NZ526912A

NZ526912A - Inhibitors of cruzipain and other cysteine proteases

Inhibitors of cruzipain and other cysteine proteases

Info

Publication number: NZ526912A
Authority: NZ; New Zealand
Prior art keywords: alkyl; compound; oxo; furan; cycloalkyl
Prior art date: 2001-01-17

Application number

NZ526912A

Other languages

English (en)

Inventor

Martin Quibell

Manoj Kumar Ramjee

Original Assignee

Amura Therapeutics Ltd

Priority date

2001-01-17

Filing date

2002-01-17

Publication date

2005-02-25

2001-01-17 Priority claimed from GBGB0101204.6A external-priority patent/GB0101204D0/en

2002-01-17 Application filed by Amura Therapeutics Ltd filed Critical Amura Therapeutics Ltd

2005-02-25 Publication of NZ526912A publication Critical patent/NZ526912A/en

Links

102000005927 Cysteine Proteases Human genes 0.000 title claims abstract description 44
108010005843 Cysteine Proteases Proteins 0.000 title claims abstract description 44
108090000711 cruzipain Proteins 0.000 title claims description 24
239000003112 inhibitor Substances 0.000 title description 43
150000001875 compounds Chemical class 0.000 claims abstract description 173
201000010099 disease Diseases 0.000 claims abstract description 22
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 22
229910052760 oxygen Inorganic materials 0.000 claims abstract description 20
239000003814 drug Substances 0.000 claims abstract description 15
229910052717 sulfur Inorganic materials 0.000 claims abstract description 15
125000000217 alkyl group Chemical group 0.000 claims abstract description 14
230000002401 inhibitory effect Effects 0.000 claims abstract description 10
-1 sulphonyl group Chemical group 0.000 claims description 80
239000000203 mixture Substances 0.000 claims description 71
102000035195 Peptidases Human genes 0.000 claims description 49
108091005804 Peptidases Proteins 0.000 claims description 49
238000003556 assay Methods 0.000 claims description 48
125000003118 aryl group Chemical group 0.000 claims description 47
230000000694 effects Effects 0.000 claims description 46
239000004365 Protease Substances 0.000 claims description 43
238000000034 method Methods 0.000 claims description 39
238000002360 preparation method Methods 0.000 claims description 35
229920006395 saturated elastomer Polymers 0.000 claims description 24
230000005764 inhibitory process Effects 0.000 claims description 22
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 19
206010001935 American trypanosomiasis Diseases 0.000 claims description 16
208000024699 Chagas disease Diseases 0.000 claims description 15
239000001257 hydrogen Substances 0.000 claims description 13
229910052739 hydrogen Inorganic materials 0.000 claims description 13
230000001225 therapeutic effect Effects 0.000 claims description 12
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 10
RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 8
238000012544 monitoring process Methods 0.000 claims description 8
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
230000008569 process Effects 0.000 claims description 8
101000761509 Homo sapiens Cathepsin K Proteins 0.000 claims description 7
108090000631 Trypsin Proteins 0.000 claims description 7
102000004142 Trypsin Human genes 0.000 claims description 7
229910052799 carbon Inorganic materials 0.000 claims description 7
125000005842 heteroatom Chemical group 0.000 claims description 7
238000000338 in vitro Methods 0.000 claims description 7
239000003550 marker Substances 0.000 claims description 7
101100495912 Arabidopsis thaliana CHR12 gene Proteins 0.000 claims description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 6
235000018417 cysteine Nutrition 0.000 claims description 6
239000012588 trypsin Substances 0.000 claims description 6
238000010200 validation analysis Methods 0.000 claims description 6
229910020008 S(O) Inorganic materials 0.000 claims description 5
125000002619 bicyclic group Chemical group 0.000 claims description 5
229910052736 halogen Inorganic materials 0.000 claims description 5
150000002367 halogens Chemical class 0.000 claims description 5
125000004404 heteroalkyl group Chemical group 0.000 claims description 5
101150020251 NR13 gene Proteins 0.000 claims description 4
238000010171 animal model Methods 0.000 claims description 4
125000000623 heterocyclic group Chemical group 0.000 claims description 4
150000002431 hydrogen Chemical group 0.000 claims description 4
125000002950 monocyclic group Chemical group 0.000 claims description 4
230000007170 pathology Effects 0.000 claims description 4
101000947094 Bos taurus Cathepsin S Proteins 0.000 claims description 3
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
239000003795 chemical substances by application Substances 0.000 claims description 3
125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
102000049698 human CTSK Human genes 0.000 claims description 3
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
101100509371 Arabidopsis thaliana CHR11 gene Proteins 0.000 claims description 2
101000983583 Homo sapiens Procathepsin L Proteins 0.000 claims description 2
102000050937 human CTSL Human genes 0.000 claims description 2
125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 2
238000011282 treatment Methods 0.000 abstract description 24
125000001424 substituent group Chemical group 0.000 abstract description 15
125000003710 aryl alkyl group Chemical group 0.000 abstract description 5
125000000753 cycloalkyl group Chemical group 0.000 abstract description 4
238000004519 manufacturing process Methods 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 143
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 96
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 92
239000000243 solution Substances 0.000 description 87
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 71
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 58
239000000758 substrate Substances 0.000 description 58
239000002904 solvent Substances 0.000 description 52
229910001868 water Inorganic materials 0.000 description 49
239000007790 solid phase Substances 0.000 description 41
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 41
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 40
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 37
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 36
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 35
238000004128 high performance liquid chromatography Methods 0.000 description 33
238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 32
239000000047 product Substances 0.000 description 29
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
239000003921 oil Substances 0.000 description 27
102000004190 Enzymes Human genes 0.000 description 25
108090000790 Enzymes Proteins 0.000 description 25
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
238000006243 chemical reaction Methods 0.000 description 25
229940088598 enzyme Drugs 0.000 description 25
239000002253 acid Substances 0.000 description 24
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
150000001732 carboxylic acid derivatives Chemical group 0.000 description 22
125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 22
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 21
238000005859 coupling reaction Methods 0.000 description 21
235000002639 sodium chloride Nutrition 0.000 description 21
RMRFFCXPLWYOOY-UHFFFAOYSA-N allyl radical Chemical compound [CH2]C=C RMRFFCXPLWYOOY-UHFFFAOYSA-N 0.000 description 20
230000008878 coupling Effects 0.000 description 20
238000010168 coupling process Methods 0.000 description 20
238000003786 synthesis reaction Methods 0.000 description 20
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
239000010410 layer Substances 0.000 description 19
238000004809 thin layer chromatography Methods 0.000 description 19
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 18
238000003818 flash chromatography Methods 0.000 description 18
230000015572 biosynthetic process Effects 0.000 description 17
235000019419 proteases Nutrition 0.000 description 17
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 16
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
239000000741 silica gel Substances 0.000 description 16
229910002027 silica gel Inorganic materials 0.000 description 16
239000011780 sodium chloride Substances 0.000 description 16
102100024940 Cathepsin K Human genes 0.000 description 15
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 14
125000005605 benzo group Chemical group 0.000 description 14
238000003776 cleavage reaction Methods 0.000 description 14
230000007017 scission Effects 0.000 description 14
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 14
239000000543 intermediate Substances 0.000 description 13
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 12
239000007787 solid Substances 0.000 description 12
108090000625 Cathepsin K Proteins 0.000 description 11
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 11
150000002148 esters Chemical class 0.000 description 11
244000045947 parasite Species 0.000 description 11
WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 11
238000004458 analytical method Methods 0.000 description 10
238000009472 formulation Methods 0.000 description 10
208000015181 infectious disease Diseases 0.000 description 10
230000002829 reductive effect Effects 0.000 description 10
239000011734 sodium Substances 0.000 description 10
QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 10
YNVOMSDITJMNET-UHFFFAOYSA-N thiophene-3-carboxylic acid Chemical compound OC(=O)C=1C=CSC=1 YNVOMSDITJMNET-UHFFFAOYSA-N 0.000 description 10
RPGUXSFNXRNACR-UHFFFAOYSA-N 2-hydroxyethyl 2-piperazin-1-ylethanesulfonate Chemical compound OCCOS(=O)(=O)CCN1CCNCC1 RPGUXSFNXRNACR-UHFFFAOYSA-N 0.000 description 9
101150041968 CDC13 gene Proteins 0.000 description 9
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 9
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 9
239000013543 active substance Substances 0.000 description 9
229960001760 dimethyl sulfoxide Drugs 0.000 description 9
229910052757 nitrogen Inorganic materials 0.000 description 9
239000012071 phase Substances 0.000 description 9
229940080818 propionamide Drugs 0.000 description 9
239000000725 suspension Substances 0.000 description 9
239000007989 BIS-Tris Propane buffer Substances 0.000 description 8
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 8
108090000613 Cathepsin S Proteins 0.000 description 8
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 8
239000004201 L-cysteine Substances 0.000 description 8
235000013878 L-cysteine Nutrition 0.000 description 8
230000004913 activation Effects 0.000 description 8
HHKZCCWKTZRCCL-UHFFFAOYSA-N bis-tris propane Chemical compound OCC(CO)(CO)NCCCNC(CO)(CO)CO HHKZCCWKTZRCCL-UHFFFAOYSA-N 0.000 description 8
239000001110 calcium chloride Substances 0.000 description 8
235000011148 calcium chloride Nutrition 0.000 description 8
229910001628 calcium chloride Inorganic materials 0.000 description 8
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 8
238000011068 loading method Methods 0.000 description 8
239000001632 sodium acetate Substances 0.000 description 8
235000017281 sodium acetate Nutrition 0.000 description 8
235000017557 sodium bicarbonate Nutrition 0.000 description 8
229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 8
238000005406 washing Methods 0.000 description 8
102100035654 Cathepsin S Human genes 0.000 description 7
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 7
229940024606 amino acid Drugs 0.000 description 7
150000001413 amino acids Chemical group 0.000 description 7
JBDSSBMEKXHSJF-UHFFFAOYSA-N cyclopentanecarboxylic acid Chemical compound OC(=O)C1CCCC1 JBDSSBMEKXHSJF-UHFFFAOYSA-N 0.000 description 7
150000002576 ketones Chemical class 0.000 description 7
125000005647 linker group Chemical group 0.000 description 7
239000007788 liquid Substances 0.000 description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
235000019833 protease Nutrition 0.000 description 7
238000000746 purification Methods 0.000 description 7
239000003826 tablet Substances 0.000 description 7
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 description 6
108090000624 Cathepsin L Proteins 0.000 description 6
102000004172 Cathepsin L Human genes 0.000 description 6
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
239000003153 chemical reaction reagent Substances 0.000 description 6
150000003997 cyclic ketones Chemical class 0.000 description 6
229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 6
VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 6
229940079593 drug Drugs 0.000 description 6
229910052943 magnesium sulfate Inorganic materials 0.000 description 6
CMWYAOXYQATXSI-UHFFFAOYSA-N n,n-dimethylformamide;piperidine Chemical compound CN(C)C=O.C1CCNCC1 CMWYAOXYQATXSI-UHFFFAOYSA-N 0.000 description 6
239000000137 peptide hydrolase inhibitor Substances 0.000 description 6
HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 6
IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
239000000651 prodrug Substances 0.000 description 6
229940002612 prodrug Drugs 0.000 description 6
108090000623 proteins and genes Proteins 0.000 description 6
HGIWJIYAECWSED-UHFFFAOYSA-N 1-amino-2-hydroxycyclopentane-1-carboxylic acid Chemical compound OC(=O)C1(N)CCCC1O HGIWJIYAECWSED-UHFFFAOYSA-N 0.000 description 5
UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 5
CKKDOLCAFILIPH-UHFFFAOYSA-N 3a-amino-4,5,6,6a-tetrahydrocyclopenta[b]furan-3-one Chemical compound C1CCC2OCC(=O)C21N CKKDOLCAFILIPH-UHFFFAOYSA-N 0.000 description 5
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
150000007513 acids Chemical class 0.000 description 5
150000001412 amines Chemical class 0.000 description 5
235000001014 amino acid Nutrition 0.000 description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
210000004027 cell Anatomy 0.000 description 5
238000010511 deprotection reaction Methods 0.000 description 5
238000011161 development Methods 0.000 description 5
201000004792 malaria Diseases 0.000 description 5
239000001301 oxygen Substances 0.000 description 5
230000003389 potentiating effect Effects 0.000 description 5
150000003839 salts Chemical class 0.000 description 5
239000000377 silicon dioxide Substances 0.000 description 5
229910000104 sodium hydride Inorganic materials 0.000 description 5
239000000126 substance Substances 0.000 description 5
235000011149 sulphuric acid Nutrition 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
150000003568 thioethers Chemical class 0.000 description 5
ALZSTTDFHZHSCA-RNVDEAKXSA-N (4s)-4-[[(2s)-2-acetamido-3-carboxypropanoyl]amino]-5-[[(2s)-1-[[(2s)-3-carboxy-1-[(4-methyl-2-oxochromen-7-yl)amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-oxopentanoic acid Chemical compound CC1=CC(=O)OC2=CC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(O)=O)NC(C)=O)C(C)C)=CC=C21 ALZSTTDFHZHSCA-RNVDEAKXSA-N 0.000 description 4
SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 4
RBIZQDIIVYJNRS-UHFFFAOYSA-N 1,3-benzothiazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2SC=NC2=C1 RBIZQDIIVYJNRS-UHFFFAOYSA-N 0.000 description 4
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 4
UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical compound C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 description 4
SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 4
NNJMFJSKMRYHSR-UHFFFAOYSA-N 4-phenylbenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=CC=C1 NNJMFJSKMRYHSR-UHFFFAOYSA-N 0.000 description 4
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 4
108090000712 Cathepsin B Proteins 0.000 description 4
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101000910979 Homo sapiens Cathepsin Z Proteins 0.000 description 4
206010027476 Metastases Diseases 0.000 description 4
241001465754 Metazoa Species 0.000 description 4
208000001132 Osteoporosis Diseases 0.000 description 4
108090000526 Papain Proteins 0.000 description 4
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
229930006000 Sucrose Natural products 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 4
241000223109 Trypanosoma cruzi Species 0.000 description 4
150000001408 amides Chemical class 0.000 description 4
238000013459 approach Methods 0.000 description 4
230000001580 bacterial effect Effects 0.000 description 4
SXTGIAYWYXVNLT-NRFANRHFSA-N benzyl n-[2-[[2-[[(2s)-5-(diaminomethylideneamino)-1-[(4-methyl-2-oxochromen-7-yl)amino]-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-2-oxoethyl]carbamate Chemical compound N([C@@H](CCCNC(N)=N)C(=O)NC1=CC=2OC(=O)C=C(C=2C=C1)C)C(=O)CNC(=O)CNC(=O)OCC1=CC=CC=C1 SXTGIAYWYXVNLT-NRFANRHFSA-N 0.000 description 4
108010079115 benzyloxycarbonyl-glycyl-glycyl-arginine-4-methylcoumaryl-7-amide Proteins 0.000 description 4
125000006268 biphenyl-3-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C([H])C(*)=C([H])C([H])=C1[H] 0.000 description 4
KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 4
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