17355-19-0Relevant articles and documents
Anti-trypanosomal activity of non-peptidic nitrile-based cysteine protease inhibitors
Burtoloso, Antonio C. B.,de Albuquerque, Sérgio,Furber, Mark,Gomes, Juliana C.,Gon?alez, Cristiana,Kenny, Peter W.,Leit?o, Andrei,Montanari, Carlos A.,Quilles, José Carlos,Ribeiro, Jean F. R.,Rocha, Josmar R.
, (2017)
The cysteine protease cruzipain is considered to be a validated target for therapeutic intervention in the treatment of Chagas disease. Anti-trypanosomal activity against the CL Brener strain of T. cruzi was observed in the 0.1 μM to 1 μM range for three nitrile-based cysteine protease inhibitors based on two scaffolds known to be associated with cathepsin K inhibition. The two compounds showing the greatest potency against the trypanosome were characterized by EC50values (0.12 μM and 0.25 μM) that were an order of magnitude lower than the corresponding Kivalues measured against cruzain, a recombinant form of cruzipain, in an enzyme inhibition assay. This implies that the anti-trypanosomal activity of these two compounds may not be explained only by the inhibition of the cruzain enzyme, thereby triggering a putative polypharmacological profile towards cysteine proteases.
Rapid Syntheses of (?)-FR901483 and (+)-TAN1251C Enabled by Complexity-Generating Photocatalytic Olefin Hydroaminoalkylation
Reich, Dominik,Trowbridge, Aaron,Gaunt, Matthew J.
supporting information, p. 2256 - 2261 (2020/01/24)
We report a common strategy to facilitate the syntheses of the polycyclic alkaloids (?)-FR901483 (1) and (+)-TAN1251C (2). A divergent synthetic strategy provides access to both natural products through a pivotal spirolactam intermediate (3), which can be accessed on a gram-scale. A photocatalytic olefin hydroaminoalkylation brings together three readily available building blocks and forges the majority of the carbon framework present in 1 and 2 in a single operation, leading to concise total syntheses. The complexity-generating photocatalytic process also provides direct access to novel non-racemic spirolactam scaffolds that are likely to be of interest to early-stage drug discovery programs.
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.
MODULATORS OF REV-ERB
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Page/Page column 120, (2015/07/16)
The subject matter herein concerns the identification and development of potent synthetic REV-ERB ligands, such as in vivo agonists and antagonists. These compounds allow for characterization of the effects of modulation of this receptor in vivo specifically on circadian behavior and metabolism, and have suitable characteristics for development of medicinal compounds useful for treatment of malconditions such as diabetes, obesity, atherosclerosis, dyslipidemia, a circadian rhythm disorder, coronary artery disease, bipolar disorder, depression, cancer, a sleep disorder, an anxiety disorder, an addiction disorder, a bone-related disorder such osteoporosis, a skeletal muscle disease, e.g., with compromised exercise capacity, or an autoimmune disorder such as psoriasis, multiple sclerosis, inflammatory bowel disease, and others.
OXOAZETIDINE DERIVATIVES, PROCESS FOR THE PREPARATION THEREOF AND USE THEREOF IN HUMAN MEDICINE AND IN COSMETICS
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Page/Page column 56, (2010/06/11)
The present invention relates to novel compounds derived from oxoazetidine corresponding to general formula (I) to the compositions containing same, to the process for preparation thereof and to the use thereof in pharmaceutical or cosmetic compositions.
MELANOCORTIN RECEPTOR ANTAGONIST COMPOUNDS, PROCESS FOR PREPARING THEM AND USE THEREOF IN HUMAN MEDICINE AND COSMETICS
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Page/Page column 23, (2010/06/11)
The present invention relates to novel melanocortin receptor antagonist compounds corresponding to the general formula (I) below, to compositions containing them, to the process for preparing them and to their use in pharmaceutical or cosmetic compositions.
MELANOCORTIN RECEPTOR MODULATORS, PROCESS FOR PREPARING THEM AND USE THEREOF IN HUMAN MEDICINE AND COSMETICS
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Page/Page column 42-43, (2010/06/11)
The present invention relates to novel melanocortin receptor modulators corresponding to the general formula (I) to compositions containing them, to the process for preparing them and to their use in pharmaceutical or cosmetic compositions.
Total synthesis of (-)-apratoxin A, 34-epimer, and its oxazoline analogue
Numajiri, Yoshitaka,Takahashi, Takashi,Doi, Takayuki
experimental part, p. 111 - 125 (2010/07/06)
A concise and convergent total synthesis of the highly cytotoxic marine natural product apratoxin A is accomplished by an 18-step linear sequence. The high sensitivity of the thiazoline, bearing an adjacent β-hydroxyl group at the C35-position, results in
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.
RCM approach for the total synthesis of cryptophycin-24 (Arenastatin A)
Tripathy, Narendra K.,Georg, Gunda I.
, p. 5309 - 5311 (2007/10/03)
An efficient total synthesis of cryptophycin-24 (arenastatin A) is reported, which features two novel synthetic strategies, the use of a RCM reaction to form the macrocycle, and the introduction of the styrene epoxide moiety prior to the macrocyclization