54322-10-0Relevant academic research and scientific papers
A facile synthesis of isotope labeled acylcarnitines
Dai, Xiaojun,Lv, Chao,Sun, Jianguo,Li, Shuwei
, p. 217 - 224 (2021)
Acylcarnitines are a big family of small molecule metabolites with various acyl groups attached to the hydroxyl moiety of l-carnitine. They are good indicators of multiple metabolic disorders. For instance, the newborn screening panel uses flow injection tandem mass spectrometry to analyze more than 30 different acylcarnitines and amino acids extracted from dried blood spots. A facile approach has been developed for the synthesis of isotope labeled acylcarnitines whose mass shift over their unlabeled counterparts can be any number in the range of 3 to 12 Da. This strategy makes it more convenient to provide authentic internal standards for acylcarnitines profiling analyses, thereby expanding their clinical applications.
TARGETED PLASMA PROTEIN DEGRADATION
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Page/Page column 172, (2021/08/14)
The present invention is directed to the bifunctional compounds and the use of such bifunctional compounds to lower plasma levels of extracellular target molecules by lysosomal degradation. Such bifunctional compounds have a cell surface receptor ligand covalently linked to a ligand that is capable of binding to an extracellular target molecule (such as a ligand for a growth factor, a cytokine, a chemokine, a hormone, a neurotransmitter, a capsid, a soluble receptor, an extracellular secreted protein, an antibody, a lipoprotein, an exosome, a virus, a cell, or a plasma membrane protein), where the cell surface receptor is associated with receptor mediated endocytosis, including asialoglycoprotein receptor (ASGPR) mediated lysosomal degradation and mannose-6-phosphate (M6PR) mediated lysosomal degradation. Pharmaceutical compositions comprising such bifunctional compounds and methods of treating a disease or disorder mediated by an extracellular molecule using such bifunctional compounds are also provided herein.
Design and synthesis of Coenzyme A analogues as Aurora kinase A inhibitors: An exploration of the roles of the pyrophosphate and pantetheine moieties
Bellany, Fiona,Tsuchiya, Yugo,Tran, Trang M.,Chan, A.W. Edith,Allan, Helen,Gout, Ivan,Tabor, Alethea B.
supporting information, (2020/09/16)
Coenzyme A (CoA) is a highly selective inhibitor of the mitotic regulatory enzyme Aurora A kinase, with a novel mode of action. Herein we report the design and synthesis of analogues of CoA as inhibitors of Aurora A kinase. We have designed and synthesised modified CoA structures as potential inhibitors, combining dicarbonyl mimics of the pyrophosphate group with a conserved adenosine headgroup and different length pantetheine-based tail groups. An analogue with a -SH group at the end of the pantotheinate tail showed the best IC50, probably due to the formation of a covalent bond with Aurora A kinase Cys290.
COMPOUNDS AND THERAPEUTIC USES THEREOF
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Page/Page column 65, (2020/05/19)
The invention relates to novel compounds with the ability to link an immune response to a defined therapeutic target, to the use of said compounds in treating cancer and infectious diseases, to compositions containing said compounds, processes for their preparation and to novel intermediates used in said process.
BIFUNCTIONAL COMPOUNDS FOR DEGRADING BTK VIA UBIQUITIN PROTEOSOME PATHWAY
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Paragraph 0688; 0689; 0690, (2020/05/21)
The present invention relates to compounds useful for degrading BTK via a ubiquitin proteolytic pathway. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.
GALNAC DERIVATIVES
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Paragraph 0130, (2019/04/11)
Modified oligonucleotides comprising a GalNAc moiety of the present disclosure along with methods of making and use, e.g., against HBV are disclosed.
PYRIDAZINE DERIVATIVES AS SMARCA2/4 DEGRADERS
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Page/Page column 125-126, (2019/11/12)
The present invention provides pyridazine derivatives of formula (I), which are therapeutically useful as SMARCA2/4 degraders. These compounds are useful in the treatment and/or prevention of diseases or disorders dependent upon SMARCA2/4 in a mammal. The present invention also provides preparation of the compounds and pharmaceutical compositions comprising at least one of the pyridazine derivatives of formula (I) or a pharmaceutically acceptable salt, or a stereoisomer thereof.
Analogue synthesis reveals decoupling of antibiofilm and β-lactam potentiation activities of a lead 2-aminoimidazole adjuvant against Mycobacterium smegmatis
Martin, Sara E.,Nguyen, Catherine M.,Basaraba, Randall J.,Melander, Christian
, p. 1403 - 1408 (2018/05/16)
Biofilm formation is one of the many mechanisms bacteria utilize to survive antibiotic treatment. It has been demonstrated that when Mycobacterium tuberculosis exists in a biofilm in vitro, it expresses phenotypic resistance to antimicrobial drugs. As the in vivo survival of M.?tuberculosis following drug treatment is potentially linked to a biofilm-like expression of drug tolerance, it is hypothesized that biofilm dispersion should increase antibiotic susceptibility and reduce the duration of the current antibiotic treatment regimen. Previously, we have identified a 2-aminoimidazole (2-AI) compound capable of dispersing and inhibiting M.?tuberculosis and M.?smegmatis biofilms in vitro. Additionally, this compound potentiated the activity of carbenicillin against M.?tuberculosis and, to a lesser degree, M.?smegmatis. Here, we describe a SAR study on this compound evaluating each derivative for biofilm dispersion and β-lactam potentiation capabilities against M.?smegmatis. This study identified a compound that improved upon the biofilm dispersion capabilities of the lead compound. Interestingly, a different compound was identified with an increased ability to potentiate a subset of β-lactam antibiotics. These compounds indicate that biofilm dispersion and potentiation capabilities may not be associated.
MODIFIED OLIGONUCLEOTIDES AND METHODS OF USE
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Paragraph 0284, (2018/04/12)
Modified oligonucleotides comprising modifications at the 2' and/or 3' positions(s) along with methods of making and use, e.g., against HBV are disclosed.
Synthesis and Th1-immunostimulatory activity of α-galactosylceramide analogues bearing a halogen-containing or selenium-containing acyl chain
Hossain, Md. Imran,Hanashima, Shinya,Nomura, Takuto,Lethu, Sébastien,Tsuchikawa, Hiroshi,Murata, Michio,Kusaka, Hiroki,Kita, Shunsuke,Maenaka, Katsumi
supporting information, p. 3687 - 3695 (2016/07/20)
A novel series of CD1d ligand α-galactosylceramides (α-GalCers) were synthesized by incorporation of the heavy atoms Br and Se in the acyl chain backbone of α-galactosyl-N-cerotoylphytosphingosine. The synthetic analogues are potent CD1d ligands and stimulate mouse invariant natural killer T (iNKT) cells to selectively enhance Th1 cytokine production. These synthetic analogues would be efficient X-ray crystallographic probes to disclose precise atomic positions of alkyl carbons and lipid–protein interactions in KRN7000/CD1d complexes.
