Full Text Journal Articles by
Author Kristi A Leonard


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Discovery and optimization of new oxadiazole substituted thiazole RORγt inverse agonists through a bioisosteric amide replacement approach.

Christoph Steeneck, Christian Gege, Olaf Kinzel, Michael Albers, Gerald Kleymann, Thomas Schlüter, Andreas Schulz, Xiaohua Xue, Maxwell D Cummings, Anne M Fourie, Kristi A Leonard, Brian Scott, James P Edwards, Thomas Hoffmann, Steven D Goldberg,

Starting from previously identified thiazole-2-carboxamides exemplified by compound 1/6, two new series of RORγt inverse agonists with significantly improved aqueous solubility, ADME parameters and oral PK properties were discovered. These scaffolds were identified from a bioisosteric amide replacement approach. Amongst the variety of heterocycles explored, a 1,3,4-oxadiazole led to compounds ... Read more >>

Bioorg. Med. Chem. Lett. (Bioorganic & Medicinal Chemistry Letters)
[2020, 30(12):127174]

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Discovery of a Gut-Restricted JAK Inhibitor for the Treatment of Inflammatory Bowel Disease.

Kristi A Leonard, Lisa A Madge, Paul J Krawczuk, Aihua Wang, Kevin D Kreutter, Genesis M Bacani, Wenying Chai, Russell C Smith, Mark S Tichenor, Michael C Harris, Ravi Malaviya, Mark Seierstad, Marguerite E Johnson, Jennifer D Venable, Suzie Kim, Gavin C Hirst, Ashok S Mathur, Tadimeti S Rao, James P Edwards, Michele C Rizzolio, Tatiana Koudriakova,

To identify Janus kinase (JAK) inhibitors that selectively target gastrointestinal tissues with limited systemic exposures, a class of imidazopyrrolopyridines with a range of physical properties was prepared and evaluated. We identified compounds with low intrinsic permeability and determined a correlation between permeability and physicochemical properties, clogP and tPSA, for a ... Read more >>

J. Med. Chem. (Journal of medicinal chemistry)
[2020, 63(6):2915-2929]

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Benzodiazepinedione inhibitors of the Hdm2:p53 complex suppress human tumor cell proliferation in vitro and sensitize tumors to doxorubicin in vivo.

Holly K Koblish, Shuyuan Zhao, Carol F Franks, Robert R Donatelli, Rose M Tominovich, Louis V LaFrance, Kristi A Leonard, Joan M Gushue, Daniel J Parks, Raul R Calvo, Karen L Milkiewicz, Juan José Marugán, Pierre Raboisson, Maxwell D Cummings, Bruce L Grasberger, Dana L Johnson, Tianbao Lu, Christopher J Molloy, Anna C Maroney,

The activity and stability of the p53 tumor suppressor are regulated by the human homologue of the mouse double minute 2 (Hdm2) oncoprotein. It has been hypothesized that small molecules disrupting the Hdm2:p53 complex would allow for the activation of p53 and result in growth suppression. We have identified small-molecule ... Read more >>

Mol. Cancer Ther. (Molecular cancer therapeutics)
[2006, 5(1):160-169]

Cited: 75 times

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Design, synthesis, and biological evaluation of novel potent and selective alphavbeta3/alphavbeta5 integrin dual inhibitors with improved bioavailability. Selection of the molecular core.

Juan José Marugán, Carl Manthey, Beth Anaclerio, Lou Lafrance, Tianbao Lu, Tom Markotan, Kristi A Leonard, Carl Crysler, Stephen Eisennagel, Malini Dasgupta, Bruce Tomczuk,

A novel series of potent and selective alpha(v)beta(3)/alpha(v)beta(5) dual( )()inhibitors was designed, synthesized, and evaluated against several integrins. These compounds were synthesized through a Mitsunobu reaction between the guanidinium mimetics and the corresponding central templates. Guanidinium mimetics with enhaced rigidity (i.e., (2-pyridylamino)propoxy versus the 2-(6-methylamino-2-pyridyl)ethoxy) led to improved activity toward ... Read more >>

J. Med. Chem. (Journal of medicinal chemistry)
[2005, 48(4):926-934]

Cited: 18 times

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The present invention relates to novel substituted indole compounds that are antagonists of alpha V (agrv) integrins, for example agrvbgr3 and agrvbgr5 integrins, their pharmaceutically acceptable salts, and pharmaceutical compositions thereof. The compounds may be used in treatment of pathological conditions mediated by agrvbgr3 and agrvbgr5 integrins, including such conditions ... Read more >>

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A transient N-O-linked Pauson-Khand strategy for the synthesis of the deschloro carbocyclic core of the palau'amines and styloguanidines.

Stefan G Koenig, Stefan M Miller, Kristi A Leonard, Ralf S Löwe, Betty C Chen, David J Austin,

A stereocontrolled route to the deschloro cyclopentyl core of the palau'amines and styloguanidines has been developed. This strategy makes use of the intramolecular Pauson-Khand cyclization of an enyne with a "transient N-O tether" to construct a five-membered carbocycle in a diastereoselective fashion. [reaction: see text] ... Read more >>

Org. Lett. (Organic letters)
[2003, 5(13):2203-2206]

Cited: 20 times

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