HRP950558A2

HRP950558A2 - Substituted 4-biarylbutric or biarylpentanoic acids and derivatives as matrix metalloprotease inhibitors

Substituted 4-biarylbutric or biarylpentanoic acids and derivatives as matrix metalloprotease inhibitors Download PDF

Info

Publication number: HRP950558A2
Authority: HR; Croatia
Prior art keywords: carbon atoms; image; mmol; alkyl; aryl
Prior art date: 1994-11-15

Application number

HR08/539,409A

Other languages

English (en)

Croatian (hr)

Inventor

Scott M Wilhelm

Original Assignee

Scott M. Wilhelm

Priority date

1994-11-15

Filing date

1995-11-14

Publication date

1997-12-31

1995-11-06 Priority claimed from US08/539,409 external-priority patent/US5789434A/en

1995-11-14 Application filed by Scott M. Wilhelm filed Critical Scott M. Wilhelm

1997-12-31 Publication of HRP950558A2 publication Critical patent/HRP950558A2/hr

Links

239000002253 acid Substances 0.000 title claims description 41
239000011159 matrix material Substances 0.000 title claims description 24
150000007513 acids Chemical class 0.000 title description 9
239000003475 metalloproteinase inhibitor Substances 0.000 title description 4
125000004432 carbon atom Chemical group C* 0.000 claims description 193
150000001875 compounds Chemical class 0.000 claims description 183
238000000034 method Methods 0.000 claims description 161
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 108
125000003118 aryl group Chemical group 0.000 claims description 99
125000000217 alkyl group Chemical group 0.000 claims description 91
238000006243 chemical reaction Methods 0.000 claims description 88
125000001424 substituent group Chemical group 0.000 claims description 62
125000001072 heteroaryl group Chemical group 0.000 claims description 60
ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 60
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 56
-1 -CHO Chemical group 0.000 claims description 47
229910052760 oxygen Inorganic materials 0.000 claims description 47
229910052717 sulfur Inorganic materials 0.000 claims description 45
125000003710 aryl alkyl group Chemical group 0.000 claims description 37
125000005842 heteroatom Chemical group 0.000 claims description 37
239000004305 biphenyl Substances 0.000 claims description 32
235000010290 biphenyl Nutrition 0.000 claims description 32
239000000463 material Substances 0.000 claims description 25
102000002274 Matrix Metalloproteinases Human genes 0.000 claims description 22
108010000684 Matrix Metalloproteinases Proteins 0.000 claims description 22
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 21
230000000694 effects Effects 0.000 claims description 21
230000008569 process Effects 0.000 claims description 21
150000003839 salts Chemical class 0.000 claims description 21
102000005741 Metalloproteases Human genes 0.000 claims description 20
108010006035 Metalloproteases Proteins 0.000 claims description 20
125000003342 alkenyl group Chemical group 0.000 claims description 17
125000000304 alkynyl group Chemical group 0.000 claims description 17
229910052736 halogen Inorganic materials 0.000 claims description 17
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 16
230000002401 inhibitory effect Effects 0.000 claims description 16
150000002148 esters Chemical class 0.000 claims description 14
206010028980 Neoplasm Diseases 0.000 claims description 13
125000004429 atom Chemical group 0.000 claims description 13
125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 13
229910052799 carbon Inorganic materials 0.000 claims description 12
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
125000003003 spiro group Chemical group 0.000 claims description 10
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 9
206010027476 Metastases Diseases 0.000 claims description 8
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical group [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 8
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 7
201000010099 disease Diseases 0.000 claims description 7
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
125000005843 halogen group Chemical group 0.000 claims description 7
150000002367 halogens Chemical class 0.000 claims description 7
229910052763 palladium Inorganic materials 0.000 claims description 7
OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 claims description 6
239000003054 catalyst Substances 0.000 claims description 6
230000006378 damage Effects 0.000 claims description 6
229910052751 metal Inorganic materials 0.000 claims description 6
239000002184 metal Substances 0.000 claims description 6
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
230000009467 reduction Effects 0.000 claims description 6
125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims description 5
150000001413 amino acids Chemical class 0.000 claims description 5
210000000845 cartilage Anatomy 0.000 claims description 5
125000001188 haloalkyl group Chemical group 0.000 claims description 5
125000004430 oxygen atom Chemical group O* 0.000 claims description 5
206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
206010053555 Arthritis bacterial Diseases 0.000 claims description 4
101150047265 COR2 gene Proteins 0.000 claims description 4
208000004575 Infectious Arthritis Diseases 0.000 claims description 4
101100467189 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) QCR2 gene Proteins 0.000 claims description 4
150000001298 alcohols Chemical class 0.000 claims description 4
125000001246 bromo group Chemical group Br* 0.000 claims description 4
125000004122 cyclic group Chemical group 0.000 claims description 4
238000010438 heat treatment Methods 0.000 claims description 4
230000009401 metastasis Effects 0.000 claims description 4
201000008482 osteoarthritis Diseases 0.000 claims description 4
201000001223 septic arthritis Diseases 0.000 claims description 4
208000025494 Aortic disease Diseases 0.000 claims description 3
206010011091 Coronary artery thrombosis Diseases 0.000 claims description 3
206010014989 Epidermolysis bullosa Diseases 0.000 claims description 3
229910018828 PO3H2 Inorganic materials 0.000 claims description 3
206010064996 Ulcerative keratitis Diseases 0.000 claims description 3
206010003246 arthritis Diseases 0.000 claims description 3
208000002528 coronary thrombosis Diseases 0.000 claims description 3
238000006114 decarboxylation reaction Methods 0.000 claims description 3
230000003412 degenerative effect Effects 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
230000008570 general process Effects 0.000 claims description 3
230000028709 inflammatory response Effects 0.000 claims description 3
210000000653 nervous system Anatomy 0.000 claims description 3
208000028169 periodontal disease Diseases 0.000 claims description 3
230000000472 traumatic effect Effects 0.000 claims description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
125000002947 alkylene group Chemical group 0.000 claims description 2
125000005015 aryl alkynyl group Chemical group 0.000 claims description 2
239000003638 chemical reducing agent Substances 0.000 claims description 2
125000004447 heteroarylalkenyl group Chemical group 0.000 claims description 2
125000005312 heteroarylalkynyl group Chemical group 0.000 claims description 2
150000003949 imides Chemical class 0.000 claims description 2
210000001503 joint Anatomy 0.000 claims description 2
125000002524 organometallic group Chemical group 0.000 claims description 2
125000001033 ether group Chemical group 0.000 claims 2
208000028911 Temporomandibular Joint disease Diseases 0.000 claims 1
230000003143 atherosclerotic effect Effects 0.000 claims 1
210000001772 blood platelet Anatomy 0.000 claims 1
239000002131 composite material Substances 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 438
239000000243 solution Substances 0.000 description 231
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 223
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 219
239000000047 product Substances 0.000 description 193
235000019439 ethyl acetate Nutrition 0.000 description 160
239000000203 mixture Substances 0.000 description 158
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 157
239000007787 solid Substances 0.000 description 148
239000011541 reaction mixture Substances 0.000 description 143
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 142
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 126
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 121
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 108
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 102
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 93
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 90
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 84
238000004809 thin layer chromatography Methods 0.000 description 77
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 75
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
229910052786 argon Inorganic materials 0.000 description 71
229910052943 magnesium sulfate Inorganic materials 0.000 description 63
235000019341 magnesium sulphate Nutrition 0.000 description 63
239000000543 intermediate Substances 0.000 description 59
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 57
238000003756 stirring Methods 0.000 description 52
239000003921 oil Substances 0.000 description 50
235000019198 oils Nutrition 0.000 description 50
239000002904 solvent Substances 0.000 description 50
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 48
239000012074 organic phase Substances 0.000 description 48
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 47
239000012043 crude product Substances 0.000 description 44
230000002829 reductive effect Effects 0.000 description 44
238000002360 preparation method Methods 0.000 description 43
239000010410 layer Substances 0.000 description 42
239000012044 organic layer Substances 0.000 description 40
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 39
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 38
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 38
238000010992 reflux Methods 0.000 description 37
235000002639 sodium chloride Nutrition 0.000 description 37
229960000583 acetic acid Drugs 0.000 description 35
239000000725 suspension Substances 0.000 description 34
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical group CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 33
239000012267 brine Substances 0.000 description 33
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 33
238000001914 filtration Methods 0.000 description 32
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 31
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 31
238000005160 1H NMR spectroscopy Methods 0.000 description 27
238000010828 elution Methods 0.000 description 26
238000004128 high performance liquid chromatography Methods 0.000 description 26
239000007858 starting material Substances 0.000 description 26
238000003818 flash chromatography Methods 0.000 description 25
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 24
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 22
239000002585 base Substances 0.000 description 22
238000000746 purification Methods 0.000 description 22
239000000741 silica gel Substances 0.000 description 21
229910002027 silica gel Inorganic materials 0.000 description 21
229960001866 silicon dioxide Drugs 0.000 description 21
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 21
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 20
238000004440 column chromatography Methods 0.000 description 19
239000013078 crystal Substances 0.000 description 19
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
150000008064 anhydrides Chemical class 0.000 description 18
238000004587 chromatography analysis Methods 0.000 description 18
239000000284 extract Substances 0.000 description 18
229910000104 sodium hydride Inorganic materials 0.000 description 18
239000008346 aqueous phase Substances 0.000 description 17
238000004458 analytical method Methods 0.000 description 16
SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 16
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 15
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
229910000027 potassium carbonate Inorganic materials 0.000 description 15
239000011780 sodium chloride Substances 0.000 description 15
238000001816 cooling Methods 0.000 description 14
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 14
229940079593 drug Drugs 0.000 description 14
239000003814 drug Substances 0.000 description 14
238000001035 drying Methods 0.000 description 14
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 14
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 13
239000012298 atmosphere Substances 0.000 description 13
238000000605 extraction Methods 0.000 description 13
239000003112 inhibitor Substances 0.000 description 13
150000004702 methyl esters Chemical class 0.000 description 13
238000005406 washing Methods 0.000 description 13
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 12
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 12
229960004132 diethyl ether Drugs 0.000 description 12
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 12
238000002156 mixing Methods 0.000 description 12
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 12
239000011734 sodium Substances 0.000 description 12
239000012230 colorless oil Substances 0.000 description 11
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 11
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 10
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 10
238000002425 crystallisation Methods 0.000 description 10
230000008025 crystallization Effects 0.000 description 10
239000012153 distilled water Substances 0.000 description 10
230000007062 hydrolysis Effects 0.000 description 10
238000006460 hydrolysis reaction Methods 0.000 description 10
235000015320 potassium carbonate Nutrition 0.000 description 10
238000001953 recrystallisation Methods 0.000 description 10
239000000377 silicon dioxide Substances 0.000 description 10
239000012312 sodium hydride Substances 0.000 description 10
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 9
238000005727 Friedel-Crafts reaction Methods 0.000 description 9
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 9
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 9
WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 9
229920001971 elastomer Polymers 0.000 description 9
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 9
239000000706 filtrate Substances 0.000 description 9
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
239000000126 substance Substances 0.000 description 9
238000010792 warming Methods 0.000 description 9
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 8
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 8
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
230000015572 biosynthetic process Effects 0.000 description 8
239000003153 chemical reaction reagent Substances 0.000 description 8
238000010790 dilution Methods 0.000 description 8
239000012895 dilution Substances 0.000 description 8
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 8
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 7
VKUYLANQOAKALN-UHFFFAOYSA-N 2-[benzyl-(4-methoxyphenyl)sulfonylamino]-n-hydroxy-4-methylpentanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(CC(C)C)C(=O)NO)CC1=CC=CC=C1 VKUYLANQOAKALN-UHFFFAOYSA-N 0.000 description 7
FPWNLURCHDRMHC-UHFFFAOYSA-N 4-chlorobiphenyl Chemical group C1=CC(Cl)=CC=C1C1=CC=CC=C1 FPWNLURCHDRMHC-UHFFFAOYSA-N 0.000 description 7
QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 7
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 7
102100030416 Stromelysin-1 Human genes 0.000 description 7
101710108790 Stromelysin-1 Proteins 0.000 description 7
UOIFTOBIGNZZSO-UHFFFAOYSA-N acetic acid;ethyl acetate;hexane Chemical compound CC(O)=O.CCCCCC.CCOC(C)=O UOIFTOBIGNZZSO-UHFFFAOYSA-N 0.000 description 7
150000001299 aldehydes Chemical class 0.000 description 7
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 7
239000012362 glacial acetic acid Substances 0.000 description 7
230000005764 inhibitory process Effects 0.000 description 7
235000012054 meals Nutrition 0.000 description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
230000020477 pH reduction Effects 0.000 description 7
239000000843 powder Substances 0.000 description 7
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
JVVXZOOGOGPDRZ-SLFFLAALSA-N [(1R,4aS,10aR)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthren-1-yl]methanamine Chemical compound NC[C@]1(C)CCC[C@]2(C)C3=CC=C(C(C)C)C=C3CC[C@H]21 JVVXZOOGOGPDRZ-SLFFLAALSA-N 0.000 description 6
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 6
239000012346 acetyl chloride Substances 0.000 description 6
239000002168 alkylating agent Substances 0.000 description 6
229940100198 alkylating agent Drugs 0.000 description 6
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 6
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