120125-44-2Relevant academic research and scientific papers
Design, synthesis, and screen of cathepsin K inhibitors
Yu, Ying-Ying,Sun, Wei,Dong, Lei,Liu, Hai-Dong,Jiang, Dan,Xiao, Jun-Hai,Yang, Xiao-Hong,Li, Song
, p. 715 - 718 (2013)
We synthesized a series of epoxysuccinic acid derivatives and evaluated their in vitro cathepsin K inhibitory activity The screening results show that the potency of compounds 9e, 9d, 9p, 9j and 9k (IC50 ≤ 0.005 μmol/L) were equal to or greater than that of the lead compound 9a. Less hydrophobic compounds showed weaker potency, which can be explained by the hydrophobic nature of the cathepsin K binding pockets.
Synthesis of N-protected α-amino aldehydes from their morpholine amide derivatives
Douat, Céline,Heitz, Annie,Martinez, Jean,Fehrentz, Jean-Alain
, p. 37 - 40 (2000)
A new method for the synthesis of N-protected α-amino aldehydes was developed. N-Protected α-amino amides of morpholine were easily prepared and then reduced with LiAlH4 to produce clean N-protected α-amino aldehydes. This new scheme of synthesis can be used with Boc, Z and Fmoc amino-protecting groups.
An Efficient Greener Approach for N-acylation of Amines in Water Using Benzotriazole Chemistry
Ibrahim, Tarek S.,Seliem, Israa A.,Panda, Siva S.,Al-Mahmoudy, Amany M.M.,Abdel-Samii, Zakaria K.M.,Alhakamy, Nabil A.,Asfour, Hani Z.,Elagawany, Mohamed
, (2020/06/17)
A straightforward, mild and cost-efficient synthesis of various arylamides in water was accomplished using versatile benzotriazole chemistry. Acylation of various amines was achieved in water at room temperature as well as under microwave irradiation. The developed protocol unfolds the synthesis of amino acid aryl amides, drug conjugates and benzimidazoles. The environmentally friendly synthesis, short reaction time, simple workup, high yields, mild conditions and free of racemization are the key advantages of this protocol.
Cytotoxic activity of synthetic chiral amino acid derivatives
de Castro, Pedro P.,Siqueira, Raoni P.,Conforte, Luiza,Franco, Chris H.J.,Bressan, Gustavo C.,Amarante, Giovanni W.
, p. 193 - 200 (2019/12/28)
Cancer is a chronic degenerative disease considered one of the most important causes of death worldwide. In this context, a series of dual-protected amino acid derivatives was synthesized and evaluated as potential novel anticancer agents. The 40 derivatives were prepared in up to three reaction steps. The cytotoxic activities were screened in vitro against a panel of tumor and non-tumor cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Among the synthesized derivatives, three of them showed promising activity against cancer cells with half-maximal inhibitory concentration (IC50) ranging between 1.7-6.1 μM. The most promising derivative, bearing both a lipophilic N-alkyl diamine moiety and a protected amino acid scaffold showed a selectivity index of 3.4 towards tumor cells. The N-alkyl diamine moiety seems to play a crucial role in the enhancement of the anticancer activity. On the other hand, the incorporation of an amino acid scaffold resulted in increase in the selectivity towards cancer cell lines.
A practical catalytic reductive amination of carboxylic acids
Andrews, Keith G.,Denton, Ross M.,Hirst, David J.,Stoll, Emma L.,Tongue, Thomas,Valette, Damien
, p. 9494 - 9500 (2020/10/02)
We report reductive alkylation reactions of amines using carboxylic acids as nominal electrophiles. The two-step reaction exploits the dual reactivity of phenylsilane and involves a silane-mediated amidation followed by a Zn(OAc)2-catalyzed amide reduction. The reaction is applicable to a wide range of amines and carboxylic acids and has been demonstrated on a large scale (305 mmol of amine). The rate differential between the reduction of tertiary and secondary amide intermediates is exemplified in a convergent synthesis of the antiretroviral medicine maraviroc. Mechanistic studies demonstrate that a residual 0.5 equivalents of carboxylic acid from the amidation step is responsible for the generation of silane reductants with augmented reactivity, which allow secondary amides, previously unreactive in zinc/phenylsilane systems, to be reduced.
Dual-protected amino acid derivatives as new antitubercular agents
de Castro, Pedro P.,Campos, Débora L.,Pavan, Fernando R.,Amarante, Giovanni W.
, p. 1576 - 1580 (2018/06/06)
Tuberculosis is an infectious disease with high incidence and growing drug-resistant rates. In an attempt to develop new antitubercular agents, 35 compounds were synthesized, most of them bearing a carbamate and enantiopure amino acid moiety. These compounds had their activity evaluated toward a Mycobacterium tuberculosis strain (ATCC 27294) and cytotoxicity against fibroblast MRC-5 cells (ATCC CCL-171). Three of the prepared derivatives presented a good antimicrobial inhibition and two of them a moderate cytotoxicity. The lipophilicity seems to play a vital role in the cell growth activity, with best results for the derivatives with a higher logP.
Access to enantiomerically enriched cis-2,3-disubstituted azetidines via diastereoselective hydrozirconation
Pradhan, Tarun K.,Krishnan, K. Syam,Vasse, Jean-Luc,Szymoniak, Jan
supporting information; experimental part, p. 1793 - 1795 (2011/06/19)
An asymmetric variant of the hydrozirconation reaction has been established starting from Boc-protected chiral allylic amines. The resulting diastereoselectively formed N-functionalized organozirconiums can be considered as promising chirons. In this case
Aminocarbonyloxymethyl ester prodrugs of flufenamic acid and diclofenac: Suppressing the rearrangement pathway in aqueous media
Ribeiro, Lina,Silva, Nuno,Iley, Jim,Rautio, Jarkko,Jaervinen, Tomi,Mota-Filipe, Helder,Moreira, Rui,Mendes, Eduarda
, p. 32 - 40 (2007/10/03)
Aminocarbonyloxymethyl ester prodrugs are known to undergo rearrangement in aqueous solutions to form the corresponding N-acylamine side product via an O → N intramolecular acyl transfer from the carbamate conjugate base. Novel aminocarbonyloxymethyl esters of diclofenac and flufenamic acid containing amino acid amide carriers were synthesized and evaluated as potential prodrugs displaying less ability to undergo rearrangement. These compounds were prepared in reasonable yield by a four-step synthetic method that uses the appropriate N-Boc-protected amino acid N-hydroxysuccinimide ester and secondary amine and chloromethyl chloroformate as key reactants. Their reactivity in pH 7.4 buffer and 80% human plasma at 37°C was assessed by RP-HPLC. The aminocarbonyloxymethyl esters containing a secondary carbamate group derived from amino acids such as glycine or phenylalanine were hydrolyzed quantitatively to the parent drug both in non-enzymatic and enzymatic conditions, with no rearrangement product being detected. The oral bioavailability in rats was determined for selected diclofenac derivatives. These derivatives displayed a bioavailability of 25 to 68% relative to that of diclofenac, probably due to their poor aqueous solubility and lipophilicity. These results suggest that further optimization of aminocarbonyloxymethyl esters as potential prodrugs for non-steroidal anti-inflammatory drugs require the use of amino acid carriers with ionizable groups to improve aqueous solubility.
Efficient transamidation of primary carboxamides by in situ activation with N,N-dialkylformamide dimethyl acetals
Dineen, Thomas A.,Zajac, Matthew A.,Myers, Andrew G.
, p. 16406 - 16409 (2007/10/03)
Two protocols for the transamidation of primary amides with primary and secondary amines, forming secondary and tertiary amides, respectively, are described. Both processes employ N,N-dialkylformamide dimethyl acetals for primary amide activation, producing N-acyl-N,N-dialkylformamidines as intermediates, as widely documented in the literature. Although the latter intermediates react irreversibly with amines by amidinyl transfer, we show that in the presence of certain Lewis acid additives efficient acyl transfer occurs, providing new and useful methods for amide exchange. In one protocol for transamidation, the N-acyl-N,N-dialkylformamidine intermediates are purified by flash-column chromatography and the purified intermediates are then treated with an amine (typically, 2.5 equiv) in the presence of scandium triflate (10 mol %) in ether to form in high yields the products of transamidation. In a second procedure, N-acyl-N,N-dialkylformamidines are generated in situ and, without isolation, are subjected to transamidation in the presence of zirconium chloride (0.5 equiv) and an amine (typically 2 equiv). A variety of different primary amides and amines are found to undergo efficient transamidation using the methods described.
Enantioselective addition of vinylzinc reagents to 3,4-dihydroisoquinoline N-oxide
Wang, Sa,Seto, Christopher T.
, p. 3979 - 3982 (2007/10/03)
Ligand 2a promotes the enantioselective addition of vinylzinc reagents to 3,4-dihydroisoquinoline N-oxide to yield chiral allylic hydroxylamines. With 0.1 equiv of the ligand, the product is obtained in up to 84% ee, whereas with 1.2 equiv of the ligand,
