Ashok Bhandari - Academia.edu (original) (raw)
Papers by Ashok Bhandari
Page 1. Discovery and Optimization of a TRAIL R2 Agonist for Cancer Therapy Yvonne M. Angell, Ash... more Page 1. Discovery and Optimization of a TRAIL R2 Agonist for Cancer Therapy Yvonne M. Angell, Ashok Bhandari, M. Nuria De Francisco, Brian T. Frederick, Jennifer M. Green, Karen Leu, Kerstin Leuther, Reuben Sana, Peter ...
Tetrahedron Letters, 2006
A general method for the solid phase synthesis of 4-hydroxy quinolinones and subsequent Pd-cataly... more A general method for the solid phase synthesis of 4-hydroxy quinolinones and subsequent Pd-catalyzed cross coupling to afford 4-substituted quinolinones has been developed. Conversion of support-bound 4-hydroxy quinolinones to 4-tosyl quinolinones and subsequent treatment with alkyl, aryl, benzylzinc halides, or arylboronic acids in the presence of catalytic amount of Pd(PPh 3 ) 4 provides 4-alkyl, aryl, or benzyl quinolinones. This method allows for the introduction of alkyl, aryl, and benzyl groups at the 4-position of the quinolinone ring, and is ideal for parallel and combinatorial chemistry library synthesis.
Bioorganic & Medicinal Chemistry Letters, 2005
The biological screening of a collection of nature occurring diterpenoids against 11b-HSD1 result... more The biological screening of a collection of nature occurring diterpenoids against 11b-HSD1 resulted in the discovery of the lead compound 1b, which pointed to the therapeutic potential for type 2 diabetes. Subsequently, an optimization project was initiated. Starting from compound 1b and its counterpart 2, the hemi-synthesis was performed on kaurenic acid scaffolds yielding 36 derivatives. Further evaluations on both human and mouse 11b-HSD revealed that seven urea derivatives exhibited significant improved potency and selectivity. Especially, the urea 19a has an IC 50 (human 11b-HSD1) ¼ 9.4 nM and selectivity index (human 11b-HSD) > 10,649. The 2D and 3D binding models of the complex 19a/11b-HSD1 were generated using docking simulations. Based on the results, the structuraleactivity relationships (SARs) of compounds 1b and 2 were also discussed.
Bioorganic & Medicinal Chemistry Letters, 2004
A novel series of inhibitors that contain an aryl a,a-difluoro-b-ketophosphonate group has been s... more A novel series of inhibitors that contain an aryl a,a-difluoro-b-ketophosphonate group has been synthesized and evaluated against protein tyrosine phosphatase 1B. These compounds exhibit strong inhibitory activity, the best of which has a K i value of 0.17 lM. These results demonstrate that aryl a,a-difluoro-b-ketophosphonates are powerful phosphotyrosine mimetics for the development of potent PTP inhibitors.
Bioorganic & Medicinal Chemistry Letters, 2008
We have synthesized and evaluated a series of triaryl sulfonamide-based PTP1B inhibitors in which... more We have synthesized and evaluated a series of triaryl sulfonamide-based PTP1B inhibitors in which a difluoro-methylenephosphonate group of a potent lead has been replaced by potential bioisosteric replacements. Several mono-or di-charged compounds (8a, 8b, and 15a) were shown exhibit inhibitory activity in the low micromolar range, demonstrating the feasibility of using this approach in identifying non-phosphonate pTyr mimetics in a small molecular scaffold. These results also provide a useful indication of the relative effectiveness of these pTyr mimetics.
Tetrahedron Letters, 2006
A new method for the synthesis of functionalized biaryl a-ketophosphonic acids has been developed... more A new method for the synthesis of functionalized biaryl a-ketophosphonic acids has been developed. The key step involves the use of sodium bromobenzoyl phosphonates to react with polymer-bound boronic acids via microwave-assisted aqueous Suzuki coupling. This approach provides rapid access to a wide range of diverse biaryl analogues containing an a-ketophosphonic acid moiety.
Cheminform, 2004
For Abstract see ChemInform Abstract in Full Text.
Journal of Combinatorial Chemistry, 1999
Functionalized 2,2′-bipyridines have long been the focus of considerable attention as ubiquitous ... more Functionalized 2,2′-bipyridines have long been the focus of considerable attention as ubiquitous chelating ligands that form coordination complexes with transition metals across virtually the entire periodic table. 1 In particular, ruthenium complexes of biyridine and related diimine ligand systems have been extensively investigated for their fascinating photophysical and electrochemical properties 2 and have found numerous applications in studies of photoinduced electron transfer, 3 artificial photosynthesis, 4 and photocatalysis. Moreover, because of the predictable coordination properties of these ligands, the bipyridines, along with higher oligopyridines, have become key building blocks in the formation of discrete metallosupramolecular species having welldefined geometries and stoichiometries. 6 In this report we disclose the first solid-phase synthesis of 2,2′-bipyridines via sequential Knoevenagel and Hantzsch condensation reactions. This work provides a foundation for future studies on the synthesis of libraries of metal-bipyridine coordination compounds and the evaluation of these complexes in screens for molecular recognition, electron and/or energy transfer, and catalysis.
Synthesis-stuttgart, 1999
Page 1. Discovery and Optimization of a TRAIL R2 Agonist for Cancer Therapy Yvonne M. Angell, Ash... more Page 1. Discovery and Optimization of a TRAIL R2 Agonist for Cancer Therapy Yvonne M. Angell, Ashok Bhandari, M. Nuria De Francisco, Brian T. Frederick, Jennifer M. Green, Karen Leu, Kerstin Leuther, Reuben Sana, Peter ...
Tetrahedron Letters, 2006
A general method for the solid phase synthesis of 4-hydroxy quinolinones and subsequent Pd-cataly... more A general method for the solid phase synthesis of 4-hydroxy quinolinones and subsequent Pd-catalyzed cross coupling to afford 4-substituted quinolinones has been developed. Conversion of support-bound 4-hydroxy quinolinones to 4-tosyl quinolinones and subsequent treatment with alkyl, aryl, benzylzinc halides, or arylboronic acids in the presence of catalytic amount of Pd(PPh 3 ) 4 provides 4-alkyl, aryl, or benzyl quinolinones. This method allows for the introduction of alkyl, aryl, and benzyl groups at the 4-position of the quinolinone ring, and is ideal for parallel and combinatorial chemistry library synthesis.
Bioorganic & Medicinal Chemistry Letters, 2005
The biological screening of a collection of nature occurring diterpenoids against 11b-HSD1 result... more The biological screening of a collection of nature occurring diterpenoids against 11b-HSD1 resulted in the discovery of the lead compound 1b, which pointed to the therapeutic potential for type 2 diabetes. Subsequently, an optimization project was initiated. Starting from compound 1b and its counterpart 2, the hemi-synthesis was performed on kaurenic acid scaffolds yielding 36 derivatives. Further evaluations on both human and mouse 11b-HSD revealed that seven urea derivatives exhibited significant improved potency and selectivity. Especially, the urea 19a has an IC 50 (human 11b-HSD1) ¼ 9.4 nM and selectivity index (human 11b-HSD) > 10,649. The 2D and 3D binding models of the complex 19a/11b-HSD1 were generated using docking simulations. Based on the results, the structuraleactivity relationships (SARs) of compounds 1b and 2 were also discussed.
Bioorganic & Medicinal Chemistry Letters, 2004
A novel series of inhibitors that contain an aryl a,a-difluoro-b-ketophosphonate group has been s... more A novel series of inhibitors that contain an aryl a,a-difluoro-b-ketophosphonate group has been synthesized and evaluated against protein tyrosine phosphatase 1B. These compounds exhibit strong inhibitory activity, the best of which has a K i value of 0.17 lM. These results demonstrate that aryl a,a-difluoro-b-ketophosphonates are powerful phosphotyrosine mimetics for the development of potent PTP inhibitors.
Bioorganic & Medicinal Chemistry Letters, 2008
We have synthesized and evaluated a series of triaryl sulfonamide-based PTP1B inhibitors in which... more We have synthesized and evaluated a series of triaryl sulfonamide-based PTP1B inhibitors in which a difluoro-methylenephosphonate group of a potent lead has been replaced by potential bioisosteric replacements. Several mono-or di-charged compounds (8a, 8b, and 15a) were shown exhibit inhibitory activity in the low micromolar range, demonstrating the feasibility of using this approach in identifying non-phosphonate pTyr mimetics in a small molecular scaffold. These results also provide a useful indication of the relative effectiveness of these pTyr mimetics.
Tetrahedron Letters, 2006
A new method for the synthesis of functionalized biaryl a-ketophosphonic acids has been developed... more A new method for the synthesis of functionalized biaryl a-ketophosphonic acids has been developed. The key step involves the use of sodium bromobenzoyl phosphonates to react with polymer-bound boronic acids via microwave-assisted aqueous Suzuki coupling. This approach provides rapid access to a wide range of diverse biaryl analogues containing an a-ketophosphonic acid moiety.
Cheminform, 2004
For Abstract see ChemInform Abstract in Full Text.
Journal of Combinatorial Chemistry, 1999
Functionalized 2,2′-bipyridines have long been the focus of considerable attention as ubiquitous ... more Functionalized 2,2′-bipyridines have long been the focus of considerable attention as ubiquitous chelating ligands that form coordination complexes with transition metals across virtually the entire periodic table. 1 In particular, ruthenium complexes of biyridine and related diimine ligand systems have been extensively investigated for their fascinating photophysical and electrochemical properties 2 and have found numerous applications in studies of photoinduced electron transfer, 3 artificial photosynthesis, 4 and photocatalysis. Moreover, because of the predictable coordination properties of these ligands, the bipyridines, along with higher oligopyridines, have become key building blocks in the formation of discrete metallosupramolecular species having welldefined geometries and stoichiometries. 6 In this report we disclose the first solid-phase synthesis of 2,2′-bipyridines via sequential Knoevenagel and Hantzsch condensation reactions. This work provides a foundation for future studies on the synthesis of libraries of metal-bipyridine coordination compounds and the evaluation of these complexes in screens for molecular recognition, electron and/or energy transfer, and catalysis.
Synthesis-stuttgart, 1999