174180-72-4Relevant academic research and scientific papers
A new and efficient synthesis of 2-azatryptophans
Crestey, Fran?ois,Collot, Valérie,Stiebing, Silvia,Rault, Sylvain
, p. 7772 - 7775 (2006)
This paper describes a new and simple synthesis of 2-azatryptophans in five steps from 2-ethylaniline. This methodology allows to obtain either the amino acid or the amino ester, according to the treatment and the reaction time, and its scaling up for multigram synthesis.
Construction of 1H-indazoles from ortho-aminobenzoximes by the Mitsunobu reaction
Conlon, Ivie L.,Konsein, Katie,Morel, Yulemni,Chan, Alexandria,Fletcher, Steven
, (2019/08/22)
Recently, there has been an upsurge in the occurrence of the indazole motif in drug discovery. Accordingly, newer, milder and more efficient routes towards their synthesis have emerged in the literature. We recently reported the Mitsunobu-triggered cyclod
Inhibition of the Cysteine Protease Human Cathepsin L by Triazine Nitriles: Amide???Heteroarene π-Stacking Interactions and Chalcogen Bonding in the S3 Pocket
Giroud, Maude,Ivkovic, Jakov,Martignoni, Mara,Fleuti, Marianne,Trapp, Nils,Haap, Wolfgang,Kuglstatter, Andreas,Benz, J?rg,Kuhn, Bernd,Schirmeister, Tanja,Diederich, Fran?ois
supporting information, p. 257 - 270 (2017/02/15)
We report an extensive “heteroarene scan” of triazine nitrile ligands of the cysteine protease human cathepsin L (hCatL) to investigate π-stacking on the peptide amide bond Gly67–Gly68 at the entrance of the S3 pocket. This heteroarene???peptide bond stacking was supported by a co-crystal structure of an imidazopyridine ligand with hCatL. Inhibitory constants (Ki) are strongly influenced by the diverse nature of the heterocycles and specific interactions with the local environment of the S3 pocket. Binding affinities vary by three orders of magnitude. All heteroaromatic ligands feature enhanced binding by comparison with hydrocarbon analogues. Predicted energetic contributions from the orientation of the local dipole moments of heteroarene and peptide bond could not be confirmed. Binding of benzothienyl (Ki=4 nm) and benzothiazolyl (Ki=17 nm) ligands was enhanced by intermolecular C?S???O=C interactions (chalcogen bonding) with the backbone C=O of Asn66 in the S3 pocket. The ligands were also tested for the related enzyme rhodesain.
HIV reverse transcriptase inhibitors
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Page/Page column 50-51, (2010/11/25)
Compounds having the structure: are HIV reverse transcriptase inhibitors, wherein A, X, Y, Z, R1 and R2 are defined herein. The compounds and their pharmaceutically acceptable salts are useful in the inhibition of HIV reverse transcriptase, the prophylaxis and treatment of infection by HIV and in the prophylaxis, delay in the onset, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.
CCK or gastrin modulating benzo ?b!?1,4! diazepines derivatives
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, (2008/06/13)
Benzo?b!?1,4!diazepine compounds of formula (I), where R1 is selected from C1 C6 alkyl, C3 -C6 cycloalkyl, phenyl, or substituted phenyl; R2 is selected from C3 -C6 alkyl, C3 C6 cycloalkyl, C3 -C6 alkenyl, benzyl, phenylC1 -C3 alkyl of substituted phenyl; or NR1 R2 together form 1,2,3,4-tetrahydroquinoline or benzazepine, mono-, di-, or trisubstituted independently with C1-6 alkyl C1-6 alkoxy or halogen substituents; p is an integer 0 or 1; q is an integer 0 or 1; r is an integer 0 or 1; t is an integer 0 or 1, provided that when r is 0 then t is 0; R3, R5, and R6 are independently hydrogen or C1-6 alkyl; R4 is C1-6 alkyl or C1-6 alkenyl; R7 is selected from the group consisting of hydrogen, C1-6 alkyl, C1-6 cycloalkyl, C1-6 alkenyl, phenyl, substituted phenyl, napthyl, heteroaryl, substituted heteroaryl, bicycloheteroaryl or substituted bicycloheteroaryl; or NR6 R7 together form a saturated 5,6, or 7 membered ring optionally interrupted by 1,2,3 or 4 N, S or O heteroatoms, with the proviso that any two O or S atoms are not bonded to each other, m is an integer selected from the group of 0, 1, 2, 3 or 4; R8 and R9 are selected from a variety of substituents; Z is hydrogen or halogen; novel intermediates, a pharmaceutical composition for treating obesity, gall bladder stasis, disorders of pancreatic secretion, methods for such treatment and processes for preparing compounds of formula (I).
Optimization of 3-(1H-Indazol-3-ylmethyl)-1,5-benzodiazepines as potent, orally active CCK-A agonists
Henke, Brad R.,Aquino, Christopher J.,Birkemo, Larry S.,Croom, Dallas K.,Dougherty Jr., Robert W.,Ervin, Gregory N.,Grizzle, Mary K.,Hirst, Gavin C.,James, Michael K.,Johnson, Michael F.,Queen, Kennedy L.,Sherrill, Ronald G.,Sugg, Elizabeth E.,Suh, Edward M.,Szewczyk, Jerzy W.,Unwalla, Rayomand J.,Yingling, Jeff,Willson, Timothy M.
, p. 2706 - 2725 (2007/10/03)
We previously described a series of 3-(1H-indazol-3-ylmethyl)-1,5- benzodiazepine CCK-A agonists exemplified by compound 1 (GW 5823), which is the first reported binding selective CCK-A full agonist demonstrating oral efficacy in a rat feeding model. In this report we describe analogs of compound 1 designed to explore changes to the CS and N1 pharmacophores and their effect on agonist activity and receptor selectivity. Agonist efficacy in this series was affected by stereoelectronic factors within the C3 moiety. Binding affinity for the CCK-A vs CCK-B receptor showed little dependence on the structure of the C3 moiety but was affected by the nature of the second substituent at CS. Structure-activity relationships at the N1- anilidoacetamide 'trigger' moiety within the C3 indazole series were also investigated. Both agonist efficacy and binding affinity within this series were modulated by variation of substituents on the Nl-anilidoacetamide moiety. Evaluation of several analogs in an in vivo mouse gallbladder emptying assay revealed compound 1 to be the most potent and efficacious of all the analogs tested. The pharmacokinetic and pharmacodynamic profile of 1 in rats is also discussed.
