2901-79-3Relevant academic research and scientific papers
N-Benzoyl amino acids as ICAM/LFA-1 inhibitors. Part 2: Structure-activity relationship of the benzoyl moiety
Burdick, Daniel J.,Marsters Jr., James C.,Aliagas-Martin, Ignacio,Stanley, Mark,Beresini, Maureen,Clark, Kevin,McDowell, Robert S.,Gadek, Thomas R.
, p. 2055 - 2059 (2004)
o-Bromobenzoyl L-tryptophan 1 inhibits the association of LFA-1 with ICAM-1 with an IC50 of 1.7μM. Evaluation of the structure-activity relationship of the benzoyl moiety shows that 2,6-di-substitutions greatly enhance potency of this class of inhibitors. Electronegative substitutions that favor a 90°angle between the benzoyl ring and the amide bond yield the most potent compounds. There is a strong correlation between the potency of the compounds and the difference between the ab initio energy at 90°and the global minima energy for given compounds. Combining the favored benzoyl substitutions with L-histidine and L-asparagine resulted in a 15-fold increase in potency over compound 1.
A Facile Approach to the Synthesis of Benzothiazoles from N-Protected Amino Acids
Arfan, M.,Fatima, T.,Mannan, A.,Tahira, A.
, p. 292 - 297 (2020/04/21)
Abstract: –A simple trituration method for the synthesis of 2-substituted benzothiazoles derived from N-protected amino acids and 2-aminothiophenol using molecular iodine as a mild Lewis acid catalyst has been proposed. The reaction occurs in one step for 20–25 min in solve-free conditions and provides the target products in excellent yields.
On the intrinsic reactivity of highly potent trypanocidal cruzain inhibitors
Batista, Pedro Henrique Jatai,Bonatto, Vinicius,Cedron, Rodrigo,Cianni, Lorenzo,De Vita, Daniela,Franco, Caio Haddad,Montanari, Carlos A.,Moraes, Carolina Borsoi,Silva, Daniel G.,Tezuka, Daiane Y.,De Albuquerque, Sérgio,Lameira, Jer?nimo,Leit?o, Andrei
supporting information, p. 1275 - 1284 (2020/12/01)
The cysteine protease cruzipain is considered to be a validated target for therapeutic intervention in the treatment of Chagas disease. Hence, peptidomimetic cruzipain inhibitors having a reactive group (known as warhead) are subject to continuous studies
Design, synthesis, and molecular docking studies of N-(9,10-anthraquinone-2-carbonyl)amino acid derivatives as xanthine oxidase inhibitors
Zhang, Ting-Jian,Li, Song-Ye,Yuan, Wei-Yan,Zhang, Yi,Meng, Fan-Hao
, p. 893 - 901 (2018/03/21)
A series of N-(9,10-anthraquinone-2-carbonyl)amino acid derivatives (1a–j) was designed and synthesized as novel xanthine oxidase inhibitors. Among them, the L/D-phenylalanine derivatives (1d and 1i) and the L/D-tryptophan derivatives (1e and 1j) were effective with micromolar level potency. In particular, the L-phenylalanine derivative 1d (IC50?=?3.0?μm) and the D-phenylalanine derivative 1i (IC50?=?2.9?μm) presented the highest potency and were both more potent than the positive control allopurinol (IC50?=?8.1?μm). Preliminary SAR analysis pointed that an aromatic amino acid fragment, for example, phenylalanine or tryptophan, was essential for the inhibition; the D-amino acid derivative presented equal or greater potency compared to its L-enantiomer; and the 9,10-anthraquinone moiety was welcome for the inhibition. Molecular simulations provided rational binding models for compounds 1d and 1i in the xanthine oxidase active pocket. As a result, compounds 1d and 1i could be promising lead compounds for further investigation.
Reactivity of α-Amino Acids in the Reaction with Esters in Aqueous–1,4-Dioxane Media
Kochetova,Kustova,Kuritsyn
, p. 80 - 85 (2018/03/09)
The kinetics of the reaction of a series of α-amino acids with 4-nitrophenyl acetate, 4-nitrophenyl benzoate, and 2,4,6-trinitrophenyl benzoate in aqueous 1,4-dioxane medium has been studied. Kinetics of the reactions involving 4-nitrophenyl acetate and 2,4,6-trinitrophenyl benzoate has complied with the Br?nsted dependence and revealed linear correlation between rate constant logarithm and the energy difference of the frontier orbitals of α-amino acids anions.
Synthesis and evaluation of oxindoles as promising inhibitors of the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1
Paul, Saurav,Roy, Ashalata,Deka, Suman Jyoti,Panda, Subhankar,Srivastava, Gopal Narayan,Trivedi, Vishal,Manna, Debasis
, p. 1640 - 1654 (2017/08/22)
Indoleamine 2,3-dioxygenase 1 (IDO1) is considered as an important therapeutic target for the treatment of cancer, chronic infections and other diseases that are associated with immune suppression. Recent developments in understanding the catalytic mechanism of the IDO1 enzyme revealed that conversion of l-tryptophan (l-Trp) to N-formylkynurenine proceeded through an epoxide intermediate state. Accordingly, we synthesized a series of 3-substituted oxindoles from l-Trp, tryptamine and isatin. Compounds with C3-substituted oxindole moieties showed moderate inhibitory activity against the purified human IDO1 enzyme. Their optimization led to the identification of potent compounds, 6, 22, 23 and 25 (IC50 = 0.19 to 0.62 μM), which are competitive inhibitors of IDO1 with respect to l-Trp. These potent compounds also showed IDO1 inhibition potencies in the low-micromolar range (IC50 = 0.33-0.49 μM) in MDA-MB-231 cells. The cytotoxicity of these potent compounds was trivial in different model cancer (MDA-MB-231, A549 and HeLa) cells and macrophage (J774A.1) cells. Stronger selectivity for the IDO1 enzyme (124 to 210-fold) over the tryptophan 2,3-dioxygenase (TDO) enzyme was also observed for these compounds. These results suggest that the oxindole moiety of the compounds could mimic the epoxide intermediate state of l-Trp. Therefore, the structural simplicity and low-micromolar inhibition potencies of these 3-substituted oxindoles make them quite attractive for further investigation of IDO1 function and immunotherapeutic applications.
COMPOUNDS FOR THE TREATMENT OF ARENAVIRUS INFECTION
-
Page/Page column 133, (2017/03/14)
The present invention relates to the use of piperazinones for inhibiting arenavirus infection in humans, other mammals, or in cell culture, to methods of treating arenavirus infection such as Lassa, Bolivian, Argentine, Venezuelan, Brazilian, Chapare and
FPR1 ANTAGONIST DERIVATIVES AND USE THEREOF
-
Paragraph 0073-0076, (2015/11/16)
A dipeptide derivative as formyl peptide receptor 1 (FPR1) antagonist is provided. The dipeptide derivative is represented by formula (I), wherein: the chiral centers in formula (I) are S and R configurations respectively; each of RK and RT is selected from a group consisting of a hydrogen, a hydroxyl group, a C1-C4 alkyl-substituted hydroxyl group, a C1-C4 alkoxyl group, a carboxylic acid group, a C1-C4 alkyl nitrile-substituted, C1-C4 alkyl-substituted or C1-C4 alkoxyl-substituted amido group, a C1-C4 alkyl-substituted ester group and a benzoyl group having a C1-C4 alkyl-substituted benzene ring; and each of RM and RS is selected from a group consisting of a hydrogen, a hydroxyl group, a phenyl group, a pyridinyl group, a carboxylic acid group, a C1-C4 alkoxyl substituted ester group, and a benzoyl group having a hydroxyl-substituted, a halogen-substituted, a C1-C4 alkoxyl-substituted or a C1-C4 alkyl-substituted benzene ring.
Design and synthesis of tryptophan containing dipeptide derivatives as formyl peptide receptor 1 antagonist
Hwang, Tsong-Long,Hung, Chih-Hao,Hsu, Ching-Yun,Huang, Yin-Ting,Tsai, Yu-Chi,Hsieh, Pei-Wen
, p. 3742 - 3755 (2013/06/27)
Our previous studies identified an Fmoc-(S,R)-tryptophan-containing dipeptide derivative, 1, which selectively inhibited neutrophil elastase release induced by formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP) in human neutrophils. In an attempt to improve pharmacological activity, a series of tryptophan-containing dipeptides were synthesized and their pharmacological activities were investigated in human neutrophils. Of these, five compounds 3, 6, 19a, 24a, and 24b exhibited potent and dual inhibitory effects on FMLP-induced superoxide anion (O2-) generation and neutrophil elastase release in neutrophils with IC50 values of 0.23/0.60, 1.88/2.47, 1.87/3.60, 0.12/0.37, and 1.32/1.03 μM, respectively. Further studies indicated that inhibition of superoxide production in human neutrophils by these dipeptides was associated with the selective inhibition of formyl peptide receptor 1 (FPR1). Furthermore, the results of structure-activity relationship studies concluded that the fragment N-benzoyl-Trp-Phe-OMe (3) was most suitable as a core structure for interaction with FPR1, and may be approved as a lead for the development of new drugs in the treatment of neutrophilic inflammatory diseases. As some of the synthesized compounds exhibited separable conformational isomers, and showed diverse bioactivities, the conformation analysis of these compounds is also discussed herein. The Royal Society of Chemistry 2013.
Synthesis, characterization, and cytotoxicity of complexes of platinum(u) with 2,2'-bipyridine and N-benzoyl-L-amino acid dianion
Zhang, Jinchao,Zhang, Fangfang,Wang, Liwei,Du, Jianlong,Wang, Shuxiang,Li, Shenghui
experimental part, p. 2159 - 2169 (2012/09/07)
Four new platinum(II) complexes (1-4) with N-benzoyl-L-amino acid and bipy were synthesized and characterized by elemental analysis, IR, UV, 1H NMR, and mass spectra. The crystal structure of 1 was determined by X-ray diffraction analysis. Cytotoxicities were measured by MTT and SRB assays. Complexes 1-4 exert cytotoxicity with selectivity against HL-60, Bel-7402, BGC-823, and KB cell lines. This suggests that amino acids and acylated groups have important effects on cytotoxicity; the cytotoxicity is also related to the species of tumor cells, but the IC50 values do not show definite correlation with the variation of amino acids and acylated groups.
