- Synthesis of Carbamide Derivatives Bearing Tetrahydroisoquinoline Moieties and Biological Evaluation as Analgesia Drugs in Mice
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Transient receptor potential vanilloid 1 (TRPV1) is a ligand-gated non-selective cation channel that is considered to be an important pain integrator. Tetrahydroisoquinoline, the prototypical antagonist of TRPV1, has a clear therapeutic potential. Here, a series of carbamide derivatives of tetrahydroisoquinoline were designed and synthesized. Preliminary biological tests suggested that the compounds I 1, I 2, and I 9 had favorable TRPV1 antagonism activity. In further studies, I 1 exhibited better antinociceptive activity than the positive control BCTC in diverse pain models. All of these results suggested that I 1 can be considered as the lead candidate for the further development of antinociceptive drugs. A novel carbamide derivative of tetrahydroisoquinoline I 1 had impressive TRPV1 antagonism activity (89.02%), exerting potency similarity with the positive control BCTC. Moreover, in mice, I 1 could significantly inhibit the reaction to pain and nociception in three different pain models, and trigger the analgesic activity in a dose-dependent manner.
- Qiu, Qianqian,Wang, Jingjie,Deng, Xin,Qian, Hai,Lin, Haiyan,Huang, Wenlong
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- AMINOPYRAZINE COMPOUNDS AS HPK1 INHIBITOR AND THE USE THEREOF
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Disclosed herein is an aminopyrazine compound of Formula (I), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and pharmaceutical compositions comprising thereof. Also disclosed is a method of treating HPK1 related disorders or diseases by using the compound disclosed herein.
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Page/Page column 107
(2021/02/26)
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- Tyrosine Kinase Inhibitor And Uses Thereof
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Disclosed is a compound of Formula (I) or a pharmaceutically acceptable salt, ester, or solvate thereof, or their stereoisomers, which can be used as tyrosine kinase inhibitor. Also disclosed is a method for preparing the compound, a pharmaceutical composition and a kit comprising the compound, and uses of the compound. The compound can be used as tyrosine kinase inhibitor, or can be used to reduce or inhibit activity of EGFR or mutant thereof, such as EGFR mutant comprising T790M mutation, in a cell, or to treat and/or prevent a disease associated with overactivity of EGFR, such as cancer.
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Paragraph 0449-0450
(2017/05/15)
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- NOVEL NUCLEOSIDE TRANSPORT INHIBITORS
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Compounds or compositions that are inhibitors and/or ligands of nucleoside transporters; and methods of treating cancer, heart disease and stroke, as well as AIDS and other infectious diseases
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Page/Page column 15
(2008/06/13)
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- Synthesis and flow cytometric evaluation of novel 1,2,3,4-tetrahydroisoquinoline conformationally constrained analogues of nitrobenzylmercaptopurine riboside (NBMPR) designed for probing its conformation when bound to the es nucleoside transporter
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Novel regioisomers of conformationally constrained analogues of the potent es nucleoside transporter ligand, nitrobenzylmercaptopurine riboside (NBMPR), designed for probing its bound (bioactive) conformation, were synthesized and evaluated as es transporter ligands by flow cytometry. Purine 6-position 5, 6, 7, or 8-nitro-1,2,3,4-tetrahydroisoquinolylpurine ribosides, in which the nitrobenzyl moiety in NBMPR has been locked into the nitro-1,2,3,4-tetrahydroisoquinoline system, were synthesized by reaction of the appropriate nitro-1,2,3,4-tetrahydroisoquinoline with 6-chloropurine riboside. Flow cytometry was performed using 5-(SAENTA)-X8-fluorescein as the competitive ligand. A high degree of variation in the es transporter binding capacity of the target compounds was observed, with the Ki values ranging from 0.45 nM for the most tightly bound compound (4) to 300 nM for the least tightly bound compound (5). The Ki of NBMPR was 0.70 nM, a little higher than that of compound 4. Compound 4 is the isomer that has the nitro group in the best orientation at the es transporter binding site compared to the other three compounds, 2, 3, and 5.
- Zhu, Zhengxiang,Furr, John,Buolamwini, John K.
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p. 831 - 837
(2007/10/03)
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