Synthesis of new enantiopure poly(hydroxy)aminooxepanes as building blocks for multivalent carbohydrate mimetics

• Léa Bouché,
• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 213–223, doi:10.3762/bjoc.10.17

• ; 1,2-oxazines; rearrangements; reductions; Introduction Since carbohydrates play a crucial role in biochemistry, compounds mimicking their structure and/or function (carbohydrate mimetics) have attracted great attention in academic research and in drug development [1][2][3]. These mimetics should not

Stereoselectively fluorinated N-heterocycles: a brief survey

• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306

• possibilities in the future of drug development. To date, the introduction of fluorine into medicinal entities [1][2] has mostly taken the form of aryl fluorination [3][4] or trifluoromethylation [5][6], and fascinating developments in synthetic methodology of this type are continuing to occur [7][8][9

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• inspiration for the development of novel synthetic methods, new biosynthetic insights and drug development. Considerably more discoveries remain to be uncovered

Synthesis of the tetracyclic core of Illicium sesquiterpenes using an organocatalyzed asymmetric Robinson annulation

• Lynnie Trzoss,
• Jing Xu,
• Michelle H. Lacoske and
• Emmanuel A. Theodorakis

Beilstein J. Org. Chem. 2013, 9, 1135–1140, doi:10.3762/bjoc.9.126

• the treatment of various neurodegenerative diseases including Alzheimer’s disease [4] and Parkinson’s disease [5]. Despite their unambiguous importance, approaches to neurotrophin-based drug development have encountered problems associated with their limited oral availability, insufficient delivery to

Study on the total synthesis of velbanamine: Chemoselective dioxygenation of alkenes with PIFA via a stop-and-flow strategy

• Huili Liu,
• Kuan Zheng,
• Xiang Lu,
• Xiaoxia Wang and
• Ran Hong

Beilstein J. Org. Chem. 2013, 9, 983–990, doi:10.3762/bjoc.9.113

• modification of these alkaloids in the context of clinical drug development still poses a challenge to synthetic and medicinal chemists. Since the first racemic synthesis of velbanamine (2) was disclosed by Büchi and co-workers in 1968, four racemic syntheses and two enantioselective syntheses have been

Recent progress in the discovery of small molecules for the treatment of amyotrophic lateral sclerosis (ALS)

• Allison S. Limpert,
• Margrith E. Mattmann and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2013, 9, 717–732, doi:10.3762/bjoc.9.82

• )-2-aminobenzothiazole], the only FDA approved compound for ALS, produced only very modest effects on disease progression in SOD1 G93A transgenic mice when administered prior to symptom onset [4]. These results highlight the limitations of these animal models in drug development and question how

• drug development focused on the modulation of glutamate signaling. In particular, evidence for an essential role of glutamate toxicity in ALS has come from the analysis of cerebrospinal fluid (CSF) from ALS patients, which shows a three-fold increase in glutamate and N-acetyl-aspartyl glutamate (NAAG

• gene have been identified in 20% of fALS patients, the creation of small molecules that specifically target SOD1 has become a popular strategy for drug development. Unfortunately, due to the relatively small patient population with these specific mutations, this strategy alone may not have a large

Asymmetric synthesis of host-directed inhibitors of myxoviruses

• Terry W. Moore,
• Kasinath Sana,
• Dan Yan,
• Pahk Thepchatri,
• John M. Ndungu,
• Manohar T. Saindane,
• Mark A. Lockwood,
• Michael G. Natchus,
• Dennis C. Liotta,
• Richard K. Plemper,
• James P. Snyder and
• Aiming Sun

Beilstein J. Org. Chem. 2013, 9, 197–203, doi:10.3762/bjoc.9.23

• Terry W. Moore Kasinath Sana Dan Yan Pahk Thepchatri John M. Ndungu Manohar T. Saindane Mark A. Lockwood Michael G. Natchus Dennis C. Liotta Richard K. Plemper James P. Snyder Aiming Sun Emory Institute for Drug Development, Emory University, 1515 Dickey Drive, Atlanta, GA 30322, USA Department of

A chemist and biologist talk to each other about caged neurotransmitters

• Graham C.R. Ellis-Davies

Beilstein J. Org. Chem. 2013, 9, 64–73, doi:10.3762/bjoc.9.8

• "? Chemist: It is well known in the pharmaceutical industry that water solubility is one of the true challenges for drug development. Often drugs are built up around rigid hydrocarbon scaffolds, such substances are inherently hydrophobic. The same issue applies to caged compounds, as in these we add aromatic

Chemical–biological characterization of a cruzain inhibitor reveals a second target and a mammalian off-target

• Jonathan W. Choy,
• Clifford Bryant,
• Claudia M. Calvet,
• Patricia S. Doyle,
• Shamila S. Gunatilleke,
• Siegfried S. F. Leung,
• Kenny K. H. Ang,
• Steven Chen,
• Jiri Gut,
• Juan A. Oses-Prieto,
• Jonathan B. Johnston,
• Michelle R. Arkin,
• Alma L. Burlingame,
• Jack Taunton,
• Matthew P. Jacobson,
• James M. McKerrow,
• Larissa M. Podust and
• Adam R. Renslo

Beilstein J. Org. Chem. 2013, 9, 15–25, doi:10.3762/bjoc.9.3

• . Despite many favorable properties, some aspects of 1 are suboptimal from a drug-development perspective. For example, compound 1 is known to be a mechanism-based (irreversible) inhibitor of CYP3A4, an enzyme responsible for the metabolism of many drugs, including 1 itself [30]. In pharmacokinetic studies

Palladium-catalyzed C–N and C–O bond formation of N-substituted 4-bromo-7-azaindoles with amides, amines, amino acid esters and phenols

• Rajendra Surasani,
• Dipak Kalita,
• A. V. Dhanunjaya Rao and
• K. B. Chandrasekhar

Beilstein J. Org. Chem. 2012, 8, 2004–2018, doi:10.3762/bjoc.8.227

• various therapeutic areas. Despite their utility in various drug-development programs in academic research and the pharmaceutical industry, methods for the synthesis of this class of compounds and functionalization of 7-azaindole scaffolds remain limited [9]. Although the literature enumerates various

• -mediated coupling of amides, amines, amino acid esters and phenols with N-protected 7-azaindole derivatives for one of our medicinally important drug-development programs. We herein report on Pd-catalyzed coupling reactions of N-protected 4-bromo-7-azaindoles with amides, amines, amino acid esters and

• architectures designed by cross-coupling strategies with the introduction of an amino acid functionality on 7-azaindole, result in new scaffolding. N-aryl-amino acids are reported as important synthetic intermediates and structural motifs for various drug-development programs by various medicinal and process

Arylglycine-derivative synthesis via oxidative sp³ C–H functionalization of α-amino esters

• Zhanwei Xu,
• Xiaoqiang Yu,
• Xiujuan Feng and
• Ming Bao

Beilstein J. Org. Chem. 2012, 8, 1564–1568, doi:10.3762/bjoc.8.178

• derivatives represent important synthetic intermediates or building blocks for drug development and natural-product synthesis [1][2]. The arylglycine moiety also occurs in several bioactive natural products [3]. Consequently, the development of convenient and efficient methods for the preparation of

Expanding the chemical diversity of spirooxindoles via alkylative pyridine dearomatization

• Chunhui Dai,
• Bo Liang and
• Corey R. J. Stephenson

Beilstein J. Org. Chem. 2012, 8, 986–993, doi:10.3762/bjoc.8.111

• activity, thus exemplifying their role in drug development [2][3][4][5][6][7][8]. Moreover, the challenging molecular architecture of spirooxindoles is appealing to chemists because it evokes novel synthetic strategies that address configurational demands and provides platforms for further reaction

Synthesis and characterization of Sant-75 derivatives as Hedgehog-pathway inhibitors

• Chao Che,
• Song Li,
• Bo Yang,
• Shengchang Xin,
• Zhixiong Yu,
• Taofeng Shao,
• Chuanye Tao,
• Shuo Lin and
• Zhen Yang

Beilstein J. Org. Chem. 2012, 8, 841–849, doi:10.3762/bjoc.8.94

• action, and thus it may serve as an interesting scaffold for drug development [35][36]. Recently, we have identified a Smo antagonist Sant-75 through zebrafish-based screening of a SAG-derived chemical library [37]. Interestingly, this antagonist differs from agonist SAG only in the chain length of the

Synthesis of oleophilic electron-rich phenylhydrazines

• Aleksandra Jankowiak and
• Piotr Kaszyński

Beilstein J. Org. Chem. 2012, 8, 275–282, doi:10.3762/bjoc.8.29

• : arylhydrazines; methodology; synthesis; Introduction Mono-arylhydrazines I are important intermediates in the synthesis of a number of heterocycles, including indoles [1] and some azoles (for example [2][3]), many of which exhibit biological activity and are used in drug development [4][5][6]. Arylhydrazines

Efficient oxidation of oleanolic acid derivatives using magnesium bis(monoperoxyphthalate) hexahydrate (MMPP): A convenient 2-step procedure towards 12-oxo-28-carboxylic acid derivatives

• Jorge A. R. Salvador,
• Vânia M. Moreira,
• Rui M. A. Pinto,
• Ana S. Leal and
• José A. Paixão

Beilstein J. Org. Chem. 2012, 8, 164–169, doi:10.3762/bjoc.8.17

• as important scaffolds for new drug development [3]. The chemistry of oleanane-type triterpenoids has been investigated with particular interest and many relevant biological and pharmacological activities of these derivatives have been reported in the literature, among which are antitumor, antiviral

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

• Ileana Dragutan,
• Valerian Dragutan,
• Carmen Mitan,
• Hermanus C.M. Vosloo,
• Lionel Delaude and
• Albert Demonceau

Beilstein J. Org. Chem. 2011, 7, 699–716, doi:10.3762/bjoc.7.81

• number of excellent books and reviews [1][2][3][4][5][6][7][8][9][10][11][12]. Natural iminosugars (i.e., alkaloids mimicking the structures of sugars, widespread in many plants or microorganisms) [12][13][14][15], as well as non-natural counterparts, are becoming important leads for drug development in

Advances in synthetic approach to and antifungal activity of triazoles

• Kumari Shalini,
• Nitin Kumar,
• Sushma Drabu and
• Pramod Kumar Sharma

Beilstein J. Org. Chem. 2011, 7, 668–677, doi:10.3762/bjoc.7.79

• antifungal for IFIs was amphotericin B. With the introduction of triazoles at the beginning of 1990s, the pace of drug development accelerated. Amphotericin B (AMB) was incorporated in three lipid formulations, whilst the first-generation triazoles (fluconazole (9) and itraconazole (10)) changed the

Identification and synthesis of impurities formed during sertindole preparation

• I. V. Sunil Kumar,
• G. S. R. Anjaneyulu and
• V. Hima Bindu

Beilstein J. Org. Chem. 2011, 7, 29–33, doi:10.3762/bjoc.7.5

• , quantification, and control of impurities in the drug substance and drug product are important parts of drug development for obtaining marketing approval. It is more challenging for an organic chemist to identify the impurities which are formed in very small quantities in a drug substance. Since most of the time

The subtle balance of weak supramolecular interactions: The hierarchy of halogen and hydrogen bonds in haloanilinium and halopyridinium salts

• Kari Raatikainen,
• Massimo Cametti and
• Kari Rissanen

Beilstein J. Org. Chem. 2010, 6, No. 4, doi:10.3762/bjoc.6.4

• systems and its potential in drug development has also been recognized [22]. The halogen bond (XB), whose terminology emphasizes the similarity with hydrogen bonding [23] can be schematically described by Y–X···A, where X is the XB donor atom (Lewis acid, electrophilic) and A is the XB acceptor atom