Modulation of tissue transglutaminase activation in disease
AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsChaitan Khosla, Thomas DiRaimondo, Cornelius Kloeck
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Abstract
Compositions and methods are provided for modulating the physiological activation of tissue transglutaminase (TG2); which methods can include inhibiting the activity of TG2 associated with inflammatory disorders, which disorders may include, without limitation, sepsis, ischemic reperfusion injury, renal fibrosis, and the like.
Claims12
An isolated compound having a structure:
- wherein:
- Z is O or NH or NCH3;
- and
- R2 is optionally substituted aryl or optionally substituted heteroaryl.
An isolated compound having a structure:
- wherein:
- R is halogen, OR1, CN, C1-C6alkyl;
- and
- R1 is H, C1-C6alkyl, or C3-C8cycloalkyl.
An isolated compound having a structure:
- wherein
- X is a bond;
- R is halogen, OR1, CN, C1-C6alkyl;
- and
- R1 is H, C1-C6alkyl, or C3-C8cycloalkyl.
An isolated compound having a structure:
- wherein
- R is halogen, OR1, CN, C1-C6alkyl;
- and
- R1 is H, C1-C6alkyl, or C3-C8cycloalkyl.
An isolated compound selected from:
- (2S,4R)-quinolin-3-ylmethyl 4-benzamido-2-((((S)-3-bromo-4,5-dihydroisoxazol-5-yl)methyl)carbamoyl)pyrrolidine-1-carboxylate;
- (2S,4R)-quinolin-3-ylmethyl 2-((((S)-3-bromo-4,5-dihydroisoxazol-5-yl)methyl) carbamoyl)-4-(2-hydroxybenzamido)pyrrolidine-1-carboxylate;
- (2S,4R)-quinolin-3-ylmethyl 2-((((S)-3-bromo-4,5-dihydroisoxazol-5-yl)methyl) carbamoyl)-4-(3-hydroxybenzamido)pyrrolidine-1-carboxylate;
- (2S,4R)-quinolin-3-ylmethyl 2-((((S)-3-bromo-4,5-dihydroisoxazol-5-yl)methyl) carbamoyl)-4-(4-hydroxybenzamido)pyrrolidine-1-carboxylate;
- (2S,4R)-quinolin-3-ylmethyl 2-((((S)-3-bromo-4,5-dihydroisoxazol-5-yl)methyl)carbamoyl)-4-(nicotinamido)pyrrolidine-1-carboxylate;
- (2S,4R)-quinolin-3-ylmethyl 2-((((S)-3-bromo-4,5-dihydroisoxazol-5-yl)methyl) carbamoyl)-4-(pyrazine-2-carboxamido)pyrrolidine-1-carboxylate;
- 1-(((3R,5S)-5-((((S)-3-bromo-4,5-dihydroisoxazol-5-yl)methyl)carbamoyl)-1-((quinolin-3-ylmethoxy)carbonyl)pyrrolidin-3-yl)carbamoyl) cyclobutanecarboxylic acid;
- (2S,4S)-quinolin-3-ylmethyl 2-((((S)-3-bromo-4,5-dihydroisoxazol-5-yl)methyl)carbamoyl)-4-phenylpyrrolidine-1-carboxylate;
- (2S,4R)-quinolin-3-ylmethyl 2-((((S)-3-bromo-4,5-dihydroisoxazol-5-yl)methyl)carbamoyl)-4-phenylpyrrolidine-1-carboxylate;
- (2S,4S)-quinolin-3-ylmethyl 2-((((S)-3-bromo-4,5-dihydroisoxazol-5-yl)methyl)carbamoyl)-4-(2-hydroxyphenyl)pyrrolidine-1-carboxylate;
- (2S,4S)-quinolin-3-ylmethyl 2-((((S)-3-bromo-4,5-dihydroisoxazol-5-yl)methyl) carbamoyl)-4-(3-hydroxyphenyl)pyrrolidine-1-carboxylate;
- (2S,4S)-quinolin-3-ylmethyl 2-((((S)-3-bromo-4,5-dihydroisoxazol-5-yl)methyl) carbamoyl)-4-(4-hydroxyphenyl)pyrrolidine-1-carboxylate;
- (2S,4S)-quinolin-3-ylmethyl 2-((((S)-3-bromo-4,5-dihydroisoxazol-5-yl)methyl) carbamoyl)-4-(3-chlorophenyl)pyrrolidine-1-carboxylate;
- (2S,4S)-quinolin-3-ylmethyl 2-((((S)-3-bromo-4,5-dihydroisoxazol-5-yl)methyl) carbamoyl)-4-(4-chlorophenyl)pyrrolidine-1-carboxylate;
- (2S,4S)-quinolin-3-ylmethyl 2-((((S)-3-bromo-4,5-dihydroisoxazol-5-yl)methyl)carbamoyl)-4-(5-fluoro-1H-indol-3-yl)pyrrolidine-1-carboxylate;
- (S)-quinolin-3-ylmethyl 2-((((S)-3-bromo-4,5-dihydroisoxazol-5-yl)methyl) carbamoyl)-4-phenyl-2,5-dihydro-1H-pyrrole-1-carboxylate.
An isolated compound (2S,4R)-quinolin-3-ylmethyl 2-((((S)-3-bromo-4,5-dihydroisoxazol-5-yl)methyl)carbamoyl)-4-(nicotinamido)pyrrolidine-1-carboxylate.
Dependencies are inferred from the claim text.