121778-71-0Relevant articles and documents
Synthesis of Water-Soluble Chiral DOTA Lanthanide Complexes with Predominantly Twisted Square Antiprism Isomers and Circularly Polarized Luminescence
Dai, Lixiong,Zhang, Junhui,Chen, Yuqing,Mackenzie, Lewis E.,Pal, Robert,Law, Ga-Lai
supporting information, p. 12506 - 12510 (2019/10/02)
One-step cyclization of a tetraazamacrocycle 5 with 70% yield in a 25-g scale was performed. Its chiral DOTA derivatives, L4, has ?93% of TSAP coordination isomer in its Eu(III) and Yb(III) complexes in aqueous solution. [GdL4]5- exhibits a high relaxivity, making it a promising and efficient MRI contrast agent. High luminescence dissymmetry factor (glum) values of 0.285 (ΔJ = 1) for [TbL3]- and 0.241 (ΔJ = 1) for [TbL4]5- in buffer solutions were recorded.
CHIRAL CYCLEN COMPOUNDS AND THEIR USES
-
Paragraph 0091; 0194, (2018/04/13)
The present invention relates to the preparation of a series of chiral DOTA, D03A, D02A, DO1A, cyclen and their metal complexes, which display properties superior to those of previous DOTA- based compounds, and hence are potentially valuable as a platform for diagnostic applications. The chiral DOTAs reveal a high abundance of twisted square antiprism (TSA) geometry favoring them to be used as potential MRI contrast agents, whereas their rapid labelling properties at mild conditions make them excellent candidates for use as radiometal chelators.
Synthesis, bioactivity, docking and molecular dynamics studies of furan-based peptides as 20s proteasome inhibitors
Sun, Qi,Xu, Bo,Niu, Yan,Xu, Fengrong,Liang, Lei,Wang, Chao,Yu, Jiapei,Yan, Gang,Wang, Wei,Jin, Hongwei,Xu, Ping
, p. 498 - 510 (2015/03/18)
Proteasome inhibitors are promising compounds for a number of therapies, including cardiovascular and eye diseases, diabetes, and cancers. We previously reported a series of furanbased peptidic inhibitors with moderate potencies against the proteasome b5 subunit, hypothesizing that the C-terminal furyl ketone motif could form a covalent bond with the catalytic residue, threonine 1. In this context, we describe further optimizations of the furan-based peptides, and a series of dipeptidic and tripeptidic inhibitors were designed and synthesized, aiming at improved potency and better solubility. Most of the tripeptidic inhibitors demonstrated improved potency and selectivity as b5 subunit inhibitors in both enzymatic and cellular assays, and good antineoplastic activities in various tumor cell lines were also observed. However, no inhibitory effects were observed for the dipeptidic compounds, which led us to presume that a noncovalent binding mode is adopted. Docking studies and molecular dynamics simulations were carried out to verify this presumption, with results showing that the distance between the furyl ketone motif and Thr1 is slightly too long to form covalent bond.
Structural and initial biological analysis of synthetic arylomycin A 2
Roberts, Tucker C.,Smith, Peter A.,Cirz, Ryan T.,Romesberg, Floyd E.
, p. 15830 - 15838 (2008/09/19)
The growing threat of untreatable bacterial infections has refocused efforts to identify new antibiotics, especially those acting by novel mechanisms. While the inhibition of pathogen proteases has proven to be a successful strategy for drug development,
Total synthesis of TMC-95A and -B via a new reaction leading to Z-enamides. Some preliminary findings as to SAR
Lin, Songnian,Yang, Zhi-Qiang,Kwok, Benjamin H. B.,Koldobskiy, Michael,Crews, Craig M.,Danishefsky, Samuel J.
, p. 6347 - 6355 (2007/10/03)
A full account of the total syntheses of proteasome inhibitors TMC-95A and -B is provided. A key feature of the syntheses involved installation of a cis-propenylamide moiety by a thermal rearrangement of an α-silylallyl amide. The scope and mechanism of the enamide-forming reaction are discussed. Also provided are some preliminary results from SAR studies. It was found that simplified analogues can retain the full potency of proteasome inhibition.
Synthesis and biological activity of new potential agonists for the human adenosine A2A receptor
Bosch, M. Pilar,Campos, Francisco,Niubó, Itziar,Rosell, Gloria,Díaz, J. Luis,Brea,Loza, M. Isabel,Guerrero, Angel
, p. 4041 - 4053 (2007/10/03)
New adenosine derivatives have been synthesized and tested as putative agonists of adenosine receptors. Compounds 2-6 derive from the introduction of several types of substituents (electron donating, electron withdrawing, and halogens) in the para-position of the phenyl ring of the parent compound 1, and compound 7 lacks the hydroxyl group of amino alcohol 1. In radioligand binding assays using recombinant human A1, A2A, A2B, and A3 receptors, all compounds showed very low or negligible affinity for A1 and A2B receptors but compounds 3, 5, and 7 displayed a remarkably potent affinity for the A2A receptor with Ki values of 1-5 nM. Bromo derivative 3 displayed a selectivity A1/A2A = 62 and A3/A2A = 16 whereas the presence of a hydroxyl group (compound 5) improved the selectivity of A 1/A2A and A3/A2A to 120- and 28-fold, respectively. When the methoxy derivative 4 lacks the hydroxyl group on the side chain (compound 7), the binding affinity for A2A is increased to 1 nM, improving selectivity ratios to 356- and 100-fold against A1 and A3, respectively. In Chinese hamster ovary cells transfected with human A2A and A2B receptors, most compounds showed a remarkable activity for the A2A receptor, except chloro derivative 2, with EC50 values ranging from 1.4 to 8.8 nM. The compounds behaved as good A2A agonists, and all were more selective than 5′-(N-ethylcarboxamino)adenosine (NECA), with A2B/A 2A ratios of cAMP accumulation ranging from 48 for compound 2 to 666 for compound 7 while the corresponding A2B/A2A ratio for NECA was only 9. Compounds 1, 3, 5, and 7 also displayed higher selectivities than NECA up to 100-fold in isolated aortas of rat and guinea pig. In guinea pig tracheal rings precontracted by carbachol, compounds 2 and 4 were more potent than adenosine (100-fold) and NECA (10-fold), whereas compounds I and 7 displayed similar effects to NECA. Pretreatment of the tracheal rings with A2, A2A, and A2B receptor antagonists 3,7-dimethyl-L-propargylxanthine, 8-(3-chlorostyryl)caffeine, and alloxazine produced a marked inhibition of the tracheal relaxations induced by compounds 1, 2, and 4, but none of the compounds showed selectivity toward any of the adenosine receptors.
HYDROXYMORPHOLINONE DERIVATIVE AND MEDICINAL USE THEREOF
-
Page 15, (2010/02/09)
A compound represented by the following formula (I) wherein R1 and R2 are each a lower alkyl group optionally having substituents, which has a calpain inhibitory activity, or a salt thereof is provided.
Syntheses of amino alcohols and chiral C2-symmetric bisoxazolines derived from O-alkylated R-4-hydroxyphenylglycine and S-tyrosine
Caplar, Vesna,Raza, Zlata,Katalenic, Darinka,Zinic, Mladen
, p. 23 - 36 (2007/10/03)
Chiral C2-symmetric bisoxazolines 1b-f and 2b,c, derived from 4′-O-alkylated R-4-hydroxyphenylglycine or S-tyrosine, were prepared. As intermediates, a series of chiral amino alcohols possessing substituted phenolic groups was prepared and fully characterized.
Novel 6-Hydroxy-3-morpholinones as cornea permeable calpain inhibitors
Nakamura, Masayuki,Miyashita, Hiroyuki,Yamaguchi, Masazumi,Shirasaki, Yoshihisa,Nakamura, Yoshikuni,Inoue, Jun
, p. 5449 - 5460 (2007/10/03)
A novel series of 6-hydroxy-3-morpholinones, in which the functional aldehyde and the hydroxy group of P2 site form a cyclic hemiacetal, was identified as calpain inhibitors. The placement of isobutyl group at the 2-position of the 3-morpholino
Synthesis of the functionalized macrocyclic core of proteasome inhibitors TMC-95A and B
Lin, Songnian,Danishefsky, Samuel J.
, p. 1967 - 1970 (2007/10/03)
An ordered assembly of four building blocks (2-5) forms the basis of the synthesis of 1, which contains the core structure of TMC-95A and B - two potent proteasome inhibitore (see scheme; TIPS = triisopropylsilyl, Cbz = benzoxycarbonyl, Boc = tert-Boc = tert-butoxycarbonyl).
