Will Kaplan

Discovery and Optimization of N-Heteroaryl Indazole LRRK2 Inhibitors

Kaitlyn M. Logan, Will Kaplan, Vladimir Simov, Hua Zhou et autres

Inhibition of leucine-rich repeat kinase 2 is a genetically supported mechanism for the treatment of Parkinson’s disease. We previously disclosed the discovery of an indazole series lead that demonstrated both safety and translational risks. The safety risks were hypothesized to be of …

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Development of Scalable Routes to 1-Bicyclo[1.1.1]pentylpyrazoles

Cayetana Zárate, Michael J. Ardolino, Gregori J. Morriello, Kaitlyn M. Logan et autres

The application of bicyclo[1.1.1]pentanes (BCPs) as phenyl bioisosteres has garnered significant attention, as these structural motifs can improve the physiochemical profiles of drug candidates. Despite the potential of using 1-bicyclo[1.1.1]pentylpyrazoles (BCPPs) as 1-phenylpyrazole bioisosteres, this area remains underexplored because of the relative …

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Modular Total Synthesis and Cell-Based Anticancer Activity Evaluation of Ouabagenin and Other Cardiotonic Steroids with Varying Degrees of Oxygenation

Hem Raj Khatri, Bijay T. Bhattarai, Will Kaplan, LI Zhong-zheng et autres

A Cu(II)-catalyzed diastereoselective Michael/aldol cascade approach is used to accomplish concise total syntheses of cardiotonic steroids with varying degrees of oxygenation including cardenolides ouabagenin, sarmentologenin, 19-hydroxysarmentogenin, and 5- epi-panogenin. These syntheses enabled the subsequent structure activity relationship (SAR) studies on 37 synthetic …

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CCDC 1862703: Experimental Crystal Structure Determination

Hem Raj Khatri, Bijay T. Bhattarai, Will Kaplan, LI Zhong-zheng et autres

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, …

CCDC 1862704: Experimental Crystal Structure Determination

Hem Raj Khatri, Bijay T. Bhattarai, Will Kaplan, LI Zhong-zheng et autres

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, …

Drug-Oriented Synthesis of Cardiotonic Steroids

Will Kaplan

Steroids are a structurally privileged class of bioactive natural products whose architecture has served as the bedrock for many valuable therapeutics throughout human history. In particular, the cardenolide sub-class of steroids, typified by ouabain and digoxin, has been used clinically since the …

Concise Enantioselective Total Synthesis of Cardiotonic Steroids 19-Hydroxysarmentogenin and Trewianin Aglycone

Will Kaplan, Hem Raj Khatri, Pavel Nagorny

The expedient and scalable approach to cardiotonic steroids carrying oxygenation at the C11- and C19-positions has been developed and applied to the total asymmetric synthesis of steroids 19-hydroxysarmentogenin and trewianin aglycone as well as to the assembly of the panogenin core. This …

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ChemInform Abstract: Concise Enantioselective Synthesis of Oxygenated Steroids via Sequential Copper(II)‐Catalyzed Michael Addition/Intramolecular Aldol Cyclization Reactions.

Nathan R. Cichowicz, Will Kaplan, Yaroslav Ya. Khomutnyk, Bijay T. Bhattarai et autres

Abstract Depending on the base used for induction of the aldol cascade reaction either natural or non‐natural steroid skeleton are selectively accessed.

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CCDC 1493024: Experimental Crystal Structure Determination

Will Kaplan, Hem Raj Khatri, Pavel Nagorny

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, …

Concise Enantioselective Synthesis of Oxygenated Steroids via Sequential Copper(II)-Catalyzed Michael Addition/Intramolecular Aldol Cyclization Reactions

Nathan R. Cichowicz, Will Kaplan, Yaroslav Ya. Khomutnyk, Bijay T. Bhattarai et autres

A new scalable enantioselective approach to functionalized oxygenated steroids is described. This strategy is based on chiral bis(oxazoline) copper(II) complex-catalyzed enantioselective and diastereoselective Michael reactions of cyclic ketoesters and enones to install vicinal quaternary and tertiary stereocenters. In addition, the utility of …

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CCDC 1440989: Experimental Crystal Structure Determination

Nathan R. Cichowicz, Will Kaplan, Yaroslav Ya. Khomutnyk, Bijay T. Bhattarai et autres

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, …

CCDC 1440988: Experimental Crystal Structure Determination

Nathan R. Cichowicz, Will Kaplan, Yaroslav Ya. Khomutnyk, Bijay T. Bhattarai et autres

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, …