CA2580219A1 - Formes polymorphes du n-(1-cyanocyclopropyl)-3-cyclopropylmethanesulfonyl-2(r)-(2,2,2-trifluoro-1(s)-(4-fluorophenyl)ethylamino)propionamide, un inhibiteur de la cysteine protease - Google Patents

Formes polymorphes du n-(1-cyanocyclopropyl)-3-cyclopropylmethanesulfonyl-2(r)-(2,2,2-trifluoro-1(s)-(4-fluorophenyl)ethylamino)propionamide, un inhibiteur de la cysteine protease Download PDF

Info

Publication number: CA2580219A1
Authority: CA; Canada
Prior art keywords: compound; theta; exhibits; formula; ray powder
Prior art date: 2004-09-17
Legal status (The legal status 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 status listed.): Abandoned

Application number

CA002580219A

Other languages

English (en)

Inventor

Sheila M. Zipfel

Soon H. Woo

Donglai Yang

Simon Bates

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Bayer Pharma AG

Original Assignee

Individual

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.)

2004-09-17

Filing date

2005-09-16

Publication date

2006-03-30

2004-09-17 Priority claimed from PCT/US2004/030442 external-priority patent/WO2005028429A2/fr

2005-09-16 Application filed by Individual filed Critical Individual

2006-03-30 Publication of CA2580219A1 publication Critical patent/CA2580219A1/fr

Status Abandoned legal-status Critical Current

Links

229940080818 propionamide Drugs 0.000 title description 28
QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 title description 8
101000749287 Clitocybe nebularis Clitocypin Proteins 0.000 title description 2
101000767029 Clitocybe nebularis Clitocypin-1 Proteins 0.000 title description 2
229940094664 Cysteine protease inhibitor Drugs 0.000 title description 2
238000000034 method Methods 0.000 claims abstract description 48
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 38
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 25
230000008569 process Effects 0.000 claims abstract description 25
201000010099 disease Diseases 0.000 claims abstract description 22
108090000613 Cathepsin S Proteins 0.000 claims abstract description 13
102100035654 Cathepsin S Human genes 0.000 claims abstract description 12
230000001404 mediated effect Effects 0.000 claims abstract description 5
150000001875 compounds Chemical class 0.000 claims description 103
238000000634 powder X-ray diffraction Methods 0.000 claims description 59
238000002425 crystallisation Methods 0.000 claims description 41
230000008025 crystallization Effects 0.000 claims description 39
239000000546 pharmaceutical excipient Substances 0.000 claims description 34
239000002904 solvent Substances 0.000 claims description 34
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 26
238000001816 cooling Methods 0.000 claims description 13
238000001157 Fourier transform infrared spectrum Methods 0.000 claims description 10
239000000126 substance Substances 0.000 claims description 8
241001465754 Metazoa Species 0.000 claims description 7
-1 N-(1-cyanocyclopropyl)-cyclopropylmethanesulfonyl-2(R)-[2,2,2-trifluoro-1(S)-(4-fluorophenyl)ethylamino]-propionamide Chemical compound 0.000 claims description 6
238000002955 isolation Methods 0.000 claims description 4
238000010951 particle size reduction Methods 0.000 claims description 4
239000011877 solvent mixture Substances 0.000 claims description 4
230000005684 electric field Effects 0.000 claims description 3
238000007669 thermal treatment Methods 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 2
NOTSCKFHTQJLMM-HOTGVXAUSA-N (2r)-n-(1-cyanocyclopropyl)-3-(cyclopropylmethylsulfonyl)-2-[[(1s)-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl]amino]propanamide Chemical compound C1=CC(F)=CC=C1[C@@H](C(F)(F)F)N[C@H](C(=O)NC1(CC1)C#N)CS(=O)(=O)CC1CC1 NOTSCKFHTQJLMM-HOTGVXAUSA-N 0.000 abstract description 5
239000000243 solution Substances 0.000 description 82
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 52
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 41
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 40
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
239000011541 reaction mixture Substances 0.000 description 39
239000000203 mixture Substances 0.000 description 37
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 33
239000007787 solid Substances 0.000 description 25
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
238000006243 chemical reaction Methods 0.000 description 23
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 17
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 17
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
238000004458 analytical method Methods 0.000 description 15
239000013078 crystal Substances 0.000 description 13
239000003921 oil Substances 0.000 description 13
235000019198 oils Nutrition 0.000 description 13
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
239000000047 product Substances 0.000 description 11
FQTDOGBWUSSSKH-SVBPBHIXSA-N (2r)-2-[[(1s)-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl]amino]-3-tritylsulfanylpropanoic acid Chemical compound C([C@@H](C(=O)O)N[C@@H](C=1C=CC(F)=CC=1)C(F)(F)F)SC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 FQTDOGBWUSSSKH-SVBPBHIXSA-N 0.000 description 10
229910052943 magnesium sulfate Inorganic materials 0.000 description 10
238000003756 stirring Methods 0.000 description 10
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
239000004480 active ingredient Substances 0.000 description 9
238000001914 filtration Methods 0.000 description 9
238000000227 grinding Methods 0.000 description 9
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 8
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
238000002441 X-ray diffraction Methods 0.000 description 8
239000012043 crude product Substances 0.000 description 8
239000003814 drug Substances 0.000 description 8
239000000706 filtrate Substances 0.000 description 8
239000010410 layer Substances 0.000 description 8
239000007788 liquid Substances 0.000 description 8
235000019341 magnesium sulphate Nutrition 0.000 description 8
238000002844 melting Methods 0.000 description 8
230000008018 melting Effects 0.000 description 8
239000000523 sample Substances 0.000 description 8
239000000725 suspension Substances 0.000 description 8
AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 8
239000012267 brine Substances 0.000 description 7
229940079593 drug Drugs 0.000 description 7
238000004128 high performance liquid chromatography Methods 0.000 description 7
235000019260 propionic acid Nutrition 0.000 description 7
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 7
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
238000003556 assay Methods 0.000 description 6
238000009472 formulation Methods 0.000 description 6
229910052757 nitrogen Inorganic materials 0.000 description 6
230000006911 nucleation Effects 0.000 description 6
238000010899 nucleation Methods 0.000 description 6
IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 6
238000002360 preparation method Methods 0.000 description 6
238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 5
239000007821 HATU Substances 0.000 description 5
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
239000004677 Nylon Substances 0.000 description 5
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
125000004432 carbon atom Chemical group C* 0.000 description 5
238000001035 drying Methods 0.000 description 5
238000010438 heat treatment Methods 0.000 description 5
239000005457 ice water Substances 0.000 description 5
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 5
238000005259 measurement Methods 0.000 description 5
229920001778 nylon Polymers 0.000 description 5
239000000843 powder Substances 0.000 description 5
238000012545 processing Methods 0.000 description 5
208000024891 symptom Diseases 0.000 description 5
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
BDQHSIMDNYIOMB-SSDOTTSWSA-N (1r)-2,2,2-trifluoro-1-(4-fluorophenyl)ethanol Chemical compound FC(F)(F)[C@H](O)C1=CC=C(F)C=C1 BDQHSIMDNYIOMB-SSDOTTSWSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
241000124008 Mammalia Species 0.000 description 4
AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
208000006673 asthma Diseases 0.000 description 4
AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
239000000463 material Substances 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
235000018102 proteins Nutrition 0.000 description 4
102000004169 proteins and genes Human genes 0.000 description 4
108090000623 proteins and genes Proteins 0.000 description 4
230000035484 reaction time Effects 0.000 description 4
229920006395 saturated elastomer Polymers 0.000 description 4
239000012047 saturated solution Substances 0.000 description 4
229910001220 stainless steel Inorganic materials 0.000 description 4
239000010935 stainless steel Substances 0.000 description 4
238000000859 sublimation Methods 0.000 description 4
230000008022 sublimation Effects 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
238000012360 testing method Methods 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
238000003828 vacuum filtration Methods 0.000 description 4
PCEIEQLJYDMRFZ-UHFFFAOYSA-N (1-cyanocyclopropyl)azanium;chloride Chemical compound Cl.N#CC1(N)CC1 PCEIEQLJYDMRFZ-UHFFFAOYSA-N 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
239000007832 Na2SO4 Substances 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
239000002253 acid Substances 0.000 description 3
239000012131 assay buffer Substances 0.000 description 3
210000004027 cell Anatomy 0.000 description 3
229940117975 chromium trioxide Drugs 0.000 description 3
WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 3
GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 3
201000010251 cutis laxa Diseases 0.000 description 3
208000035475 disorder Diseases 0.000 description 3
238000004090 dissolution Methods 0.000 description 3
230000000694 effects Effects 0.000 description 3
239000000284 extract Substances 0.000 description 3
230000002401 inhibitory effect Effects 0.000 description 3
238000010992 reflux Methods 0.000 description 3
239000000741 silica gel Substances 0.000 description 3
229910002027 silica gel Inorganic materials 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
238000001228 spectrum Methods 0.000 description 3
230000009885 systemic effect Effects 0.000 description 3
238000002604 ultrasonography Methods 0.000 description 3
DLMYFMLKORXJPO-FQEVSTJZSA-N (2R)-2-amino-3-[(triphenylmethyl)thio]propanoic acid Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(SC[C@H](N)C(O)=O)C1=CC=CC=C1 DLMYFMLKORXJPO-FQEVSTJZSA-N 0.000 description 2
HRIPVXSRVSVPPR-UHFFFAOYSA-N 1-(benzhydrylideneamino)cyclopropane-1-carbonitrile Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)=NC1(C#N)CC1 HRIPVXSRVSVPPR-UHFFFAOYSA-N 0.000 description 2
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
VRLJFRODHVSTIK-UHFFFAOYSA-N 2-(benzhydrylideneamino)acetonitrile Chemical compound C=1C=CC=CC=1C(=NCC#N)C1=CC=CC=C1 VRLJFRODHVSTIK-UHFFFAOYSA-N 0.000 description 2
206010003210 Arteriosclerosis Diseases 0.000 description 2
208000037260 Atherosclerotic Plaque Diseases 0.000 description 2
208000023328 Basedow disease Diseases 0.000 description 2
206010006448 Bronchiolitis Diseases 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
208000024172 Cardiovascular disease Diseases 0.000 description 2
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 2
XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 2
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 2
206010014561 Emphysema Diseases 0.000 description 2
201000009273 Endometriosis Diseases 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
208000015023 Graves' disease Diseases 0.000 description 2
208000030836 Hashimoto thyroiditis Diseases 0.000 description 2
238000004566 IR spectroscopy Methods 0.000 description 2
XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
201000011152 Pemphigus Diseases 0.000 description 2
206010035226 Plasma cell myeloma Diseases 0.000 description 2
201000004681 Psoriasis Diseases 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
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 2
RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 2
206010067584 Type 1 diabetes mellitus Diseases 0.000 description 2
238000009825 accumulation Methods 0.000 description 2
239000000443 aerosol Substances 0.000 description 2
230000000172 allergic effect Effects 0.000 description 2
230000000735 allogeneic effect Effects 0.000 description 2
230000030741 antigen processing and presentation Effects 0.000 description 2
239000006286 aqueous extract Substances 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
208000010668 atopic eczema Diseases 0.000 description 2
238000005102 attenuated total reflection Methods 0.000 description 2
230000008901 benefit Effects 0.000 description 2
HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 2
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
230000037396 body weight Effects 0.000 description 2
238000009835 boiling Methods 0.000 description 2
206010006451 bronchitis Diseases 0.000 description 2
235000011089 carbon dioxide Nutrition 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
239000012230 colorless oil Substances 0.000 description 2
238000007906 compression Methods 0.000 description 2
230000006835 compression Effects 0.000 description 2
238000004807 desolvation Methods 0.000 description 2
238000010790 dilution Methods 0.000 description 2
239000012895 dilution Substances 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
125000004494 ethyl ester group Chemical group 0.000 description 2
239000012065 filter cake Substances 0.000 description 2
239000011888 foil Substances 0.000 description 2
238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 2
230000028993 immune response Effects 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
206010025135 lupus erythematosus Diseases 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
238000003801 milling Methods 0.000 description 2
239000002480 mineral oil Substances 0.000 description 2
235000010446 mineral oil Nutrition 0.000 description 2
238000012544 monitoring process Methods 0.000 description 2
201000006417 multiple sclerosis Diseases 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
210000000056 organ Anatomy 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
239000002245 particle Substances 0.000 description 2
201000001976 pemphigus vulgaris Diseases 0.000 description 2
KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 2
239000012071 phase Substances 0.000 description 2
230000000704 physical effect Effects 0.000 description 2
208000022256 primary systemic amyloidosis Diseases 0.000 description 2
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
238000000746 purification Methods 0.000 description 2
238000000275 quality assurance Methods 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
230000002829 reductive effect Effects 0.000 description 2
206010039073 rheumatoid arthritis Diseases 0.000 description 2
150000003839 salts Chemical class 0.000 description 2
238000005549 size reduction Methods 0.000 description 2
238000010583 slow cooling Methods 0.000 description 2
239000002002 slurry Substances 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
238000000527 sonication Methods 0.000 description 2
230000035882 stress Effects 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
239000006228 supernatant Substances 0.000 description 2
WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
AITNMTXHTIIIBB-UHFFFAOYSA-N 1-bromo-4-fluorobenzene Chemical compound FC1=CC=C(Br)C=C1 AITNMTXHTIIIBB-UHFFFAOYSA-N 0.000 description 1
AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 1
238000005160 1H NMR spectroscopy Methods 0.000 description 1
LUKLMXJAEKXROG-UHFFFAOYSA-N 2,2,2-trifluoro-1-(4-fluorophenyl)ethanone Chemical compound FC1=CC=C(C(=O)C(F)(F)F)C=C1 LUKLMXJAEKXROG-UHFFFAOYSA-N 0.000 description 1
GWTBCUWZAVMAQV-UHFFFAOYSA-N 2,2,2-trifluoro-1-methoxyethanol Chemical compound COC(O)C(F)(F)F GWTBCUWZAVMAQV-UHFFFAOYSA-N 0.000 description 1
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
XFKYKTBPRBZDFG-UHFFFAOYSA-N 2-aminoacetonitrile;hydrochloride Chemical compound Cl.NCC#N XFKYKTBPRBZDFG-UHFFFAOYSA-N 0.000 description 1
PBVAJRFEEOIAGW-UHFFFAOYSA-N 3-[bis(2-carboxyethyl)phosphanyl]propanoic acid;hydrochloride Chemical compound Cl.OC(=O)CCP(CCC(O)=O)CCC(O)=O PBVAJRFEEOIAGW-UHFFFAOYSA-N 0.000 description 1
RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
208000024827 Alzheimer disease Diseases 0.000 description 1
208000023275 Autoimmune disease Diseases 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
241000283707 Capra Species 0.000 description 1
229940122805 Cathepsin S inhibitor Drugs 0.000 description 1
108010084457 Cathepsins Proteins 0.000 description 1
102000005600 Cathepsins Human genes 0.000 description 1
241000282994 Cervidae Species 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
208000000094 Chronic Pain Diseases 0.000 description 1
229910002483 Cu Ka Inorganic materials 0.000 description 1
108010005843 Cysteine Proteases Proteins 0.000 description 1
102000005927 Cysteine Proteases Human genes 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
241000283086 Equidae Species 0.000 description 1
241000283074 Equus asinus Species 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
239000007995 HEPES buffer Substances 0.000 description 1
102100030595 HLA class II histocompatibility antigen gamma chain Human genes 0.000 description 1
241000282412 Homo Species 0.000 description 1
101001082627 Homo sapiens HLA class II histocompatibility antigen gamma chain Proteins 0.000 description 1
108010001336 Horseradish Peroxidase Proteins 0.000 description 1
208000019468 Iatrogenic Disease Diseases 0.000 description 1
239000007836 KH2PO4 Substances 0.000 description 1
239000004201 L-cysteine Substances 0.000 description 1
235000013878 L-cysteine Nutrition 0.000 description 1
ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
229930182816 L-glutamine Natural products 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
238000005481 NMR spectroscopy Methods 0.000 description 1
206010028980 Neoplasm Diseases 0.000 description 1
239000000020 Nitrocellulose Substances 0.000 description 1
241000283973 Oryctolagus cuniculus Species 0.000 description 1
240000007594 Oryza sativa Species 0.000 description 1
235000007164 Oryza sativa Nutrition 0.000 description 1
208000002193 Pain Diseases 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
241001494479 Pecora Species 0.000 description 1
102000035195 Peptidases Human genes 0.000 description 1
108091005804 Peptidases Proteins 0.000 description 1
108010033276 Peptide Fragments Proteins 0.000 description 1
102000007079 Peptide Fragments Human genes 0.000 description 1
239000004793 Polystyrene Substances 0.000 description 1
239000004365 Protease Substances 0.000 description 1
239000012979 RPMI medium Substances 0.000 description 1
238000001069 Raman spectroscopy Methods 0.000 description 1
239000012722 SDS sample buffer Substances 0.000 description 1
229940124639 Selective inhibitor Drugs 0.000 description 1
XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
241000282898 Sus scrofa Species 0.000 description 1
PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 1
239000004809 Teflon Substances 0.000 description 1
229920006362 Teflon® Polymers 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
GUMFXMMDJLWNTM-SSDOTTSWSA-N [(1r)-2,2,2-trifluoro-1-(4-fluorophenyl)ethyl] trifluoromethanesulfonate Chemical compound FC1=CC=C([C@@H](OS(=O)(=O)C(F)(F)F)C(F)(F)F)C=C1 GUMFXMMDJLWNTM-SSDOTTSWSA-N 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000009471 action Effects 0.000 description 1
239000008186 active pharmaceutical agent Substances 0.000 description 1
239000000654 additive Substances 0.000 description 1
230000002411 adverse Effects 0.000 description 1
230000032683 aging Effects 0.000 description 1
238000013019 agitation Methods 0.000 description 1
238000004164 analytical calibration Methods 0.000 description 1
239000012296 anti-solvent Substances 0.000 description 1
239000000427 antigen Substances 0.000 description 1
210000000612 antigen-presenting cell Anatomy 0.000 description 1
102000036639 antigens Human genes 0.000 description 1
108091007433 antigens Proteins 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
239000003125 aqueous solvent Substances 0.000 description 1
239000003849 aromatic solvent Substances 0.000 description 1
238000010533 azeotropic distillation Methods 0.000 description 1
VCOVUYXJMHMVNV-FMYROPPKSA-N benzyl n-[(2s)-1-[[(2s)-1-[[(2s)-5-(diaminomethylideneamino)-1-[(4-methyl-2-oxochromen-7-yl)amino]-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound N([C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NC=1C=C2OC(=O)C=C(C)C2=CC=1)C(=O)OCC1=CC=CC=C1 VCOVUYXJMHMVNV-FMYROPPKSA-N 0.000 description 1
OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
239000000872 buffer Substances 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
239000002775 capsule Substances 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
239000000969 carrier Substances 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
ZDQWVKDDJDIVAL-UHFFFAOYSA-N catecholborane Chemical compound C1=CC=C2O[B]OC2=C1 ZDQWVKDDJDIVAL-UHFFFAOYSA-N 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
235000010980 cellulose Nutrition 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
230000008859 change Effects 0.000 description 1
238000012512 characterization method Methods 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
238000004296 chiral HPLC Methods 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
239000008119 colloidal silica Substances 0.000 description 1
238000002485 combustion reaction Methods 0.000 description 1
230000001276 controlling effect Effects 0.000 description 1
239000013058 crude material Substances 0.000 description 1
239000002178 crystalline material Substances 0.000 description 1
230000001351 cycling effect Effects 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000001514 detection method Methods 0.000 description 1
238000011161 development Methods 0.000 description 1
230000018109 developmental process Effects 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
238000002050 diffraction method Methods 0.000 description 1
SXZIXHOMFPUIRK-UHFFFAOYSA-N diphenylmethanimine Chemical compound C=1C=CC=CC=1C(=N)C1=CC=CC=C1 SXZIXHOMFPUIRK-UHFFFAOYSA-N 0.000 description 1
229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
238000004821 distillation Methods 0.000 description 1
238000009826 distribution Methods 0.000 description 1
230000005670 electromagnetic radiation Effects 0.000 description 1
238000001962 electrophoresis Methods 0.000 description 1
210000002257 embryonic structure Anatomy 0.000 description 1
BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
235000013861 fat-free Nutrition 0.000 description 1
235000013312 flour Nutrition 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
239000002223 garnet Substances 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000000499 gel Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
229910052732 germanium Inorganic materials 0.000 description 1
GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 description 1
239000011521 glass Substances 0.000 description 1
239000008103 glucose Substances 0.000 description 1
235000001727 glucose Nutrition 0.000 description 1
YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
150000002334 glycols Chemical class 0.000 description 1
150000008282 halocarbons Chemical class 0.000 description 1
230000036541 health Effects 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
239000012535 impurity Substances 0.000 description 1
238000000099 in vitro assay Methods 0.000 description 1
238000011534 incubation Methods 0.000 description 1
230000006698 induction Effects 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
238000002329 infrared spectrum Methods 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
108010028930 invariant chain Proteins 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
238000011068 loading method Methods 0.000 description 1
239000006166 lysate Substances 0.000 description 1
239000012139 lysis buffer Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
238000013178 mathematical model Methods 0.000 description 1
238000010907 mechanical stirring Methods 0.000 description 1
239000000155 melt Substances 0.000 description 1
239000012528 membrane Substances 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
229960002216 methylparaben Drugs 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
235000013336 milk Nutrition 0.000 description 1
239000008267 milk Substances 0.000 description 1
210000004080 milk Anatomy 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
235000019796 monopotassium phosphate Nutrition 0.000 description 1
206010028417 myasthenia gravis Diseases 0.000 description 1
MVLMQGYYLCWMFP-UHFFFAOYSA-N neodymium yttrium Chemical compound [Y].[Nd] MVLMQGYYLCWMFP-UHFFFAOYSA-N 0.000 description 1
229920001220 nitrocellulos Polymers 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
230000008520 organization Effects 0.000 description 1
238000012856 packing Methods 0.000 description 1
230000007170 pathology Effects 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
239000006187 pill Substances 0.000 description 1
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
229920000136 polysorbate Polymers 0.000 description 1
229920000053 polysorbate 80 Polymers 0.000 description 1
229920002223 polystyrene Polymers 0.000 description 1
GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
229960003415 propylparaben Drugs 0.000 description 1
239000005297 pyrex Substances 0.000 description 1
230000005855 radiation Effects 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
238000004007 reversed phase HPLC Methods 0.000 description 1
235000009566 rice Nutrition 0.000 description 1
238000002390 rotary evaporation Methods 0.000 description 1
238000010079 rubber tapping Methods 0.000 description 1
230000007017 scission Effects 0.000 description 1
238000006748 scratching Methods 0.000 description 1
230000002393 scratching effect Effects 0.000 description 1
238000012216 screening Methods 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
229910052710 silicon Inorganic materials 0.000 description 1
239000010703 silicon Substances 0.000 description 1
235000020183 skimmed milk Nutrition 0.000 description 1
RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
229940054269 sodium pyruvate Drugs 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
238000000371 solid-state nuclear magnetic resonance spectroscopy Methods 0.000 description 1
239000012453 solvate Substances 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
239000003549 soybean oil Substances 0.000 description 1
235000012424 soybean oil Nutrition 0.000 description 1
230000003595 spectral effect Effects 0.000 description 1
238000004611 spectroscopical analysis Methods 0.000 description 1
238000009987 spinning Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
238000003860 storage Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000000758 substrate Substances 0.000 description 1
FRGKKTITADJNOE-UHFFFAOYSA-N sulfanyloxyethane Chemical compound CCOS FRGKKTITADJNOE-UHFFFAOYSA-N 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000007916 tablet composition Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
238000012546 transfer Methods 0.000 description 1
230000009466 transformation Effects 0.000 description 1
238000000844 transformation Methods 0.000 description 1
230000007704 transition Effects 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical class OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
GRGCWBWNLSTIEN-UHFFFAOYSA-N trifluoromethanesulfonyl chloride Chemical compound FC(F)(F)S(Cl)(=O)=O GRGCWBWNLSTIEN-UHFFFAOYSA-N 0.000 description 1
GZXOHHPYODFEGO-UHFFFAOYSA-N triglycine sulfate Chemical class NCC(O)=O.NCC(O)=O.NCC(O)=O.OS(O)(=O)=O GZXOHHPYODFEGO-UHFFFAOYSA-N 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
235000013311 vegetables Nutrition 0.000 description 1
239000000230 xanthan gum Substances 0.000 description 1
229920001285 xanthan gum Polymers 0.000 description 1
229940082509 xanthan gum Drugs 0.000 description 1
235000010493 xanthan gum Nutrition 0.000 description 1
239000008096 xylene Substances 0.000 description 1
150000003738 xylenes Chemical class 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
- C07C317/48—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Immunology (AREA)
Neurology (AREA)
Pulmonology (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Diabetes (AREA)
Dermatology (AREA)
Rheumatology (AREA)
Reproductive Health (AREA)
Physical Education & Sports Medicine (AREA)
Orthopedic Medicine & Surgery (AREA)
Endocrinology (AREA)
Pain & Pain Management (AREA)
Hospice & Palliative Care (AREA)
Heart & Thoracic Surgery (AREA)
Transplantation (AREA)
Hematology (AREA)
Urology & Nephrology (AREA)
Psychiatry (AREA)
Obesity (AREA)
Emergency Medicine (AREA)
Cardiology (AREA)
Gynecology & Obstetrics (AREA)
Pregnancy & Childbirth (AREA)
Vascular Medicine (AREA)

CA002580219A 2004-09-17 2005-09-16 Formes polymorphes du n-(1-cyanocyclopropyl)-3-cyclopropylmethanesulfonyl-2(r)-(2,2,2-trifluoro-1(s)-(4-fluorophenyl)ethylamino)propionamide, un inhibiteur de la cysteine protease Abandoned CA2580219A1 (fr)

Applications Claiming Priority (7)

Application Number	Priority Date	Filing Date	Title
PCT/US2004/030442 WO2005028429A2 (fr)	2003-09-18	2004-09-17	Composes contenant un haloalkyle utilise comme inhibiteurs de cysteine protease
USPCT/US2004/030442		2004-09-17
US10/943,768 US7547701B2 (en)	2003-09-18	2004-09-17	Haloalkyl containing compounds as cysteine protease inhibitors
US10/943,768		2004-09-17
US66424405P	2005-03-21	2005-03-21
US60/664,244		2005-03-21
PCT/US2005/033074 WO2006034006A1 (fr)	2004-09-17	2005-09-16	Formes polymorphes du n-(1-cyanocyclopropyl)-3-cyclopropylméthanesulfonyl-2(r)-(2,2,2-trifluoro-1(s)-(4-fluorophényl)éthylamino)propionamide, un inhibiteur de la cystéine protéase

Publications (1)

Publication Number	Publication Date
CA2580219A1 true CA2580219A1 (fr)	2006-03-30

Family

ID=35515616

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002580219A Abandoned CA2580219A1 (fr)	2004-09-17	2005-09-16	Formes polymorphes du n-(1-cyanocyclopropyl)-3-cyclopropylmethanesulfonyl-2(r)-(2,2,2-trifluoro-1(s)-(4-fluorophenyl)ethylamino)propionamide, un inhibiteur de la cysteine protease

Country Status (5)

Country	Link
EP (1)	EP1797032A1 (fr)
JP (1)	JP2008513473A (fr)
AU (1)	AU2005287048A1 (fr)
CA (1)	CA2580219A1 (fr)
WO (1)	WO2006034006A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US7893093B2 (en) *	2005-03-22	2011-02-22	Virobay, Inc.	Sulfonyl containing compounds as cysteine protease inhibitors
EP3946332A1 (fr)	2019-04-05	2022-02-09	Université de Bretagne Occidentale	Inhibiteurs du récepteur 2 activé par une protéase pour le traitement d'une neuropathie sensorielle induite par une intoxication neurotoxique marine

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP4991295B2 (ja) *	2003-09-18	2012-08-01	ビロベイ，インコーポレイティド	システイン・プロテアーゼ阻害剤としてのハロアルキルを含む化合物

2005
- 2005-09-16 CA CA002580219A patent/CA2580219A1/fr not_active Abandoned
- 2005-09-16 AU AU2005287048A patent/AU2005287048A1/en not_active Abandoned
- 2005-09-16 JP JP2007532482A patent/JP2008513473A/ja active Pending
- 2005-09-16 EP EP05798153A patent/EP1797032A1/fr not_active Withdrawn
- 2005-09-16 WO PCT/US2005/033074 patent/WO2006034006A1/fr not_active Ceased

Also Published As

Publication number	Publication date
AU2005287048A1 (en)	2006-03-30
JP2008513473A (ja)	2008-05-01
EP1797032A1 (fr)	2007-06-20
WO2006034006A1 (fr)	2006-03-30

Publication	Publication Date	Title
JP4603528B2 (ja)	2010-12-22	選択的アンドロゲン受容体の大規模合成
JP6727216B2 (ja)	2020-07-22	疾患の治療のためのｋｄｍ１ａ阻害剤
ES2522579T3 (es)	2014-11-17	Compuestos, composiciones y métodos
JP5718647B2 (ja)	2015-05-13	カテプシンｂの阻害剤
JP6579623B2 (ja)	2019-09-25	軟骨形成を誘導するための化合物及び方法
AU779321B2 (en)	2005-01-20	Antipicornaviral compounds and compositions, their pharmaceutical uses, and materials for their synthesis
WO2018233633A1 (fr)	2018-12-27	Inhibiteur de ssao
HU219224B (en)	2001-03-28	Sulphonamido and sulphonamido-carbonyl-pyridine-2-carboxylic acid amides, pharmaceutical preparatives containing them and process for producing them
JP6906608B2 (ja)	2021-07-21	細菌アミノアシル−ｔＲＮＡシンセターゼの阻害剤としての２−アミノ−Ｎ−（アリールスルフィニル）−アセトアミド化合物
BRPI0711310A2 (pt)	2011-12-06	inibidores de p38 map cinase
RU2570900C2 (ru)	2015-12-20	Новое соединение и его применение в медицине
WO2010131663A1 (fr)	2010-11-18	Derive d'oxamide
CA2566053A1 (fr)	2005-12-01	Composes de phenyl carboxamide utilisables comme inhibiteurs de beta secretase dans le traitement de la maladie d'alzheimer
WO2025021115A1 (fr)	2025-01-30	Dérivé de pyrrolidine polysubstitué, son procédé de préparation et son utilisation
JP7775186B2 (ja)	2025-11-25	アクチビン受容体様キナーゼ阻害剤の塩及び結晶形態
EP3280711A1 (fr)	2018-02-14	Nouveaux composés de pyridinium
CA2580219A1 (fr)	2006-03-30	Formes polymorphes du n-(1-cyanocyclopropyl)-3-cyclopropylmethanesulfonyl-2(r)-(2,2,2-trifluoro-1(s)-(4-fluorophenyl)ethylamino)propionamide, un inhibiteur de la cysteine protease
CN108349876B (zh)	2021-03-02	一种取代的联苯基化合物及其药物组合物
KR20200081359A (ko)	2020-07-07	2-(5-(4-(2-모르폴리노에톡시)페닐)피리딘-2-일)-n-벤질아세트아미드의 고체 형태
EP1819704B1 (fr)	2008-07-09	Derive amide de l'acide pyrrolopyridine-2-carboxylique utile en tant qu'inhibiteur de la glycogene-phosphorylase
US8278484B2 (en)	2012-10-02	Process for preparing a benzoylbenzeneacetamide derivative
KR101377860B1 (ko)	2014-03-25	페난트렌온 화합물, 조성물 및 방법
WO2023198172A1 (fr)	2023-10-19	Composé oxadiazole, composition pharmaceutique le comprenant et son utilisation
KR20070060118A (ko)	2007-06-12	시스테인 프로테아제 억제제ｎ-(１-시아노시클로프로필)-３-시클로프로필메탄술포닐-２(ｒ)-(２,２,２-트리플루오로-1(ｓ)-(４-플루오로페닐)에틸아미노)프로피온아미드의 다형체
JP2006512378A (ja)	2006-04-13	３−置換−４−アリールキノリン−２−オン誘導体のアトロプ異性体

Legal Events

Date	Code	Title	Description
2010-09-16	FZDE	Dead