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Judith Huggan

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Organization: University of Strathclyde
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Identification and development of the 1,4-benzodiazepin-2-one and quinazoline-2,4-dione scaffolds as submicromolar inhibitors of HAT
Co-reporter:Rachel L. Clark, Carol J. Clements, Michael P. Barrett, Simon P. Mackay, Rajendra P. Rathnam, George Owusu-Dapaah, John Spencer, Judith K. Huggan
Bioorganic & Medicinal Chemistry 2012 Volume 20(Issue 20) pp:6019-6033
Publication Date(Web):15 October 2012
DOI:10.1016/j.bmc.2012.08.049
A library of 1,4-benzodiazepines has been synthesised and evaluated for activity against Trypanosoma brucei, a causative parasite of Human African Trypanosomiasis (HAT). The most potent of these derivatives has an MIC value of 0.97 μM. Herein we report the design, synthesis and biological evaluation of the abovementioned compounds.A library of 1,4-benzodiazepines and quinazoline-2,4-diones has been synthesised that display MIC values as low as 0.97 μM against Trypanosoma brucei.
Prophylactic and therapeutic treatment with a synthetic analogue of a parasitic worm product prevents experimental arthritis and inhibits IL-1β production via NRF2-mediated counter-regulation of the inflammasome
Co-reporter:Justyna Rzepecka, Miguel A. Pineda, Lamyaa Al-Riyami, David T. Rodgers, Judith K. Huggan, Felicity E. Lumb, Abedawn I. Khalaf, Paul J. Meakin, Marlene Corbet, Michael L. Ashford, Colin J. Suckling, Margaret M. Harnett, William Harnett
Journal of Autoimmunity (June 2015) Volume 60() pp:59-73
Publication Date(Web):1 June 2015
DOI:10.1016/j.jaut.2015.04.005
•SMA-12b is a mimetic of the active PC-moiety of the helminth immunomodulator, ES-62.•SMA-12b effectively protects mice against collagen-induced arthritis (CIA).•SMA-12b downregulates IL-1β and inflammasome genes via activation of NRF2.•SMA-12b reduces IL-1β in the joints of mice with CIA.Rheumatoid arthritis (RA) remains a debilitating autoimmune condition as many patients are refractory to existing conventional and biologic therapies, and hence successful development of novel treatments remains a critical requirement. Towards this, we now describe a synthetic drug-like small molecule analogue, SMA-12b, of an immunomodulatory parasitic worm product, ES-62, which acts both prophylactically and therapeutically against collagen-induced arthritis (CIA) in mice. Mechanistic analysis revealed that SMA-12b modifies the expression of a number of inflammatory response genes, particularly those associated with the inflammasome in mouse bone marrow-derived macrophages and indeed IL-1β was the most down-regulated gene. Consistent with this, IL-1β was significantly reduced in the joints of mice with CIA treated with SMA-12b. SMA-12b also increased the expression of a number of genes associated with anti-oxidant responses that are controlled by the transcription factor NRF2 and critically, was unable to inhibit expression of IL-1β by macrophages derived from the bone marrow of NRF2−/− mice. Collectively, these data suggest that SMA-12b could provide the basis of an entirely novel approach to fulfilling the urgent need for new treatments for RA.Download full-size image
4-Chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-2-amine
4-Chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-2-amine
CAS:873792-88-2
4-Chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-2-amine
Acetamide, N-(4-chloro-1H-pyrrolo[2,3-d]pyrimidin-2-yl)-2,2,2-trifluoro-
Acetamide, N-(4-chloro-1H-pyrrolo[2,3-d]pyrimidin-2-yl)-2,2,2-trifluoro-
CAS:873792-85-9
Acetamide, N-(4-chloro-1H-pyrrolo[2,3-d]pyrimidin-2-yl)-2,2,2-trifluoro-
4-THIAZOLECARBOXYLIC ACID, 2-AMINO-5-(2-PHENYLETHYL)-, METHYL ESTER
4-THIAZOLECARBOXYLIC ACID, 2-AMINO-5-(2-PHENYLETHYL)-, METHYL ESTER
CAS:710348-76-8
4-THIAZOLECARBOXYLIC ACID, 2-AMINO-5-(2-PHENYLETHYL)-, METHYL ESTER
2,4,6-Pyrimidinetriamine, 5-(2-nitro-1-phenylethyl)-
2,4,6-Pyrimidinetriamine, 5-(2-nitro-1-phenylethyl)-
CAS:591254-73-8
2,4,6-Pyrimidinetriamine, 5-(2-nitro-1-phenylethyl)-
4-THIAZOLECARBOXYLIC ACID, 2-(ACETYLAMINO)-5-(1-METHYLETHYL)-
4-THIAZOLECARBOXYLIC ACID, 2-(ACETYLAMINO)-5-(1-METHYLETHYL)-
CAS:566947-03-3
4-THIAZOLECARBOXYLIC ACID, 2-(ACETYLAMINO)-5-(1-METHYLETHYL)-
4(1H)-Pyrimidinone, 2,6-diamino-5-(2-nitro-1-phenylethyl)-
4(1H)-Pyrimidinone, 2,6-diamino-5-(2-nitro-1-phenylethyl)-
CAS:259145-29-4
4(1H)-Pyrimidinone, 2,6-diamino-5-(2-nitro-1-phenylethyl)-
4H-Pyrrolo[2,3-d]pyrimidin-4-one,2-amino-3,7-dihydro-5-phenyl-
4H-Pyrrolo[2,3-d]pyrimidin-4-one,2-amino-3,7-dihydro-5-phenyl-
CAS:259145-28-3
4H-Pyrrolo[2,3-d]pyrimidin-4-one,2-amino-3,7-dihydro-5-phenyl-
4(1H)-Pyrimidinone, 2,6-diamino-5-[1-(nitromethyl)-3-phenylpropyl]-
4(1H)-Pyrimidinone, 2,6-diamino-5-[1-(nitromethyl)-3-phenylpropyl]-
CAS:259145-27-2
4(1H)-Pyrimidinone, 2,6-diamino-5-[1-(nitromethyl)-3-phenylpropyl]-
1H-Pyrrolo[2,3-d]pyrimidine-2,4-diamine, 5-phenyl-
1H-Pyrrolo[2,3-d]pyrimidine-2,4-diamine, 5-phenyl-
CAS:170170-15-7
1H-Pyrrolo[2,3-d]pyrimidine-2,4-diamine, 5-phenyl-
Benzene, [(3E)-4-nitro-3-butenyl]-
Benzene, [(3E)-4-nitro-3-butenyl]-
CAS:169775-70-6
Benzene, [(3E)-4-nitro-3-butenyl]-