Diastereoisomers of 2-benzyl-2, 3-dihydro-2-(1H-inden-2-yl)-1H-inden-1-ol: Potential anti-inflammatory agents

Sheridan, Helen; Walsh, John; Cogan, C.; Jordan, Michael R.; McCabe, Tom; Passante, Egle; Frankish, Neil

doi:10.1016/j.bmcl.2009.08.060

Cited by 26 publications

(30 citation statements)

References 13 publications

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“…Triflic acid was also able to catalyze the reaction, but in only 28% yield (entry 10). Lower yields were also obtained in solvent different from toluene (entries [11][12][13][14][15]. Finally, more sterically hindered silyl enol ethers 4b and 4c led to inferior results when compared to trimethylsilyl enol ether 4a (entries 16 and 17).…”

Section: Scheme 2 Azidation Of Keto Ester 1amentioning

confidence: 99%

Azidation of β-Keto Esters and Silyl Enol Ethers with a Benziodoxole Reagent

2013

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The efficient azidation of -keto esters and silyl enol ethers using a benziodoxole-derived azide transfer reagent is reported. The azidation of cyclic -keto esters could be achieved in up to quantitative yields in the absence of any catalyst. In the case of less reactive linear -keto esters and silyl enol ethers, complete conversion and good yields could be obtained by using a zinc catalyst. Azides are extremely useful functional groups in synthetic chemistry.1 They are easily reduced to amines, but are themselves non-basic. They consequently constitute ideal amine precursors in multi-step synthesis. Furthermore, cycloaddition of azides with alkynes, especially catalyzed by copper, has become the most impressive example of "Click" chemistry, as it is completely orthogonal to other functionalities and can run under mild conditions without the need to exclude oxygen or moisture. This reaction is now one of the most often used functionalization methods for biomolecules and polymers.2 In this context, new methods to introduce azides, especially in complex molecules, are urgently needed.Most approaches to access azides are based on the use of nucleophilic sodium azide. In contrast, the introduction of azides onto nucleophiles is much less developed. Such reactions would be especially useful to access -azido carbonyl compounds, which are important building (2) (a) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K.

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Section: Scheme 2 Azidation Of Keto Ester 1amentioning

confidence: 99%

Azidation of β-Keto Esters and Silyl Enol Ethers with a Benziodoxole Reagent

2013

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“…Compounds PH21and PH22 are single enantiomers separated from PH5, being ( 1R, 2R ) and ( 1S, 2S ) ‐2‐benzyl‐2,3‐dihydro‐2‐(1H‐inden‐2‐yl)‐1H‐idnen‐1‐ol), respectively. Details of the synthesis, separation, characterisation and confirmation of structure by X‐ray diffraction of these compounds are described elsewhere …”

Section: Methodsmentioning

confidence: 99%

“…Details of the synthesis, separation, characterisation and confirmation of structure by X-ray diffraction of these compounds are described elsewhere. [11,12,19] A total of 123 mice were used in this study. All animal research work reported in this article have been carried out in the Comparative Medicine Unit, Trinity College Dublin, a Health Products Regulatory Authority (HPRA) approved establishment that operates in accordance with Directive 2010/63/EU and its Irish transposition S.I No 543 of 2012.…”

Section: Methodsmentioning

confidence: 99%

The indane diastereoisomers, PH2 and PH5: divergence between their effects in delayed-type hypersensitivity models and a model of colitis

Frankish

McHale

Sheridan

2017

Journal of Pharmacy and Pharmacology

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ObjectivesCompounds PH2 and PH5 are distereoisomers of novel indane compounds, synthesised as analogues of secondary metabolites of the fern, Onychium. In this study, we compare their effects on a variety of inflammatory models.MethodsIn an effort to extend our knowledge of their anti‐inflammatory profile, we have investigated their activity in two models of delayed‐type hypersensitivity (DTH); the methylated bovine serum albumin model (mBSA) and the oxazolone contact hypersensitivity (CHS) model, on IL2 release from Jurkat cells and in the dextran sulphate sodium (DSS) murine model of inflammatory bowel disease.Key findingsBoth diastereoisomers are equipotent in reducing paw swelling in the mBSA model and in inhibiting interleukin (IL) 2 release from Jurkat cells. They are equally ineffective in the oxazolone contact hypersensitivity model (CHS). Only the diastereoisomer, PH5, protects against DSS‐induced colitis and of its two enantiomers, only the S,S‐enantiomer, PH22, possesses this activity. PH2 is ineffective in the DSS model.ConclusionsThe results suggest that the beneficial effect of PH5, and its enantiomer PH22, in the DSS model is a consequence of an action on a target specific to the colitis model. The implications of such data suggest an unknown target in this disease model that may be exploited to therapeutic advantage.

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“…Although preliminary findings indicated that no correlation existed between the structure and dual activity of these compounds, mast cell stabilizing compounds with superior activity to that of DSCG emerged from this study (Sheridan et al ., ). In later studies, diastereomers of a benzylated indanol dimer compound as exemplified by 3 and 4 , which maintain the indanol and indenyl structural fragments were synthesized and shown to demonstrate dual mast cell stabilizing and anti‐inflammatory effects in a range of in vitro and in vivo studies (Sheridan et al ., ). While the data generated on the indane dimer series of compounds was encouraging, further studies were conducted to elucidate the exact features in these structural types that were necessary for activity.…”

Section: Sources Of Mast Cell Stabilizersmentioning

confidence: 97%

Twenty‐first century mast cell stabilizers

Finn

Walsh

2013

British J Pharmacology

119

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Mast cell stabilizing drugs inhibit the release of allergic mediators from mast cells and are used clinically to prevent allergic reactions to common allergens. Despite the relative success of the most commonly prescribed mast cell stabilizer, disodium cromoglycate, in use for the preventative treatment of bronchial asthma, allergic conjunctivitis and vernal keratoconjunctivitis, there still remains an urgent need to design new substances that are less expensive and require less frequent dosing schedules. In this regard, recent developments towards the discovery of the next generation of mast cell stabilizing drugs has included studies on substances isolated from natural sources, biological, newly synthesized compounds and drugs licensed for other indications. The diversity of natural products evaluated range from simple phenols, alkaloids, terpenes to simple amino acids. While in some cases their precise mode of action remains unknown it has nevertheless sparked interest in the development of synthetic derivatives with improved pharmacological properties. Within the purely synthetic class of inhibitors, particular attention has been devoted to the inhibition of important signalling molecules including spleen TK and JAK3. The statin class of cholesterol-lowering drugs as well as nilotinib, a TK inhibitor, are just some examples of clinically used drugs that have been evaluated for their anti-allergic properties. Here, we examine each approach under investigation, summarize the test data generated and offer suggestions for further preclinical evaluation before their therapeutic potential can be realized.

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Diastereoisomers of 2-benzyl-2, 3-dihydro-2-(1H-inden-2-yl)-1H-inden-1-ol: Potential anti-inflammatory agents

Cited by 26 publications

References 13 publications

Azidation of β-Keto Esters and Silyl Enol Ethers with a Benziodoxole Reagent

Azidation of β-Keto Esters and Silyl Enol Ethers with a Benziodoxole Reagent

The indane diastereoisomers, PH2 and PH5: divergence between their effects in delayed-type hypersensitivity models and a model of colitis

Twenty‐first century mast cell stabilizers

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