SK11462002A3 - Inhibítory katepsínu K na báze dipeptidového nitrilu, spôsob ich prípravy a farmaceutická kompozícia, ktorá ich obsahuje - Google Patents

Inhibítory katepsínu K na báze dipeptidového nitrilu, spôsob ich prípravy a farmaceutická kompozícia, ktorá ich obsahuje Download PDF

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Publication number: SK11462002A3
Authority: SK; Slovakia
Prior art keywords: benzamide; cyclohexyl; mmol; piperazin; carbon atoms
Prior art date: 2000-02-10

Application number

SK1146-2002A

Other languages

English (en)

Slovak (sk)

Inventor

Martin Missbach

Original Assignee

Novartis Ag

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2000-02-10

Filing date

2001-02-08

Publication date

2003-01-09

2001-02-08 Application filed by Novartis Ag filed Critical Novartis Ag

2003-01-09 Publication of SK11462002A3 publication Critical patent/SK11462002A3/sk

Links

102000004171 Cathepsin K Human genes 0.000 title claims abstract description 23
108090000625 Cathepsin K Proteins 0.000 title claims abstract description 23
239000003112 inhibitor Substances 0.000 title abstract description 8
108010016626 Dipeptides Proteins 0.000 title abstract description 6
150000002825 nitriles Chemical class 0.000 title abstract description 6
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 40
150000003839 salts Chemical class 0.000 claims abstract description 19
125000000217 alkyl group Chemical group 0.000 claims abstract description 18
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 18
201000010099 disease Diseases 0.000 claims abstract description 17
229910052799 carbon Inorganic materials 0.000 claims abstract description 14
150000002148 esters Chemical class 0.000 claims abstract description 8
238000011321 prophylaxis Methods 0.000 claims abstract description 7
230000001225 therapeutic effect Effects 0.000 claims abstract description 3
150000001875 compounds Chemical class 0.000 claims description 47
-1 cyanomethyl-carbamoyl Chemical group 0.000 claims description 28
238000000034 method Methods 0.000 claims description 18
229910052739 hydrogen Inorganic materials 0.000 claims description 11
239000001257 hydrogen Substances 0.000 claims description 11
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
125000000753 cycloalkyl group Chemical group 0.000 claims description 7
125000003545 alkoxy group Chemical group 0.000 claims description 6
125000003118 aryl group Chemical group 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 6
238000005859 coupling reaction Methods 0.000 claims description 5
LLCRBOWRJOUJAE-UHFFFAOYSA-N n-[1-(cyanomethylcarbamoyl)cyclohexyl]-4-(4-propylpiperazin-1-yl)benzamide Chemical compound C1CN(CCC)CCN1C1=CC=C(C(=O)NC2(CCCCC2)C(=O)NCC#N)C=C1 LLCRBOWRJOUJAE-UHFFFAOYSA-N 0.000 claims description 5
230000008878 coupling Effects 0.000 claims description 4
238000010168 coupling process Methods 0.000 claims description 4
IWZIDQPPNCCYAC-UHFFFAOYSA-N n-[1-(cyanomethylcarbamoyl)cyclohexyl]-4-[1-(2-methoxyethyl)piperidin-4-yl]benzamide Chemical compound C1CN(CCOC)CCC1C1=CC=C(C(=O)NC2(CCCCC2)C(=O)NCC#N)C=C1 IWZIDQPPNCCYAC-UHFFFAOYSA-N 0.000 claims description 4
PYKQDVPUSUWRLU-UHFFFAOYSA-N n-[1-(cyanomethylcarbamoyl)cyclohexyl]-4-[4-(2-methoxyethyl)piperazin-1-yl]benzamide Chemical compound C1CN(CCOC)CCN1C1=CC=C(C(=O)NC2(CCCCC2)C(=O)NCC#N)C=C1 PYKQDVPUSUWRLU-UHFFFAOYSA-N 0.000 claims description 4
238000002360 preparation method Methods 0.000 claims description 4
LODYSJGWLOLPIL-UHFFFAOYSA-N n-[1-(cyanomethylcarbamoyl)cyclohexyl]-4-(1-propylpiperidin-4-yl)benzamide Chemical compound C1CN(CCC)CCC1C1=CC=C(C(=O)NC2(CCCCC2)C(=O)NCC#N)C=C1 LODYSJGWLOLPIL-UHFFFAOYSA-N 0.000 claims description 3
239000004480 active ingredient Substances 0.000 claims description 2
150000001558 benzoic acid derivatives Chemical class 0.000 claims description 2
239000003814 drug Substances 0.000 claims description 2
ROAPYRPINGRSJH-UHFFFAOYSA-N n-[1-(cyanomethylcarbamoyl)cyclohexyl]-4-(1-propan-2-ylpiperidin-4-yl)benzamide Chemical compound C1CN(C(C)C)CCC1C1=CC=C(C(=O)NC2(CCCCC2)C(=O)NCC#N)C=C1 ROAPYRPINGRSJH-UHFFFAOYSA-N 0.000 claims description 2
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 183
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 108
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 93
239000000203 mixture Substances 0.000 description 65
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 57
239000007787 solid Substances 0.000 description 47
239000000843 powder Substances 0.000 description 45
239000002904 solvent Substances 0.000 description 43
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 37
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 26
229910052938 sodium sulfate Inorganic materials 0.000 description 26
235000011152 sodium sulphate Nutrition 0.000 description 26
238000001704 evaporation Methods 0.000 description 24
239000000284 extract Substances 0.000 description 24
230000008020 evaporation Effects 0.000 description 23
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 22
238000010992 reflux Methods 0.000 description 22
239000000047 product Substances 0.000 description 19
RUWBBBUXZRUXBG-UHFFFAOYSA-N 1-amino-n-(cyanomethyl)cyclohexane-1-carboxamide Chemical compound N#CCNC(=O)C1(N)CCCCC1 RUWBBBUXZRUXBG-UHFFFAOYSA-N 0.000 description 18
238000002844 melting Methods 0.000 description 18
230000008018 melting Effects 0.000 description 18
229910000029 sodium carbonate Inorganic materials 0.000 description 18
238000001816 cooling Methods 0.000 description 16
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 16
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 14
IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
239000012071 phase Substances 0.000 description 14
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
238000005160 1H NMR spectroscopy Methods 0.000 description 13
JYYOBHFYCIDXHH-UHFFFAOYSA-N carbonic acid;hydrate Chemical compound O.OC(O)=O JYYOBHFYCIDXHH-UHFFFAOYSA-N 0.000 description 13
238000003818 flash chromatography Methods 0.000 description 13
238000011282 treatment Methods 0.000 description 13
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
239000000741 silica gel Substances 0.000 description 12
229910002027 silica gel Inorganic materials 0.000 description 12
230000015572 biosynthetic process Effects 0.000 description 11
239000000243 solution Substances 0.000 description 11
238000003786 synthesis reaction Methods 0.000 description 11
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
239000002253 acid Substances 0.000 description 9
125000001424 substituent group Chemical group 0.000 description 9
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
241000124008 Mammalia Species 0.000 description 7
208000001132 Osteoporosis Diseases 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
229910000027 potassium carbonate Inorganic materials 0.000 description 7
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
238000000338 in vitro Methods 0.000 description 6
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
239000011541 reaction mixture Substances 0.000 description 6
102000005600 Cathepsins Human genes 0.000 description 5
108010084457 Cathepsins Proteins 0.000 description 5
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 5
206010028980 Neoplasm Diseases 0.000 description 5
239000008346 aqueous phase Substances 0.000 description 5
229910052757 nitrogen Inorganic materials 0.000 description 5
239000012074 organic phase Substances 0.000 description 5
201000008482 osteoarthritis Diseases 0.000 description 5
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
WOXWUZCRWJWTRT-UHFFFAOYSA-N 1-amino-1-cyclohexanecarboxylic acid Chemical compound OC(=O)C1(N)CCCCC1 WOXWUZCRWJWTRT-UHFFFAOYSA-N 0.000 description 4
206010061218 Inflammation Diseases 0.000 description 4
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
239000012298 atmosphere Substances 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
238000001727 in vivo Methods 0.000 description 4
230000004054 inflammatory process Effects 0.000 description 4
RHYSZRWNEVEGHT-UHFFFAOYSA-N methyl 4-(4-benzylpiperazin-1-yl)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1N1CCN(CC=2C=CC=CC=2)CC1 RHYSZRWNEVEGHT-UHFFFAOYSA-N 0.000 description 4
BFFGYMOQOGMTBM-UHFFFAOYSA-N methyl 4-piperazin-1-ylbenzoate Chemical compound C1=CC(C(=O)OC)=CC=C1N1CCNCC1 BFFGYMOQOGMTBM-UHFFFAOYSA-N 0.000 description 4
QQQMCQRQWVXBOY-UHFFFAOYSA-N methyl 4-pyridin-4-ylbenzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=CC=NC=C1 QQQMCQRQWVXBOY-UHFFFAOYSA-N 0.000 description 4
125000004433 nitrogen atom Chemical group N* 0.000 description 4
239000000725 suspension Substances 0.000 description 4
IWUKEARREIYNCJ-UHFFFAOYSA-N 4-(4-propan-2-ylpiperazin-1-yl)benzoic acid;hydrochloride Chemical compound Cl.C1CN(C(C)C)CCN1C1=CC=C(C(O)=O)C=C1 IWUKEARREIYNCJ-UHFFFAOYSA-N 0.000 description 3
NEMQUINYCCWSOC-UHFFFAOYSA-N 4-[hydroxy(methoxy)boranyl]benzoic acid Chemical compound COB(O)C1=CC=C(C(O)=O)C=C1 NEMQUINYCCWSOC-UHFFFAOYSA-N 0.000 description 3
UTBULQCHEUWJNV-UHFFFAOYSA-N 4-phenylpiperidine Chemical compound C1CNCCC1C1=CC=CC=C1 UTBULQCHEUWJNV-UHFFFAOYSA-N 0.000 description 3
101000761509 Homo sapiens Cathepsin K Proteins 0.000 description 3
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Natural products OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
DFNYGALUNNFWKJ-UHFFFAOYSA-N aminoacetonitrile Chemical compound NCC#N DFNYGALUNNFWKJ-UHFFFAOYSA-N 0.000 description 3
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235000018417 cysteine Nutrition 0.000 description 3
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
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229910052736 halogen Inorganic materials 0.000 description 3
102000049698 human CTSK Human genes 0.000 description 3
230000002401 inhibitory effect Effects 0.000 description 3
KEPUOPNHBBPRIM-UHFFFAOYSA-N methyl 4-(4-propylpiperazin-1-yl)benzoate Chemical compound C1CN(CCC)CCN1C1=CC=C(C(=O)OC)C=C1 KEPUOPNHBBPRIM-UHFFFAOYSA-N 0.000 description 3
MSEBQGULDWDIRW-UHFFFAOYSA-N methyl 4-fluorobenzoate Chemical compound COC(=O)C1=CC=C(F)C=C1 MSEBQGULDWDIRW-UHFFFAOYSA-N 0.000 description 3
DIMMWJMQHSAHRJ-UHFFFAOYSA-N n-[1-(cyanomethylcarbamoyl)cyclohexyl]-4-(1-methylpiperidin-4-yl)benzamide Chemical compound C1CN(C)CCC1C1=CC=C(C(=O)NC2(CCCCC2)C(=O)NCC#N)C=C1 DIMMWJMQHSAHRJ-UHFFFAOYSA-N 0.000 description 3
RYHKIRNTBAFNTA-UHFFFAOYSA-N n-[1-(cyanomethylcarbamoyl)cyclohexyl]-4-(4-ethylpiperazin-1-yl)benzamide Chemical compound C1CN(CC)CCN1C1=CC=C(C(=O)NC2(CCCCC2)C(=O)NCC#N)C=C1 RYHKIRNTBAFNTA-UHFFFAOYSA-N 0.000 description 3
XBSPQMUYTGKKCQ-UHFFFAOYSA-N n-[1-(cyanomethylcarbamoyl)cyclohexyl]-4-(4-propan-2-ylpiperazin-1-yl)benzamide Chemical compound C1CN(C(C)C)CCN1C1=CC=C(C(=O)NC2(CCCCC2)C(=O)NCC#N)C=C1 XBSPQMUYTGKKCQ-UHFFFAOYSA-N 0.000 description 3
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 3
229910003446 platinum oxide Inorganic materials 0.000 description 3
206010039073 rheumatoid arthritis Diseases 0.000 description 3
239000011734 sodium Substances 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
239000012258 stirred mixture Substances 0.000 description 3
WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 3
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 2
BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 2
DPSBGWLMCAVDNY-UHFFFAOYSA-N 1-(4-phenylpiperidin-1-yl)ethanone Chemical compound C1CN(C(=O)C)CCC1C1=CC=CC=C1 DPSBGWLMCAVDNY-UHFFFAOYSA-N 0.000 description 2
IQXXEPZFOOTTBA-UHFFFAOYSA-N 1-benzylpiperazine Chemical compound C=1C=CC=CC=1CN1CCNCC1 IQXXEPZFOOTTBA-UHFFFAOYSA-N 0.000 description 2
ZETXHVRPKUXQIT-UHFFFAOYSA-N 1-methyl-4-phenylpiperidine Chemical compound C1CN(C)CCC1C1=CC=CC=C1 ZETXHVRPKUXQIT-UHFFFAOYSA-N 0.000 description 2
ZEMZPXWZVTUONV-UHFFFAOYSA-N 2-(2-dicyclohexylphosphanylphenyl)-n,n-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 ZEMZPXWZVTUONV-UHFFFAOYSA-N 0.000 description 2
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YPJVOPJJYJIULR-UHFFFAOYSA-N 2-[4-(2-methoxyethyl)piperazin-1-yl]benzoic acid;hydrochloride Chemical compound Cl.C1CN(CCOC)CCN1C1=CC=CC=C1C(O)=O YPJVOPJJYJIULR-UHFFFAOYSA-N 0.000 description 2
AQETWMXWQOAEBI-UHFFFAOYSA-N 4-(1-methylpiperidin-4-yl)benzoic acid;hydrochloride Chemical compound Cl.C1CN(C)CCC1C1=CC=C(C(O)=O)C=C1 AQETWMXWQOAEBI-UHFFFAOYSA-N 0.000 description 2
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NQXIEWIFTRSCDG-UHFFFAOYSA-N 4-(4-ethylpiperazin-1-yl)benzoic acid;hydrochloride Chemical compound Cl.C1CN(CC)CCN1C1=CC=C(C(O)=O)C=C1 NQXIEWIFTRSCDG-UHFFFAOYSA-N 0.000 description 2
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LSZJIROITWZRJF-UHFFFAOYSA-N 9h-fluoren-9-ylmethyl 4-[4-[[1-(cyanomethylcarbamoyl)cyclohexyl]carbamoyl]phenyl]piperazine-1-carboxylate Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1COC(=O)N(CC1)CCN1C(C=C1)=CC=C1C(=O)NC1(C(=O)NCC#N)CCCCC1 LSZJIROITWZRJF-UHFFFAOYSA-N 0.000 description 2
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RRLOOYQHUHGIRJ-UHFFFAOYSA-M sodium;ethyl sulfate Chemical compound [Na+].CCOS([O-])(=O)=O RRLOOYQHUHGIRJ-UHFFFAOYSA-M 0.000 description 1
241000894007 species Species 0.000 description 1
238000004611 spectroscopical analysis Methods 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
239000011593 sulfur Chemical group 0.000 description 1
239000007916 tablet composition Substances 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 1
210000002700 urine Anatomy 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P33/06—Antimalarials
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Physical Education & Sports Medicine (AREA)
Rheumatology (AREA)
Orthopedic Medicine & Surgery (AREA)
Immunology (AREA)
Tropical Medicine & Parasitology (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Hematology (AREA)
Neurology (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Endocrinology (AREA)
Diabetes (AREA)
Transplantation (AREA)
Obesity (AREA)
Vascular Medicine (AREA)
Pain & Pain Management (AREA)
Urology & Nephrology (AREA)
Pulmonology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Hydrogenated Pyridines (AREA)
Peptides Or Proteins (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Plural Heterocyclic Compounds (AREA)

SK1146-2002A 2000-02-10 2001-02-08 Inhibítory katepsínu K na báze dipeptidového nitrilu, spôsob ich prípravy a farmaceutická kompozícia, ktorá ich obsahuje SK11462002A3 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB0003111.2A GB0003111D0 (en)	2000-02-10	2000-02-10	Organic compounds
PCT/EP2001/001359 WO2001058886A1 (en)	2000-02-10	2001-02-08	Dipeptide nitrile cathepsin k inhibitors

Publications (1)

Publication Number	Publication Date
SK11462002A3 true SK11462002A3 (sk)	2003-01-09

Family

ID=9885359

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1146-2002A SK11462002A3 (sk)	2000-02-10	2001-02-08	Inhibítory katepsínu K na báze dipeptidového nitrilu, spôsob ich prípravy a farmaceutická kompozícia, ktorá ich obsahuje

Country Status (30)

Country	Link
US (4)	US6642239B2 (pl)
EP (1)	EP1254124B1 (pl)
JP (1)	JP3942895B2 (pl)
KR (1)	KR100544553B1 (pl)
CN (2)	CN1636980A (pl)
AR (1)	AR029466A1 (pl)
AT (1)	ATE402930T1 (pl)
AU (1)	AU764334B2 (pl)
BR (1)	BR0108118A (pl)
CA (1)	CA2396158C (pl)
CO (1)	CO5261578A1 (pl)
CZ (1)	CZ20022721A3 (pl)
DE (1)	DE60135087D1 (pl)
ES (1)	ES2310177T3 (pl)
GB (1)	GB0003111D0 (pl)
HU (1)	HUP0300148A3 (pl)
IL (1)	IL150406A0 (pl)
MX (1)	MXPA02007768A (pl)
MY (1)	MY122826A (pl)
NO (1)	NO20023780L (pl)
NZ (1)	NZ519940A (pl)
PE (1)	PE20020220A1 (pl)
PL (1)	PL200119B1 (pl)
PT (1)	PT1254124E (pl)
RU (2)	RU2265601C2 (pl)
SK (1)	SK11462002A3 (pl)
TR (1)	TR200201752T2 (pl)
TW (1)	TWI258473B (pl)
WO (1)	WO2001058886A1 (pl)
ZA (1)	ZA200206218B (pl)

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ES2270898T3 (es) *	1999-12-24	2007-04-16	F. Hoffmann-La Roche Ag	Derivados de nitrilo como inhibidores de catepsina k.
DE60132975T2 (de) *	2000-01-06	2009-02-26	Merck Frosst Canada Inc., Kirkland	Neue substanzen und verbindungen als protease-inhibitoren
GB0003111D0 (en) *	2000-02-10	2000-03-29	Novartis Ag	Organic compounds

2000
- 2000-02-10 GB GBGB0003111.2A patent/GB0003111D0/en not_active Ceased
2001
- 2001-02-02 TW TW090102220A patent/TWI258473B/zh not_active IP Right Cessation
- 2001-02-06 MY MYPI20010514A patent/MY122826A/en unknown
- 2001-02-07 US US09/778,302 patent/US6642239B2/en not_active Expired - Fee Related
- 2001-02-08 SK SK1146-2002A patent/SK11462002A3/sk not_active Application Discontinuation
- 2001-02-08 TR TR2002/01752T patent/TR200201752T2/xx unknown
- 2001-02-08 AT AT01919270T patent/ATE402930T1/de active
- 2001-02-08 CN CNA2004100909449A patent/CN1636980A/zh active Pending
- 2001-02-08 JP JP2001558437A patent/JP3942895B2/ja not_active Expired - Fee Related
- 2001-02-08 ES ES01919270T patent/ES2310177T3/es not_active Expired - Lifetime
- 2001-02-08 CN CNB018048099A patent/CN1183122C/zh not_active Expired - Fee Related
- 2001-02-08 HU HU0300148A patent/HUP0300148A3/hu unknown
- 2001-02-08 IL IL15040601A patent/IL150406A0/xx unknown
- 2001-02-08 WO PCT/EP2001/001359 patent/WO2001058886A1/en not_active Ceased
- 2001-02-08 EP EP01919270A patent/EP1254124B1/en not_active Expired - Lifetime
- 2001-02-08 DE DE60135087T patent/DE60135087D1/de not_active Expired - Lifetime
- 2001-02-08 MX MXPA02007768A patent/MXPA02007768A/es active IP Right Grant
- 2001-02-08 CZ CZ20022721A patent/CZ20022721A3/cs unknown
- 2001-02-08 BR BR0108118-7A patent/BR0108118A/pt not_active Application Discontinuation
- 2001-02-08 KR KR1020027010280A patent/KR100544553B1/ko not_active Expired - Fee Related
- 2001-02-08 RU RU2002123350/04A patent/RU2265601C2/ru not_active IP Right Cessation
- 2001-02-08 PE PE2001000139A patent/PE20020220A1/es not_active Application Discontinuation
- 2001-02-08 NZ NZ519940A patent/NZ519940A/en unknown
- 2001-02-08 AR ARP010100563A patent/AR029466A1/es not_active Application Discontinuation
- 2001-02-08 RU RU2005108133/04A patent/RU2293732C2/ru active
- 2001-02-08 PT PT01919270T patent/PT1254124E/pt unknown
- 2001-02-08 PL PL357901A patent/PL200119B1/pl unknown
- 2001-02-08 AU AU46426/01A patent/AU764334B2/en not_active Ceased
- 2001-02-08 CA CA002396158A patent/CA2396158C/en not_active Expired - Fee Related
- 2001-02-12 CO CO01010168A patent/CO5261578A1/es not_active Application Discontinuation
2002
- 2002-08-05 ZA ZA200206218A patent/ZA200206218B/en unknown
- 2002-08-09 NO NO20023780A patent/NO20023780L/no unknown
2003
- 2003-04-09 US US10/410,377 patent/US20030203919A1/en not_active Abandoned
2005
- 2005-08-03 US US11/195,747 patent/US20050267129A1/en not_active Abandoned
2007
- 2007-04-23 US US11/738,878 patent/US20070191392A1/en not_active Abandoned

Also Published As

Publication number	Publication date
US20050267129A1 (en)	2005-12-01
CN1183122C (zh)	2005-01-05
HK1050197A1 (en)	2003-06-13
NZ519940A (en)	2004-02-27
RU2293732C2 (ru)	2007-02-20
CN1636980A (zh)	2005-07-13
ES2310177T3 (es)	2009-01-01
US20010016207A1 (en)	2001-08-23
US6642239B2 (en)	2003-11-04
RU2265601C2 (ru)	2005-12-10
KR100544553B1 (ko)	2006-01-24
TR200201752T2 (tr)	2002-10-21
IL150406A0 (en)	2002-12-01
KR20020072310A (ko)	2002-09-14
BR0108118A (pt)	2003-02-25
ZA200206218B (en)	2003-08-05
US20070191392A1 (en)	2007-08-16
PT1254124E (pt)	2008-11-03
RU2002123350A (ru)	2004-01-10
WO2001058886A1 (en)	2001-08-16
NO20023780D0 (no)	2002-08-09
US20030203919A1 (en)	2003-10-30
CO5261578A1 (es)	2003-03-31
CZ20022721A3 (cs)	2002-11-13
PE20020220A1 (es)	2002-03-25
ATE402930T1 (de)	2008-08-15
DE60135087D1 (de)	2008-09-11
AR029466A1 (es)	2003-07-02
JP3942895B2 (ja)	2007-07-11
CA2396158C (en)	2010-02-02
JP2003522764A (ja)	2003-07-29
HUP0300148A2 (en)	2003-05-28
AU764334B2 (en)	2003-08-14
RU2005108133A (ru)	2006-09-10
PL357901A1 (pl)	2004-07-26
TWI258473B (en)	2006-07-21
NO20023780L (no)	2002-08-09
MXPA02007768A (es)	2002-10-11
HUP0300148A3 (en)	2005-04-28
EP1254124A1 (en)	2002-11-06
EP1254124B1 (en)	2008-07-30
AU4642601A (en)	2001-08-20
MY122826A (en)	2006-05-31
GB0003111D0 (en)	2000-03-29
CA2396158A1 (en)	2001-08-16
PL200119B1 (pl)	2008-12-31
CN1398260A (zh)	2003-02-19

Legal Events

Date	Code	Title	Description
2010-04-07	FC9A	Refused patent application

Publication	Publication Date	Title
SK11462002A3 (sk)	2003-01-09	Inhibítory katepsínu K na báze dipeptidového nitrilu, spôsob ich prípravy a farmaceutická kompozícia, ktorá ich obsahuje
EP0395312B1 (en)	1999-05-12	Piperazine derivatives
RU2356890C2 (ru)	2009-05-27	Производные 1-пиперазин- и 1-гомопиперазинкарбоксилатов, их получение и их применение в терапии
JP2008506744A (ja)	2008-03-06	α７ニコチン性アセチルコリン受容体の調節物質およびそれらの治療への使用
JP4293988B2 (ja)	2009-07-08	塩基性非ペプチド性ブラジキニンアンタゴニスト及びそれから得られた医薬組成物
NZ583815A (en)	2012-03-30	Aryl Sulfonamides with an Analgesic Action
EA008921B1 (ru)	2007-08-31	Производные бензолсульфонамидов, способ их получения и их применение для лечения боли
JP2011500782A (ja)	2011-01-06	ブラジキニンｂ１拮抗剤としての新規非ペプチド誘導体
WO2000048993A1 (en)	2000-08-24	Arylaminoalkylamides
US5541326A (en)	1996-07-30	Piperazine Derivatives
EP1383753A1 (en)	2004-01-28	Piperazine-benzamide derivatives useful as apob-100 and/or mtp inhibitor
NO169895B (no)	1992-05-11	Analogifremgangsmaate for fremstilling av terapeutisk aktive substituerte fenylalkyl (piperazinyl eller homopiperazinyl)alkyl tioler og -tiokarbamate
JP2004175737A (ja)	2004-06-24	医薬組成物
HK1050197B (en)	2005-05-13	Dipeptide nitrile cathepsin k inhibitors
HK1077820A (en)	2006-02-24	Dipeptide nitrile cathepsin k inhibitors