55400-94-7Relevant academic research and scientific papers
MACROCYCLIC COMPOUNDS USEFUL AS CHITINASE INHIBITORS
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Paragraph 0127; 0180-0181; 0194, (2021/07/29)
The present invention relates to macrocyclic compounds of formula (I) and their use as chitinase inhibitors as well as to pharmaceutical compositions and methods of preparation thereof. The compounds can in particular be used in the treatment, prevention and/or amelioration of asthma.
An expedient strategy for the diversity-oriented synthesis of macrocyclic compounds with natural product-like characteristics
Ciardiello, Joe J.,Galloway, Warren R.J.D.,O'Connor, Cornelius J.,Sore, Hannah F.,Stokes, Jamie E.,Wu, Yuteng,Spring, David R.
, p. 3567 - 3578 (2016/07/06)
Naturally-derived macrocyclic compounds are associated with a diverse range of biological activities, including antibacterial effects, and there are over 100 marketed macrocycle drugs derived from natural products. However, synthetic macrocycles are widely considered to be poorly explored in antibiotic development (indeed, within drug discovery in general). This has been attributed to challenges associated with the generation of such compounds. Whilst there are synthetic methods that can produce large collections of structurally similar macrocycles (i.e., compounds with varying appendages based around similar core macrocyclic ring architectures) there is a relative dearth of strategies for the efficient generation of more structurally diverse macrocycle collections in which there is greater variation in the nature of macrocyclic scaffolds present. Such macrocycle collections should contain compounds with a broad range of biological activities (including antibacterial activities) and the requisite robust synthetic methodology useful for analogue synthesis and lead optimization once an active compound has been identified in a biological screen. Herein, we describe a new and expedient diversity-oriented synthesis (DOS) strategy for the generation of a library of novel structurally diverse macrocyclic compounds with a high level of scaffold diversity. The strategy is concise, proceeds from readily-available starting materials, is modular in nature and features a variety of macrocyclisation techniques. In this proof-of-concept study, the synthesis of several previously unreported macrocyclic compounds was achieved. Each of these macrocycles was based around a distinct molecular scaffold and contained natural product-like structural features (e.g., three-dimensionality and multiple hydrogen bond donors and acceptors) as well as synthetic handles for potential further elaboration. The successful generation of these macrocycles demonstrates the feasibility of the new DOS strategy as a synthetic platform for library generation.
INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION
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Page/Page column 117, (2014/10/18)
The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection. Formule (I)
Novel macrocyclic amidinoureas: Potent non-azole antifungals active against wild-type and resistant Candida species
Sanguinetti, Maurizio,Sanfilippo, Stefania,Castagnolo, Daniele,Sanglard, Dominique,Posteraro, Brunella,Donzellini, Giovanni,Botta, Maurizio
supporting information, p. 852 - 857 (2013/10/01)
Novel macrocyclic amidinourea derivatives 11, 18, and 25 were synthesized and evaluated as antifungal agents against wild-type and fluconazole resistant Candida species. Macrocyclic compounds 11 and 18 were synthesized through a convergent approach using as a key step a ring-closing metathesis macrocyclization reaction, whereas compounds 25 were obtained by our previously reported synthetic pathway. All the macrocyclic amidinoureas showed antifungal activity toward different Candida species higher or comparable to fluconazole and resulted highly active against fluconazole resistant Candida strains showing in many cases minimum inhibitory concentration values lower than voriconazole.
Structure-activity relationships of semisynthetic mumbaistatin analogs
Lee, Taek Soon,Das, Abhirup,Khosla, Chaitan
, p. 5207 - 5218 (2008/03/13)
Mumbaistatin (1), a new anthraquinone natural product, is one of the most potent known inhibitors of hepatic glucose-6-phosphate translocase, an important target for the treatment of type II diabetes. Its availability, however, has been limited due to its extremely low yield from the natural source. Starting from DMAC (5, 3,8-dihydroxyanthraquinone-2-carboxylic acid), a structurally related polyketide product of engineered biosynthesis, we developed a facile semisynthetic method that afforded a variety of mumbaistatin analogs within five steps. This work was facilitated by the initial development of a DMAC overproduction system. In addition to reinforcing the biological significance of the anthraquinone moiety of mumbaistatin, several semisynthetic analogs were found to have low micromolar potency against the translocase in vitro. Two of them were also active in glucose release assays from primary hepatocytes. The synergistic combination of biosynthesis and synthesis is a promising avenue for the discovery of new bioactive substances.
Reduction of Cp2ZrCl2 with mischmetall: A new method for generating an efficient "Cp2Zr" equivalent
Denhez, Clement,Medegan, Sedami,Helion, Florence,Namy, Jean-Louis,Vasse, Jean-Luc,Szymoniak, Jan
, p. 2945 - 2947 (2007/10/03)
A "Cp2Zr" equivalent is generated under mild conditions (THF, room temperature) by reducing Cp2ZrCl2 with cheap and readily available mischmetall (an alloy of Ce, La, Nd, and Pr). Coupling reactions, including those of terminal alkynes, can efficiently be achieved by using this reagent.
