MXPA06001888A - Inhibidores de catepsina s. - Google Patents
Inhibidores de catepsina s.Info
- Publication number
- MXPA06001888A MXPA06001888A MXPA06001888A MXPA06001888A MXPA06001888A MX PA06001888 A MXPA06001888 A MX PA06001888A MX PA06001888 A MXPA06001888 A MX PA06001888A MX PA06001888 A MXPA06001888 A MX PA06001888A MX PA06001888 A MXPA06001888 A MX PA06001888A
- Authority
- MX
- Mexico
- Prior art keywords
- group
- substituted
- member selected
- independently
- alkyl
- Prior art date
Links
- 102000005600 Cathepsins Human genes 0.000 title claims abstract description 38
- 108010084457 Cathepsins Proteins 0.000 title claims abstract description 38
- 239000003112 inhibitor Substances 0.000 title description 23
- 150000001875 compounds Chemical class 0.000 claims abstract description 143
- 108090000613 Cathepsin S Proteins 0.000 claims abstract description 88
- 102100035654 Cathepsin S Human genes 0.000 claims abstract description 88
- 230000005764 inhibitory process Effects 0.000 claims abstract description 56
- 238000000034 method Methods 0.000 claims abstract description 55
- 239000000203 mixture Substances 0.000 claims abstract description 30
- -1 benzyloxymethyl Chemical group 0.000 claims description 85
- 125000005842 heteroatom Chemical group 0.000 claims description 70
- 229910052757 nitrogen Inorganic materials 0.000 claims description 69
- 229910052739 hydrogen Inorganic materials 0.000 claims description 65
- 229910052760 oxygen Inorganic materials 0.000 claims description 64
- 229910052717 sulfur Inorganic materials 0.000 claims description 62
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 43
- 125000001072 heteroaryl group Chemical group 0.000 claims description 42
- 125000000623 heterocyclic group Chemical group 0.000 claims description 38
- 125000000217 alkyl group Chemical group 0.000 claims description 36
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 30
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 22
- 229910052731 fluorine Inorganic materials 0.000 claims description 19
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 18
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 18
- 241000124008 Mammalia Species 0.000 claims description 18
- 125000004432 carbon atom Chemical group C* 0.000 claims description 18
- 229910052801 chlorine Inorganic materials 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 17
- 229920006395 saturated elastomer Polymers 0.000 claims description 15
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 14
- 229910052799 carbon Inorganic materials 0.000 claims description 14
- 229920001774 Perfluoroether Polymers 0.000 claims description 13
- 229910052794 bromium Inorganic materials 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 150000001602 bicycloalkyls Chemical group 0.000 claims description 8
- 230000000694 effects Effects 0.000 claims description 8
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 8
- 229940002612 prodrug Drugs 0.000 claims description 7
- 239000000651 prodrug Substances 0.000 claims description 7
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000002883 imidazolyl group Chemical group 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 6
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 5
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 4
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 4
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 4
- 125000002757 morpholinyl group Chemical group 0.000 claims description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 claims description 3
- 108010081348 HRT1 protein Hairy Proteins 0.000 claims description 3
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 claims description 3
- 241001465754 Metazoa Species 0.000 claims description 3
- 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 125000005062 perfluorophenyl group Chemical group FC1=C(C(=C(C(=C1F)F)F)F)* 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- 125000003107 substituted aryl group Chemical group 0.000 claims description 3
- 125000004417 unsaturated alkyl group Chemical group 0.000 claims description 3
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 claims 1
- 125000004173 1-benzimidazolyl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N1* 0.000 claims 1
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims 1
- BZPYEPIHNBDTTF-SNVBAGLBSA-N [(2R)-1-(5-fluoro-2,3-dihydroindol-1-yl)-3-hydroxypropan-2-yl] carbamate Chemical compound C(N)(O[C@H](CN1CCC2=CC(=CC=C12)F)CO)=O BZPYEPIHNBDTTF-SNVBAGLBSA-N 0.000 claims 1
- 108010044467 Isoenzymes Proteins 0.000 abstract description 26
- 230000002401 inhibitory effect Effects 0.000 abstract description 12
- 201000010099 disease Diseases 0.000 abstract description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 170
- 238000006243 chemical reaction Methods 0.000 description 85
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 59
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 58
- 235000019439 ethyl acetate Nutrition 0.000 description 57
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 48
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
- 239000002904 solvent Substances 0.000 description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 42
- 239000012044 organic layer Substances 0.000 description 36
- 239000000243 solution Substances 0.000 description 34
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 30
- 238000005481 NMR spectroscopy Methods 0.000 description 28
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 25
- 235000019341 magnesium sulphate Nutrition 0.000 description 24
- 239000000758 substrate Substances 0.000 description 23
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- 238000003756 stirring Methods 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 19
- 239000007787 solid Substances 0.000 description 19
- 239000000460 chlorine Substances 0.000 description 17
- 239000000047 product Substances 0.000 description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- 230000015572 biosynthetic process Effects 0.000 description 16
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 16
- 239000000463 material Substances 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- 108090000625 Cathepsin K Proteins 0.000 description 14
- 102000004190 Enzymes Human genes 0.000 description 14
- 108090000790 Enzymes Proteins 0.000 description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 239000002253 acid Substances 0.000 description 14
- 229940088598 enzyme Drugs 0.000 description 14
- 108090000712 Cathepsin B Proteins 0.000 description 13
- 238000003786 synthesis reaction Methods 0.000 description 13
- 102000004171 Cathepsin K Human genes 0.000 description 12
- 230000001419 dependent effect Effects 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- 102000004225 Cathepsin B Human genes 0.000 description 11
- 108090000624 Cathepsin L Proteins 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 11
- 102000004172 Cathepsin L Human genes 0.000 description 9
- 229910052736 halogen Inorganic materials 0.000 description 9
- 150000002367 halogens Chemical class 0.000 description 9
- 150000003254 radicals Chemical class 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 238000010898 silica gel chromatography Methods 0.000 description 9
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 229960000956 coumarin Drugs 0.000 description 8
- 235000001671 coumarin Nutrition 0.000 description 8
- 229910000027 potassium carbonate Inorganic materials 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 7
- 150000007513 acids Chemical class 0.000 description 7
- 230000002860 competitive effect Effects 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 6
- 238000010494 dissociation reaction Methods 0.000 description 6
- 230000005593 dissociations Effects 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 102000005927 Cysteine Proteases Human genes 0.000 description 5
- 108010005843 Cysteine Proteases Proteins 0.000 description 5
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 125000002947 alkylene group Chemical group 0.000 description 5
- 239000012298 atmosphere Substances 0.000 description 5
- 229910000085 borane Inorganic materials 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
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- 238000012544 monitoring process Methods 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- NXLNNXIXOYSCMB-UHFFFAOYSA-N (4-nitrophenyl) carbonochloridate Chemical compound [O-][N+](=O)C1=CC=C(OC(Cl)=O)C=C1 NXLNNXIXOYSCMB-UHFFFAOYSA-N 0.000 description 4
- IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 description 4
- JVVRCYWZTJLJSG-UHFFFAOYSA-N 4-dimethylaminophenol Chemical compound CN(C)C1=CC=C(O)C=C1 JVVRCYWZTJLJSG-UHFFFAOYSA-N 0.000 description 4
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 4
- 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 4
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- 206010061218 Inflammation Diseases 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 150000001336 alkenes Chemical group 0.000 description 4
- 125000003342 alkenyl group Chemical group 0.000 description 4
- 239000000427 antigen Substances 0.000 description 4
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- 238000005259 measurement Methods 0.000 description 4
- 229940098779 methanesulfonic acid Drugs 0.000 description 4
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 4
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
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- IPRDZAMUYMOJTA-UHFFFAOYSA-N 5,6-dichloro-1h-benzimidazole Chemical compound C1=C(Cl)C(Cl)=CC2=C1NC=N2 IPRDZAMUYMOJTA-UHFFFAOYSA-N 0.000 description 3
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- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 3
- 229940122805 Cathepsin S inhibitor Drugs 0.000 description 3
- 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
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- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 3
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- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
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- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- VELAOFLNAYZVNM-NSHDSACASA-N tert-butyl n-[(2s)-1-(4-methoxyanilino)propan-2-yl]carbamate Chemical compound COC1=CC=C(NC[C@H](C)NC(=O)OC(C)(C)C)C=C1 VELAOFLNAYZVNM-NSHDSACASA-N 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 125000003831 tetrazolyl group Chemical group 0.000 description 3
- 125000000335 thiazolyl group Chemical group 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- 125000001425 triazolyl group Chemical group 0.000 description 3
- HURBVFYCLCMKGU-NSHDSACASA-N (2s)-2-cyclopropyl-2-(phenylmethoxycarbonylamino)acetic acid Chemical compound N([C@H](C(=O)O)C1CC1)C(=O)OCC1=CC=CC=C1 HURBVFYCLCMKGU-NSHDSACASA-N 0.000 description 2
- MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/08—Radicals containing only hydrogen and carbon atoms
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- A—HUMAN NECESSITIES
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/63—Esters of sulfonic acids
- C07C309/72—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C309/73—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton to carbon atoms of non-condensed six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Immunology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pulmonology (AREA)
- Diabetes (AREA)
- Biomedical Technology (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Emergency Medicine (AREA)
- Pain & Pain Management (AREA)
- Endocrinology (AREA)
- Transplantation (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Dermatology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US49685803P | 2003-08-20 | 2003-08-20 | |
| US10/922,362 US7256207B2 (en) | 2003-08-20 | 2004-08-18 | Inhibitors of cathepsin S |
| PCT/US2004/027316 WO2005018568A2 (en) | 2003-08-20 | 2004-08-19 | Inhibitors of cathepsin s |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA06001888A true MXPA06001888A (es) | 2006-05-31 |
Family
ID=34221426
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MXPA06001888A MXPA06001888A (es) | 2003-08-20 | 2004-08-19 | Inhibidores de catepsina s. |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US7256207B2 (enExample) |
| EP (1) | EP1658274A4 (enExample) |
| JP (1) | JP2007502844A (enExample) |
| AU (1) | AU2004266151B2 (enExample) |
| BR (1) | BRPI0413755A (enExample) |
| CA (1) | CA2534489A1 (enExample) |
| MX (1) | MXPA06001888A (enExample) |
| WO (1) | WO2005018568A2 (enExample) |
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| US7256207B2 (en) * | 2003-08-20 | 2007-08-14 | Irm Llc | Inhibitors of cathepsin S |
| TWI389897B (zh) | 2005-02-22 | 2013-03-21 | Chugai Pharmaceutical Co Ltd | 1- (2H) -isoquinolinone derivatives |
| US7751835B2 (en) * | 2005-10-04 | 2010-07-06 | Airvana, Inc. | Non-circular paging areas |
| WO2011069298A1 (en) * | 2009-12-11 | 2011-06-16 | F. Hoffmann-La Roche Ag | Novel cyclopropane indolinone derivatives |
| GB2476823B (en) | 2010-01-11 | 2012-05-02 | Subsea 7 Contracting Uk Ltd | Improvements relating to abandonment and recovery of pipelines |
| CN113272286B (zh) * | 2019-01-22 | 2024-04-16 | 阿德弗里奥药品有限责任公司 | 制备4-(2,2,3,3-四氟丙基)吗啉的方法 |
| EP3946332A1 (en) | 2019-04-05 | 2022-02-09 | Université de Bretagne Occidentale | Protease-activated receptor-2 inhibitors for the treatment of sensory neuropathy induced by a marine neurotoxic poisoning |
Family Cites Families (34)
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| US4499295A (en) | 1983-05-09 | 1985-02-12 | G. D. Searle & Co. | Protease inhibitors |
| US5374623A (en) | 1992-08-20 | 1994-12-20 | Prototek, Inc. | Cysteine protease inhibitors effective for in vivo use |
| DE69406083T2 (de) | 1993-04-28 | 1998-02-26 | Ihara Chemical Ind Co | Aminosäureamide, bakterizide für gartenbau und landwirtschaft sowie herstellungverfahren |
| US5648514A (en) | 1994-12-29 | 1997-07-15 | Allergan | Substituted acetylenes having retinoid-like biological activity |
| US5691368A (en) | 1995-01-11 | 1997-11-25 | Hoechst Marion Roussel, Inc. | Substituted oxazolidine calpain and/or cathepsin B inhibitors |
| US5849711A (en) | 1995-06-06 | 1998-12-15 | Athena Neurosciences, Inc. | Cathepsin and methods and compositions for inhibition thereof |
| TW438591B (en) | 1995-06-07 | 2001-06-07 | Arris Pharm Corp | Reversible cysteine protease inhibitors |
| AU1118097A (en) | 1995-10-30 | 1997-05-22 | Smithkline Beecham Corporation | Protease inhibitors |
| EA199700087A1 (ru) | 1995-10-30 | 1998-04-30 | Смитклайн Бичам Корпорейшн | Способ ингибирования катепсина к |
| DE19610784A1 (de) * | 1996-03-19 | 1997-09-25 | Hoechst Ag | Fluoralkyl- und Fluoralkoxysubstituierte heterocyclische Bradykinin-Antagonisten, Verfahren zu ihrer Herstellung und ihre Verwendung |
| US5840733A (en) | 1996-07-01 | 1998-11-24 | Redcell, Canada, Inc. | Methods and compositions for producing novel conjugates of thrombin inhibitors and endogenous carriers resulting in anti-thrombins with extended lifetimes |
| US5916887A (en) | 1996-09-23 | 1999-06-29 | National Research Council Of Canada | 4-substituted-3-(2-amino-2-cycloalkyl methyl)-acetamido azetidin-2-one derivatives as cysteine proteinase regulators |
| US6004933A (en) | 1997-04-25 | 1999-12-21 | Cortech Inc. | Cysteine protease inhibitors |
| CN1255162A (zh) | 1997-05-08 | 2000-05-31 | 史密丝克莱恩比彻姆公司 | 蛋白酶抑制剂 |
| GB9723407D0 (en) | 1997-11-05 | 1998-01-07 | Ciba Geigy Ag | Organic compounds |
| GB9903548D0 (en) | 1999-02-16 | 1999-04-07 | Novartis Ag | Organic compounds |
| US6395897B1 (en) | 1999-03-02 | 2002-05-28 | Boehringer Ingelheim Pharmaceuticals, Inc. | Nitrile compounds useful as reversible inhibitors of #9 cathepsin 5 |
| EP1178958B1 (en) | 1999-03-15 | 2004-02-18 | Axys Pharmaceuticals, Inc. | N-cyanomethyl amides as protease inhibitors |
| US6313117B1 (en) * | 1999-07-30 | 2001-11-06 | Boehringer Ingelheim Pharmaceuticals, Inc. | Succinate derivative compounds useful as cysteine protease inhibitors |
| WO2001019816A1 (en) | 1999-09-13 | 2001-03-22 | Boehringer Ingelheim Pharmaceuticals, Inc. | Novel spiroheterocyclic compounds useful as reversible inhibitors of cysteine proteases |
| US6420364B1 (en) | 1999-09-13 | 2002-07-16 | Boehringer Ingelheim Pharmaceuticals, Inc. | Compound useful as reversible inhibitors of cysteine proteases |
| MXPA02008931A (es) * | 2000-03-16 | 2003-02-10 | Hoffmann La Roche | Derivados de acido carboxilico como antagonistas ip. |
| MXPA03001421A (es) | 2000-08-14 | 2004-01-26 | Johnson & Johnson | Pirazoles sustituidos. |
| BRPI0113286B8 (pt) | 2000-08-14 | 2021-05-25 | Johnson & Johnson | pirazóis substituídos e composição farmacêutica compreendendo os mesmos. |
| ATE324372T1 (de) | 2000-08-14 | 2006-05-15 | Ortho Mcneil Pharm Inc | Substituierte pyrazole |
| IL156577A0 (en) | 2000-12-22 | 2004-01-04 | Axys Pharm Inc | Selective cathepsin s inhibitors and pharmaceutical compositions containing the same |
| AU2002242500A1 (en) | 2001-03-02 | 2002-09-19 | Merck Frosst Canada And Co. | Cathepsin cysteine protease inhibitors |
| JP4365094B2 (ja) | 2001-03-02 | 2009-11-18 | メルク フロスト カナダ リミテツド | カテプシンシステインプロテアーゼ阻害薬 |
| WO2002070519A1 (en) | 2001-03-05 | 2002-09-12 | Axys Pharmaceuticals, Inc. | Monobactams as cathepsin k inhibitors |
| US20050107616A1 (en) | 2001-08-03 | 2005-05-19 | David Gene Barrett | Alpha-ketoamide derivatives as cathepsin k inhibitors |
| US20030144234A1 (en) | 2001-08-30 | 2003-07-31 | Buxton Francis Paul | Methods for the treatment of chronic pain and compositions therefor |
| EP1448554A1 (en) * | 2001-10-09 | 2004-08-25 | SmithKline Beecham Corporation | Propylcarbamate derivatives as inhibitors of serine and cysteine proteases |
| WO2004000838A1 (en) | 2002-06-24 | 2003-12-31 | Axys Pharmaceuticals, Inc. | Peptidic compounds as cysteine protease inhibitors |
| US7256207B2 (en) * | 2003-08-20 | 2007-08-14 | Irm Llc | Inhibitors of cathepsin S |
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Also Published As
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| AU2004266151B2 (en) | 2007-08-02 |
| AU2004266151A1 (en) | 2005-03-03 |
| US7507755B2 (en) | 2009-03-24 |
| CA2534489A1 (en) | 2005-03-03 |
| US7256207B2 (en) | 2007-08-14 |
| JP2007502844A (ja) | 2007-02-15 |
| US20070259873A1 (en) | 2007-11-08 |
| US20050107368A1 (en) | 2005-05-19 |
| WO2005018568A2 (en) | 2005-03-03 |
| WO2005018568A3 (en) | 2005-09-09 |
| EP1658274A2 (en) | 2006-05-24 |
| EP1658274A4 (en) | 2008-11-12 |
| BRPI0413755A (pt) | 2006-10-31 |
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