69397-87-1Relevant articles and documents
Discovery of a 3,4,5-trisubstituted-1,2,4-triazole agonist with high affinity and selectivity at the somatostatin subtype-4 (sst4) receptor
Daryaei, Iman,Sandoval, Karin,Witt, Ken,Kontoyianni, Maria,Michael Crider
supporting information, p. 2083 - 2090 (2019/01/04)
A series of compounds containing a 1,2,4-triazole moiety were synthesized, targeting the somatostatin receptor subtype-4 (sst4). Compounds were developed in which the Phe6/Phe7/Phe11, Trp8, and Lys9 mimetic groups were interchanged at positions 3, 4, and 5 of the 1,2,4-triazole ring. The 1,2,4-triazoles containing an 2-(imidazol-4-yl)ethyl substituent at position-3 demonstrated moderate binding affinity at sst4. 1,2,4-Triazoles containing an (indol-3-yl)methyl substituent at position-5 lacked affinity at sst4. The 1,2,4-triazoles containing an aminopropyl group at position-4 showed enhanced binding affinity compared to the 3-position. One compound with an 3-(imidazol-4-yl)propyl group at position-4 (compound 44) imparted high affinity and selectivity at sst4 (sst2A = >10000 nM; sst4 = 19 nM), acting as an agonist (EC50 = 6.8 nM). Docking 44 into a model-built structure of sst4 pointed to differences in its binding versus the other low-affinity compounds and was also in line with one of the two previously reported binding modes. A virtual screening (VS) experiment, employing two separate docking algorithms, was able to score 44 among the top-ranked poses. In summary, compound 44 represents a novel and promising lead structure towards the development of a clinically viable sst4 agonist for the treatment of conditions ranging from Alzheimer's disease to chronic pain.
Design, synthesis and activity evaluation of some novel indole derivatives
He, Dian,Yang, Zhu-Qing,Hou, Meng
, p. 1729 - 1734 (2015/03/04)
A series of novel indole derivatives as CDK4 inhibitors were designed and synthesized though the condensation reaction between the indolic acid and the corresponding substituted amine. The key step of our synthetic process is the efficient condensation reaction conducted by two different methods. The MTT and kinase assays were conducted used to assess the antitumor activity and cyclin-dependent kinases (CDKs) inhibitory activity. The most active compound 8b has an IC50 of 10-25 μM for the inhibition of four different tumor cells and CDK4. The higher activities of 8b were influenced by more conformational freedom resulted form the non-planar structure and by the stronger hydrogen bonding capability. Thus, the strategy we adapt to design potent, non-toxic CDK4 inhibitors is successful.
Enantioselective copper-catalyzed construction of aryl pyrroloindolines via an arylation-cyclization cascade
Zhu, Shaolin,MacMillan, David W. C.
, p. 10815 - 10818 (2012/08/07)
An enantioselective arylation-cyclization cascade has been accomplished using a combination of diaryliodonium salts and asymmetric copper catalysis. These mild catalytic conditions provide a new strategy for the enantioselective construction of pyrroloindolines, an important alkaloid structural motif that is commonly found among biologically active natural products.
