Synthesis of novel mast cell-stabilising and anti-allergic 1,2,3,4-tetrahydro-1-naphthalenols and related compounds

Barlow, James W.; McHugh, Aengus P.; Woods, Orla; Walsh, John

doi:10.1016/j.ejmech.2011.01.073

Cited by 14 publications

(8 citation statements)

References 26 publications

(20 reference statements)

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“…Initial studies involved replacement of one of the indane units by a tetralin skeleton in the overall molecular framework of the compounds. Replacement of either the indanol or indenyl moiety of these diasteroisomers by the corresponding tetralol or dihydronaphthalene groups to give the benzylated dimer alcohols 5 and 6 resulted in these compounds exhibiting potent mass cell stabilization activity against several elicitors including; compound 48/80 ( 5 ; IC 50 4.1 μM, 6 ; IC 50 7.7 μM), concanavalin A( 5 ; IC 50 0.75 μM, 6 ; IC 50 3.6 μM) and calcium ionophore A23187 5 ; IC 50 10 μM, 6 ; IC 50 4.7 μM), in the RPMC assay (Barlow et al ., ). Similarly, potent mast cell stabilizing activity was observed against compound 48/80‐induced release (IC 50 value of 3.3 μM) when the indanol core of 3 was deconstructed to give the naphthalenyl analogue 6 (Barlow et al ., ).…”

Section: Sources Of Mast Cell Stabilizersmentioning

confidence: 99%

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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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Section: Sources Of Mast Cell Stabilizersmentioning

confidence: 99%

“…Twenty-first century mast cell stabilizers against compound 48/80-induced release (IC50 value of 3.3 mM) when the indanol core of 3 was deconstructed to give the naphthalenyl analogue 6 (Barlow et al, 2011a). Earlier concurrent studies also identified a series of aminoindanones, including 7, 8 and 9.…”

Section: Bjpmentioning

confidence: 99%

Twenty‐first century mast cell stabilizers

Finn

Walsh

2013

British J Pharmacology

119

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“…Starting materials, which were not commercially available, were synthesized according to literature procedures; (1H-inden-3-yloxy)trimethylsilane (3a), 21 (3,4-dihydro-1-naphthalenyloxy)-(trimethyl)silane (3b), 22 trimethyl(1-phenylprop-1-enyloxy)silane (9), 23 (1-(tert-butylthio)vinyloxy)trimethylsilane (6). 24 General procedure for enantioselective α-enolation with cyclic silyl(enol)ethers A solution of the catalyst (20 mol%) in acetone (0.0625 M, 0.82 mL) was prepared in a vial equipped with a magnetic stir bar at −78 °C under an argon atmosphere.…”

Section: Generalmentioning

confidence: 99%

Asymmetric organocatalytic SOMO reactions of enol silanes and silyl ketene (thio)acetals

2014

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Organocatalytic SOMO reactions can provide access to various α-functionalized carbonyl compounds. Chiral imidazolidinones catalysed the organo-SOMO reactions of aldehydes and ketones with cyclic and acyclic enol silanes. The resulting chiral dicarbonyl compounds were obtained in yields of up to 80% and enantiomeric purities of up to 90% ee. Under the SOMO conditions, silyl ketene acetals did not afford the desired products. However, silyl ketene thioacetal could be employed, and the corresponding product was isolated with useful enantiomeric purity of 82% ee.

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“…An extensive literature survey revealed that various reagents, such as Al 2 O 3 , 10 (t-BuO) 3 Al, 11 HCl, amberlyst-29, CH 3 SO 3 H, NaOH, Triton-B, p-dimethylaminopyridine, 12 TiCl 4 , 12,13 and amberlyst-15, 12,14 have been explored for C-C Scheme 1 Synthesis of precursor (8a). bond formation of 1-tetralone (8c).…”

Section: Chemistrymentioning

confidence: 99%