the local anesthetic is expanded.
2-THIOXOTHIAZOLIDIN-4-ONE DERIVATIVES ACTIVE AS TRANSTHYRETIN LIGANDS AND USES THEREOF
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Paragraph 00314; 00315, (2016/06/15)
Compounds of formula (II) are provided for stabilizing protein transthyretin (TTR) and inhibiting amyloid fibril formation, for example, transthyretin-mediated amyloid fibril formation, and for treating, preventing, or ameliorating one or more symptoms of amyloid diseases, for example, transthyretin-related amyloidosis (ATTR).
Molecular Mechanism of Action of 5,6-Dihydroxytryptamine. Synthesis and Biological Evaluation of 4-Methyl-, 7-Methyl-, and 4,7-Dimethyl-5,6-dihydroxytryptamines
Sinhababu, Achintya K.,Ghosh, Anil K.,Borchardt, Ronald T.
, p. 1273 - 1279 (2007/10/02)
The major mechanism by which the serotonin neurotoxin 5,6-dihydroxytryptamine (5,6-DHT) expresses its neurodegenerative action may involve alkylation of biological nucleophiles by the electrophilic quinoid autoxidation products.To determine the relative importance of various sites on these autoxidation products toward alkylation we have rationally designed and synthesized 4-Me-5,6-DHT (16a), 7-Me-5,6-DHT (16b), and 4,7-Me2-5,6-DHT (16c).The indole nucleus of these analogues was constructed by the reductive cyclization of the corresponding 2,β-dinitrostyrenes, and the aminoethyl side chain was introduced via gramine methiodides.Redox data showed that all the analogues are more readily oxidized compared to 5,6-DHT.The biological activity was evaluated in differentiated neuroblastoma N-2a cells in culture.The order of inhibitory potency, as determined by measuring the inhibition of incorporation of thymidine into DNA, was 16c >> 16a > 5,6-DHT 16b.The order of affinity (expressed as IC50 values in μM) for serotonergic uptake as determined by measuring their inhibition of -5-HT uptake was 5,6-DHT (4) > 16c (20) > 16a (23) > 16b (52).The results of these studies established that these rationally designed C-methylated analogues of 5,6-DHT are suitable probes for elucidating the molecular mechanism of action of 5,6-DHT.
