UA90138C2

UA90138C2 - Альфа-кетоамідні сполуки як інгібітори цистеїнових протеаз

Альфа-кетоамідні сполуки як інгібітори цистеїнових протеаз Download PDF

Info

Publication number: UA90138C2
Authority: UA; Ukraine
Prior art keywords: ylmethanesulfonylmethyl; compound according; alkyl; haloalkyl; hydrogen
Prior art date: 2005-03-21

Application number

UAA200711596A

Other languages

English (en)

Russian (ru)

Ukrainian (uk)

Inventor

Майкл Граупе

Джон О. Линк

Майкл Г. Роупел

Original Assignee

Вайробей, Инк.

Priority date

2005-03-21

Filing date

2006-03-17

Publication date

2010-04-12

2006-03-17 Application filed by Вайробей, Инк. filed Critical Вайробей, Инк.

2010-04-12 Publication of UA90138C2 publication Critical patent/UA90138C2/uk

Links

-1 Alpha ketoamide compounds Chemical class 0.000 title claims description 431
239000002852 cysteine proteinase inhibitor Substances 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 234
229910052796 boron Inorganic materials 0.000 claims abstract description 11
125000000217 alkyl group Chemical group 0.000 claims description 97
125000001188 haloalkyl group Chemical group 0.000 claims description 84
239000001257 hydrogen Substances 0.000 claims description 69
229910052739 hydrogen Inorganic materials 0.000 claims description 69
125000003118 aryl group Chemical group 0.000 claims description 64
125000001072 heteroaryl group Chemical group 0.000 claims description 47
150000002431 hydrogen Chemical class 0.000 claims description 43
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 40
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 39
125000003545 alkoxy group Chemical group 0.000 claims description 35
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 35
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 35
125000000753 cycloalkyl group Chemical group 0.000 claims description 30
150000004820 halides Chemical class 0.000 claims description 30
125000003710 aryl alkyl group Chemical group 0.000 claims description 29
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 28
125000004475 heteroaralkyl group Chemical group 0.000 claims description 28
150000003839 salts Chemical class 0.000 claims description 28
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 27
125000004432 carbon atom Chemical group C* 0.000 claims description 24
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 24
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 23
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 23
125000004438 haloalkoxy group Chemical group 0.000 claims description 23
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 22
229910052799 carbon Inorganic materials 0.000 claims description 20
125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 18
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 17
125000002723 alicyclic group Chemical group 0.000 claims description 16
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 16
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 16
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 15
125000004093 cyano group Chemical group *C#N 0.000 claims description 15
125000002252 acyl group Chemical group 0.000 claims description 14
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 13
125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 11
125000004103 aminoalkyl group Chemical group 0.000 claims description 10
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 10
229910052757 nitrogen Inorganic materials 0.000 claims description 10
125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 9
125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 9
125000004104 aryloxy group Chemical group 0.000 claims description 9
125000005226 heteroaryloxycarbonyl group Chemical group 0.000 claims description 9
125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
125000002102 aryl alkyloxo group Chemical group 0.000 claims description 8
125000002993 cycloalkylene group Chemical group 0.000 claims description 8
125000005553 heteroaryloxy group Chemical group 0.000 claims description 8
125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 7
125000004980 cyclopropylene group Chemical group 0.000 claims description 6
125000001424 substituent group Chemical group 0.000 claims description 6
125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 5
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 3
125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 2
125000006588 heterocycloalkylene group Chemical group 0.000 claims description 2
125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 2
125000001475 halogen functional group Chemical group 0.000 claims 3
125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims 1
IPWFJLQDVFKJDU-UHFFFAOYSA-N pentanamide Chemical compound CCCCC(N)=O IPWFJLQDVFKJDU-UHFFFAOYSA-N 0.000 claims 1
125000005009 perfluoropropyl group Chemical group FC(C(C(F)(F)F)(F)F)(F)* 0.000 claims 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
238000000034 method Methods 0.000 abstract description 62
230000008569 process Effects 0.000 abstract description 36
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 35
201000010099 disease Diseases 0.000 abstract description 31
102000005600 Cathepsins Human genes 0.000 abstract description 19
108010084457 Cathepsins Proteins 0.000 abstract description 19
102000005927 Cysteine Proteases Human genes 0.000 abstract description 11
108010005843 Cysteine Proteases Proteins 0.000 abstract description 11
239000008194 pharmaceutical composition Substances 0.000 abstract description 10
230000001404 mediated effect Effects 0.000 abstract description 9
102000035195 Peptidases Human genes 0.000 abstract description 6
108091005804 Peptidases Proteins 0.000 abstract description 6
239000004365 Protease Substances 0.000 abstract description 5
239000003112 inhibitor Substances 0.000 abstract description 4
229910052700 potassium Inorganic materials 0.000 abstract description 4
229910052731 fluorine Inorganic materials 0.000 abstract description 3
229910052717 sulfur Inorganic materials 0.000 abstract description 3
239000000243 solution Substances 0.000 description 87
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 81
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
239000011541 reaction mixture Substances 0.000 description 50
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
239000000203 mixture Substances 0.000 description 41
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 37
238000006243 chemical reaction Methods 0.000 description 36
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
239000002253 acid Substances 0.000 description 28
235000019439 ethyl acetate Nutrition 0.000 description 28
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 25
239000003124 biologic agent Substances 0.000 description 25
150000003254 radicals Chemical class 0.000 description 25
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
241001465754 Metazoa Species 0.000 description 21
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
239000003814 drug Substances 0.000 description 21
239000012044 organic layer Substances 0.000 description 21
230000002829 reductive effect Effects 0.000 description 21
238000011282 treatment Methods 0.000 description 21
239000007787 solid Substances 0.000 description 20
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 19
230000015572 biosynthetic process Effects 0.000 description 18
230000028993 immune response Effects 0.000 description 18
239000002904 solvent Substances 0.000 description 17
238000003786 synthesis reaction Methods 0.000 description 17
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
239000010410 layer Substances 0.000 description 16
125000006239 protecting group Chemical group 0.000 description 16
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
239000000872 buffer Substances 0.000 description 15
HWDVTQAXQJQROO-UHFFFAOYSA-N cyclopropylazanide Chemical compound [NH-]C1CC1 HWDVTQAXQJQROO-UHFFFAOYSA-N 0.000 description 15
230000007062 hydrolysis Effects 0.000 description 14
238000006460 hydrolysis reaction Methods 0.000 description 14
230000008105 immune reaction Effects 0.000 description 14
238000000746 purification Methods 0.000 description 14
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
230000007170 pathology Effects 0.000 description 13
241000282414 Homo sapiens Species 0.000 description 12
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
238000004519 manufacturing process Methods 0.000 description 12
238000007792 addition Methods 0.000 description 11
239000007864 aqueous solution Substances 0.000 description 11
238000011161 development Methods 0.000 description 11
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
239000002585 base Substances 0.000 description 10
150000001721 carbon Chemical group 0.000 description 10
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 10
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 10
239000003795 chemical substances by application Substances 0.000 description 9
229940079593 drug Drugs 0.000 description 9
230000000694 effects Effects 0.000 description 9
230000005764 inhibitory process Effects 0.000 description 9
239000000546 pharmaceutical excipient Substances 0.000 description 9
235000019260 propionic acid Nutrition 0.000 description 9
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 9
238000003756 stirring Methods 0.000 description 9
239000004215 Carbon black (E152) Substances 0.000 description 8
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
NQPDZGIKBAWPEJ-UHFFFAOYSA-N Valeric acid Natural products CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 8
229930195733 hydrocarbon Natural products 0.000 description 8
239000003960 organic solvent Substances 0.000 description 8
HUPQYPMULVBQDL-UHFFFAOYSA-N pentanoic acid Chemical compound CCCCC(O)=O.CCCCC(O)=O HUPQYPMULVBQDL-UHFFFAOYSA-N 0.000 description 8
239000000047 product Substances 0.000 description 8
238000002560 therapeutic procedure Methods 0.000 description 8
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 7
125000004429 atom Chemical group 0.000 description 7
108090000623 proteins and genes Proteins 0.000 description 7
229940124597 therapeutic agent Drugs 0.000 description 7
230000001225 therapeutic effect Effects 0.000 description 7
PAJPWUMXBYXFCZ-UHFFFAOYSA-N 1-aminocyclopropanecarboxylic acid Chemical compound OC(=O)C1(N)CC1 PAJPWUMXBYXFCZ-UHFFFAOYSA-N 0.000 description 6
SFWWGMKXCYLZEG-UHFFFAOYSA-N 3-methylmorpholine Chemical compound CC1COCCN1 SFWWGMKXCYLZEG-UHFFFAOYSA-N 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
239000012267 brine Substances 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
230000002401 inhibitory effect Effects 0.000 description 6
239000003921 oil Substances 0.000 description 6
235000019198 oils Nutrition 0.000 description 6
239000002243 precursor Substances 0.000 description 6
102000004169 proteins and genes Human genes 0.000 description 6
206010039073 rheumatoid arthritis Diseases 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
235000017557 sodium bicarbonate Nutrition 0.000 description 6
239000011780 sodium chloride Substances 0.000 description 6
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
238000012360 testing method Methods 0.000 description 6
102000004190 Enzymes Human genes 0.000 description 5
108090000790 Enzymes Proteins 0.000 description 5
210000004027 cell Anatomy 0.000 description 5
239000003638 chemical reducing agent Substances 0.000 description 5
230000002255 enzymatic effect Effects 0.000 description 5
229940088598 enzyme Drugs 0.000 description 5
150000002148 esters Chemical class 0.000 description 5
239000000284 extract Substances 0.000 description 5
125000005843 halogen group Chemical group 0.000 description 5
150000007529 inorganic bases Chemical class 0.000 description 5
239000000463 material Substances 0.000 description 5
238000013178 mathematical model Methods 0.000 description 5
238000012544 monitoring process Methods 0.000 description 5
150000007530 organic bases Chemical class 0.000 description 5
235000018102 proteins Nutrition 0.000 description 5
239000012279 sodium borohydride Substances 0.000 description 5
229910000033 sodium borohydride Inorganic materials 0.000 description 5
239000000126 substance Substances 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 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
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 4
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 4
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
108090000712 Cathepsin B Proteins 0.000 description 4
102000004225 Cathepsin B Human genes 0.000 description 4
108090000625 Cathepsin K Proteins 0.000 description 4
102000004171 Cathepsin K Human genes 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
241000699666 Mus <mouse, genus> Species 0.000 description 4
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
239000012298 atmosphere Substances 0.000 description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
239000012230 colorless oil Substances 0.000 description 4
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 4
208000035475 disorder Diseases 0.000 description 4
229910052943 magnesium sulfate Inorganic materials 0.000 description 4
235000019341 magnesium sulphate Nutrition 0.000 description 4
125000002950 monocyclic group Chemical group 0.000 description 4
230000003472 neutralizing effect Effects 0.000 description 4
229910052760 oxygen Inorganic materials 0.000 description 4
239000001301 oxygen Substances 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
238000002360 preparation method Methods 0.000 description 4
239000000651 prodrug Substances 0.000 description 4
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229920006395 saturated elastomer Polymers 0.000 description 4
238000000926 separation method Methods 0.000 description 4
AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 4
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 4
BDQHSIMDNYIOMB-UHFFFAOYSA-N 2,2,2-trifluoro-1-(4-fluorophenyl)ethanol Chemical compound FC(F)(F)C(O)C1=CC=C(F)C=C1 BDQHSIMDNYIOMB-UHFFFAOYSA-N 0.000 description 3
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 3
XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 3
241000238631 Hexapoda Species 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
206010035226 Plasma cell myeloma Diseases 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
150000008064 anhydrides Chemical class 0.000 description 3
239000000427 antigen Substances 0.000 description 3
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102000036639 antigens Human genes 0.000 description 3
208000006673 asthma Diseases 0.000 description 3
210000003719 b-lymphocyte Anatomy 0.000 description 3
AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
ZDQWVKDDJDIVAL-UHFFFAOYSA-N catecholborane Chemical compound C1=CC=C2O[B]OC2=C1 ZDQWVKDDJDIVAL-UHFFFAOYSA-N 0.000 description 3
229940125898 compound 5 Drugs 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
210000003743 erythrocyte Anatomy 0.000 description 3
125000004185 ester group Chemical group 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
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239000012458 free base Substances 0.000 description 3
125000004476 heterocycloamino group Chemical group 0.000 description 3
239000008241 heterogeneous mixture Substances 0.000 description 3
150000002466 imines Chemical class 0.000 description 3
125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 description 3
229910052740 iodine Inorganic materials 0.000 description 3
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 3
AMIXWJQKUQVEEC-UHFFFAOYSA-N isocyanocyclopropane Chemical compound [C-]#[N+]C1CC1 AMIXWJQKUQVEEC-UHFFFAOYSA-N 0.000 description 3
125000004498 isoxazol-4-yl group Chemical group O1N=CC(=C1)* 0.000 description 3
239000007788 liquid Substances 0.000 description 3
239000012280 lithium aluminium hydride Substances 0.000 description 3
230000008018 melting Effects 0.000 description 3
238000002844 melting Methods 0.000 description 3
150000007522 mineralic acids Chemical class 0.000 description 3
230000004048 modification Effects 0.000 description 3
238000012986 modification Methods 0.000 description 3
FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 3
150000007524 organic acids Chemical class 0.000 description 3
210000002997 osteoclast Anatomy 0.000 description 3
238000007254 oxidation reaction Methods 0.000 description 3
238000012545 processing Methods 0.000 description 3
235000019419 proteases Nutrition 0.000 description 3
125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 3
125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 3
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 3
125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 3
230000009467 reduction Effects 0.000 description 3
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239000000725 suspension Substances 0.000 description 3
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229910052725 zinc Inorganic materials 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1