SK24899A3 - Bidentate metalloprotease inhibitors - Google Patents

Bidentate metalloprotease inhibitors Download PDF

Info

Publication number: SK24899A3
Authority: SK; Slovakia
Prior art keywords: compounds; alkyl; mmol; heteroaryl; aryl
Prior art date: 1996-08-28

Application number

SK248-99A

Other languages

English (en)

Slovak (sk)

Inventor

Neil Gregory Almstead

Biswanath De

Rimma Sandler Bradley

Garry Steven Garrett

John Emory Ii Marlin

John Mcmillan Mciver

Zhe Wang

Yetunde Olabisi Taiwo

Original Assignee

Procter & Gamble

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.)

1996-08-28

Filing date

1997-08-22

Publication date

2000-04-10

1997-08-22 Application filed by Procter & Gamble filed Critical Procter & Gamble

2000-04-10 Publication of SK24899A3 publication Critical patent/SK24899A3/sk

Links

239000003475 metalloproteinase inhibitor Substances 0.000 title description 8
150000001875 compounds Chemical class 0.000 claims abstract description 193
102000005741 Metalloproteases Human genes 0.000 claims abstract description 68
108010006035 Metalloproteases Proteins 0.000 claims abstract description 68
201000010099 disease Diseases 0.000 claims abstract description 67
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 67
-1 acyloxyamide Chemical class 0.000 claims abstract description 66
238000000034 method Methods 0.000 claims abstract description 61
230000000694 effects Effects 0.000 claims abstract description 41
150000003839 salts Chemical class 0.000 claims abstract description 11
150000002148 esters Chemical class 0.000 claims abstract description 8
230000003287 optical effect Effects 0.000 claims abstract description 8
150000003949 imides Chemical class 0.000 claims abstract description 7
239000000203 mixture Substances 0.000 claims description 78
125000003118 aryl group Chemical group 0.000 claims description 36
125000000217 alkyl group Chemical group 0.000 claims description 34
125000001072 heteroaryl group Chemical group 0.000 claims description 31
238000002360 preparation method Methods 0.000 claims description 22
125000000623 heterocyclic group Chemical group 0.000 claims description 21
229910052739 hydrogen Inorganic materials 0.000 claims description 19
239000001257 hydrogen Substances 0.000 claims description 18
125000004404 heteroalkyl group Chemical group 0.000 claims description 17
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
125000003545 alkoxy group Chemical group 0.000 claims description 16
229910052717 sulfur Inorganic materials 0.000 claims description 16
125000005842 heteroatom Chemical group 0.000 claims description 14
150000002431 hydrogen Chemical group 0.000 claims description 14
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
239000011593 sulfur Substances 0.000 claims description 11
241000124008 Mammalia Species 0.000 claims description 10
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
229910052757 nitrogen Inorganic materials 0.000 claims description 9
229910052760 oxygen Inorganic materials 0.000 claims description 9
239000001301 oxygen Substances 0.000 claims description 9
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 8
125000000753 cycloalkyl group Chemical group 0.000 claims description 8
125000003282 alkyl amino group Chemical group 0.000 claims description 7
125000001769 aryl amino group Chemical group 0.000 claims description 7
125000004104 aryloxy group Chemical group 0.000 claims description 7
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 7
125000004043 oxo group Chemical group O=* 0.000 claims description 7
125000004947 alkyl aryl amino group Chemical group 0.000 claims description 6
125000003277 amino group Chemical group 0.000 claims description 6
125000004663 dialkyl amino group Chemical group 0.000 claims description 6
125000004414 alkyl thio group Chemical group 0.000 claims description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
229910052799 carbon Inorganic materials 0.000 claims description 4
125000003003 spiro group Chemical group 0.000 claims description 4
125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 4
150000001721 carbon Chemical group 0.000 claims description 3
125000004986 diarylamino group Chemical group 0.000 claims description 3
LKDRXBCSQODPBY-AMVSKUEXSA-N L-(-)-Sorbose Chemical compound OCC1(O)OC[C@H](O)[C@@H](O)[C@@H]1O LKDRXBCSQODPBY-AMVSKUEXSA-N 0.000 claims description 2
125000004452 carbocyclyl group Chemical group 0.000 claims description 2
125000005843 halogen group Chemical group 0.000 claims description 2
125000005553 heteroaryloxy group Chemical group 0.000 claims description 2
125000006588 heterocycloalkylene group Chemical group 0.000 claims description 2
238000006467 substitution reaction Methods 0.000 claims description 2
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 2
125000002877 alkyl aryl group Chemical group 0.000 claims 1
150000001408 amides Chemical class 0.000 claims 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 1
150000003463 sulfur Chemical class 0.000 claims 1
125000004001 thioalkyl group Chemical group 0.000 claims 1
125000004055 thiomethyl group Chemical group [H]SC([H])([H])* 0.000 claims 1
239000003112 inhibitor Substances 0.000 abstract description 31
102000004190 Enzymes Human genes 0.000 abstract description 13
108090000790 Enzymes Proteins 0.000 abstract description 13
239000008194 pharmaceutical composition Substances 0.000 abstract description 6
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 192
239000000243 solution Substances 0.000 description 107
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 96
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 71
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 56
238000011282 treatment Methods 0.000 description 43
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 38
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 38
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 35
238000006243 chemical reaction Methods 0.000 description 35
239000000460 chlorine Substances 0.000 description 35
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
239000000741 silica gel Substances 0.000 description 32
229910002027 silica gel Inorganic materials 0.000 description 32
239000000126 substance Substances 0.000 description 30
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
239000002904 solvent Substances 0.000 description 24
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 23
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 22
239000000047 product Substances 0.000 description 21
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
230000015572 biosynthetic process Effects 0.000 description 20
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 20
239000003921 oil Substances 0.000 description 20
235000019198 oils Nutrition 0.000 description 20
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical group C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 19
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 19
235000019270 ammonium chloride Nutrition 0.000 description 18
125000004432 carbon atom Chemical group C* 0.000 description 18
235000019441 ethanol Nutrition 0.000 description 18
239000007787 solid Substances 0.000 description 18
238000003786 synthesis reaction Methods 0.000 description 18
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 18
239000011541 reaction mixture Substances 0.000 description 17
235000017557 sodium bicarbonate Nutrition 0.000 description 17
229910000030 sodium bicarbonate Inorganic materials 0.000 description 17
BONFHEJHYXHJLU-UHFFFAOYSA-N 2-ethyl-1-(4-methoxyphenyl)sulfonylpiperidine Chemical compound CCC1CCCCN1S(=O)(=O)C1=CC=C(OC)C=C1 BONFHEJHYXHJLU-UHFFFAOYSA-N 0.000 description 16
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 16
239000003795 chemical substances by application Substances 0.000 description 16
238000004587 chromatography analysis Methods 0.000 description 16
239000003937 drug carrier Substances 0.000 description 16
239000003480 eluent Substances 0.000 description 16
239000012044 organic layer Substances 0.000 description 16
210000001519 tissue Anatomy 0.000 description 16
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
239000012230 colorless oil Substances 0.000 description 14
125000001183 hydrocarbyl group Chemical group 0.000 description 14
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
239000012043 crude product Substances 0.000 description 13
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 12
229940088598 enzyme Drugs 0.000 description 12
DUYAAUVXQSMXQP-UHFFFAOYSA-N ethanethioic S-acid Chemical compound CC(S)=O DUYAAUVXQSMXQP-UHFFFAOYSA-N 0.000 description 12
229910052786 argon Inorganic materials 0.000 description 11
206010003246 arthritis Diseases 0.000 description 11
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 10
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 10
125000006239 protecting group Chemical group 0.000 description 10
238000002390 rotary evaporation Methods 0.000 description 10
229960002920 sorbitol Drugs 0.000 description 10
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 9
239000002552 dosage form Substances 0.000 description 9
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 9
235000010356 sorbitol Nutrition 0.000 description 9
239000000600 sorbitol Substances 0.000 description 9
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
241001465754 Metazoa Species 0.000 description 8
206010028980 Neoplasm Diseases 0.000 description 8
239000002253 acid Substances 0.000 description 8
125000004122 cyclic group Chemical group 0.000 description 8
235000011187 glycerol Nutrition 0.000 description 8
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
238000003756 stirring Methods 0.000 description 8
239000000725 suspension Substances 0.000 description 8
206010061218 Inflammation Diseases 0.000 description 7
238000003556 assay Methods 0.000 description 7
125000004429 atom Chemical group 0.000 description 7
239000002775 capsule Substances 0.000 description 7
239000000969 carrier Substances 0.000 description 7
230000004054 inflammatory process Effects 0.000 description 7
239000004615 ingredient Substances 0.000 description 7
239000003446 ligand Substances 0.000 description 7
239000007788 liquid Substances 0.000 description 7
229910052943 magnesium sulfate Inorganic materials 0.000 description 7
235000019341 magnesium sulphate Nutrition 0.000 description 7
239000011734 sodium Substances 0.000 description 7
239000007921 spray Substances 0.000 description 7
238000010561 standard procedure Methods 0.000 description 7
239000003826 tablet Substances 0.000 description 7
SMJRBWINMFUUDS-UHFFFAOYSA-M thien-2-ylacetate Chemical compound [O-]C(=O)CC1=CC=CS1 SMJRBWINMFUUDS-UHFFFAOYSA-M 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 6
102000029816 Collagenase Human genes 0.000 description 6
108060005980 Collagenase Proteins 0.000 description 6
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 6
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 6
229930195725 Mannitol Natural products 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
229920002472 Starch Polymers 0.000 description 6
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 6
229930006000 Sucrose Natural products 0.000 description 6
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 6
OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
230000015556 catabolic process Effects 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
239000000284 extract Substances 0.000 description 6
239000000796 flavoring agent Substances 0.000 description 6
235000003599 food sweetener Nutrition 0.000 description 6
239000000594 mannitol Substances 0.000 description 6
235000010355 mannitol Nutrition 0.000 description 6
102000004169 proteins and genes Human genes 0.000 description 6
108090000623 proteins and genes Proteins 0.000 description 6
238000010992 reflux Methods 0.000 description 6
235000019698 starch Nutrition 0.000 description 6
239000005720 sucrose Substances 0.000 description 6
IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical class NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 6
239000003765 sweetening agent Substances 0.000 description 6
DUYAAUVXQSMXQP-UHFFFAOYSA-M thioacetate Chemical compound CC([S-])=O DUYAAUVXQSMXQP-UHFFFAOYSA-M 0.000 description 6
DTJVECUKADWGMO-UHFFFAOYSA-N 4-methoxybenzenesulfonyl chloride Chemical compound COC1=CC=C(S(Cl)(=O)=O)C=C1 DTJVECUKADWGMO-UHFFFAOYSA-N 0.000 description 5
108010010803 Gelatin Proteins 0.000 description 5
206010027476 Metastases Diseases 0.000 description 5
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
208000025865 Ulcer Diseases 0.000 description 5
206010064996 Ulcerative keratitis Diseases 0.000 description 5
150000001299 aldehydes Chemical class 0.000 description 5
229910021529 ammonia Inorganic materials 0.000 description 5
125000003710 aryl alkyl group Chemical group 0.000 description 5
150000001728 carbonyl compounds Chemical class 0.000 description 5
239000001768 carboxy methyl cellulose Substances 0.000 description 5
239000003086 colorant Substances 0.000 description 5
239000003085 diluting agent Substances 0.000 description 5
239000003995 emulsifying agent Substances 0.000 description 5
238000009472 formulation Methods 0.000 description 5
239000008273 gelatin Substances 0.000 description 5
229920000159 gelatin Polymers 0.000 description 5
235000019322 gelatine Nutrition 0.000 description 5
235000011852 gelatine desserts Nutrition 0.000 description 5
239000007924 injection Substances 0.000 description 5
238000002347 injection Methods 0.000 description 5
239000010410 layer Substances 0.000 description 5
239000000314 lubricant Substances 0.000 description 5
201000008482 osteoarthritis Diseases 0.000 description 5
238000007911 parenteral administration Methods 0.000 description 5
239000000843 powder Substances 0.000 description 5
230000037390 scarring Effects 0.000 description 5
239000007858 starting material Substances 0.000 description 5
125000001424 substituent group Chemical group 0.000 description 5
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 5
239000000454 talc Substances 0.000 description 5
235000012222 talc Nutrition 0.000 description 5
229910052623 talc Inorganic materials 0.000 description 5
238000002560 therapeutic procedure Methods 0.000 description 5
230000008354 tissue degradation Effects 0.000 description 5
XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 4
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 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
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 4
239000004215 Carbon black (E152) Substances 0.000 description 4
102000000422 Matrix Metalloproteinase 3 Human genes 0.000 description 4
102000035195 Peptidases Human genes 0.000 description 4
108091005804 Peptidases Proteins 0.000 description 4
239000002202 Polyethylene glycol Substances 0.000 description 4
239000004365 Protease Substances 0.000 description 4
101710172711 Structural protein Proteins 0.000 description 4
230000033228 biological regulation Effects 0.000 description 4
201000011510 cancer Diseases 0.000 description 4
210000004027 cell Anatomy 0.000 description 4
235000010980 cellulose Nutrition 0.000 description 4
229920002678 cellulose Polymers 0.000 description 4
239000001913 cellulose Substances 0.000 description 4
229960002424 collagenase Drugs 0.000 description 4
238000001816 cooling Methods 0.000 description 4
238000006731 degradation reaction Methods 0.000 description 4
239000000945 filler Substances 0.000 description 4
235000013355 food flavoring agent Nutrition 0.000 description 4
239000000499 gel Substances 0.000 description 4
230000035876 healing Effects 0.000 description 4
229930195733 hydrocarbon Natural products 0.000 description 4
238000001727 in vivo Methods 0.000 description 4
208000015181 infectious disease Diseases 0.000 description 4
230000002401 inhibitory effect Effects 0.000 description 4
208000014674 injury Diseases 0.000 description 4
239000008101 lactose Substances 0.000 description 4
235000019359 magnesium stearate Nutrition 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
230000003647 oxidation Effects 0.000 description 4
238000007254 oxidation reaction Methods 0.000 description 4
229920001223 polyethylene glycol Polymers 0.000 description 4
239000003755 preservative agent Substances 0.000 description 4
230000002265 prevention Effects 0.000 description 4
150000003254 radicals Chemical class 0.000 description 4
108091007196 stromelysin Proteins 0.000 description 4
125000004434 sulfur atom Chemical group 0.000 description 4
239000000375 suspending agent Substances 0.000 description 4
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 4
230000009466 transformation Effects 0.000 description 4
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 4
RNHDAKUGFHSZEV-UHFFFAOYSA-N 1,4-dioxane;hydrate Chemical compound O.C1COCCO1 RNHDAKUGFHSZEV-UHFFFAOYSA-N 0.000 description 3
NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical class C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 3
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
241000416162 Astragalus gummifer Species 0.000 description 3
229920002261 Corn starch Polymers 0.000 description 3
ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 3
239000001856 Ethyl cellulose Substances 0.000 description 3
108010026132 Gelatinases Proteins 0.000 description 3
102000013382 Gelatinases Human genes 0.000 description 3
208000019693 Lung disease Diseases 0.000 description 3
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 3
235000021355 Stearic acid Nutrition 0.000 description 3
229920001615 Tragacanth Polymers 0.000 description 3
QOTUIIJRVXKSJU-YFKPBYRVSA-N [(3s)-pyrrolidin-3-yl]methanol Chemical compound OC[C@H]1CCNC1 QOTUIIJRVXKSJU-YFKPBYRVSA-N 0.000 description 3
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
230000001154 acute effect Effects 0.000 description 3
235000010443 alginic acid Nutrition 0.000 description 3
229920000615 alginic acid Polymers 0.000 description 3
239000000783 alginic acid Substances 0.000 description 3
229960001126 alginic acid Drugs 0.000 description 3
150000004781 alginic acids Chemical class 0.000 description 3
125000003342 alkenyl group Chemical group 0.000 description 3
MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 3
238000002399 angioplasty Methods 0.000 description 3
239000003963 antioxidant agent Substances 0.000 description 3
235000006708 antioxidants Nutrition 0.000 description 3
208000006673 asthma Diseases 0.000 description 3
230000001580 bacterial effect Effects 0.000 description 3
239000011230 binding agent Substances 0.000 description 3
229910000085 borane Inorganic materials 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910000019 calcium carbonate Inorganic materials 0.000 description 3
235000011132 calcium sulphate Nutrition 0.000 description 3
RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 3
238000004040 coloring Methods 0.000 description 3
230000021615 conjugation Effects 0.000 description 3
210000004087 cornea Anatomy 0.000 description 3
230000008878 coupling Effects 0.000 description 3
238000010168 coupling process Methods 0.000 description 3
238000005859 coupling reaction Methods 0.000 description 3
239000013058 crude material Substances 0.000 description 3
230000006378 damage Effects 0.000 description 3
230000007850 degeneration Effects 0.000 description 3
230000001419 dependent effect Effects 0.000 description 3
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
238000009826 distribution Methods 0.000 description 3
239000006196 drop Substances 0.000 description 3
229940079593 drug Drugs 0.000 description 3
239000003814 drug Substances 0.000 description 3
239000000839 emulsion Substances 0.000 description 3
235000019325 ethyl cellulose Nutrition 0.000 description 3
229920001249 ethyl cellulose Polymers 0.000 description 3
230000003176 fibrotic effect Effects 0.000 description 3
239000012467 final product Substances 0.000 description 3
239000007789 gas Substances 0.000 description 3
208000024693 gingival disease Diseases 0.000 description 3
239000008187 granular material Substances 0.000 description 3
150000004820 halides Chemical class 0.000 description 3
150000002500 ions Chemical class 0.000 description 3
239000000463 material Substances 0.000 description 3
239000011159 matrix material Substances 0.000 description 3
230000035800 maturation Effects 0.000 description 3
229920000609 methyl cellulose Polymers 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
239000001923 methylcellulose Substances 0.000 description 3
235000010981 methylcellulose Nutrition 0.000 description 3
125000002950 monocyclic group Chemical group 0.000 description 3
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 3
208000028169 periodontal disease Diseases 0.000 description 3
HXEACLLIILLPRG-UHFFFAOYSA-N pipecolic acid Chemical compound OC(=O)C1CCCCN1 HXEACLLIILLPRG-UHFFFAOYSA-N 0.000 description 3
125000003367 polycyclic group Chemical group 0.000 description 3
229920005862 polyol Polymers 0.000 description 3
150000003077 polyols Chemical class 0.000 description 3
230000003389 potentiating effect Effects 0.000 description 3
238000011321 prophylaxis Methods 0.000 description 3
235000013772 propylene glycol Nutrition 0.000 description 3
238000000746 purification Methods 0.000 description 3
238000007086 side reaction Methods 0.000 description 3
210000001626 skin fibroblast Anatomy 0.000 description 3
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 3
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 3
239000008107 starch Substances 0.000 description 3
239000008117 stearic acid Substances 0.000 description 3
239000000758 substrate Substances 0.000 description 3
235000000346 sugar Nutrition 0.000 description 3
208000024891 symptom Diseases 0.000 description 3
230000009885 systemic effect Effects 0.000 description 3
235000010487 tragacanth Nutrition 0.000 description 3
239000000196 tragacanth Substances 0.000 description 3
229940116362 tragacanth Drugs 0.000 description 3
238000011269 treatment regimen Methods 0.000 description 3
230000004614 tumor growth Effects 0.000 description 3
230000036269 ulceration Effects 0.000 description 3
235000015112 vegetable and seed oil Nutrition 0.000 description 3
239000008158 vegetable oil Substances 0.000 description 3
239000000080 wetting agent Substances 0.000 description 3
LWZATQDWEXAGQR-LLVKDONJSA-N (2r)-1-(4-methoxyphenyl)sulfonylpyrrolidine-2-carboxylic acid Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N1[C@@H](C(O)=O)CCC1 LWZATQDWEXAGQR-LLVKDONJSA-N 0.000 description 2
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 2
RRRAPFHBNRPFSV-BXUZGUMPSA-N (2r,4r)-1-(4-butoxyphenyl)sulfonyl-4-hydroxypyrrolidine-2-carboxylic acid Chemical compound C1=CC(OCCCC)=CC=C1S(=O)(=O)N1[C@@H](C(O)=O)C[C@@H](O)C1 RRRAPFHBNRPFSV-BXUZGUMPSA-N 0.000 description 2
YBWUYYVFHIGKPL-LDYMZIIASA-N (2r,4r)-4-hydroxy-1-(4-methoxyphenyl)sulfonylpyrrolidine-2-carboxylic acid Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N1[C@@H](C(O)=O)C[C@@H](O)C1 YBWUYYVFHIGKPL-LDYMZIIASA-N 0.000 description 2
KIVBPNLNUFWMAG-VIFPVBQESA-N (3s)-1-(4-methoxyphenyl)sulfonylpyrrolidin-3-ol Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N1C[C@@H](O)CC1 KIVBPNLNUFWMAG-VIFPVBQESA-N 0.000 description 2
REDSEXWGKAYROX-MNOVXSKESA-N (4s)-4-(hydroxymethyl)-1-[(1r)-1-phenylethyl]pyrrolidin-2-one Chemical compound N1([C@H](C)C=2C=CC=CC=2)C[C@@H](CO)CC1=O REDSEXWGKAYROX-MNOVXSKESA-N 0.000 description 2
LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical group N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 description 2
ACAZZMWZSGFLHA-UHFFFAOYSA-N 1-[1-(4-methoxyphenyl)sulfonylpiperidin-2-yl]-1-(1,3-thiazol-2-yl)propane-2-thione Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N1C(C(C(C)=S)C=2SC=CN=2)CCCC1 ACAZZMWZSGFLHA-UHFFFAOYSA-N 0.000 description 2
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
ZUIAAACKSYQKAI-UHFFFAOYSA-N 2-ethenyl-1-(4-methoxyphenyl)sulfonylpiperidine Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N1C(C=C)CCCC1 ZUIAAACKSYQKAI-UHFFFAOYSA-N 0.000 description 2
FDAMVVHYWSPPFN-UHFFFAOYSA-N 2-sulfonylpyrrolidine Chemical compound O=S(=O)=C1CCCN1 FDAMVVHYWSPPFN-UHFFFAOYSA-N 0.000 description 2
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
HGKWMUBXVMFXNC-UHFFFAOYSA-N 4-butoxybenzenesulfonyl chloride Chemical compound CCCCOC1=CC=C(S(Cl)(=O)=O)C=C1 HGKWMUBXVMFXNC-UHFFFAOYSA-N 0.000 description 2
208000030507 AIDS Diseases 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
102000008186 Collagen Human genes 0.000 description 2
108010035532 Collagen Proteins 0.000 description 2
201000004624 Dermatitis Diseases 0.000 description 2
206010053177 Epidermolysis Diseases 0.000 description 2
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
108010037362 Extracellular Matrix Proteins Proteins 0.000 description 2
102000010834 Extracellular Matrix Proteins Human genes 0.000 description 2
206010016654 Fibrosis 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
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
108090000288 Glycoproteins Proteins 0.000 description 2
102000003886 Glycoproteins Human genes 0.000 description 2
229920002907 Guar gum Polymers 0.000 description 2
206010019280 Heart failures Diseases 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
235000019483 Peanut oil Nutrition 0.000 description 2
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
FPCGLVSIUWVZRS-AEFFLSMTSA-N S-[[(2R,4S)-4-acetylsulfanyl-1-(4-butoxyphenyl)sulfonylpyrrolidin-2-yl]methyl] ethanethioate Chemical compound C1=CC(OCCCC)=CC=C1S(=O)(=O)N1[C@@H](CSC(C)=O)C[C@H](SC(C)=O)C1 FPCGLVSIUWVZRS-AEFFLSMTSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
208000027418 Wounds and injury Diseases 0.000 description 2
QENDKLNKUVHFSD-SNVBAGLBSA-N [(2r)-1-(4-methoxyphenyl)sulfonylpyrrolidin-2-yl]methanol Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N1[C@@H](CO)CCC1 QENDKLNKUVHFSD-SNVBAGLBSA-N 0.000 description 2
230000002159 abnormal effect Effects 0.000 description 2
125000002252 acyl group Chemical group 0.000 description 2
239000000443 aerosol Substances 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
150000001336 alkenes Chemical class 0.000 description 2
125000004183 alkoxy alkyl group Chemical group 0.000 description 2
125000002947 alkylene group Chemical group 0.000 description 2
125000000304 alkynyl group Chemical group 0.000 description 2
125000000266 alpha-aminoacyl group Chemical group 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
125000000129 anionic group Chemical group 0.000 description 2
239000002518 antifoaming agent Substances 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
230000001363 autoimmune Effects 0.000 description 2
230000005784 autoimmunity Effects 0.000 description 2
230000008901 benefit Effects 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
235000019445 benzyl alcohol Nutrition 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 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
230000001588 bifunctional effect Effects 0.000 description 2
230000004071 biological effect Effects 0.000 description 2
210000004369 blood Anatomy 0.000 description 2
239000008280 blood Substances 0.000 description 2
210000004204 blood vessel Anatomy 0.000 description 2
210000000988 bone and bone Anatomy 0.000 description 2
UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
239000000872 buffer Substances 0.000 description 2
239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
239000008112 carboxymethyl-cellulose Substances 0.000 description 2
125000002091 cationic group Chemical group 0.000 description 2
230000001413 cellular effect Effects 0.000 description 2
210000003169 central nervous system Anatomy 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
229940112822 chewing gum Drugs 0.000 description 2
235000015218 chewing gum Nutrition 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
PMMYEEVYMWASQN-QWWZWVQMSA-N cis-4-hydroxy-D-proline Chemical compound O[C@H]1C[NH2+][C@@H](C([O-])=O)C1 PMMYEEVYMWASQN-QWWZWVQMSA-N 0.000 description 2
238000003776 cleavage reaction Methods 0.000 description 2
238000000576 coating method Methods 0.000 description 2
239000003240 coconut oil Substances 0.000 description 2
235000019864 coconut oil Nutrition 0.000 description 2
229920001436 collagen Polymers 0.000 description 2
239000007891 compressed tablet Substances 0.000 description 2
235000005687 corn oil Nutrition 0.000 description 2
239000002285 corn oil Substances 0.000 description 2
239000008120 corn starch Substances 0.000 description 2
239000000287 crude extract Substances 0.000 description 2
239000010779 crude oil Substances 0.000 description 2
UQHKFADEQIVWID-UHFFFAOYSA-N cytokinin Natural products C1=NC=2C(NCC=C(CO)C)=NC=NC=2N1C1CC(O)C(CO)O1 UQHKFADEQIVWID-UHFFFAOYSA-N 0.000 description 2
239000004062 cytokinin Substances 0.000 description 2
230000020335 dealkylation Effects 0.000 description 2
238000006900 dealkylation reaction Methods 0.000 description 2
230000000593 degrading effect Effects 0.000 description 2
WQOXQRCZOLPYPM-UHFFFAOYSA-N dimethyl disulfide Chemical compound CSSC WQOXQRCZOLPYPM-UHFFFAOYSA-N 0.000 description 2
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
239000007884 disintegrant Substances 0.000 description 2
239000000975 dye Substances 0.000 description 2
150000002118 epoxides Chemical class 0.000 description 2
150000002170 ethers Chemical class 0.000 description 2
210000002744 extracellular matrix Anatomy 0.000 description 2
208000030533 eye disease Diseases 0.000 description 2
235000019634 flavors Nutrition 0.000 description 2
239000011737 fluorine Substances 0.000 description 2
229910052731 fluorine Inorganic materials 0.000 description 2
235000019253 formic acid Nutrition 0.000 description 2
239000012634 fragment Substances 0.000 description 2
125000000524 functional group Chemical group 0.000 description 2
239000008103 glucose Substances 0.000 description 2
239000000665 guar gum Substances 0.000 description 2
235000010417 guar gum Nutrition 0.000 description 2
229960002154 guar gum Drugs 0.000 description 2
150000002430 hydrocarbons Chemical group 0.000 description 2
230000036039 immunity Effects 0.000 description 2
230000003053 immunization Effects 0.000 description 2
238000002649 immunization Methods 0.000 description 2
238000003018 immunoassay Methods 0.000 description 2
230000002163 immunogen Effects 0.000 description 2
239000007943 implant Substances 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
230000003993 interaction Effects 0.000 description 2
230000001788 irregular Effects 0.000 description 2
HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 description 2
150000003951 lactams Chemical class 0.000 description 2
235000010445 lecithin Nutrition 0.000 description 2
239000000787 lecithin Substances 0.000 description 2
229940067606 lecithin Drugs 0.000 description 2
230000007774 longterm Effects 0.000 description 2
231100000053 low toxicity Toxicity 0.000 description 2
239000007937 lozenge Substances 0.000 description 2
230000001404 mediated effect Effects 0.000 description 2
238000002844 melting Methods 0.000 description 2
230000008018 melting Effects 0.000 description 2
210000004379 membrane Anatomy 0.000 description 2
239000012528 membrane Substances 0.000 description 2
230000009401 metastasis Effects 0.000 description 2
150000004702 methyl esters Chemical class 0.000 description 2
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 2
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
CXQTTWVBUDFUNO-UHFFFAOYSA-N methyl piperidine-2-carboxylate Chemical compound COC(=O)C1CCCCN1 CXQTTWVBUDFUNO-UHFFFAOYSA-N 0.000 description 2
229960002216 methylparaben Drugs 0.000 description 2
238000002156 mixing Methods 0.000 description 2
230000004048 modification Effects 0.000 description 2
238000012986 modification Methods 0.000 description 2
238000012544 monitoring process Methods 0.000 description 2
125000002757 morpholinyl group Chemical group 0.000 description 2
201000006417 multiple sclerosis Diseases 0.000 description 2
229910000069 nitrogen hydride Inorganic materials 0.000 description 2
239000002674 ointment Substances 0.000 description 2
239000004006 olive oil Substances 0.000 description 2
235000008390 olive oil Nutrition 0.000 description 2
239000006186 oral dosage form Substances 0.000 description 2
210000000056 organ Anatomy 0.000 description 2
125000004430 oxygen atom Chemical group O* 0.000 description 2
239000000312 peanut oil Substances 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
125000004344 phenylpropyl group Chemical group 0.000 description 2
239000008363 phosphate buffer Substances 0.000 description 2
239000002504 physiological saline solution Substances 0.000 description 2
RJUAEBLXGFKZMS-UHFFFAOYSA-N piperidin-1-ylmethanol Chemical compound OCN1CCCCC1 RJUAEBLXGFKZMS-UHFFFAOYSA-N 0.000 description 2
229920000136 polysorbate Polymers 0.000 description 2
229920001592 potato starch Polymers 0.000 description 2
238000012545 processing Methods 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
125000004076 pyridyl group Chemical group 0.000 description 2
HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 2
238000010791 quenching Methods 0.000 description 2
239000003507 refrigerant Substances 0.000 description 2
NQDXXNYOLDUYJN-UHFFFAOYSA-N s-[[1-(4-butoxyphenyl)sulfonylpiperidin-2-yl]methyl] ethanethioate Chemical compound C1=CC(OCCCC)=CC=C1S(=O)(=O)N1C(CSC(C)=O)CCCC1 NQDXXNYOLDUYJN-UHFFFAOYSA-N 0.000 description 2
235000019204 saccharin Nutrition 0.000 description 2
229940081974 saccharin Drugs 0.000 description 2
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
230000007017 scission Effects 0.000 description 2
150000003335 secondary amines Chemical class 0.000 description 2
230000035945 sensitivity Effects 0.000 description 2
210000002966 serum Anatomy 0.000 description 2
239000008159 sesame oil Substances 0.000 description 2
235000011803 sesame oil Nutrition 0.000 description 2
238000010898 silica gel chromatography Methods 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 2
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
150000008163 sugars Chemical class 0.000 description 2
229940124530 sulfonamide Drugs 0.000 description 2
150000003456 sulfonamides Chemical class 0.000 description 2
238000001356 surgical procedure Methods 0.000 description 2
230000008961 swelling Effects 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
150000003512 tertiary amines Chemical class 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
150000003553 thiiranes Chemical class 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
150000003573 thiols Chemical class 0.000 description 2
230000006032 tissue transformation Effects 0.000 description 2
238000011200 topical administration Methods 0.000 description 2
230000008733 trauma Effects 0.000 description 2
239000003981 vehicle Substances 0.000 description 2
238000005303 weighing Methods 0.000 description 2
239000008096 xylene Substances 0.000 description 2
150000003738 xylenes Chemical class 0.000 description 2
NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
RQEUFEKYXDPUSK-SSDOTTSWSA-N (1R)-1-phenylethanamine Chemical compound C[C@@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-SSDOTTSWSA-N 0.000 description 1
JHHZLHWJQPUNKB-BYPYZUCNSA-N (3s)-pyrrolidin-3-ol Chemical compound O[C@H]1CCNC1 JHHZLHWJQPUNKB-BYPYZUCNSA-N 0.000 description 1
MWZKWGGTLODHMZ-UHFFFAOYSA-N 1-ethyl-4-(4-methoxyphenyl)sulfonylpiperidine Chemical compound C1CN(CC)CCC1S(=O)(=O)C1=CC=C(OC)C=C1 MWZKWGGTLODHMZ-UHFFFAOYSA-N 0.000 description 1
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
PNDPGZBMCMUPRI-HVTJNCQCSA-N 10043-66-0 Chemical compound [131I][131I] PNDPGZBMCMUPRI-HVTJNCQCSA-N 0.000 description 1
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
238000005160 1H NMR spectroscopy Methods 0.000 description 1
JAHNSTQSQJOJLO-UHFFFAOYSA-N 2-(3-fluorophenyl)-1h-imidazole Chemical compound FC1=CC=CC(C=2NC=CN=2)=C1 JAHNSTQSQJOJLO-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 description 1
FPVUWZFFEGYCGB-UHFFFAOYSA-N 5-methyl-3h-1,3,4-thiadiazole-2-thione Chemical compound CC1=NN=C(S)S1 FPVUWZFFEGYCGB-UHFFFAOYSA-N 0.000 description 1
CFGKWSDAMXTRHE-UHFFFAOYSA-N 5-oxo-1-(1-phenylethyl)pyrrolidine-3-carboxylic acid Chemical compound C=1C=CC=CC=1C(C)N1CC(C(O)=O)CC1=O CFGKWSDAMXTRHE-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
241000224422 Acanthamoeba Species 0.000 description 1
208000024827 Alzheimer disease Diseases 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
108010011485 Aspartame Proteins 0.000 description 1
201000001320 Atherosclerosis Diseases 0.000 description 1
208000023275 Autoimmune disease Diseases 0.000 description 1
NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
BESVEYMKUKWYLR-UHFFFAOYSA-N C=1C=CC=CC=1P(C=1C=CC=CC=1)(CI)C1=CC=CC=C1 Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(CI)C1=CC=CC=C1 BESVEYMKUKWYLR-UHFFFAOYSA-N 0.000 description 1
GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
101100048447 Caenorhabditis elegans unc-4 gene Proteins 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
208000031229 Cardiomyopathies Diseases 0.000 description 1
229910020194 CeH2 Inorganic materials 0.000 description 1
229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
208000009043 Chemical Burns Diseases 0.000 description 1
208000018380 Chemical injury Diseases 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
206010010984 Corneal abrasion Diseases 0.000 description 1
208000028006 Corneal injury Diseases 0.000 description 1
208000011231 Crohn disease Diseases 0.000 description 1
201000003883 Cystic fibrosis Diseases 0.000 description 1
241000701022 Cytomegalovirus Species 0.000 description 1
ONIBWKKTOPOVIA-SCSAIBSYSA-N D-Proline Chemical compound OC(=O)[C@H]1CCCN1 ONIBWKKTOPOVIA-SCSAIBSYSA-N 0.000 description 1
229930182820 D-proline Natural products 0.000 description 1
NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
206010012438 Dermatitis atopic Diseases 0.000 description 1
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
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 1
LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
241001125671 Eretmochelys imbricata Species 0.000 description 1
239000005977 Ethylene Substances 0.000 description 1
229920003134 Eudragit® polymer Polymers 0.000 description 1
108050001049 Extracellular proteins Proteins 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
201000005569 Gout Diseases 0.000 description 1
208000031886 HIV Infections Diseases 0.000 description 1
208000037357 HIV infectious disease Diseases 0.000 description 1
208000009889 Herpes Simplex Diseases 0.000 description 1
206010019973 Herpes virus infection Diseases 0.000 description 1
241000282412 Homo Species 0.000 description 1
PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
208000022559 Inflammatory bowel disease Diseases 0.000 description 1
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
229910010082 LiAlH Inorganic materials 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
235000019759 Maize starch Nutrition 0.000 description 1
102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 1
108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 1
201000009906 Meningitis Diseases 0.000 description 1
244000246386 Mentha pulegium Species 0.000 description 1
235000016257 Mentha pulegium Nutrition 0.000 description 1
235000004357 Mentha x piperita Nutrition 0.000 description 1
VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
102000006386 Myelin Proteins Human genes 0.000 description 1
108010083674 Myelin Proteins Proteins 0.000 description 1
WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 1
102000003729 Neprilysin Human genes 0.000 description 1
108090000028 Neprilysin Proteins 0.000 description 1
208000008589 Obesity Diseases 0.000 description 1
241000283973 Oryctolagus cuniculus Species 0.000 description 1
208000001132 Osteoporosis Diseases 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
206010033799 Paralysis Diseases 0.000 description 1
239000004372 Polyvinyl alcohol Substances 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
108010067787 Proteoglycans Proteins 0.000 description 1
241000589517 Pseudomonas aeruginosa Species 0.000 description 1
201000004681 Psoriasis Diseases 0.000 description 1
206010037660 Pyrexia Diseases 0.000 description 1
208000033464 Reiter syndrome Diseases 0.000 description 1
206010063837 Reperfusion injury Diseases 0.000 description 1
206010061494 Rhinovirus infection Diseases 0.000 description 1
241000220010 Rhode Species 0.000 description 1
206010039705 Scleritis Diseases 0.000 description 1
206010039710 Scleroderma Diseases 0.000 description 1
206010040047 Sepsis Diseases 0.000 description 1
102000007562 Serum Albumin Human genes 0.000 description 1
108010071390 Serum Albumin Proteins 0.000 description 1
244000000231 Sesamum indicum Species 0.000 description 1
235000003434 Sesamum indicum Nutrition 0.000 description 1
229920001800 Shellac Polymers 0.000 description 1
241000700584 Simplexvirus Species 0.000 description 1
206010061363 Skeletal injury Diseases 0.000 description 1
208000028990 Skin injury Diseases 0.000 description 1
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
GKLVYJBZJHMRIY-OUBTZVSYSA-N Technetium-99 Chemical compound [99Tc] GKLVYJBZJHMRIY-OUBTZVSYSA-N 0.000 description 1
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
208000026062 Tissue disease Diseases 0.000 description 1
241000700647 Variola virus Species 0.000 description 1
208000036142 Viral infection Diseases 0.000 description 1
240000008042 Zea mays Species 0.000 description 1
235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
235000002017 Zea mays subsp mays Nutrition 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
101710204001 Zinc metalloprotease Proteins 0.000 description 1
206010000210 abortion Diseases 0.000 description 1
231100000176 abortion Toxicity 0.000 description 1
150000001241 acetals Chemical class 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000004913 activation Effects 0.000 description 1
239000013543 active substance Substances 0.000 description 1
125000004442 acylamino group Chemical group 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
125000004423 acyloxy group Chemical group 0.000 description 1
239000003513 alkali Substances 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
208000026935 allergic disease Diseases 0.000 description 1
230000009285 allergic inflammation Effects 0.000 description 1
125000005336 allyloxy group Chemical group 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
208000022531 anorexia Diseases 0.000 description 1
230000002924 anti-infective effect Effects 0.000 description 1
229940121363 anti-inflammatory agent Drugs 0.000 description 1
239000002260 anti-inflammatory agent Substances 0.000 description 1
210000000628 antibody-producing cell Anatomy 0.000 description 1
239000000729 antidote Substances 0.000 description 1
239000000427 antigen Substances 0.000 description 1
102000036639 antigens Human genes 0.000 description 1
108091007433 antigens Proteins 0.000 description 1
229960005475 antiinfective agent Drugs 0.000 description 1
229940125687 antiparasitic agent Drugs 0.000 description 1
239000003096 antiparasitic agent Substances 0.000 description 1
239000012300 argon atmosphere Substances 0.000 description 1
125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
238000007080 aromatic substitution reaction Methods 0.000 description 1
210000001188 articular cartilage Anatomy 0.000 description 1
125000001691 aryl alkyl amino group Chemical group 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
239000000605 aspartame Substances 0.000 description 1
IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
235000010357 aspartame Nutrition 0.000 description 1
229960003438 aspartame Drugs 0.000 description 1
201000008937 atopic dermatitis Diseases 0.000 description 1
XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 1
239000002585 base Substances 0.000 description 1
210000002469 basement membrane Anatomy 0.000 description 1
229960001716 benzalkonium Drugs 0.000 description 1
229960000686 benzalkonium chloride Drugs 0.000 description 1
125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 description 1
CYDRXTMLKJDRQH-UHFFFAOYSA-N benzododecinium Chemical compound CCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 CYDRXTMLKJDRQH-UHFFFAOYSA-N 0.000 description 1
125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
239000012965 benzophenone Substances 0.000 description 1
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
125000002619 bicyclic group Chemical group 0.000 description 1
235000010290 biphenyl Nutrition 0.000 description 1
239000004305 biphenyl Substances 0.000 description 1
AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 description 1
210000000746 body region Anatomy 0.000 description 1
206010006451 bronchitis Diseases 0.000 description 1
125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
125000002837 carbocyclic group Chemical group 0.000 description 1
150000001718 carbodiimides Chemical class 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
125000004181 carboxyalkyl group Chemical group 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
210000000748 cardiovascular system Anatomy 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
229940081734 cellulose acetate phthalate Drugs 0.000 description 1
238000000262 chemical ionisation mass spectrometry Methods 0.000 description 1
239000007910 chewable tablet Substances 0.000 description 1
235000015111 chews Nutrition 0.000 description 1
210000001612 chondrocyte Anatomy 0.000 description 1
230000007882 cirrhosis Effects 0.000 description 1
208000019425 cirrhosis of liver Diseases 0.000 description 1
230000015271 coagulation Effects 0.000 description 1
238000005345 coagulation Methods 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
206010009887 colitis Diseases 0.000 description 1
210000001072 colon Anatomy 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
230000001268 conjugating effect Effects 0.000 description 1
230000008602 contraction Effects 0.000 description 1
230000001276 controlling effect Effects 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
235000005822 corn Nutrition 0.000 description 1
208000029078 coronary artery disease Diseases 0.000 description 1
239000006071 cream Substances 0.000 description 1
239000013078 crystal Substances 0.000 description 1
125000002592 cumenyl group Chemical group C1(=C(C=CC=C1)*)C(C)C 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
230000021953 cytokinesis Effects 0.000 description 1
230000002548 cytokinetic effect Effects 0.000 description 1
206010061428 decreased appetite Diseases 0.000 description 1
230000007547 defect Effects 0.000 description 1
238000011161 development Methods 0.000 description 1
230000018109 developmental process Effects 0.000 description 1
206010012601 diabetes mellitus Diseases 0.000 description 1
SIPUZPBQZHNSDW-UHFFFAOYSA-N diisobutylaluminium hydride Substances CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
229940043279 diisopropylamine Drugs 0.000 description 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
238000004821 distillation Methods 0.000 description 1
PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
230000001516 effect on protein Effects 0.000 description 1
229920001971 elastomer Polymers 0.000 description 1
238000000921 elemental analysis Methods 0.000 description 1
239000003974 emollient agent Substances 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
238000003821 enantio-separation Methods 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
210000000981 epithelium Anatomy 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
238000006266 etherification reaction Methods 0.000 description 1
229960004667 ethyl cellulose Drugs 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
229940093471 ethyl oleate Drugs 0.000 description 1
KGAWPIXNSIYQPC-UHFFFAOYSA-N ethyl piperidine-2-carboxylate;hydrochloride Chemical compound Cl.CCOC(=O)C1CCCCN1 KGAWPIXNSIYQPC-UHFFFAOYSA-N 0.000 description 1
208000016253 exhaustion Diseases 0.000 description 1
210000003414 extremity Anatomy 0.000 description 1
239000003889 eye drop Substances 0.000 description 1
229940012356 eye drops Drugs 0.000 description 1
230000004761 fibrosis Effects 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
239000008369 fruit flavor Substances 0.000 description 1
238000007306 functionalization reaction Methods 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
208000007565 gingivitis Diseases 0.000 description 1
239000011521 glass Substances 0.000 description 1
230000003779 hair growth Effects 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
108060003552 hemocyanin Proteins 0.000 description 1
208000006454 hepatitis Diseases 0.000 description 1
231100000283 hepatitis Toxicity 0.000 description 1
125000004474 heteroalkylene group Chemical group 0.000 description 1
235000001050 hortel pimenta Nutrition 0.000 description 1
208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
229920001477 hydrophilic polymer Polymers 0.000 description 1
239000003752 hydrotrope Substances 0.000 description 1
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
125000002768 hydroxyalkyl group Chemical group 0.000 description 1
229960002591 hydroxyproline Drugs 0.000 description 1
235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
239000001863 hydroxypropyl cellulose Substances 0.000 description 1
229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
206010020718 hyperplasia Diseases 0.000 description 1
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
210000000987 immune system Anatomy 0.000 description 1
230000002637 immunotoxin Effects 0.000 description 1
229940051026 immunotoxin Drugs 0.000 description 1
239000002596 immunotoxin Substances 0.000 description 1
231100000608 immunotoxin Toxicity 0.000 description 1
238000012606 in vitro cell culture Methods 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
239000003701 inert diluent Substances 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
208000027866 inflammatory disease Diseases 0.000 description 1
238000002329 infrared spectrum Methods 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000007913 intrathecal administration Methods 0.000 description 1
230000007794 irritation Effects 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
206010023332 keratitis Diseases 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
BWHLPLXXIDYSNW-UHFFFAOYSA-N ketorolac tromethamine Chemical compound OCC(N)(CO)CO.OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 BWHLPLXXIDYSNW-UHFFFAOYSA-N 0.000 description 1
210000003127 knee Anatomy 0.000 description 1
208000032839 leukemia Diseases 0.000 description 1
239000006193 liquid solution Substances 0.000 description 1
MHCFAGZWMAWTNR-UHFFFAOYSA-M lithium perchlorate Chemical compound [Li+].[O-]Cl(=O)(=O)=O MHCFAGZWMAWTNR-UHFFFAOYSA-M 0.000 description 1
229910001486 lithium perchlorate Inorganic materials 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
239000006210 lotion Substances 0.000 description 1
210000004072 lung Anatomy 0.000 description 1
206010025135 lupus erythematosus Diseases 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
201000004792 malaria Diseases 0.000 description 1
238000007726 management method Methods 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
238000013507 mapping Methods 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
229940041616 menthol Drugs 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
NTNUDYROPUKXNA-UHFFFAOYSA-N methyl 2-(triphenyl-$l^{5}-phosphanylidene)acetate Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OC)C1=CC=CC=C1 NTNUDYROPUKXNA-UHFFFAOYSA-N 0.000 description 1
SMYHRJOQEVSCKS-UHFFFAOYSA-N methyl 4-hydroxybenzoate;propyl 4-hydroxybenzoate Chemical compound COC(=O)C1=CC=C(O)C=C1.CCCOC(=O)C1=CC=C(O)C=C1 SMYHRJOQEVSCKS-UHFFFAOYSA-N 0.000 description 1
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
LVHBHZANLOWSRM-UHFFFAOYSA-N methylenebutanedioic acid Natural products OC(=O)CC(=C)C(O)=O LVHBHZANLOWSRM-UHFFFAOYSA-N 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
125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
230000004899 motility Effects 0.000 description 1
210000000214 mouth Anatomy 0.000 description 1
210000003097 mucus Anatomy 0.000 description 1
201000006938 muscular dystrophy Diseases 0.000 description 1
210000005012 myelin Anatomy 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
210000000944 nerve tissue Anatomy 0.000 description 1
208000015122 neurodegenerative disease Diseases 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
230000037311 normal skin Effects 0.000 description 1
230000008481 normal tissue growth Effects 0.000 description 1
230000000269 nucleophilic effect Effects 0.000 description 1
235000020824 obesity Nutrition 0.000 description 1
239000007935 oral tablet Substances 0.000 description 1
229940096978 oral tablet Drugs 0.000 description 1
206010033103 otosclerosis Diseases 0.000 description 1
230000016087 ovulation Effects 0.000 description 1
208000021090 palsy Diseases 0.000 description 1
210000000496 pancreas Anatomy 0.000 description 1
230000035515 penetration Effects 0.000 description 1
239000007967 peppermint flavor Substances 0.000 description 1
201000001245 periodontitis Diseases 0.000 description 1
210000005105 peripheral blood lymphocyte Anatomy 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
229940068968 polysorbate 80 Drugs 0.000 description 1
229920000053 polysorbate 80 Polymers 0.000 description 1
229940100467 polyvinyl acetate phthalate Drugs 0.000 description 1
229920002451 polyvinyl alcohol Polymers 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
229940069328 povidone Drugs 0.000 description 1
150000003138 primary alcohols Chemical class 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
230000008569 process Effects 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
229960003415 propylparaben Drugs 0.000 description 1
208000023958 prostate neoplasm Diseases 0.000 description 1
201000001474 proteinuria Diseases 0.000 description 1
230000017854 proteolysis Effects 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
239000008213 purified water Substances 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
230000001698 pyrogenic effect Effects 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
230000005855 radiation Effects 0.000 description 1
239000000376 reactant Substances 0.000 description 1
208000002574 reactive arthritis Diseases 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000008929 regeneration Effects 0.000 description 1
238000011069 regeneration method Methods 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
230000000241 respiratory effect Effects 0.000 description 1
208000037803 restenosis Diseases 0.000 description 1
230000002207 retinal effect Effects 0.000 description 1
206010039073 rheumatoid arthritis Diseases 0.000 description 1
238000006798 ring closing metathesis reaction Methods 0.000 description 1
125000006413 ring segment Chemical group 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
210000003296 saliva Anatomy 0.000 description 1
238000007127 saponification reaction Methods 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
208000013223 septicemia Diseases 0.000 description 1
239000004208 shellac Substances 0.000 description 1
ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
229940113147 shellac Drugs 0.000 description 1
235000013874 shellac Nutrition 0.000 description 1
230000035939 shock Effects 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
230000037380 skin damage Effects 0.000 description 1
208000017520 skin disease Diseases 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
239000004299 sodium benzoate Substances 0.000 description 1
235000010234 sodium benzoate Nutrition 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
239000011775 sodium fluoride Substances 0.000 description 1
235000013024 sodium fluoride Nutrition 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
239000004296 sodium metabisulphite Substances 0.000 description 1
235000010262 sodium metabisulphite Nutrition 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
HTMDLQGFGSQOLM-UHFFFAOYSA-N sodium;5-methyl-2-propan-2-ylcyclohexan-1-olate Chemical compound [Na+].CC(C)C1CCC(C)CC1[O-] HTMDLQGFGSQOLM-UHFFFAOYSA-N 0.000 description 1
239000012453 solvate Substances 0.000 description 1
150000003413 spiro compounds Chemical class 0.000 description 1
210000000952 spleen Anatomy 0.000 description 1
230000007480 spreading Effects 0.000 description 1
238000003892 spreading Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
150000003457 sulfones Chemical class 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
FWMUJAIKEJWSSY-UHFFFAOYSA-N sulfur dichloride Chemical compound ClSCl FWMUJAIKEJWSSY-UHFFFAOYSA-N 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
230000035900 sweating Effects 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
238000007910 systemic administration Methods 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
229940033663 thimerosal Drugs 0.000 description 1
125000003396 thiol group Chemical group [H]S* 0.000 description 1
BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical group C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
230000017423 tissue regeneration Effects 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
239000012049 topical pharmaceutical composition Substances 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
210000002700 urine Anatomy 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
230000009385 viral infection Effects 0.000 description 1
239000001993 wax Substances 0.000 description 1
230000037303 wrinkles Effects 0.000 description 1
239000000230 xanthan gum Substances 0.000 description 1
235000010493 xanthan gum Nutrition 0.000 description 1
229920001285 xanthan gum Polymers 0.000 description 1
229940082509 xanthan gum Drugs 0.000 description 1
125000005023 xylyl group Chemical group 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1
238000013316 zoning Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
- A—HUMAN NECESSITIES
- 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
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- 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
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/46—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
- C07D207/48—Sulfur atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/92—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with a hetero atom directly attached to the ring nitrogen atom
- C07D211/96—Sulfur atom
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Rheumatology (AREA)
Physical Education & Sports Medicine (AREA)
Dermatology (AREA)
Pain & Pain Management (AREA)
Ophthalmology & Optometry (AREA)
Orthopedic Medicine & Surgery (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Plural Heterocyclic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Confectionery (AREA)
Pyrrole Compounds (AREA)
Cosmetics (AREA)

SK248-99A 1996-08-28 1997-08-22 Bidentate metalloprotease inhibitors SK24899A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US2474696P	1996-08-28	1996-08-28
PCT/US1997/014554 WO1998008814A1 (en)	1996-08-28	1997-08-22	Bidentate metalloprotease inhibitors

Publications (1)

Publication Number	Publication Date
SK24899A3 true SK24899A3 (en)	2000-04-10

Family

ID=21822181

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK248-99A SK24899A3 (en)	1996-08-28	1997-08-22	Bidentate metalloprotease inhibitors

Country Status (20)

Country	Link
US (1)	US6121272A (cs)
EP (1)	EP0923547A1 (cs)
JP (1)	JP2000516954A (cs)
KR (1)	KR20000035921A (cs)
CN (1)	CN1228767A (cs)
AU (1)	AU4074097A (cs)
BR (1)	BR9712792A (cs)
CA (1)	CA2263914A1 (cs)
CO (1)	CO5420196A1 (cs)
CZ (1)	CZ62499A3 (cs)
HU (1)	HUP0000616A2 (cs)
ID (1)	ID18417A (cs)
IL (1)	IL128665A0 (cs)
NO (1)	NO990896L (cs)
PE (1)	PE109298A1 (cs)
PL (1)	PL331803A1 (cs)
SK (1)	SK24899A3 (cs)
TR (1)	TR199900401T2 (cs)
WO (1)	WO1998008814A1 (cs)
ZA (1)	ZA977697B (cs)

Families Citing this family (23)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA2298617A1 (en)	1997-07-31	1999-02-11	Yetunde Olabisi Taiwo	Acyclic metalloprotease inhibitors
US6410580B1 (en)	1998-02-04	2002-06-25	Novartis Ag	Sulfonylamino derivatives which inhibit matrix-degrading metalloproteinases
JP4750272B2 (ja)	1998-02-04	2011-08-17	ノバルティスアーゲー	マトリックス分解メタロプロテイナーゼを阻害するスルホニルアミノ誘導体
US6846478B1 (en)	1998-02-27	2005-01-25	The Procter & Gamble Company	Promoting whole body health
IL140040A0 (en)	1998-06-03	2002-02-10	Guilford Pharm Inc	N-linked sulfonamides of n-heterocyclic carboxylic acids or carboxylic acid isosteres
WO2000017162A1 (en)	1998-09-21	2000-03-30	Takeda Chemical Industries, Ltd.	Novel thiol derivatives, process for producing the same and utilization thereof
US6858598B1 (en)	1998-12-23	2005-02-22	G. D. Searle & Co.	Method of using a matrix metalloproteinase inhibitor and one or more antineoplastic agents as a combination therapy in the treatment of neoplasia
BR0008716A (pt)	1999-03-03	2002-09-24	Procter & Gamble	Inibidores de metaloprotease contendo alquenil ou alquinil
MXPA01008857A (es)	1999-03-03	2002-07-02	Procter & Gamble	Inhibidores de metaloproteasa dihetero sustituidos.
AU6499000A (en) *	1999-08-05	2001-03-05	Procter & Gamble Company, The	Multivalent compounds
AU6388500A (en) *	1999-08-05	2001-03-05	Procter & Gamble Company, The	Multivalent sulfonamides
US7253169B2 (en)	1999-11-12	2007-08-07	Gliamed, Inc.	Aza compounds, pharmaceutical compositions and methods of use
EP1244670B1 (en)	1999-12-21	2006-03-08	MGI GP, Inc.	Hydantoin derivative compounds, pharmaceutical compositions, and methods of using same
US8283135B2 (en)	2000-06-30	2012-10-09	The Procter & Gamble Company	Oral care compositions containing combinations of anti-bacterial and host-response modulating agents
MXPA03000043A (es)	2000-06-30	2003-10-15	Procter & Gamble	Promocion de la salud en todo el cuerpo.
KR100613196B1 (ko) *	2000-07-19	2006-08-18	에프. 호프만-라 로슈 아게	메탈로프로테아제 억제제로서의 피롤리딘 유도체
CN1620433A (zh)	2000-07-19	2005-05-25	霍夫曼-拉罗奇有限公司	作为内皮肽转化酶抑制剂的吡咯烷衍生物
MXPA03000504A (es) *	2000-07-19	2003-06-24	Hoffmann La Roche	Derivados de pirimidina.
FR2819252A1 (fr) *	2001-01-11	2002-07-12	Servier Lab	Nouveaux derives d'acide hydroxamique, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
JP2005500270A (ja) *	2001-05-29	2005-01-06	ギルフォードファーマシュウティカルズインコーポレイテッド	手術の結果として発生した神経損傷を治療するための方法
JP4580866B2 (ja) *	2002-12-19	2010-11-17	バーテックスファーマシューティカルズインコーポレイテッド	Ｔａｃｅのインヒビター
US7897776B2 (en)	2007-04-23	2011-03-01	Salutria Pharmaceuticals Llc	Sulfonamide containing compounds for treatment of inflammatory disorders
CN106905183B (zh) *	2017-02-24	2018-07-31	三峡大学	一类含氨基的ɑ-酰氧基羰基酰胺类衍生物，制备方法及其应用

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3501489A (en) *	1966-01-21	1970-03-17	American Home Prod	1-phenylsulfonyl-2-(2-thiazolin-2-yl-oxy and thiol) pyrrolidines
US4695575A (en) *	1984-11-13	1987-09-22	Janssen Pharmaceutica, N.V.	4-[(bicycle heterocyclyl)-methyl and -hetero]-piperidines
IL74140A (en) *	1984-04-10	1988-05-31	Robins Co Inc A H	Substituted n-((amino)alkyl)-1-pyrrolidine,-1-piperidine and-1-homopiperidine-carboxamides and pharmaceutical compositions containing them
US4595700A (en) *	1984-12-21	1986-06-17	G. D. Searle & Co.	Thiol based collagenase inhibitors
GB8515934D0 (en) *	1985-06-24	1985-07-24	Janssen Pharmaceutica Nv	(4-piperidinomethyl and-hetero)purines
IT1215590B (it) *	1987-06-29	1990-02-14	Roussel Maestretti Spa	Derivati della 1-benzene solfonil 2-oco 5-alchiltio pirrolidina, un loro procedimentodi preparazione e il loro impiegocome stostanze medicinali.
GB8814813D0 (en) *	1988-06-22	1988-07-27	Beecham Group Plc	Novel compounds
DE4011172A1 (de) *	1990-04-06	1991-10-10	Degussa	Verbindungen zur bekaempfung von pflanzenkrankheiten
US5244908A (en) *	1990-07-30	1993-09-14	Takeda Chemical Industries, Ltd.	Imidazopyridine derivatives and their pharmaceutical use
JPH05125029A (ja) *	1991-11-06	1993-05-21	Yamanouchi Pharmaceut Co Ltd	新規なアミド化合物又はその塩
US6090785A (en) *	1992-10-15	2000-07-18	Merck & Co., Inc.	Substituted N-carboxyalkylpeptidyl derivatives as antidegenerative agents
US5455258A (en) *	1993-01-06	1995-10-03	Ciba-Geigy Corporation	Arylsulfonamido-substituted hydroxamic acids
US5470834A (en) *	1993-10-06	1995-11-28	Florida State University	Sulfoximine and suldodiimine matrix metalloproteinase inhibitors
US5455262A (en) *	1993-10-06	1995-10-03	Florida State University	Mercaptosulfide metalloproteinase inhibitors
CA2193691A1 (en) *	1994-06-22	1995-12-28	Andrew Miller	Metalloproteinase inhibitors
JP3923079B2 (ja) *	1995-07-31	2007-05-30	塩野義製薬株式会社	ホスホリパーゼａ２阻害活性を有するピロリジン誘導体
ES2233275T3 (es) *	1995-12-08	2005-06-16	Agouron Pharmaceuticals, Inc.	Intermediarios que sirven para la preparacion de inhibidores de metaloproteinasas.

1997
- 1997-07-09 BR BR9712792-2A patent/BR9712792A/pt unknown
- 1997-08-22 AU AU40740/97A patent/AU4074097A/en not_active Withdrawn
- 1997-08-22 CZ CZ99624A patent/CZ62499A3/cs unknown
- 1997-08-22 CN CN97197547A patent/CN1228767A/zh active Pending
- 1997-08-22 HU HU0000616A patent/HUP0000616A2/hu unknown
- 1997-08-22 TR TR1999/00401T patent/TR199900401T2/xx unknown
- 1997-08-22 IL IL12866597A patent/IL128665A0/xx unknown
- 1997-08-22 SK SK248-99A patent/SK24899A3/sk unknown
- 1997-08-22 JP JP10511714A patent/JP2000516954A/ja active Pending
- 1997-08-22 PL PL97331803A patent/PL331803A1/xx unknown
- 1997-08-22 KR KR1019997001657A patent/KR20000035921A/ko not_active Ceased
- 1997-08-22 CA CA002263914A patent/CA2263914A1/en not_active Abandoned
- 1997-08-22 WO PCT/US1997/014554 patent/WO1998008814A1/en not_active Ceased
- 1997-08-22 EP EP97938411A patent/EP0923547A1/en not_active Withdrawn
- 1997-08-26 US US08/918,318 patent/US6121272A/en not_active Expired - Fee Related
- 1997-08-27 ZA ZA9407697A patent/ZA977697B/xx unknown
- 1997-08-27 CO CO97049500A patent/CO5420196A1/es not_active Application Discontinuation
- 1997-08-28 PE PE1997000772A patent/PE109298A1/es not_active Application Discontinuation
- 1997-08-28 ID IDP972998A patent/ID18417A/id unknown
1999
- 1999-02-25 NO NO990896A patent/NO990896L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
PL331803A1 (en)	1999-08-02
HUP0000616A2 (en)	2000-07-28
EP0923547A1 (en)	1999-06-23
US6121272A (en)	2000-09-19
WO1998008814A1 (en)	1998-03-05
ZA977697B (en)	1998-02-23
ID18417A (id)	1998-04-09
NO990896L (no)	1999-04-20
KR20000035921A (ko)	2000-06-26
JP2000516954A (ja)	2000-12-19
CN1228767A (zh)	1999-09-15
NO990896D0 (no)	1999-02-25
PE109298A1 (es)	1999-01-31
TR199900401T2 (xx)	1999-05-21
BR9712792A (pt)	1999-12-14
IL128665A0 (en)	2000-01-31
CA2263914A1 (en)	1998-03-05
CO5420196A1 (es)	2004-07-30
AU4074097A (en)	1998-03-19
CZ62499A3 (cs)	1999-07-14

Publication	Publication Date	Title
EP0923561B1 (en)	2002-10-23	Heterocyclic metalloprotease inhibitors
KR100339296B1 (ko)	2002-06-03	헤테로고리성 메탈로프로테아제 억제제
SK24899A3 (en)	2000-04-10	Bidentate metalloprotease inhibitors
US6469000B1 (en)	2002-10-22	1,3-diheterocyclic metalloprotease inhibitors
KR100323272B1 (ko)	2002-02-06	치환된 시클릭 아민 메탈로프로테아제 저해제
EP0927183B1 (en)	2004-07-28	Spirocyclic metalloprotease inhibitors
MXPA99002064A (en)	1999-09-20	Heterocyclic metalloprotease inhibitors
MXPA99002067A (en)	1999-09-20	Heterocyclic metalloprotease inhibitors
MXPA99002065A (en)	1999-09-20	Bidentate metalloprotease inhibitors
HK1021184B (en)	2005-04-29	Spirocyclic metalloprotease inhibitors