52605-49-9Relevant articles and documents
Synthesis and fluorescence properties of aminocyanopyrrole and aminocyanothiophene esthers for biomedical and bioimaging applications
Agrebi, Asma,Allouche, Fatma,Alves, Sérgio,Baleiz?o, Carlos,Cherif, Oussama,Farinha, José Paulo
, (2020/03/11)
We prepared a series of substituted aminocyanopyrroles and another of aminocynaothiophenes. We describe an efficient new one-step synthetic strategy via the condensation of an alkyl sarcosinate and ethoxymethylenemalononitrile, through a Gewald-like reaction. The UV–visible absorption and steady-state and time resolved fluorescence properties of some representative compounds, as well as their acid-base behavior, is also presented. The compounds might be useful for medicinal applications and as bioimaging probes.
Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis
Siebert, David C.B.,Sommer, Roman,Pogorevc, Domen,Hoffmann, Michael,Wenzel, Silke C.,Müller, Rolf,Titz, Alexander
supporting information, p. 2922 - 2929 (2019/12/23)
The argyrins are secondary metabolites from myxobacteria with antibiotic activity against Pseudomonas aeruginosa. Studying their structure–activity relationship is hampered by the complexity of the chemical total synthesis. Mutasynthesis is a promising approach where simpler and fully synthetic intermediates of the natural product’s biosynthesis can be biotechnologically incorporated. Here, we report the synthesis of a series of tripeptide thioesters as mutasynthons containing the native sequence with a dehydroalanine (Dha) Michael acceptor attached to a sarcosine (Sar) and derivatives. Chemical synthesis of the native sequence D-Ala-Dha-Sar thioester required revision of the sequential peptide synthesis into a convergent strategy where the thioester with sarcosine was formed before coupling to the Dha-containing dipeptide.
Structure-activity relationship study of hypoxia-activated prodrugs for proteoglycan-targeted chemotherapy in chondrosarcoma
Ghedira, Donia,Voissière, Aurélien,Peyrode, Caroline,Kraiem, Jamil,Gerard, Yvain,Maubert, Elise,Vivier, Magali,Miot-Noirault, Elisabeth,Chezal, Jean-Michel,Farhat, Farhat,Weber, Valérie
, p. 51 - 67 (2018/09/13)
Due to an abundant chondrogenic, poorly vascularized and particularly hypoxic extracellular matrix, chondrosarcoma, a malignant cartilaginous tumour, is chemo- and radio-resistant. Surgical resection with wide margins remains the mainstay of treatment. To address the lack of therapy, our strategy aims to increase anticancer drugs targeting and delivery in the tumour, by leveraging specific chondrosarcoma hallmarks: an extensive cartilaginous extracellular matrix, namely the high negative fixed charge density and severe chronic hypoxia. A dual targeted therapy for chondrosarcoma was investigated by conjugation of a hypoxia-activated prodrug (HAP) to quaternary ammonium (QA) functions which exhibit a high affinity for polyanionic sites of proteoglycans (PGs), the major components of the chondrosarcoma extracellular matrix. Based on preclinical results, an imidazole prodrug, ICF05016, was identified and provided the basis for a lead optimization study. A series of 27 QA-phosphoramide mustard conjugates, differing by the type of QA function and the length of the alkyl linker, was yielded by a common multi-step sequence involving phosphorylation of a key 2-nitroimidazole alcohol. Then, a screening was realized by surface plasmon resonance technology to assess biomolecular interactions between QA derivatives and aggrecan, the most abundant PG in chondrosarcoma. Results revealed that affinity depends more on the type of QA function, than on the linker length. Moreover, the presence of a benzyl group enhanced affinity to aggrecan. Twelve compounds were shortlisted and evaluated for antiproliferative activity (i.e., growth inhibiting concentration 50), under normoxic and hypoxic conditions using the human extraskeletal myeloid chondrosarcoma cell line (HEMC-SS). For all prodrugs, hypoxic selectivity was maintained and even increased, compared with the lead. From this study, compound 31f emerged as the most effective PG-targeted HAPs with a dissociation constant of 2.10 μM in the SPR experiment, a hypoxia cytotoxicity ratio of 24 and an efficient reductive cleavage under chemical and enzymatic conditions.
INHIBITORS OF HEPATITIS C VIRUS POLYMERASE
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Paragraph 409; 410; 411, (2016/10/11)
The present invention provides, among other things, compounds represented by the general Formula I: (I) and pharmaceutically acceptable salts thereof, wherein L and A (and further substituents) are as defined in classes and subclasses herein and compositions (e.g., pharmaceutical compositions) comprising such compounds, which compounds are useful as inhibitors of hepatitis C virus polymerase, and thus are useful, for example, as medicaments for the treatment of HCV infection.
PHOSPHONAMIDATE COMPOUNDS
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, (2008/06/13)
Phosphonamidates of the formula STR1 wherein X is a substituted or unsubstituted imino or amino acid or ester. These compounds possess angiotensin converting enzyme activity and are thus useful as hypotensive agents.
Phosphonamidate compounds
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, (2008/06/13)
Phosphonamidates of the formula STR1 wherein X is an amino acid or ester. These compounds possess angiotensin converting enzyme inhibition activity and enkephalinase inhibition activity. Thus they are useful as hypotensive and analgesic agents.
An Improved Synthesis of 1-Methyl-2,5-piperazinedione
Harris, Thomas D.,Reilly, Thimothy J.,DelPrincipe, Joseph A.
, p. 423 - 424 (2007/10/02)
A new synthesis of 1-methyl-2,5-piperazinedione in three steps starting from sarcosine is described.This method proceeds in higher overall yield (49 percent) than previous methods.
