172833-41-9Relevant academic research and scientific papers
Design and synthesis of selective keto-1,2,4-oxadiazole-based tryptase inhibitors
Palmer, James T.,Rydzewski, Robert M.,Mendonca, Rohan V.,Sperandio, David,Spencer, Jeffrey R.,Hirschbein, Bernard L.,Lohman, Julia,Beltman, Jeri,Nguyen, Margaret,Liu, Liang
, p. 3434 - 3439 (2006)
Using a scaleable, directed library approach based on orthogonally protected advanced intermediates, we have prepared a series of potent keto-1,2,4-oxadiazoles designed to explore the P2 binding pocket of human mast cell tryptase, while buildin
Dynamics Determine Signaling in a Multicomponent System Associated with Rheumatoid Arthritis
Lindgren, Cecilia,Tyagi, Mohit,Viljanen, Johan,Toms, Johannes,Ge, Changrong,Zhang, Naru,Holmdahl, Rikard,Kihlberg, Jan,Linusson, Anna
, p. 4774 - 4790 (2018/05/15)
Strategies that target multiple components are usually required for treatment of diseases originating from complex biological systems. The multicomponent system consisting of the DR4 major histocompatibility complex type II molecule, the glycopeptide CII259-273 from type II collagen, and a T-cell receptor is associated with development of rheumatoid arthritis (RA). We introduced non-native amino acids and amide bond isosteres into CII259-273 and investigated the effect on binding to DR4 and the subsequent T-cell response. Molecular dynamics simulations revealed that complexes between DR4 and derivatives of CII259-273 were highly dynamic. Signaling in the overall multicomponent system was found to depend on formation of an appropriate number of dynamic intramolecular hydrogen bonds between DR4 and CII259-273, together with the positioning of the galactose moiety of CII259-273 in the DR4 binding groove. Interestingly, the system tolerated modifications at several positions in CII259-273, indicating opportunities to use analogues to increase our understanding of how rheumatoid arthritis develops and for evaluation as vaccines to treat RA.
Design of novel, potent, and selective human β-tryptase inhibitors based on α-keto-[1,2,4]-oxadiazoles
Lee, Chang-Sun,Liu, Weili,Sprengeler, Paul A.,Somoza, John R.,Janc, James W.,Sperandio, David,Spencer, Jeffrey R.,Green, Michael J.,McGrath, Mary E.
, p. 4036 - 4040 (2007/10/03)
A series of novel α-keto-[1,2,4]-oxadiazoles has been synthesized as human tryptase inhibitors for evaluation as a new class of anti-asthmatic agent. The inhibitor design is focused on using a prime-side hydrophobic pocket and the S2 pocket of β-tryptase
Novel, potent, selective, and orally bioavailable human βII-tryptase inhibitors
Sperandio, David,Tai, Vincent W.-F.,Lohman, Julia,Hirschbein, Bernie,Mendonca, Rohan,Lee, Chang-Sun,Spencer, Jeffrey R.,Janc, James,Nguyen, Margaret,Beltman, Jerlyn,Sprengeler, Paul,Scheerens, Heleen,Lin, Tong,Liu, Liang,Gadre, Ashwini,Kellogg, Alisha,Green, Michael J.,McGrath, Mary E.
, p. 4085 - 4089 (2007/10/03)
The synthesis of novel [1,2,4]oxadiazoles and their structure-activity relationship (SAR) for the inhibition of tryptase and related serine proteases is presented. Elaboration of the P′-side afforded potent, selective, and orally bioavailable tryptase inhibitors.
ACTIVE KETONE INHIBITORS OF TRYPTASE
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Page/Page column 106, (2008/06/13)
The present invention related to certain active tetracyclic ketone inhibitors of tryptase, pharmaceutical composition comprising these compounds and methods of treating asthma, allergic rhinitis, and/or Chronic Obstructive Pulmonary Disease utilizing thes
Synthesis and antinociceptive activity of some novel nonpeptide derivatives of interleukin-1β (193-195) sequence
Fantetti, Lia,Adembri, Giorgio,Giotti, Alberto,Masini, Ilaria,Roncucci, Gabrio
, p. 137 - 143 (2007/10/03)
The synthesis of a new series of nonpeptide derivatives of interleukin- 1β sequence is described. Compounds have been investigated for their relative activity regarding antinociception and suppression of inflammation. Several compounds with R1(
