3.4.22.51 additional information pro-region of the trypanosomal enzyme inhibits the enzyme function, cystatins and kininogens are inhibitors, overview: inhibitors 2 3.4.22.51 additional information in general immunoglobulin G fractions isolated from rabbits immunised with rabbit apha2-macroglobulin-recombinant catalytic domain of congopain-complexes are the most inhibitory towards the proteolytic activity of congopain. Antibodies produced by rabbits immunised with recombinant catalytic domain of congopain in Freund's adjuvant are generally found to weakly inhibit congopain with a maximum of 40% 2 3.4.22.51 additional information synthesis of 2-hydrazolyl-4-thiazolidinones based on multicomponent reactions and biological evaluation against Trypanosoma cruzi, inhibitory potencies and cytotoxic effects, molecular modeling and QSAR studies, overview. No inhibition by (RS)-2-(2-(2-bromobenzylidene)hydrazono)-3-methyl-4-oxo-5-thiazolidine-N-methylacetamide and (Z)-((2-(4-fluorobenzylidene)hydrazono)-3-methyl-5-methoxycarbonylmethylene)thiazolidin-4-one at 0.1 mM 2 3.4.22.51 additional information synthesis and inhibitory effects against cruzipaon of a series of thirty-three chalcone and seven hydrazide derivatives, overview 2 3.4.22.51 additional information AM1 semi-empirical molecular modeling studies analysing cruzain inhibitory activity, overview 2 3.4.22.51 additional information 0.01% (v/v) of Triton X-100 does not interfere with enzyme activity 2 3.4.22.51 additional information not inhibited by CA-074-OMe 2 3.4.22.51 additional information the AS2 site as a target for the design of cruzain inhibitors is limited 2 3.4.22.51 additional information apolar substituents or halogen atom substitution at the aryl position improved cruzain inhibition and antiparasitic activity in comparison to unsubstituted thiosemicarbazone 2 3.4.22.51 additional information nitrile-based inhibitors are efficient inhibitors of cruzain that bind by forming a covalent bond with this enzyme 2 3.4.22.51 Triton X-100 non-specific inhibition in the presence of 0.02% (v/v) Triton X-100 61 3.4.22.51 1,10-phenanthroline - 62 3.4.22.51 iodoacetamide - 67 3.4.22.51 Urea 70% inhibition at 5 M 116 3.4.22.51 leupeptin - 217 3.4.22.51 leupeptin 1 microM 217 3.4.22.51 captopril - 469 3.4.22.51 chymostatin - 511 3.4.22.51 antipain - 520 3.4.22.51 E-64 - 559 3.4.22.51 E-64 complete inhibition at 0.1 mM inhibitor and 140 nM enzyme 559 3.4.22.51 guanidine hydrochloride activates at low concentrations but inhibits above 2 M 1048 3.4.22.51 alpha2-Macroglobulin 40% inhibition at a 1:1 ratio of cruzipain and alpha2-macroglobulin 1068 3.4.22.51 heparan sulfate - 1073 3.4.22.51 trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane irreversible inhibitor 1306 3.4.22.51 trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane - 1306 3.4.22.51 trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane 1 microM 1306 3.4.22.51 cystatin - 1600 3.4.22.51 cystatin C - 1994 3.4.22.51 nifurtimox 25 microM 3221 3.4.22.51 KSCN activates at low concentrations but inhibits above 1 M 3346 3.4.22.51 azocasein substrate inhibition 4081 3.4.22.51 chicken cystatin - 4082 3.4.22.51 nitrofurazone a 5-nitro-2-furfurylidenesemicarbazone, presents 90% inhibitory activity against amastigotes in LLC-MK2 cell culture infected with amastigote and trypomastigote forms of the parasite, leads to parasite recrudescence in trypomastigotes on the 15th day at 0.005 mM 4346 3.4.22.51 Amphotericin B - 5518 3.4.22.51 primaquine active against cruzipain, design of selective prodrugs Lys-Arg-primaquine, Phe-Ala-primaquine, and Phe-Arg-primaquine to be cleaved by the enzyme in vivo and selectively inhibiting it, overview 5715 3.4.22.51 Human cystatin C - 6677 3.4.22.51 benzyloxycarbonyl-Phe-Arg-aminomethyl coumarin substrate inhibition 6785 3.4.22.51 cystatin A - 7539 3.4.22.51 chagasin - 7723 3.4.22.51 chagasin computational protocol allows the identification and prediction of thermodynamics binding energy parameters for cruzipain/chagasin-like heterodimers 7723 3.4.22.51 cystatin B - 9663 3.4.22.51 (p-methoxyphenylthiolato-S)[2,6-bis[(mercapto-kappaS)methyl]pyridine-kappaN] oxorhenium(V) - 10222 3.4.22.51 Stefin A - 10951 3.4.22.51 L-kininogen - 11007 3.4.22.51 L-kininogen high molecular weight kininogen, inhibition decreases 10fold in presence of 0.1 mM heparan sulfate 11007 3.4.22.51 Stefin B - 12910 3.4.22.51 propeptide of cruzipain PCZ, is also a good inhibitor of brucipain from Trypanosoma brucei. The propeptide of cruzipain does not inhibit human cathepsins S, K or B or papain at the tested concentrations, and moderately inhibits human cathepsin V. Human cathepsin F is very efficiently inhibited (Ki of 32 picomol/L) 14203 3.4.22.51 benznidazole presents 80% inhibitory activity against amastigotes in LLC-MK2 cell culture infected with amastigote and trypomastigote forms of the parasite, leads to parasite recrudescence in trypomastigotes on the 15th day at 0.01 mM 14356 3.4.22.51 aceto[2,6-bis[(butylthio-jS)methyl]phenyl-kappaC]-,(SP-4-3)-palladium(II) - 14671 3.4.22.51 chloro[2,2'-(thio-kappaS)bis[ethanethiolato-kappaS]] oxorhenium(V) - 14672 3.4.22.51 (methanethiolato)[2,2'-(thio-kappaS)bis[ethanethiolato-kappaS]] oxorhenium (V) - 14673 3.4.22.51 (2E)-3-(1,3-benzodioxol-5-yl)-1-(2-hydroxyphenyl)prop-2-en-1-one - 18875 3.4.22.51 N-carbobenzoxy-VVR-4-nitroanilide strong substrate inhibition 22137 3.4.22.51 (3S,5R,10R)-N-benzyl-3-(2-methylpropyl)-2-oxo-10-[(E)-2-(phenylsulfonyl)ethenyl]-1,4-diazecane-5-carboxamide - 26088 3.4.22.51 (3S,5R,11R)-N-benzyl-3-(2-methylpropyl)-2-oxo-11-[(E)-2-(phenylsulfonyl)ethenyl]-1,4-diazacycloundecane-5-carboxamide - 26089 3.4.22.51 Nalpha-[(2R,3E)-2-benzyl-4-(phenylsulfonyl)but-3-enoyl]-N-[(4-methylpiperazin-1-yl)carbonyl]-L-phenylalaninamide - 26159 3.4.22.51 chagasin mutant W93A - 26678 3.4.22.51 chagasin mutant P30A - 26679 3.4.22.51 chagasin mutant T31A - 26680 3.4.22.51 chagasin mutant T31V - 26681 3.4.22.51 chagasin mutant T31S - 26682 3.4.22.51 chagasin mutant T31Y - 26683 3.4.22.51 chagasin mutant T32A - 26684 3.4.22.51 chagasin mutant T32S - 26685 3.4.22.51 chagasin mutant T32Y - 26686 3.4.22.51 chagasin mutant T32V - 26687 3.4.22.51 chagasin mutant T31A/T32A - 26688 3.4.22.51 diaceto[2-[(2-pyridinyl-kappaN)methyl]-phenyl-kappaC]Au(III)-,(SP-4-3) - 26689 3.4.22.51 (2(1H)-pyridinethionato-kappaS2)[2,6-bis[(mercapto-KappaS)methyl]pyridine-kappaN1] oxorhenium(V) - 26690 3.4.22.51 benzofuroxan-5-carboxaldehyde thiosemicarbazone 0.1 mM, 7% of inhibition 38987 3.4.22.51 N4-allyl benzofuroxan-5-carboxaldehyde thiosemicarbazone 0.1 mM, 36% of inhibition 38988 3.4.22.51 4-(benzofuroxan-5-ylmethyloxy)benzaldehyde amidinohydrazone - 38989 3.4.22.51 (2E)-3-(1,3-benzodioxol-5-yl)-1-(4-bromophenyl)prop-2-en-1-one - 40282 3.4.22.51 (2E)-3-(4-methoxyphenyl)-1-(naphthalen-2-yl)prop-2-en-1-one - 41852 3.4.22.51 L-trans-epoxysuccinylleucylamido(4-guanidino)butane strong inhibitor 51152 3.4.22.51 L-trans-epoxysuccinylleucylamido(4-guanidino)butane - 51152 3.4.22.51 benzyloxycarbonyl-Phe-Ala-fluoromethylketone - 51551 3.4.22.51 (3Z)-1H-indole-2,3-dione 3-thiosemicarbazone IC50: 0.008 mM 58573 3.4.22.51 (3Z)-5-methyl-1H-indole-2,3-dione 3-thiosemicarbazone IC50: 0.02-0.05 mM 58574 3.4.22.51 5-fluoro-1H-indole-2,3-dione IC50: 0.03 mM 58575 3.4.22.51 (3Z)-5-chloro-1H-indole-2,3-dione 3-thiosemicarbazone IC50: 0.021 mM 58576 3.4.22.51 (3Z)-5-bromo-1H-indole-2,3-dione 3-thiosemicarbazone IC50: 0.02 mM 58577 3.4.22.51 (3Z)-5-iodo-1H-indole-2,3-dione 3-thiosemicarbazone IC50: 0.009 mM 58578 3.4.22.51 (3Z)-5-nitro-1H-indole-2,3-dione 3-thiosemicarbazone IC50: 0.03 mM 58579 3.4.22.51 (3Z)-5,7-dimethyl-1H-indole-2,3-dione 3-thiosemicarbazone IC50: 0.016 mM 58580 3.4.22.51 (3Z)-5-chloro-7-methyl-1H-indole-2,3-dione 3-thiosemicarbazone IC50: 0.0105 mM 58581 3.4.22.51 1-(2,5-dimethylbenzyl)-5-methyl-1H-indole-2,3-dione IC50: 0.08 mM 58582 3.4.22.51 1-(3-methoxybenzyl)-5-methyl-1H-indole-2,3-dione IC50: 0.002 mM 58583 3.4.22.51 1-(biphenyl-2-ylmethyl)-5-methyl-1H-indole-2,3-dione IC50: 0.0028 mM 58584 3.4.22.51 5-chloro-1-(4-chlorobenzyl)-1H-indole-2,3-dione IC50: 0.006 mM 58585 3.4.22.51 1-benzyl-5-chloro-1H-indole-2,3-dione IC50: 0.09 mM 58586 3.4.22.51 1-benzyl-5-iodo-1H-indole-2,3-dione IC50: 0.09 mM 58587 3.4.22.51 (1E)-1-(3,4-dichlorophenyl)propan-1-one thiosemicarbazone IC50: 30 nM 58588 3.4.22.51 (1E)-1-(3,4-dichlorophenyl)pentan-1-one thiosemicarbazone IC50: 19 nM 58589 3.4.22.51 (E)-cyclohexyl(3,4-dichlorophenyl)methanone thiosemicarbazone IC50: 3000 nM 58590 3.4.22.51 (1E,2E)-1-(3,4-dichlorophenyl)-3-phenylprop-2-en-1-one thiosemicarbazone IC50: 30 nM 58591 3.4.22.51 (E)-(3,4-dichlorophenyl)(4-methylphenyl)methanone thiosemicarbazone IC50: 40 nM 58592 3.4.22.51 (E)-(3,4-dichlorophenyl)(2-phenylcyclopropyl)methanone thiosemicarbazone IC50: 30 nM 58593 3.4.22.51 (1E)-1-(3-bromophenyl)propan-1-one thiosemicarbazone IC50: 310 nM 58594 3.4.22.51 benzyl 5-chloro-2,3-dioxoindoline-1-carboxylate IC50: 0.08 mM 60883 3.4.22.51 (1E)-1-(3,4-dichlorophenyl)-2-phenylethan-1-one thiosemicarbazone IC50: 80 nM 60884 3.4.22.51 (1Z)-1-(3,4-dichlorophenyl)-2-phenoxyethan-1-one thiosemicarbazone IC50: 30 nM 60885 3.4.22.51 (1E)-1-(3,4-dichlorophenyl)-3-phenylpropan-1-one thiosemicarbazone IC50: 40 nM 60886 3.4.22.51 K11777 the chemotherapeutical drug targets the major cysteine protease cruzain and disrupts amastigote intracellular development. The mechanism of drug resistance, in primary epimastigotes, is due to secretion of inactive, unprocessed cruzain 69563 3.4.22.51 K11777 - 69563 3.4.22.51 chagasin mutant delta T31-T32 - 75440 3.4.22.51 2-(N-4-chloro-benzylidenehydrazino)-4-trifluoromethyl-pyrimidine 100 microM, 80% inhibitory effect 75441 3.4.22.51 2-(N-benzylidenehydrazino)-4-trifluoromethylpyrimidine 100 microM, 30% inhibitory effect 75442 3.4.22.51 2-(N-2-methyl-benzylidenehydrazino)-4-trifluoromethyl-pyrimidine 100 microM, 45% inhibitory effect 75443 3.4.22.51 2-(N-4-methyl-benzylidenehydrazino)-4-trifluoromethyl-pyrimidine 100 microM, 40% inhibitory effect 75444 3.4.22.51 2-(N-4-methoxy-benzylidenehydrazino)-4-trifluoromethyl-pyrimidine 100 microM, 40% inhibitory effect 75445 3.4.22.51 2-(N-4-nitro-benzylidenehydrazino)-4-trifluoromethylpyrimidine 100 microM, 50% inhibitory effect 75446 3.4.22.51 2-(N-2-methyl-benzylidenehydrazino)-6-methyl-4-trifluoromethyl-pyrimidine 100 microM, 45% inhibitory effect 75447 3.4.22.51 2-(N-2-methoxy-benzylidenehydrazino)-6-methyl-4-trifluoromethyl-pyrimidine 100 microM, 20% inhibitory effect 75448 3.4.22.51 2-(N-4-chloro-benzylidenehydrazino)-6-methyl-4-trifluoro-methyl-pyrimidine 100 microM, 60% inhibitory effect 75449 3.4.22.51 N-phenyl benzofuroxan-5-carboxaldehyde thiosemicarbazone - 75450 3.4.22.51 4-(benzofuroxan-5-ylmethyloxy)benzaldehyde semicarbazone 0.1 mM, 36% of inhibition 75451 3.4.22.51 4-(benzofuroxan-5-ylmethyloxy)benzaldehyde thiosemicarbazone - 75452 3.4.22.51 2-[(benzofuroxan-5-yl)methylene]-1-(2-hydroxybenzylidene)hydrazine - 75453 3.4.22.51 2-[(benzofuroxan-5-yl)methylene]-1-(4-hydroxybenzylidene)hydrazine - 75454 3.4.22.51 2-[(benzofuroxan-5-yl)methylene]-1-(5-bromo-2-hydroxybenzylidene)hydrazine - 75455 3.4.22.51 chagasin mutant Y89S - 75456 3.4.22.51 chagasin mutant Y89F - 75457 3.4.22.51 chagasin mutant T32E - 75458 3.4.22.51 (E/Z)-N'-(2-hydroxybenzylidene)-3-phenylquinoxaline-2-hydrazide 25 microM 75459 3.4.22.51 (E/Z)-N'-(2-hydroxybenzylidene)-3-methylquinoxaline-2-hydrazide 25 microM 75460 3.4.22.51 hydroxymethylnitrofurazone presents 100% inhibitory activity against amastigotes in LLC-MK2 cell culture infected with amastigote and trypomastigote forms of the parasite, leads to complete inhibition in trypomastigotes at 0.005 mM 86538 3.4.22.51 (2E)-1-(2'-hydroxy,3'-bromo,4',6'-dimethoxyphenyl)-3-(1-naphthyl)-2-propen-1-one - 86539 3.4.22.51 (2E)-1-(3-bromo-2-hydroxy-4,6-dimethoxyphenyl)-3-(3-nitrophenyl)prop-2-en-1-one - 86540 3.4.22.51 (2E)-1-(3-bromo-2-hydroxy-4,6-dimethoxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-one - 86541 3.4.22.51 (2E)-1-(2'-hydroxy-3'-bromo-4',6'-dimethoxyphenyl)-3-(4-buthoxyphenyl)-2-propen-1- one - 86542 3.4.22.51 (2E)-1-(1,3-benzodioxol-5-yl)-3-(2,6-dichlorophenyl)-2-propen-1-one - 86543 3.4.22.51 (2E)-3-(4-bromophenyl)-1-(3a,7a-dihydro-1,3-benzodioxol-5-yl)prop-2-en-1-one - 86544 3.4.22.51 (2E)-1-(3a,7a-dihydro-1,3-benzodioxol-5-yl)-3-(4-methoxyphenyl)prop-2-en-1-one - 86545 3.4.22.51 (2E)-1-(4-hydroxy-1,3-benzodioxol-5-yl)-3-(2,4,5-trimethoxyphenyl)prop-2-en-1-one - 86546 3.4.22.51 (2E)-1-(3a,7a-dihydro-1,3-benzodioxol-5-yl)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one - 86547 3.4.22.51 (2E)-1-(3a,7a-dihydro-1,3-benzodioxol-5-yl)-3-(4-methylphenyl)prop-2-en-1-one - 86548 3.4.22.51 (2E)-1-(1,3-benzodioxol-5-yl)-3-(1-naphthyl)-2-propen-1-one - 86549 3.4.22.51 (2E)-1-(3a,7a-dihydro-1,3-benzodioxol-5-yl)-3-phenylprop-2-en-1-one - 86550 3.4.22.51 (2E)-1-(1,3-benzodioxol-5-yl)-3-(2-chlorophenyl)-2-propen-1-one - 86551 3.4.22.51 (2E)-1-(1,3-benzodioxol-5-yl)-3-(5-methylfuran-2-yl)-2-propen-1-one - 86552 3.4.22.51 (2E)-1-(3a,7a-dihydro-1,3-benzodioxol-5-yl)-3-(3-methoxyphenyl)prop-2-en-1-one - 86553 3.4.22.51 (2E)-1-(1,3-benzodioxol-5-yl)-3-(thiophen-2-yl)-2-propen-1-one - 86554 3.4.22.51 (2E)-1-(1,3-benzodioxol-5-yl)-3-(3-methoxy-4-phenoxyphenyl)prop-2-en-1-one - 86555 3.4.22.51 (2E)-1-(1,3-benzodioxol-5-yl)-3-(4-buthoxyphenyl)-2-propen-1-one - 86556 3.4.22.51 (2E)-1-(2-naphthyl)-3-(2,6-dimethoxyphenyl)-2-propen-1-one - 86557 3.4.22.51 (2E)-3-(4-fluorophenyl)-1-(naphthalen-2-yl)prop-2-en-1-one - 86558 3.4.22.51 (2E)-3-(1,3-benzodioxol-5-yl)-1-(naphthalen-2-yl)prop-2-en-1-one - 86559 3.4.22.51 (2E)-1,3-di(naphthalen-2-yl)prop-2-en-1-one - 86560 3.4.22.51 (2E)-1-(2-naphthyl)-3-(5-methylfuran-2-yl)-2-propen-1-one - 86561 3.4.22.51 (2E)-1,3-bis(2,4,5-trimethoxyphenyl)prop-2-en-1-one - 86562 3.4.22.51 (2E)-1-(2',4',5'-trimethoxyphenyl)-3-(1-naphthyl)-2-propen-1-one - 86563 3.4.22.51 (2E)-1-(2',4',5'-trimethoxyphenyl)-3-(thiophen-2-yl)-2-propen-1-one - 86564 3.4.22.51 (2E)-3-(3-methoxyphenyl)-1-(2,4,5-trimethoxyphenyl)prop-2-en-1-one - 86565 3.4.22.51 (2E)-1-(2,4-dimethoxyphenyl)-3-(2,4,5-trimethoxyphenyl)prop-2-en-1-one - 86566 3.4.22.51 (2E)-3-[4-(benzyloxy)-3-methoxyphenyl]-1-(2,4-dimethoxyphenyl)prop-2-en-1-one - 86567 3.4.22.51 N'-[(E)-(4-bromophenyl)methylidene]-3,4,5-trimethoxybenzohydrazide - 86568 3.4.22.51 3,4,5-trimethoxy-N'-[(E)-(4-nitrophenyl)methylidene]benzohydrazide - 86569 3.4.22.51 (2E)-N'-(3'-bromo-4'-hydroxy-5'-methoxybenzilidene)-3,4,5-trimethoxybenzohydrazide - 86570 3.4.22.51 (2E)-N'-(4'-hydroxy-5'-methoxybenzilidene)-3,4,5-trimethoxybenzohydrazide - 86571 3.4.22.51 3,4,5-trimethoxy-N'-[(E)-naphthalen-1-ylmethylidene]benzohydrazide - 86572 3.4.22.51 (2E)-N'-(4'-buthoxybenzilidene)-3,4,5-trimethoxybenzohydrazide - 86573 3.4.22.51 N'-[(E)-(2,6-dichlorophenyl)methylidene]-3,4,5-trimethoxybenzohydrazide - 86574 3.4.22.51 [(S)-1-carboxy-2-phenylethyl]-carbamoyl-L-Arg-L-Val-arginal - 112993 3.4.22.51 biotin-Phe-Ala-fluoromethylketone - 113148 3.4.22.51 N-carbobenzoxy-FA-diazomethylketone inhibition in vivo 113931 3.4.22.51 N-carbobenzoxy-FF-diazomethylketone inhibition in vivo 113932 3.4.22.51 N-carbobenzoxy-FK-acyloxymethylketone inhibition in vivo 113933 3.4.22.51 pregnancy zone protein 50% inhibition at a 1:1 ratio of cruzipain and pregnancy zone protein 114278 3.4.22.51 3-(4-[(1S)-1,2-dimethyl-1-[(quinolin-6-ylmethyl)amino]propyl]-1H-1,2,3-triazol-1-yl)-2-oxoheptyl 2,6-bis(trifluoromethyl)benzoate 10 microM 146925 3.4.22.51 (2S)-2-(1-[1-[(Z)-1-chloro-2-(phenylsulfonyl)ethenyl]pentyl]-1H-1,2,3-triazol-4-yl)-3-methyl-N-(quinolin-6-ylmethyl)butan-2-amine 10 microM 150393 3.4.22.51 (2S)-3-methyl-2-(1-[1-[(E)-2-(phenylsulfonyl)ethenyl]pentyl]-1H-1,2,3-triazol-4-yl)-N-(quinolin-6-ylmethyl)butan-2-amine 10 microM 150415 3.4.22.51 3-(4-[(1S)-1,2-dimethyl-1-[(quinolin-6-ylmethyl)amino]propyl]-1H-1,2,3-triazol-1-yl)-1-(2,3,5,6-tetrafluorophenoxy)heptan-2-one 10 microM 150530 3.4.22.51 3-(4-[(1S)-1,2-dimethyl-1-[(quinolin-6-ylmethyl)amino]propyl]-1H-1,2,3-triazol-1-yl)-2-oxoheptyl 2,6-dimethylbenzoate 10 microM 150531 3.4.22.51 3-(4-[(1S)-1-[(1,3-benzothiazol-6-ylmethyl)amino]-1,2-dimethylpropyl]-1H-1,2,3-triazol-1-yl)-1-(2,3,5,6-tetrafluorophenoxy)heptan-2-one 10 microM 150532 3.4.22.51 3-(4-[(1S)-1-[(1,3-benzothiazol-6-ylmethyl)amino]-1,2-dimethylpropyl]-1H-1,2,3-triazol-1-yl)-2-oxoheptyl 2,6-bis(trifluoromethyl)benzoate 10 microM 150533 3.4.22.51 Nalpha-[(2R,3E)-2-benzyl-4-(phenylsulfonyl)but-3-enoyl]-N-(morpholin-4-ylcarbonyl)-L-phenylalaninamide - 150761 3.4.22.51 2-(N-2-hydroxy-benzylidenehydrazino)-4-trifluoromethyl-pyrimidine 100 microM 151718 3.4.22.51 2-(N-2-methoxy-benzylidenehydrazino)-4-trifluoromethyl-pyrimidine 100 microM 151719 3.4.22.51 2-(N-1-phenyl-ethylidenehydrazino)-4-trifluoromethylpyrimidine 100 microM 151720 3.4.22.51 2-(N-benzylidenehydrazino)-5-methyl-4-trifluoromethyl-pyrimidine 100 microM 151721 3.4.22.51 2-(N-2-methyl-benzylidenehydrazino)-5-methyl-4-trifluoromethyl-pyrimidine 100 microM 151722 3.4.22.51 2-(N-2-hydroxy-benzylidenehydrazino)-5-methyl-4-trifluoromethyl-pyrimidine 100 microM 151723 3.4.22.51 2-(N-2-methoxy-benzylidenehydrazino)-5-methyl-4-trifluoromethyl-pyrimidine 100 microM 151724 3.4.22.51 2-(N-4-methyl-benzylidenehydrazino)-5-methyl-4-trifluoromethyl-pyrimidine 100 microM 151725 3.4.22.51 2-(N-4-chloro-benzylidenehydrazino)-5-methyl-4-trifluoro-methyl-pyrimidine 100 microM 151726 3.4.22.51 2-(N-4-methoxy-benzylidenehydrazino)-5-methyl-4-trifluoromethyl-pyrimidine 100 microM 151727 3.4.22.51 2-(N-4-nitro-benzylidenehydrazino)-5-methyl-4-trifluoromethyl-pyrimidine 100 microM 151728 3.4.22.51 2-(N-1-phenyl-ethylidenehydrazino)-5-methyl-4-trifluoro-methyl-pyrimidine 100 microM 151729 3.4.22.51 2-(N-benzylidenehydrazino)-6-methyl-4-trifluoromethyl-pyrimidine 100 microM 151730 3.4.22.51 2-(N-2-hydroxy-benzylidenehydrazino)-6-methyl-4-trifluoromethyl-pyrimidine 100 microM 151731 3.4.22.51 2-(N-4-methyl-benzylidenehydrazino)-6-methyl-4-trifluoromethyl-pyrimidine 100 microM 151732 3.4.22.51 2-(N-4-methoxy-benzylidenehydrazino)-6-methyl-4-trifluoro-methyl-pyrimidine 100 microM 151733 3.4.22.51 2-(N-4-nitro-benzylidenehydrazino)-6-methyl-4-trifluoro-methyl-pyrimidine 100 microM 151734 3.4.22.51 2-(N-1-phenyl-ethylidenehydrazino)-6-methyl-4-trifluoro-methyl-pyrimidine 100 microM 151735 3.4.22.51 (E/Z)-N'-benzylidene-3-phenylquinoxaline-2-hydrazide 25 microM, inhibition of parasite growth 151736 3.4.22.51 (E/Z)-N'-(4-fluorobenzylidene)-3-phenylquinoxaline-2-hydrazide 25 microM, inhibition of parasite growth 151737 3.4.22.51 (E/Z)-N'-(4-bromobenzylidene)-3-phenylquinoxaline-2-hydrazide 25 microM, inhibition of parasite growth 151738 3.4.22.51 (E/Z)-N'-(4-chlorobenzylidene)-3-phenylquinoxaline-2-hydrazide 25 microM, inhibition of parasite growth 151739 3.4.22.51 (E/Z)-N'-(2-chlorobenzylidene)-3-phenylquinoxaline-2-hydrazide 25 microM, inhibition of parasite growth 151740 3.4.22.51 (E/Z)-N'-(3-chlorobenzylidene)-3-phenylquinoxaline-2-hydrazide 25 microM, inhibition of parasite growth 151741 3.4.22.51 (E/Z)-N'-(4-hydroxybenzylidene)-3-phenylquinoxaline-2-hydrazide 25 microM, inhibition of parasite growth 151742 3.4.22.51 (E/Z)-N'-(4-dimethylaminobenzylidene)-3-phenylquinoxaline-2-hydrazide 25 microM, inhibition of parasite growth 151743 3.4.22.51 (E/Z)-N'-(4-nitrobenzylidene)-3-phenylquinoxaline-2-hydrazide 25 microM, inhibition of parasite growth 151744 3.4.22.51 (E/Z)-N'-(4-isopropylbenzylidene)-3-phenylquinoxaline-2-hydrazide 25 microM, inhibition of parasite growth 151745 3.4.22.51 (E/Z)-N'-(pyridin-4-ylmethylene)-3-phenylquinoxaline-2-hydrazide 25 microM, inhibition of parasite growth 151746 3.4.22.51 (E/Z)-N'-(pyridin-2-ylmethylene)-3-phenylquinoxaline-2-hydrazide 25 microM, inhibition of parasite growth 151747 3.4.22.51 (E/Z)-N'-(furfurylidene)-3-phenylquinoxaline-2-hydrazide 25 microM, inhibition of parasite growth 151748 3.4.22.51 (E/Z)-N'-(2-hhenylidene)-3-phenylquinoxaline-2-hydrazide 25 microM, inhibition of parasite growth 151749 3.4.22.51 [(2Z)-2-[(2Z)-(4-methoxybenzylidene)hydrazinylidene]-4-oxo-1,3-thiazolidin-5-yl]acetic acid 38% inhibition at 0.1 mM inhibitor and 140 nM enzyme 167861 3.4.22.51 [(2Z)-4-oxo-2-[(2Z)-(thiophen-2-ylmethylidene)hydrazinylidene]-1,3-thiazolidin-5-yl]acetic acid 34% inhibition at 0.1 mM inhibitor and 140 nM enzyme 167862 3.4.22.51 [(2Z)-2-[(2Z)-(2-fluorobenzylidene)hydrazinylidene]-4-oxo-1,3-thiazolidin-5-yl]acetic acid 6% inhibition at 0.1 mM inhibitor and 140 nM enzyme 167863 3.4.22.51 [(2Z)-2-[(2Z)-(4-nitrobenzylidene)hydrazinylidene]-4-oxo-1,3-thiazolidin-5-yl]acetic acid 4% inhibition at 0.1 mM inhibitor and 140 nM enzyme 167864 3.4.22.51 [(2Z)-2-[(2Z)-(4-chlorobenzylidene)hydrazinylidene]-4-oxo-1,3-thiazolidin-5-yl]acetic acid 11% inhibition at 0.1 mM inhibitor and 140 nM enzyme 167865 3.4.22.51 2-[(2Z)-2-[(2Z)-benzylidenehydrazinylidene]-4-oxo-1,3-thiazolidin-5-yl]-N-methylacetamide 3% inhibition at 0.1 mM inhibitor and 140 nM enzyme 167866 3.4.22.51 N-methyl-2-[(2Z)-4-oxo-2-[(2Z)-(2-sulfanylbenzylidene)hydrazinylidene]-1,3-thiazolidin-5-yl]acetamide 27% inhibition at 0.1 mM inhibitor and 140 nM enzyme 167867 3.4.22.51 2-[(2Z)-2-[(2Z)-(4-methoxybenzylidene)hydrazinylidene]-4-oxo-1,3-thiazolidin-5-yl]-N-methylacetamide 22% inhibition at 0.1 mM inhibitor and 140 nM enzyme 167868 3.4.22.51 2-[(2Z)-2-[(2Z)-(4-chlorobenzylidene)hydrazinylidene]-3-methyl-4-oxo-1,3-thiazolidin-5-yl]-N-methylacetamide 7% inhibition at 0.1 mM inhibitor and 140 nM enzyme 167869 3.4.22.51 2-[(2Z)-2-[(2Z)-(4-fluorobenzylidene)hydrazinylidene]-3-methyl-4-oxo-1,3-thiazolidin-5-yl]-N-methylacetamide 3% inhibition at 0.1 mM inhibitor and 140 nM enzyme 167870 3.4.22.51 2-[(2Z)-2-[(2Z)-(3-bromobenzylidene)hydrazinylidene]-3-methyl-4-oxo-1,3-thiazolidin-5-yl]-N-methylacetamide 17% inhibition at 0.1 mM inhibitor and 140 nM enzyme 167871 3.4.22.51 2-[(2Z)-2-[(2Z)-[1-(3-bromophenyl)ethylidene]hydrazinylidene]-3-methyl-4-oxo-1,3-thiazolidin-5-yl]-N-methylacetamide 22% inhibition at 0.1 mM inhibitor and 140 nM enzyme 167872 3.4.22.51 N-methyl-2-[(2Z)-3-methyl-4-oxo-2-[(2Z)-[4-(trifluoromethyl)benzylidene]hydrazinylidene]-1,3-thiazolidin-5-yl]acetamide 27% inhibition at 0.1 mM inhibitor and 140 nM enzyme 167873 3.4.22.51 methyl (2E)-[(2Z)-2-[(2Z)-(4-methoxybenzylidene)hydrazinylidene]-4-oxo-1,3-thiazolidin-5-ylidene]ethanoate 7% inhibition at 0.1 mM inhibitor and 140 nM enzyme 167874 3.4.22.51 methyl (2E)-[(2Z)-2-[(2Z)-(4-chlorobenzylidene)hydrazinylidene]-3-methyl-4-oxo-1,3-thiazolidin-5-ylidene]ethanoate 75% inhibition at 0.1 mM inhibitor and 140 nM enzyme 167875 3.4.22.51 methyl (2E)-[(2Z)-3-methyl-4-oxo-2-[(2Z)-[4-(trifluoromethyl)benzylidene]hydrazinylidene]-1,3-thiazolidin-5-ylidene]ethanoate 65% inhibition at 0.1 mM inhibitor and 140 nM enzyme 167876 3.4.22.51 methyl (2E)-[(2Z)-2-[(2Z)-(4-methoxybenzylidene)hydrazinylidene]-3-methyl-4-oxo-1,3-thiazolidin-5-ylidene]ethanoate 71% inhibition at 0.1 mM inhibitor and 140 nM enzyme 167877 3.4.22.51 6-[(E)-2-(phenylsulfonyl)ethenyl]-2,1,3-benzoxadiazole 1-oxide - 200734 3.4.22.51 (2E)-2-{4-[(3-oxido-2,1,3-benzoxadiazol-5-yl)methoxy]benzylidene}hydrazinecarboximidamide - 200735 3.4.22.51 (3-oxido-2,1,3-benzoxadiazol-5-yl)methyl (2E)-2-(4-hydroxybenzylidene)hydrazinecarbimidothioate - 200736 3.4.22.51 N-phenyl-N'-(2-phenylethyl)piperazine-1-carboximidamide 3.2% inhibition at 0.1 mM, at pH 5.3, temperature not specified in the publication 200737 3.4.22.51 N'-benzyl-N-phenylpiperazine-1-carboximidamide 5.4% inhibition at 0.1 mM, at pH 5.3, temperature not specified in the publication 200738 3.4.22.51 N,N'-diphenylpiperazine-1-carboximidamide 6.3% inhibition at 0.1 mM, at pH 5.3, temperature not specified in the publication 200739 3.4.22.51 N'-(furan-2-ylmethyl)-N-phenylpiperazine-1-carboximidamide 10% inhibition at 0.1 mM, at pH 5.3, temperature not specified in the publication 200740 3.4.22.51 5-[4-(N-phenyl-N'-phenylethyl)amidinopiperazin-1-yl methyl]benzo[1,2-c]1,2,5-oxadiazole N-oxide - 201825 3.4.22.51 5-[4-(N-benzyl-N'-phenyl)amidinopiperazin-1-ylmethyl]benzo[1,2-c]1,2,5-oxadiazole N-oxide - 201826 3.4.22.51 5-[4-(N,N'-diphenyl)amidinopiperazin-1-ylmethyl]benzo[1,2-c]1,2,5-oxadiazole N-oxide - 201827 3.4.22.51 5-[4-(N-furyl-N'-phenyl)amidinopiperazin-1-ylmethyl]benzo[1,2-c]1,2,5-oxadiazole N-oxide - 201828 3.4.22.51 2,2-dimethyl-5-[4-(N-phenyl-N'-phenylethyl)amidinopiperazin-1-ylmethyl]-2H-benzimidazole 1,3-di-N-oxide - 201829 3.4.22.51 5-[4-(N-benzyl-N'-phenyl)amidinopiperazin-1-ylmethyl]-2,2-dimethyl-2H-benzimidazole 1,3-di-N-oxide - 201830 3.4.22.51 5-[4-(N-furyl-N'-phenyl)amidinopiperazin-1-ylmethyl]-2,2-dimethyl-2H-benzimidazole 1,3-di-N-oxide - 201831 3.4.22.51 VS4 - 201832 3.4.22.51 Nfx - 201833 3.4.22.51 Bnz - 201834 3.4.22.51 (m-bromophenyl)ethylketone thiosemicarbazone - 201835 3.4.22.51 (2E)-2-[1-([1,1'-biphenyl]-4-yl)-2-(4-bromophenoxy)ethylidene]hydrazine-1-carbothioamide 0.05 mM, 11.8% inhibition, 23°C, pH 5.5; 0.05 mM, 88.9% inhibition, 23°C, pH 5.5 235417 3.4.22.51 (2E)-2-[2-(4-bromophenoxy)-1-(4-bromophenyl)ethylidene]hydrazine-1-carbothioamide 0.05 mM, 67.5% inhibition, 23°C, pH 5.5 235418 3.4.22.51 (2E)-2-[2-(4-bromophenoxy)-1-(4-chlorophenyl)ethylidene]hydrazine-1-carbothioamide 0.05 mM, 53.1% inhibition, 23°C, pH 5.5 235419 3.4.22.51 (2E)-2-[2-(4-bromophenoxy)-1-(4-fluorophenyl)ethylidene]-N-methylhydrazine-1-carbothioamide 0.05 mM, 30.0% inhibition, 23°C, pH 5.5 235420 3.4.22.51 (2E)-2-[2-(4-bromophenoxy)-1-(4-fluorophenyl)ethylidene]-N-phenylhydrazine-1-carbothioamide 0.05 mM, 35.0% inhibition, 23°C, pH 5.5 235421 3.4.22.51 (2E)-2-[2-(4-bromophenoxy)-1-(4-fluorophenyl)ethylidene]hydrazine-1-carbothioamide 0.05 mM, 38.7% inhibition, 23°C, pH 5.5 235422 3.4.22.51 (2E)-2-[2-(4-bromophenoxy)-1-(4-methoxyphenyl)ethylidene]-N-methylhydrazine-1-carbothioamide 0.05 mM, 29.8% inhibition, 23°C, pH 5.5 235423 3.4.22.51 (2E)-2-[2-(4-bromophenoxy)-1-(4-methoxyphenyl)ethylidene]-N-phenylhydrazine-1-carbothioamide 0.05 mM, 42.8% inhibition, 23°C, pH 5.5 235424 3.4.22.51 (2E)-2-[2-(4-bromophenoxy)-1-(4-methoxyphenyl)ethylidene]hydrazine-1-carbothioamide 0.05 mM, 70.9% inhibition, 23°C, pH 5.5 235425 3.4.22.51 (2E)-2-[2-(4-bromophenoxy)-1-(4-methylphenyl)ethylidene]hydrazine-1-carbothioamide 0.05 mM, 67.6% inhibition, 23°C, pH 5.5 235426 3.4.22.51 (2E)-2-[2-(4-bromophenoxy)-1-(naphthalen-1-yl)ethylidene]hydrazine-1-carbothioamide 0.05 mM, 73.6% inhibition, 23°C, pH 5.5 235427 3.4.22.51 (2Z)-2-[1-(4-bromophenyl)-2-(2,3-dichlorophenoxy)ethylidene]hydrazine-1-carbothioamide 0.05 mM, 81.8% inhibition, 23°C, pH 5.5 235528 3.4.22.51 (2Z)-2-[1-(4-bromophenyl)-2-(2-chlorophenoxy)ethylidene]hydrazine-1-carbothioamide 0.05 mM, 58.9% inhibition, 23°C, pH 5.5 235529 3.4.22.51 (2Z)-2-[1-(4-bromophenyl)-2-(3,4-dichlorophenoxy)ethylidene]hydrazine-1-carbothioamide 0.05 mM, 99.1% inhibition, 23°C, pH 5.5 235530 3.4.22.51 (2Z)-2-[1-(4-bromophenyl)-2-(3-chloro-4-fluorophenoxy)ethylidene]hydrazine-1-carbothioamide 0.05 mM, 93.7% inhibition, 23°C, pH 5.5 235531 3.4.22.51 (2Z)-2-[1-(4-bromophenyl)-2-(3-chlorophenoxy)ethylidene]hydrazine-1-carbothioamide 0.05 mM,51.8 % inhibition, 23°C, pH 5.5 235532 3.4.22.51 (2Z)-2-[1-(4-bromophenyl)-2-(3-methoxyphenoxy)ethylidene]hydrazine-1-carbothioamide 0.05 mM, 62.8% inhibition, 23°C, pH 5.5 235533 3.4.22.51 (2Z)-2-[1-(4-bromophenyl)-2-(4-chlorophenoxy)ethylidene]hydrazine-1-carbothioamide 0.05 mM, 76.3% inhibition, 23°C, pH 5.5 235534 3.4.22.51 (2Z)-2-[1-(4-bromophenyl)-2-(4-ethylphenoxy)ethylidene]hydrazine-1-carbothioamide 0.05 mM, 75.1% inhibition, 23°C, pH 5.5 235535 3.4.22.51 (2Z)-2-[1-(4-bromophenyl)-2-(4-fluorophenoxy)ethylidene]hydrazine-1-carbothioamide 0.05 mM, 84.0% inhibition, 23°C, pH 5.5 235536 3.4.22.51 (2Z)-2-[1-(4-bromophenyl)-2-(4-iodophenoxy)ethylidene]hydrazine-1-carbothioamide 0.05 mM, 63.3% inhibition, 23°C, pH 5.5 235537 3.4.22.51 (2Z)-2-[1-(4-bromophenyl)-2-(4-methoxyphenoxy)ethylidene]hydrazine-1-carbothioamide 0.05 mM, 75.8% inhibition, 23°C, pH 5.5 235538 3.4.22.51 (2Z)-2-[1-(4-bromophenyl)-2-(4-tert-butylphenoxy)ethylidene]hydrazine-1-carbothioamide 0.05 mM, 85.3% inhibition, 23°C, pH 5.5 235539 3.4.22.51 (2Z)-2-[1-(4-bromophenyl)-2-phenoxyethylidene]hydrazine-1-carbothioamide 0.05 mM, 61.8% inhibition, 23°C, pH 5.5 235540 3.4.22.51 (2Z)-2-[1-(4-bromophenyl)-2-[(naphthalen-1-yl)oxy]ethylidene]hydrazine-1-carbothioamide - 235541 3.4.22.51 (2Z)-2-[1-(4-bromophenyl)-2-[(naphthalen-2-yl)oxy]ethylidene]hydrazine-1-carbothioamide 0.05 mM, 72.1% inhibition, 23°C, pH 5.5 235542 3.4.22.51 (2Z)-2-[1-(4-bromophenyl)-2-[4-(propan-2-yl)phenoxy]ethylidene]hydrazine-1-carbothioamide 0.05 mM, 49.7% inhibition, 23°C, pH 5.5 235543 3.4.22.51 (2Z)-2-[2-(3-bromophenoxy)-1-(4-bromophenyl)ethylidene]hydrazine-1-carbothioamide 0.05 mM, 81.3% inhibition, 23°C, pH 5.5 235544 3.4.22.51 (5R)-5-(3,4-difluorophenyl)-3-[2-[(5S)-5-(furan-2-yl)-3-(4-methylphenyl)-4,5-dihydro-1H-pyrazol-1-yl]-2-oxoethyl]-5-methylimidazolidine-2,4-dione in the epimastigote form, the inhibitor does not show trypanocidal effects, against bloodstream trypomastigotes the LC50 value is greater than 0.250 mM 235630 3.4.22.51 1-[(5R)-3,5-di(furan-2-yl)-4,5-dihydro-1H-pyrazol-1-yl]-2-([5-[(5S)-5-methyl-4,5,6,7-tetrahydro-1-benzothiophen-2-yl]-1,3,4-oxadiazol-2-yl]sulfanyl)ethanone in the epimastigote form, the inhibitor does not show trypanocidal effects, against bloodstream trypomastigotes the LC50 value is greater than 0.250 mM 235891 3.4.22.51 4-amino-6-methyl-3-([2-[(5R)-3-(naphthalen-2-yl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl]-2-oxoethyl]sulfanyl)-1,2,4-triazin-5(4H)-one shows trypanocidal activity, promising structure in the search for new agents to treat Chagas disease 236227 3.4.22.51 N-(1-cyanocyclopropyl)-Nalpha-(phenylacetyl)-L-phenylalaninamide pKi: 6.4 (-log(Ki/M)) 236568 3.4.22.51 N-(1-cyanocyclopropyl)-Nalpha-[(4-fluorophenyl)acetyl]-L-phenylalaninamide pKi: 6.3 (-log(Ki/M)) 236569 3.4.22.51 N-(1-cyanocyclopropyl)-Nalpha-[(4-hydroxyphenyl)acetyl]-L-phenylalaninamide pKi: 7.0 (-log(Ki/M)) 236570 3.4.22.51 N-(1-cyanocyclopropyl)-Nalpha-[(4-iodophenyl)acetyl]-L-phenylalaninamide pKi: 7.2 (-log(Ki/M)) 236571 3.4.22.51 N-(1-cyanocyclopropyl)-Nalpha-[(4-methylphenyl)acetyl]-L-phenylalaninamide pKi: 6.6 (-log(Ki/M)) 236572 3.4.22.51 N-(1-cyanocyclopropyl)-Nalpha-[(pyridin-4-yl)acetyl]-L-phenylalaninamide pKi: 5.9 (-log(Ki/M)) 236573 3.4.22.51 N-(1-cyanocyclopropyl)-Nalpha-[[4-(trifluoromethyl)phenyl]acetyl]-L-phenylalaninamide pKi: 6.6 (-log(Ki/M)) 236574 3.4.22.51 N-[4-methyl-3-(piperidin-1-ylsulfonyl)phenyl]-4-oxo-4-(3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)butanamide weak inhibitor shows trypanocidal activity, against bloodstream trypomastigotes the LC50 value is greater than 0.250 mM 236922 3.4.22.51 Nalpha-benzoyl-N-(1-cyanocyclopropyl)-L-phenylalaninamide - 237035 3.4.22.51 Nalpha-benzoyl-N-(2-cyanopropan-2-yl)-L-phenylalaninamide - 237036 3.4.22.51 Nalpha-benzoyl-N-(cyanomethyl)-L-phenylalaninamide - 237037 3.4.22.51 Nalpha-[(3-chlorophenyl)acetyl]-N-(1-cyanocyclopropyl)-L-phenylalaninamide pKi: 6,4 (-log(Ki/M)); pKi: 6.6 (-log(Ki/M)) 237038 3.4.22.51 Nalpha-[(4-bromophenyl)acetyl]-N-(1-cyanocyclopropyl)-L-phenylalaninamide pKi: 6.9 (-log(Ki/M)) 237039 3.4.22.51 Nalpha-[(4-chlorophenyl)acetyl]-N-(1-cyanocyclopropyl)-L-phenylalaninamide pKi: 7.2 (-log(Ki/M)) 237040 3.4.22.51 S-methyl thiomethanesulfonate - 239878 3.4.22.51 benzoyl-Tyr-Ala-fluoromethyl ketone - 239879 3.4.22.51 benzoyl-Tyr-Ala-chloromethyl ketone first quantum mechanics/molecular mechanics studies show that benzoyl-Tyr-Ala-chloromethyl ketone is a good candidate for the development of a proper inhibitor of cruzain, which in turn can be used in the treatment of Chagas desease 239880 3.4.22.51 N-(4-([(2Z)-2-(4-bromophenyl)-2-(2-carbamothioylhydrazinylidene)ethyl]oxy)phenyl)acetamide 0.05 mM, 80.7% inhibition, 23°C, pH 5.5 239881 3.4.22.51 (2Z)-2-(2-[([1,1'-biphenyl]-3-yl)oxy]-1-(4-bromophenyl)ethylidene)hydrazine-1-carbothioamide 0.05 mM, 65.4% inhibition, 23°C, pH 5.5 239882 3.4.22.51 (2Z)-2-(2-[([1,1'-biphenyl]-4-yl)oxy]-1-(4-bromophenyl)ethylidene)hydrazine-1-carbothioamide 0.05 mM, 63.7% inhibition, 23°C, pH 5.5 239883 3.4.22.51 (2S)-N-(cyanomethyl)-3-phenyl-2-(phenylformamido)-propanamide i.e. Neq0409, inhibition is enthalpy driven with a clear detrimental contribution of the entropy difference to the free binding energy 239884 3.4.22.51 (2S)-N-(1-cyano-1-methylethyl)-3-phenyl-2-(phenylformamido)propanamide i.e. Neq0410, inhibition is enthalpy driven with a clear detrimental contribution of the entropy difference to the free binding energy 239885 3.4.22.51 (2S)-N-(1-cyanocyclopropyl)-3-phenyl-2-(phenylformamido)propanamide i.e. Neq0570, inhibition is enthalpy driven with a clear detrimental contribution of the entropy difference to the free binding energy 239886