Browsing CHEM Faculty Scholarship by Author "Alliston, Kevin R."
Now showing items 1-20 of 36
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1,2,5-Thiadiazolidin-3-one 1,1-dioxide-based heterocyclic sulfides are potent inhibitors of human tryptase
Wong, Tzutshin; Groutas, Christopher S.; Mohan, Swathi; Lai, Zhong; Alliston, Kevin R.; Vu, Nga T.; Schechter, Norman M.; Groutas, William C. (Elsevier, 2005-04-01)We describe herein the design, synthesis, and in vitro biochemical evaluation of a series of potent, time-dependent inhibitors of the mast cell-derived serine protease tryptase. The inhibitors were readily obtained by ... -
Broad-spectrum antivirals against 3C or 3C-like proteases of picornaviruses, noroviruses, and coronaviruses
Kim, Yunjeong; Lovell, Scott; Tiew, Kok-Chuan; Mandadapu, Sivakoteswara Rao; Alliston, Kevin R.; Battaile, Kevin P.; Groutas, William C.; Chang, Kyeong-Ok (American Society of Microbiology, 2012-08-22)Phylogenetic analysis has demonstrated that some positive-sense RNA viruses can be classified into the picornavirus-like supercluster, which includes picornaviruses, caliciviruses, and coronaviruses. These viruses possess ... -
Chiral multisubstrate inhibitors of dopamine beta-monooxygenase: evidence for dual modes of interaction
Wimalasena, Kandatege; Wimalasena, D. Shyamali; Dharmasena, Silpadipathialage; Haines, Donovan C.; Alliston, Kevin R. (American Chemical Society, 1997-06-10)The electronic and steric constraints of the dopamine beta-monooxygenase (DbetaM; E.C. 1.14.17.1) active site were studied using a series of chiral bisubstrate inhibitors. The (R) and (S) enantiomers of 5-phenyl-2-thiooxazolidone ... -
Cyclosulfamide-based derivatives as inhibitors of noroviruses
Dou, Dengfeng; Mandadapu, Sivakoteswara Rao; Alliston, Kevin R.; Kim, Yunjeong; Chang, Kyeong-Ok; Groutas, William C. (Elsevier, 2011-10-20)An optimization campaign focused on improving pharmacological activity and physicochemical properties of a recently-identified class of cyclosulfamide-based norovirus inhibitors has been carried out. Dimeric compound 4 was ... -
Design and synthesis of inhibitors of noroviruses by scaffold hopping
Dou, Dengfeng; Mandadapu, Sivakoteswara Rao; Alliston, Kevin R.; Kim, Yunjeong; Chang, Kyeong-Ok; Groutas, William C. (Elsevier, 2011-10-01)A scaffold hopping strategy was employed to identify new chemotypes that inhibit noroviruses. The replacement of the cyclosulfamide scaffold by an array of heterocyclic scaffolds lead to the identification of additional ... -
Design, synthesis and characterization of novel 1,2-benzisothiazol-3(2H)-one and 1,3,4-oxadiazole hybrid derivatives: Potent inhibitors of Dengue and West Nile virus NS2B/NS3 proteases
Lai, Huiguo; Dou, Dengfeng; Aravapalli, Sridhar; Teramoto, Tadahisa; Lushington, Gerald H.; Mwania, Tom M.; Alliston, Kevin R.; Eichhorn, David M.; Padmanabhan, Radhakrishnan; Groutas, William C. (PERGAMON-ELSEVIER SCIENCE LTD, 2013-01)1,2-Benzisothiazol-3(2H)-ones and 1,3,4-oxadiazoles individually have recently attracted considerable interest in drug discovery, including as antibacterial and antifungal agents. In this study, a series of functionalized ... -
Design, synthesis, and bioevaluation of viral 3C and 3C-like protease inhibitors
Prior, Allan M.; Kim, Yunjeong; Weerasekara, Sahani; Moroze, Meghan; Alliston, Kevin R.; Uy, Roxanne Adeline Z.; Groutas, William C.; Chang, Kyeong-Ok; Hua, Duy H. (Elsevier Ltd, 2013-12-01)A class of tripeptidyl transition state inhibitors containing a P1 glutamine surrogate, a P2 leucine, and a P3 arylalanines, was found to potently inhibit Norwalk virus replication in enzyme and cell based assays. An array ... -
Design, synthesis, and evaluation of inhibitors of Norwalk virus 3C protease
Tiew, Kok-Chuan; He, Guijia; Aravapalli, Sridhar; Mandadapu, Sivakoteswara Rao; Gunnam, Mallikarjuna Reddy; Alliston, Kevin R.; Lushington, Gerald H.; Kim, Yunjeong; Chang, Kyeong-Ok; Groutas, William C. (Elsevier, 2011-09-15)The first series of peptidyl aldehyde inhibitors that incorporate in their structure a glutamine surrogate has been designed and synthesized based on the known substrate specificity of Norwalk virus 3C protease. The ... -
Design, synthesis, and evaluation of novel prodrugs of transition state inhibitors of norovirus 3CL protease
Kankanamalage, Anushka C. Galasiti; Kim, Yunjeong; Rathnayake, Athri D.; Alliston, Kevin R.; Butler, Michelle M.; Cardinale, Steven C.; Bowlin, Terry L.; Groutas, William C.; Chang, Kyeong-Ok (American Chemical Society, 2017-07-03)Ester and carbamate prodrugs of aldehyde bisulfite adduct inhibitors were synthesized in order to improve their pharmacokinetic and pharmacodynamic properties. The inhibitory activity of the compounds against norovirus ... -
Design, synthesis, and in vitro evaluation of inhibitors of human leukocyte elastase based on a functionalized cyclic sulfamide scaffold
Zhong, Jiaying; Gan, Xiangdong; Alliston, Kevin R.; Groutas, William C. (Elsevier, 2004-02-01)The design of novel functionalized templates capable of binding to the active site of serine proteases could potentially lead to the development of potent and highly selective non-covalent inhibitors of these enzymes. Using ... -
Design, synthesis, and in vitro evaluation of potential West Nile virus protease inhibitors based on the 1-oxo-1,2,3,4-tetrahydroisoquinoline and 1-oxo-1,2-dihydroisoquinoline scaffolds
Dou, Dengfeng; Viwanathan, Prasanth; Li, Yi; He, Guijia; Alliston, Kevin R.; Lushington, Gerald H.; Brown-Clay, Joshua D.; Padmanabhan, Radhakrishnan; Groutas, William C. (American Chemical Society, 2010-11-08)The 1-oxo-1, 2, 3, 4-tetrahydroisoquinoline and 1-Oxo-1, 2-dihydroisoquinoline scaffolds were utilized in the design and solution phase synthesis of focused libraries of compounds for screening against West Nile Virus (WNV) ... -
Dual function inhibitors of relevance to chronic obstructive pulmonary disease
Dou, Dengfeng; He, Guijia; Alliston, Kevin R.; Groutas, William C. (Elsevier, 2011-05-15)The general strategy and rationale underlying the design of COPD therapeutics that possess protease inhibitory activity and are also capable of releasing a species that attenuates inflammation by inhibiting caspase-1, are ... -
Inactivation of human neutrophil elastase by 1,2,5-thiadiazolidin-3-one 1,1 dioxide-based sulfonamides
Li, Yi; Yang, Qingliang; Dou, Dengfeng; Alliston, Kevin R.; Groutas, William C. (Elsevier, 2008-01-15)The interaction of a series of 1,2,5-thiadiazolidin-3-one 1,1 dioxide-based sulfonamides with neutrophil-derived serine proteases was investigated. The nature of the amino acid component, believed to be oriented toward the ... -
Inhibition of Dengue virus and West Nile virus proteases by click chemistry-derived benz[d]isothiazol-3(2H)-one derivatives
Tiew, Kok-Chuan; Dou, Dengfeng; Teramoto, Tadahisa; Lai, Huiguo; Alliston, Kevin R.; Lushington, Gerald H.; Padmanabhan, Radhakrishnan; Groutas, William C. (Elsevier, 2012-02)Two click chemistry-derived focused libraries based on the benz[d]isothiazol-3(2H)-one scaffold were synthesized and screened against Dengue virus and West Nile virus NS2B-NS3 proteases. Several compounds (4l, 7j-n) displayed ... -
Inhibition of norovirus 3CL protease by bisulfite adducts of transition state inhibitors
Mandadapu, Sivakoteswara Rao; Gunnam, Mallikarjuna Reddy; Tiew, Kok-Chuan; Uy, Roxanne Adeline Z.; Prior, Allan M.; Alliston, Kevin R.; Hua, Duy H.; Kim, Yunjeong; Chang, Kyeong-Ok; Groutas, William C. (PERGAMON-ELSEVIER SCIENCE LTD, 2013-01)Noroviruses are the most common cause of acute viral gastroenteritis, accounting for >21 million cases annually in the US alone. Norovirus infections constitute an important health problem for which there are no specific ... -
Inhibition of serine proteases by a new class of cyclosulfamide-based carbamylating agents
Yang, Qingliang; Li, Yi; Dou, Dengfeng; Gan, Xiangdong; Mohan, Swathi; Groutas, Christopher S.; Stevenson, Laura E.; Lai, Zhong; Alliston, Kevin R.; Zhong, Jiaying; Williams, Todd D.; Groutas, William C. (Elsevier, 2008-07-15)A new class of carbamylating agents based on the cyclosulfamide scaffold is reported. These compounds were found to be efficient time-dependent inhibitors of human neutrophil elastase (HNE). Exploitation of the three sites ... -
Inhibitors of Dengue Virus and West Nile Virus proteases based on the aminobenzamide scaffold
Aravapalli, Sridhar; Lai, Huiguo; Teramoto, Tadahisa; Alliston, Kevin R.; Lushington, Gerald H.; Ferguson, Eron L.; Padmanabhan, Radhakrishnan; Groutas, William C. (Elsevier, 2012-05-10)Dengue and West Nile viruses (WNV) are mosquito-borne members of flaviviruses that cause significant morbidity and mortality. There is no approved vaccine or antiviral drugs for human use to date. In this study, a series ... -
Inhibitors of human neutrophil elastase based on a highly functionalized N-amino-4-imidazolidinone scaffold
He, Guijia; Dou, Dengfeng; Wei, Liuqing; Alliston, Kevin R.; Groutas, William C. (Elsevier, 2010-09-01)A series of compounds based on the N-amino-4-imidazolidinone scaffold was synthesized and screened against human neutrophil elastase (HNE). These studies lead to the identification of a selective, low micromolar reversible ... -
Macrocyclic Inhibitors of 3C and 3C-like Proteases of Picornavirus, Norovirus, and Coronavirus
Mandadapu, Sivakoteswara Rao; Weerawarna, Pathum M.; Prior, Allan M.; Uy, Roxanne Adeline Z.; Aravapalli, Sridhar; Alliston, Kevin R.; Lushington, Gerald H.; Kim, Yunjeong; Hua, Duy H.; Chang, Kyeong-Ok; Groutas, William C. (Elsevier, 2013-05-16)The design, synthesis, and in vitro evaluation of the first macrocyclic inhibitor of 3C and 3C-like proteases of picornavirus, norovirus, and coronavirus are reported. The in vitro inhibitory activity (50% effective ... -
Mechanism-based inactivation of human leukocyte elastase via an enzyme-induced sulfonamide fragmentation process
Wei, Liuqing; Lai, Zhong; Gan, Xiangdong; Alliston, Kevin R.; Zhong, Jiaying; Epp, Jeffrey B.; Tu, Juan; Perera, Asiri B.; Van Stipdonk, Michael J.; Groutas, William C. (Elsevier, 2004-09-01)We describe herein the design and in vitro biochemical evaluation of a novel class of mechanism-based inhibitors of human leukocyte elastase (HLE) that inactivate the enzyme via an unprecedented enzyme-induced sulfonamide ...