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.
Iodide/H2O2 catalyzed intramolecular oxidative amination for the synthesis of 3,20-pyrrolidinyl spirooxindoles
Gao, Yu-Ting,Jin, Xiao-Yang,Liu, Qi,Liu, An-Di,Cheng, Liang,Wang, Dong,Liu, Li
supporting information, (2018/09/12)
An ammonium iodide/hydrogen peroxide-mediated intramolecular oxidative amination of 3-aminoalkyl-2-oxindoles was achieved, affording the corresponding 3,20-pyrrolidinyl spirooxindoles and their 6- or 7-membered analogous in moderate to high yields. This metal-free procedure features very mild reaction conditions, non-toxicity and easily handled hydrogen peroxide as a clean oxidant.
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.
Syntheses of strychnine, norfluorocurarine, dehydrodesacetylretuline, and valparicine enabled by intramolecular cycloadditions of Zincke aldehydes
Martin, David B. C.,Nguyen, Lucas Q.,Vanderwal, Christopher D.
experimental part, p. 17 - 46 (2012/02/04)
A full account of the development of the base-mediated intramolecular Diels-Alder cycloadditions of tryptamine-derived Zincke aldehydes is described. This important complexity-generating transformation provides the tetracyclic core of many indole monoterpene alkaloids in only three steps from commercially available starting materials and played a key role in short syntheses of norfluorocurarine (five steps), dehydrodesacetylretuline (six steps), valparicine (seven steps), and strychnine (six steps). Reasonable mechanistic possibilities for this reaction, a surprisingly facile dimerization of the products, and an unexpected cycloreversion to regenerate Zincke aldehydes under specific conditions are also discussed.
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.
Tyrosine Kinase Inhibitors. 2. Synthesis of 2,2'-Dithiobis(iH-indole-3-alkanamides) and Investigation of Their Inhibitory Activity against Epidermal Growth Factor Receptor and pp60v-src Protein Tyrosine Kinases
Thompson, Andrew M.,Fry, David W.,Kraker, Alan J.,Denny, William A.
, p. 598 - 609 (2007/10/02)
A series of amide analogues of the 2,2'-dithiobis(1H-indole-3-alkanoic acid) class of tyrosine kinase inhibitors have been prepared, by reaction of 1H-indole-3-alkanamides (8) with S2Cl2, and separation of the desired disulfides from the initial mixtures of mono-, di-, and trisulfides formed. These amides were evaluated in vitro against epidermal growth factor receptor and pp60v-src protein tyrosine kinases. Inhibitory activity against EGF receptor tyrosine kinase was chain-length dependent, with the propanamides being the most effective. Hydrogen bond donor capabilities in the amide function did not appear to be necessary, with an N-benzylamide being the most potent (IC50 = 0.85 μM). Further substitution on the benzyl ring did not increase potency, and substitution in the α-position of the propanamide side chain was acceptable. A water-soluble α-NH2 derivative showed good inhibitory activity toward the enzyme, was a potent inhibitor of cell growth in fibroblasts, and selectively inhibited intracellular tyrosine phosphorylation patterns. The nonreceptor kinase pp60v-src was in general much more sensitive than EGF receptor kinase to inhibition by these compounds, but with less pronounced structure-activity relationships.
