880361-72-8Relevant articles and documents
Design, Synthesis, and Pharmacological Evaluation of Second-Generation Tetrahydroisoquinoline-Based CXCR4 Antagonists with Favorable ADME Properties
Nguyen, Huy H.,Kim, Michelle B.,Wilson, Robert J.,Butch, Christopher J.,Kuo, Katie M.,Miller, Eric J.,Tahirovic, Yesim A.,Jecs, Edgars,Truax, Valarie M.,Wang, Tao,Sum, Chi S.,Cvijic, Mary E.,Schroeder, Gretchen M.,Wilson, Lawrence J.,Liotta, Dennis C.
, p. 7168 - 7188 (2018)
CXCR4 is a G-protein-coupled receptor that interacts with its cognate ligand, CXCL12, to synchronize many physiological responses and pathological processes. Disruption of the CXCL12-CXCR4 circuitry by small-molecule antagonists has emerged as a promising strategy for cancer intervention. We previously disclosed a hit-to-lead effort that led to the discovery of a series of tetrahydroisoquinoline-based CXCR4 antagonists exemplified by the lead compound TIQ15. Herein, we describe our medicinal-chemistry efforts toward the redesign of TIQ15 as a result of high mouse-microsomal clearance, potent CYP2D6 inhibition, and poor membrane permeability. Guided by the in vitro ADME data of TIQ15, structural modifications were executed to provide compound 12a, which demonstrated a reduced potential for first-pass metabolism while maintaining CXCR4 potency. Subsequent SAR studies and multiparameter optimization of 12a resulted in the identification of compound 25o, a highly potent, selective, and metabolically stable CXCR4 antagonist possessing good intestinal permeability and low risk of CYP-mediated drug-drug interactions.
Base-Promoted Tandem Synthesis of 2-Azaaryl Tetrahydroquinolines
Chen, Shuguang,Yang, Langxuan,Shang, Yongjia,Mao, Jianyou,Walsh, Patrick J.
supporting information, p. 1594 - 1599 (2021/03/08)
A novel method to synthesize 2-azaaryl tetrahydroquinolines by the base-promoted tandem reaction of azaaryl methyl amines and styrene derivatives is reported (over 30 examples, yields up to 95%). Mechanistic probe experiments demonstrate that the deprotonation of the benzylic C-H bond and the addition to the styrene vinyl group proceeds via the SNAr mechanism.
CHEMOKINE CXCR4 RECEPTOR MODULATORS AND USES RELATED THERETO
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Page/Page column 103, (2018/09/19)
The disclosure relates to chemokine CXCR4 receptor modulators and uses related thereto. The receptor modulators can be formulated to form pharmaceutical compositions comprising the disclosed compounds or pharmaceutically acceptable salts or prodrugs thereof. The compositions may be used for managing CXCR4 related conditions, typically prevention or treatment of viral infections abnormal cellular proliferation, retinal degeneration, inflammatory diseases, or as an immunostimulant or immunosuppressant or for managing cancer and may be administered with another active ingredient such as an antiviral agent or chemotherapeutic agent.
Multi-substituted amine compound and its preparation and use (by machine translation)
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Paragraph 0284-0288, (2018/04/27)
The invention belongs to the field of medical technology, in particular, the present invention provides the following formula I shown multi-substituted amine compound or its isomer or its pharmaceutically acceptable salt, ester, prodrug or hydrate, its pharmaceutical composition, preparation method thereof and its use in the preparation of medicine for treating aids in use. The compound or pharmaceutical composition containing the compound can be used as an inhibitor for inhibiting HIV integrase with LEDGF/p75 between protein - protein interaction and HIV integrase dimerization, then can be used for the treatment of aids. . (by machine translation)
