JP2001512138A - Ｖｌａ−４が介在する白血球付着を阻害するベンジル化合物 - Google Patents

Ｖｌａ−４が介在する白血球付着を阻害するベンジル化合物

Info

Publication number: JP2001512138A
Authority: JP; Japan
Prior art keywords: phenylalanine; prolyl; sulfonyl; substituted; toluene
Prior art date: 1997-07-31
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Withdrawn

Application number

JP2000505191A

Other languages

English (en)

Japanese (ja)

Inventor

ユージン・ディ・ソーセット

クリストファー・エム・セムコ

マイケル・エー・プレイス

ルイス・ジョン・ロンバルド

アンドレイ・ダブリュ・コンラディ

フランシーヌ・エス・グラント

ダレン・ビー・ドレッセン

マイケル・エス・ダッペン

Original Assignee

エラン・ファーマシューティカルズ・インコーポレーテッド

アメリカン・ホーム・プロダクツ・コーポレーション

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.)

1997-07-31

Filing date

1998-07-31

Publication date

2001-08-21

1998-07-31 Application filed by エラン・ファーマシューティカルズ・インコーポレーテッド, アメリカン・ホーム・プロダクツ・コーポレーション filed Critical エラン・ファーマシューティカルズ・インコーポレーテッド

2001-08-21 Publication of JP2001512138A publication Critical patent/JP2001512138A/ja

Status Withdrawn legal-status Critical Current

Links

108010008212 Integrin alpha4beta1 Proteins 0.000 title claims abstract description 49
230000001404 mediated effect Effects 0.000 title claims abstract description 23
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 title claims description 19
230000023404 leukocyte cell-cell adhesion Effects 0.000 title abstract description 10
150000001875 compounds Chemical class 0.000 claims abstract description 245
201000006417 multiple sclerosis Diseases 0.000 claims abstract description 13
206010028980 Neoplasm Diseases 0.000 claims abstract description 11
208000006673 asthma Diseases 0.000 claims abstract description 10
208000027866 inflammatory disease Diseases 0.000 claims abstract description 9
206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 9
201000001320 Atherosclerosis Diseases 0.000 claims abstract description 8
208000022559 Inflammatory bowel disease Diseases 0.000 claims abstract description 8
206010027476 Metastases Diseases 0.000 claims abstract description 7
206010012601 diabetes mellitus Diseases 0.000 claims abstract description 7
230000009401 metastasis Effects 0.000 claims abstract description 7
208000024827 Alzheimer disease Diseases 0.000 claims abstract description 6
206010012289 Dementia Diseases 0.000 claims abstract description 6
208000031225 myocardial ischemia Diseases 0.000 claims abstract description 6
238000002054 transplantation Methods 0.000 claims abstract description 5
-1 2,4,6-trimethylphenyl Chemical group 0.000 claims description 252
125000000623 heterocyclic group Chemical group 0.000 claims description 176
238000000034 method Methods 0.000 claims description 140
125000001072 heteroaryl group Chemical group 0.000 claims description 139
125000000217 alkyl group Chemical group 0.000 claims description 88
125000003118 aryl group Chemical group 0.000 claims description 55
125000000547 substituted alkyl group Chemical group 0.000 claims description 54
239000001257 hydrogen Substances 0.000 claims description 49
229910052739 hydrogen Inorganic materials 0.000 claims description 49
125000003107 substituted aryl group Chemical group 0.000 claims description 49
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 47
229910052757 nitrogen Inorganic materials 0.000 claims description 37
OZMPCLDAZMPJKH-OALUTQOASA-N (2s)-2-[[(2s)-1-(4-methylphenyl)sulfonylpyrrolidine-2-carbonyl]amino]-3-phenylpropanoic acid Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(O)=O)CCC1 OZMPCLDAZMPJKH-OALUTQOASA-N 0.000 claims description 36
125000001424 substituent group Chemical group 0.000 claims description 34
125000000753 cycloalkyl group Chemical group 0.000 claims description 33
125000004432 carbon atom Chemical group C* 0.000 claims description 28
125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 27
150000002148 esters Chemical class 0.000 claims description 24
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 23
210000000265 leukocyte Anatomy 0.000 claims description 22
229920006395 saturated elastomer Polymers 0.000 claims description 18
239000008194 pharmaceutical composition Substances 0.000 claims description 16
229960003767 alanine Drugs 0.000 claims description 15
150000004702 methyl esters Chemical group 0.000 claims description 15
150000003839 salts Chemical class 0.000 claims description 14
125000004494 ethyl ester group Chemical group 0.000 claims description 13
229910052717 sulfur Chemical group 0.000 claims description 13
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
125000003545 alkoxy group Chemical group 0.000 claims description 12
125000005415 substituted alkoxy group Chemical group 0.000 claims description 12
229910052799 carbon Inorganic materials 0.000 claims description 11
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
125000000000 cycloalkoxy group Chemical group 0.000 claims description 11
125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 10
230000001154 acute effect Effects 0.000 claims description 10
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
229910052760 oxygen Inorganic materials 0.000 claims description 10
239000001301 oxygen Substances 0.000 claims description 10
239000011593 sulfur Chemical group 0.000 claims description 10
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 10
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
125000005338 substituted cycloalkoxy group Chemical group 0.000 claims description 9
206010009900 Colitis ulcerative Diseases 0.000 claims description 8
208000011231 Crohn disease Diseases 0.000 claims description 8
201000006704 Ulcerative Colitis Diseases 0.000 claims description 8
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 7
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 7
125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 7
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 7
235000004279 alanine Nutrition 0.000 claims description 7
239000012472 biological sample Substances 0.000 claims description 7
125000005842 heteroatom Chemical group 0.000 claims description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 6
206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 5
206010012438 Dermatitis atopic Diseases 0.000 claims description 5
206010061218 Inflammation Diseases 0.000 claims description 5
208000004852 Lung Injury Diseases 0.000 claims description 5
201000004681 Psoriasis Diseases 0.000 claims description 5
208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 5
206010038910 Retinitis Diseases 0.000 claims description 5
206010069363 Traumatic lung injury Diseases 0.000 claims description 5
206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 5
208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 5
201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 5
201000008937 atopic dermatitis Diseases 0.000 claims description 5
230000004054 inflammatory process Effects 0.000 claims description 5
231100000515 lung injury Toxicity 0.000 claims description 5
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
201000008383 nephritis Diseases 0.000 claims description 5
XYEOALKITRFCJJ-UHFFFAOYSA-N o-benzylhydroxylamine Chemical compound NOCC1=CC=CC=C1 XYEOALKITRFCJJ-UHFFFAOYSA-N 0.000 claims description 5
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
DBUZBTZXIHIIOJ-ROUUACIJSA-N (2s)-2-[[(2s)-1-(3,5-dichlorophenyl)sulfonylpyrrolidine-2-carbonyl]amino]-3-phenylpropanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)[C@H]1N(CCC1)S(=O)(=O)C=1C=C(Cl)C=C(Cl)C=1)C1=CC=CC=C1 DBUZBTZXIHIIOJ-ROUUACIJSA-N 0.000 claims description 4
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 4
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
GMPKIPWJBDOURN-UHFFFAOYSA-N Methoxyamine Chemical compound CON GMPKIPWJBDOURN-UHFFFAOYSA-N 0.000 claims description 4
208000006011 Stroke Diseases 0.000 claims description 4
150000001408 amides Chemical class 0.000 claims description 4
206010014599 encephalitis Diseases 0.000 claims description 4
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
125000006413 ring segment Chemical group 0.000 claims description 4
ZWQIKKDLVPEKLA-PGFLUOATSA-N 2-[(4-methylphenyl)sulfonylamino]-4-[1-[(2S)-pyrrolidine-2-carbonyl]cyclohexa-2,4-dien-1-yl]butanoic acid Chemical compound C1(=CC=C(C=C1)S(=O)(=O)NC(CCC1(CC=CC=C1)C([C@H]1NCCC1)=O)C(=O)O)C ZWQIKKDLVPEKLA-PGFLUOATSA-N 0.000 claims description 3
208000018152 Cerebral disease Diseases 0.000 claims description 3
UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 3
ZXKINMCYCKHYFR-UHFFFAOYSA-N aminooxidanide Chemical compound [O-]N ZXKINMCYCKHYFR-UHFFFAOYSA-N 0.000 claims description 3
125000004429 atom Chemical group 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
125000001153 fluoro group Chemical group F* 0.000 claims description 3
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
DFCDTIVDYCKWQK-GARIHTGFSA-N (2R)-2-[(4-methylphenyl)sulfonylamino]-3-[1-[(2S)-pyrrolidine-2-carbonyl]cyclohexa-2,4-dien-1-yl]propanoic acid Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N[C@@H](C(O)=O)CC1(C(=O)[C@H]2NCCC2)C=CC=CC1 DFCDTIVDYCKWQK-GARIHTGFSA-N 0.000 claims description 2
125000005988 1,1-dioxo-thiomorpholinyl group Chemical group 0.000 claims description 2
125000001305 1,2,4-triazol-3-yl group Chemical group [H]N1N=C([*])N=C1[H] 0.000 claims description 2
125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 2
125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 2
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 2
125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 2
125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 2
125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 2
125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 2
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
229940000635 beta-alanine Drugs 0.000 claims description 2
UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims description 2
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
NTNZTEQNFHNYBC-UHFFFAOYSA-N ethyl 2-aminoacetate Chemical compound CCOC(=O)CN NTNZTEQNFHNYBC-UHFFFAOYSA-N 0.000 claims description 2
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 2
NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 claims description 2
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 2
125000001544 thienyl group Chemical group 0.000 claims description 2
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 4
150000002431 hydrogen Chemical group 0.000 claims 3
125000004574 piperidin-2-yl group Chemical group N1C(CCCC1)* 0.000 claims 2
239000008186 active pharmaceutical agent Substances 0.000 claims 1
125000004273 azetidin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])C1([H])* 0.000 claims 1
210000002418 meninge Anatomy 0.000 claims 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
125000004570 thiomorpholin-3-yl group Chemical group N1C(CSCC1)* 0.000 claims 1
238000011282 treatment Methods 0.000 abstract description 20
230000002757 inflammatory effect Effects 0.000 abstract description 7
208000030507 AIDS Diseases 0.000 abstract description 5
208000014644 Brain disease Diseases 0.000 abstract description 4
241000124008 Mammalia Species 0.000 abstract 1
238000005481 NMR spectroscopy Methods 0.000 description 224
239000000203 mixture Substances 0.000 description 103
238000006243 chemical reaction Methods 0.000 description 90
238000003786 synthesis reaction Methods 0.000 description 77
230000015572 biosynthetic process Effects 0.000 description 76
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
238000004949 mass spectrometry Methods 0.000 description 69
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 63
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 57
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 49
239000000047 product Substances 0.000 description 48
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 46
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
210000004027 cell Anatomy 0.000 description 41
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 38
239000000460 chlorine Substances 0.000 description 38
125000004435 hydrogen atom Chemical group [H]* 0.000 description 37
239000003921 oil Substances 0.000 description 37
235000019198 oils Nutrition 0.000 description 37
239000007787 solid Substances 0.000 description 32
229940024606 amino acid Drugs 0.000 description 31
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
235000001014 amino acid Nutrition 0.000 description 30
239000004480 active ingredient Substances 0.000 description 28
239000000243 solution Substances 0.000 description 28
125000003342 alkenyl group Chemical group 0.000 description 26
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 25
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 25
238000003556 assay Methods 0.000 description 24
125000005017 substituted alkenyl group Chemical group 0.000 description 23
125000000304 alkynyl group Chemical group 0.000 description 22
125000002887 hydroxy group Chemical group [H]O* 0.000 description 22
229960005190 phenylalanine Drugs 0.000 description 22
238000002360 preparation method Methods 0.000 description 22
239000011541 reaction mixture Substances 0.000 description 22
235000019439 ethyl acetate Nutrition 0.000 description 21
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 20
239000002253 acid Substances 0.000 description 20
238000009472 formulation Methods 0.000 description 20
239000003701 inert diluent Substances 0.000 description 20
239000011734 sodium Substances 0.000 description 20
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 19
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 19
125000004426 substituted alkynyl group Chemical group 0.000 description 19
CWNPOQFCIIFQDM-UHFFFAOYSA-N 3-nitrobenzyl alcohol Chemical compound OCC1=CC=CC([N+]([O-])=O)=C1 CWNPOQFCIIFQDM-UHFFFAOYSA-N 0.000 description 18
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
150000001413 amino acids Chemical class 0.000 description 18
125000004104 aryloxy group Chemical group 0.000 description 18
230000027455 binding Effects 0.000 description 18
201000010099 disease Diseases 0.000 description 18
125000005553 heteroaryloxy group Chemical group 0.000 description 18
125000005844 heterocyclyloxy group Chemical group 0.000 description 18
108010044426 integrins Proteins 0.000 description 18
102000006495 integrins Human genes 0.000 description 18
239000000543 intermediate Substances 0.000 description 18
125000005000 thioaryl group Chemical group 0.000 description 18
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 17
238000005859 coupling reaction Methods 0.000 description 17
239000004615 ingredient Substances 0.000 description 16
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 16
125000004001 thioalkyl group Chemical class 0.000 description 16
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 description 15
102100023543 Vascular cell adhesion protein 1 Human genes 0.000 description 15
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
239000012074 organic phase Substances 0.000 description 15
239000003153 chemical reaction reagent Substances 0.000 description 14
238000003818 flash chromatography Methods 0.000 description 14
238000001727 in vivo Methods 0.000 description 14
238000010626 work up procedure Methods 0.000 description 14
150000001412 amines Chemical class 0.000 description 13
239000002585 base Substances 0.000 description 13
238000010168 coupling process Methods 0.000 description 13
239000002904 solvent Substances 0.000 description 13
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 12
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
239000003814 drug Substances 0.000 description 12
238000001914 filtration Methods 0.000 description 12
150000003573 thiols Chemical class 0.000 description 12
CGPHGPCHVUSFFA-NSHDSACASA-N (2s)-1-(4-methylphenyl)sulfonylpyrrolidine-2-carboxylic acid Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1[C@H](C(O)=O)CCC1 CGPHGPCHVUSFFA-NSHDSACASA-N 0.000 description 11
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 11
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 11
125000002252 acyl group Chemical group 0.000 description 11
125000003277 amino group Chemical group 0.000 description 11
239000012267 brine Substances 0.000 description 11
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 11
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
239000003826 tablet Substances 0.000 description 11
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 10
229920002472 Starch Polymers 0.000 description 10
230000000903 blocking effect Effects 0.000 description 10
230000006378 damage Effects 0.000 description 10
PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 10
239000008107 starch Substances 0.000 description 10
235000019698 starch Nutrition 0.000 description 10
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 10
PMMYEEVYMWASQN-IMJSIDKUSA-N trans-4-Hydroxy-L-proline Natural products O[C@@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-IMJSIDKUSA-N 0.000 description 10
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
125000004423 acyloxy group Chemical group 0.000 description 9
230000008878 coupling Effects 0.000 description 9
239000012043 crude product Substances 0.000 description 9
229940079593 drug Drugs 0.000 description 9
210000002889 endothelial cell Anatomy 0.000 description 9
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
239000011780 sodium chloride Substances 0.000 description 9
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 8
150000003862 amino acid derivatives Chemical class 0.000 description 8
125000001769 aryl amino group Chemical class 0.000 description 8
125000004181 carboxyalkyl group Chemical group 0.000 description 8
239000003054 catalyst Substances 0.000 description 8
125000004093 cyano group Chemical group *C#N 0.000 description 8
238000001704 evaporation Methods 0.000 description 8
230000008020 evaporation Effects 0.000 description 8
125000005241 heteroarylamino group Chemical class 0.000 description 8
235000019359 magnesium stearate Nutrition 0.000 description 8
229910052763 palladium Inorganic materials 0.000 description 8
239000000546 pharmaceutical excipient Substances 0.000 description 8
229960002429 proline Drugs 0.000 description 8
210000001519 tissue Anatomy 0.000 description 8
RJSQINMKOSOUGT-UHFFFAOYSA-N 3,5-dichlorobenzenesulfonyl chloride Chemical compound ClC1=CC(Cl)=CC(S(Cl)(=O)=O)=C1 RJSQINMKOSOUGT-UHFFFAOYSA-N 0.000 description 7
125000004442 acylamino group Chemical group 0.000 description 7
239000008346 aqueous phase Substances 0.000 description 7
150000001721 carbon Chemical group 0.000 description 7
230000007062 hydrolysis Effects 0.000 description 7
238000006460 hydrolysis reaction Methods 0.000 description 7
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 7
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
GDPHNAZHHDEGFH-UHFFFAOYSA-N 1-[carbamimidoyl-(diaminomethylideneamino)sulfamoyl]-1-(diaminomethylideneamino)guanidine Chemical class N(C(=N)N)N(C(=N)N)S(=O)(=O)N(C(=N)N)NC(=N)N GDPHNAZHHDEGFH-UHFFFAOYSA-N 0.000 description 6
125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
241001465754 Metazoa Species 0.000 description 6
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
239000000443 aerosol Substances 0.000 description 6
125000000266 alpha-aminoacyl group Chemical group 0.000 description 6
239000000427 antigen Substances 0.000 description 6
102000036639 antigens Human genes 0.000 description 6
108091007433 antigens Proteins 0.000 description 6
239000007864 aqueous solution Substances 0.000 description 6
125000005325 aryloxy aryl group Chemical group 0.000 description 6
239000002775 capsule Substances 0.000 description 6
238000007796 conventional method Methods 0.000 description 6
229910052736 halogen Inorganic materials 0.000 description 6
150000002367 halogens Chemical class 0.000 description 6
238000005984 hydrogenation reaction Methods 0.000 description 6
230000028709 inflammatory response Effects 0.000 description 6
239000000843 powder Substances 0.000 description 6
125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 6
229910052708 sodium Inorganic materials 0.000 description 6
235000017557 sodium bicarbonate Nutrition 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
238000006467 substitution reaction Methods 0.000 description 6
238000010189 synthetic method Methods 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
NONOKGVFTBWRLD-UHFFFAOYSA-N thioisocyanate group Chemical group S(N=C=O)N=C=O NONOKGVFTBWRLD-UHFFFAOYSA-N 0.000 description 6
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 5
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 5
201000009906 Meningitis Diseases 0.000 description 5
229920000168 Microcrystalline cellulose Polymers 0.000 description 5
NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 5
239000003513 alkali Substances 0.000 description 5
230000008499 blood brain barrier function Effects 0.000 description 5
210000001218 blood-brain barrier Anatomy 0.000 description 5
201000011510 cancer Diseases 0.000 description 5
150000001718 carbodiimides Chemical class 0.000 description 5
150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
239000000284 extract Substances 0.000 description 5
125000000524 functional group Chemical group 0.000 description 5
239000007789 gas Substances 0.000 description 5
239000007903 gelatin capsule Substances 0.000 description 5
125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 5
230000003301 hydrolyzing effect Effects 0.000 description 5
150000002440 hydroxy compounds Chemical class 0.000 description 5
238000000338 in vitro Methods 0.000 description 5
239000012948 isocyanate Substances 0.000 description 5
150000002513 isocyanates Chemical class 0.000 description 5
238000002844 melting Methods 0.000 description 5
230000008018 melting Effects 0.000 description 5
VSDUZFOSJDMAFZ-VIFPVBQESA-N methyl L-phenylalaninate Chemical compound COC(=O)[C@@H](N)CC1=CC=CC=C1 VSDUZFOSJDMAFZ-VIFPVBQESA-N 0.000 description 5
235000019813 microcrystalline cellulose Nutrition 0.000 description 5
239000008108 microcrystalline cellulose Substances 0.000 description 5
229940016286 microcrystalline cellulose Drugs 0.000 description 5
239000006199 nebulizer Substances 0.000 description 5
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 5
210000000056 organ Anatomy 0.000 description 5
239000002245 particle Substances 0.000 description 5
238000012746 preparative thin layer chromatography Methods 0.000 description 5
230000002829 reductive effect Effects 0.000 description 5
238000010992 reflux Methods 0.000 description 5
230000004044 response Effects 0.000 description 5
239000000741 silica gel Substances 0.000 description 5
229910002027 silica gel Inorganic materials 0.000 description 5
238000003756 stirring Methods 0.000 description 5
SRQOBFXQILTASR-JTQLQIEISA-N (2s)-1-(3,5-dichlorophenyl)sulfonylpyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1S(=O)(=O)C1=CC(Cl)=CC(Cl)=C1 SRQOBFXQILTASR-JTQLQIEISA-N 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 4
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
108010016626 Dipeptides Proteins 0.000 description 4
108090000790 Enzymes Proteins 0.000 description 4
102000004190 Enzymes Human genes 0.000 description 4
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 4
210000001744 T-lymphocyte Anatomy 0.000 description 4
CKUAXEQHGKSLHN-UHFFFAOYSA-N [C].[N] Chemical compound [C].[N] CKUAXEQHGKSLHN-UHFFFAOYSA-N 0.000 description 4
238000005917 acylation reaction Methods 0.000 description 4
150000001299 aldehydes Chemical class 0.000 description 4
229910052784 alkaline earth metal Inorganic materials 0.000 description 4
XKMRRTOUMJRJIA-UHFFFAOYSA-N ammonia nh3 Chemical compound N.N XKMRRTOUMJRJIA-UHFFFAOYSA-N 0.000 description 4
150000008064 anhydrides Chemical class 0.000 description 4
230000001363 autoimmune Effects 0.000 description 4
FPRSPUHXEPWUBZ-HNNXBMFYSA-N benzyl (2s)-2-amino-3-phenylpropanoate Chemical compound C([C@H](N)C(=O)OCC=1C=CC=CC=1)C1=CC=CC=C1 FPRSPUHXEPWUBZ-HNNXBMFYSA-N 0.000 description 4
125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 4
CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 4
239000011203 carbon fibre reinforced carbon Substances 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
238000001035 drying Methods 0.000 description 4
238000010931 ester hydrolysis Methods 0.000 description 4
238000000605 extraction Methods 0.000 description 4
150000004820 halides Chemical class 0.000 description 4
125000005843 halogen group Chemical group 0.000 description 4
230000004968 inflammatory condition Effects 0.000 description 4
230000003993 interaction Effects 0.000 description 4
239000010410 layer Substances 0.000 description 4
239000003446 ligand Substances 0.000 description 4
239000006187 pill Substances 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
125000006239 protecting group Chemical group 0.000 description 4
238000000746 purification Methods 0.000 description 4
125000004076 pyridyl group Chemical group 0.000 description 4
210000002966 serum Anatomy 0.000 description 4
238000010898 silica gel chromatography Methods 0.000 description 4
150000003462 sulfoxides Chemical class 0.000 description 4
125000004434 sulfur atom Chemical group 0.000 description 4
239000000829 suppository Substances 0.000 description 4
239000000725 suspension Substances 0.000 description 4
208000024891 symptom Diseases 0.000 description 4
239000006188 syrup Substances 0.000 description 4
235000020357 syrup Nutrition 0.000 description 4
150000003512 tertiary amines Chemical class 0.000 description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 4
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 4
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
206010003210 Arteriosclerosis Diseases 0.000 description 3
208000037260 Atherosclerotic Plaque Diseases 0.000 description 3
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 3
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 3
102000000844 Cell Surface Receptors Human genes 0.000 description 3
108010001857 Cell Surface Receptors Proteins 0.000 description 3
DZLNHFMRPBPULJ-GSVOUGTGSA-N D-thioproline Chemical compound OC(=O)[C@H]1CSCN1 DZLNHFMRPBPULJ-GSVOUGTGSA-N 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical group OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
102000016359 Fibronectins Human genes 0.000 description 3
108010067306 Fibronectins Proteins 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
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 3
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 3
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 3
229930182821 L-proline Natural products 0.000 description 3
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 3
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 3
208000016285 Movement disease Diseases 0.000 description 3
206010033799 Paralysis Diseases 0.000 description 3
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 3
229930006000 Sucrose Natural products 0.000 description 3
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 3
150000001266 acyl halides Chemical class 0.000 description 3
125000006598 aminocarbonylamino group Chemical group 0.000 description 3
238000010171 animal model Methods 0.000 description 3
239000012911 assay medium Substances 0.000 description 3
XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 3
230000004071 biological effect Effects 0.000 description 3
230000037396 body weight Effects 0.000 description 3
150000004657 carbamic acid derivatives Chemical class 0.000 description 3
150000003857 carboxamides Chemical class 0.000 description 3
150000001244 carboxylic acid anhydrides Chemical class 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
239000012230 colorless oil Substances 0.000 description 3
238000004440 column chromatography Methods 0.000 description 3
125000000392 cycloalkenyl group Chemical group 0.000 description 3
230000006735 deficit Effects 0.000 description 3
230000003111 delayed effect Effects 0.000 description 3
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
231100000673 dose–response relationship Toxicity 0.000 description 3
238000012377 drug delivery Methods 0.000 description 3
230000000694 effects Effects 0.000 description 3
239000000839 emulsion Substances 0.000 description 3
201000002491 encephalomyelitis Diseases 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
239000000796 flavoring agent Substances 0.000 description 3
102000037865 fusion proteins Human genes 0.000 description 3
108020001507 fusion proteins Proteins 0.000 description 3
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
230000028993 immune response Effects 0.000 description 3
210000000987 immune system Anatomy 0.000 description 3
150000002576 ketones Chemical class 0.000 description 3
239000008101 lactose Substances 0.000 description 3
239000007788 liquid Substances 0.000 description 3
210000004185 liver Anatomy 0.000 description 3
238000002595 magnetic resonance imaging Methods 0.000 description 3
239000000463 material Substances 0.000 description 3
239000011159 matrix material Substances 0.000 description 3
230000007246 mechanism Effects 0.000 description 3
238000006386 neutralization reaction Methods 0.000 description 3
239000012299 nitrogen atmosphere Substances 0.000 description 3
239000002953 phosphate buffered saline Substances 0.000 description 3
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 3
FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 3
125000003386 piperidinyl group Chemical group 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
238000001556 precipitation Methods 0.000 description 3
230000008569 process Effects 0.000 description 3
239000000523 sample Substances 0.000 description 3
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 3
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
239000000126 substance Substances 0.000 description 3
239000005720 sucrose Substances 0.000 description 3
150000003461 sulfonyl halides Chemical class 0.000 description 3
230000006103 sulfonylation Effects 0.000 description 3
238000005694 sulfonylation reaction Methods 0.000 description 3
239000000454 talc Substances 0.000 description 3
229910052623 talc Inorganic materials 0.000 description 3
235000012222 talc Nutrition 0.000 description 3
238000012360 testing method Methods 0.000 description 3
238000004809 thin layer chromatography Methods 0.000 description 3
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
XNRRDBJRLNJVMF-GKAPJAKFSA-N (2s)-3-(dimethylamino)-n-(ethyliminomethylidene)pyrrolidine-2-carboxamide Chemical compound CCN=C=NC(=O)[C@H]1NCCC1N(C)C XNRRDBJRLNJVMF-GKAPJAKFSA-N 0.000 description 2
PIRXUBXPDYOLBL-IRXDYDNUSA-N (2s,3s)-1-(4-methylphenyl)sulfonyl-3-phenylpyrrolidine-2-carboxylic acid Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1[C@H](C(O)=O)[C@H](C=2C=CC=CC=2)CC1 PIRXUBXPDYOLBL-IRXDYDNUSA-N 0.000 description 2
UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
NILQLFBWTXNUOE-UHFFFAOYSA-N 1-aminocyclopentanecarboxylic acid Chemical compound OC(=O)C1(N)CCCC1 NILQLFBWTXNUOE-UHFFFAOYSA-N 0.000 description 2
PAJPWUMXBYXFCZ-UHFFFAOYSA-N 1-aminocyclopropanecarboxylic acid Chemical compound OC(=O)C1(N)CC1 PAJPWUMXBYXFCZ-UHFFFAOYSA-N 0.000 description 2
FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
ASSKVPFEZFQQNQ-UHFFFAOYSA-N 2-benzoxazolinone Chemical compound C1=CC=C2OC(O)=NC2=C1 ASSKVPFEZFQQNQ-UHFFFAOYSA-N 0.000 description 2
YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 2
PYSGFFTXMUWEOT-UHFFFAOYSA-N 3-(dimethylamino)propan-1-ol Chemical compound CN(C)CCCO PYSGFFTXMUWEOT-UHFFFAOYSA-N 0.000 description 2
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
GRDXCFKBQWDAJH-UHFFFAOYSA-N 4-acetamidobenzenesulfonyl chloride Chemical compound CC(=O)NC1=CC=C(S(Cl)(=O)=O)C=C1 GRDXCFKBQWDAJH-UHFFFAOYSA-N 0.000 description 2
DBMFYTQPPBBKHI-UHFFFAOYSA-N 4-cyanobenzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C(C#N)C=C1 DBMFYTQPPBBKHI-UHFFFAOYSA-N 0.000 description 2
DTJVECUKADWGMO-UHFFFAOYSA-N 4-methoxybenzenesulfonyl chloride Chemical compound COC1=CC=C(S(Cl)(=O)=O)C=C1 DTJVECUKADWGMO-UHFFFAOYSA-N 0.000 description 2
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 2
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
108091003079 Bovine Serum Albumin Proteins 0.000 description 2
241000244203 Caenorhabditis elegans Species 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
COLNVLDHVKWLRT-MRVPVSSYSA-N D-phenylalanine Chemical compound OC(=O)[C@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-MRVPVSSYSA-N 0.000 description 2
229930182832 D-phenylalanine Natural products 0.000 description 2
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
241000257303 Hymenoptera Species 0.000 description 2
108010022222 Integrin beta1 Proteins 0.000 description 2
102000012355 Integrin beta1 Human genes 0.000 description 2
OBSIQMZKFXFYLV-QMMMGPOBSA-N L-phenylalanine amide Chemical compound NC(=O)[C@@H](N)CC1=CC=CC=C1 OBSIQMZKFXFYLV-QMMMGPOBSA-N 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
239000012359 Methanesulfonyl chloride Substances 0.000 description 2
241001024304 Mino Species 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 2
SCIFESDRCALIIM-UHFFFAOYSA-N N-Me-Phenylalanine Natural products CNC(C(O)=O)CC1=CC=CC=C1 SCIFESDRCALIIM-UHFFFAOYSA-N 0.000 description 2
SCIFESDRCALIIM-VIFPVBQESA-N N-methyl-L-phenylalanine Chemical compound C[NH2+][C@H](C([O-])=O)CC1=CC=CC=C1 SCIFESDRCALIIM-VIFPVBQESA-N 0.000 description 2
208000031481 Pathologic Constriction Diseases 0.000 description 2
241001494479 Pecora Species 0.000 description 2
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
241000700159 Rattus Species 0.000 description 2
102100030852 Run domain Beclin-1-interacting and cysteine-rich domain-containing protein Human genes 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
206010052779 Transplant rejections Diseases 0.000 description 2
239000007983 Tris buffer Substances 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
208000027418 Wounds and injury Diseases 0.000 description 2
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 2
230000002378 acidificating effect Effects 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
230000004913 activation Effects 0.000 description 2
239000013543 active substance Substances 0.000 description 2
230000001464 adherent effect Effects 0.000 description 2
239000002671 adjuvant Substances 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
230000000172 allergic effect Effects 0.000 description 2
230000000735 allogeneic effect Effects 0.000 description 2
JXUFISIHEZOBPI-UHFFFAOYSA-N amidosulfurous acid Chemical class NS(O)=O JXUFISIHEZOBPI-UHFFFAOYSA-N 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
150000001503 aryl iodides Chemical class 0.000 description 2
208000010668 atopic eczema Diseases 0.000 description 2
210000003651 basophil Anatomy 0.000 description 2
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
DZBUGLKDJFMEHC-UHFFFAOYSA-N benzoquinolinylidene Natural products C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 2
239000012964 benzotriazole Substances 0.000 description 2
ABNDFSOIUFLJAH-UHFFFAOYSA-N benzyl thiocyanate Chemical compound N#CSCC1=CC=CC=C1 ABNDFSOIUFLJAH-UHFFFAOYSA-N 0.000 description 2
238000001574 biopsy Methods 0.000 description 2
210000001185 bone marrow Anatomy 0.000 description 2
210000004556 brain Anatomy 0.000 description 2
125000001246 bromo group Chemical group Br* 0.000 description 2
235000013877 carbamide Nutrition 0.000 description 2
125000002837 carbocyclic group Chemical group 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
125000005352 carboxycycloalkyl group Chemical group 0.000 description 2
150000001735 carboxylic acids Chemical class 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
125000001309 chloro group Chemical group Cl* 0.000 description 2
125000004965 chloroalkyl group Chemical group 0.000 description 2
208000023819 chronic asthma Diseases 0.000 description 2
230000001684 chronic effect Effects 0.000 description 2
WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 2
210000001072 colon Anatomy 0.000 description 2
230000021615 conjugation Effects 0.000 description 2
125000006165 cyclic alkyl group Chemical group 0.000 description 2
230000001419 dependent effect Effects 0.000 description 2
238000002059 diagnostic imaging Methods 0.000 description 2
150000001987 diarylethers Chemical class 0.000 description 2
ISOLMABRZPQKOV-UHFFFAOYSA-N diethyl 2-acetamidopropanedioate Chemical compound CCOC(=O)C(NC(C)=O)C(=O)OCC ISOLMABRZPQKOV-UHFFFAOYSA-N 0.000 description 2
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 2
238000007865 diluting Methods 0.000 description 2
238000010790 dilution Methods 0.000 description 2
239000012895 dilution Substances 0.000 description 2
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
210000003038 endothelium Anatomy 0.000 description 2
239000012055 enteric layer Substances 0.000 description 2
210000003979 eosinophil Anatomy 0.000 description 2
125000004185 ester group Chemical group 0.000 description 2
VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 2
CJGXMNONHNZEQQ-UHFFFAOYSA-N ethyl 2-amino-3-phenylpropanoate Chemical compound CCOC(=O)C(N)CC1=CC=CC=C1 CJGXMNONHNZEQQ-UHFFFAOYSA-N 0.000 description 2
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 2
208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 2
GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 2
238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
239000013022 formulation composition Substances 0.000 description 2
230000006870 function Effects 0.000 description 2
125000002541 furyl group Chemical group 0.000 description 2
239000008187 granular material Substances 0.000 description 2
238000011597 hartley guinea pig Methods 0.000 description 2
210000002216 heart Anatomy 0.000 description 2
BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
238000000099 in vitro assay Methods 0.000 description 2
239000012442 inert solvent Substances 0.000 description 2
238000001802 infusion Methods 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
208000014674 injury Diseases 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
210000001503 joint Anatomy 0.000 description 2
HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 description 2
238000002372 labelling Methods 0.000 description 2
239000002502 liposome Substances 0.000 description 2
229940057995 liquid paraffin Drugs 0.000 description 2
210000004698 lymphocyte Anatomy 0.000 description 2
210000002540 macrophage Anatomy 0.000 description 2
230000014759 maintenance of location Effects 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
239000002609 medium Substances 0.000 description 2
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
BNSOPXHDOLHEQV-NSHDSACASA-N methyl (2s)-1-(3,5-dichlorophenyl)sulfonylpyrrolidine-2-carboxylate Chemical compound COC(=O)[C@@H]1CCCN1S(=O)(=O)C1=CC(Cl)=CC(Cl)=C1 BNSOPXHDOLHEQV-NSHDSACASA-N 0.000 description 2
HQEIPVHJHZTMDP-JEDNCBNOSA-N methyl (2s)-pyrrolidine-2-carboxylate;hydrochloride Chemical compound Cl.COC(=O)[C@@H]1CCCN1 HQEIPVHJHZTMDP-JEDNCBNOSA-N 0.000 description 2
YEPNFOMBMXWUOG-UHFFFAOYSA-N methyl 2-amino-4-phenylbutanoate Chemical compound COC(=O)C(N)CCC1=CC=CC=C1 YEPNFOMBMXWUOG-UHFFFAOYSA-N 0.000 description 2
HUNUAFNLLYVTQD-UHFFFAOYSA-N methyl 2-chlorosulfonylbenzoate Chemical compound COC(=O)C1=CC=CC=C1S(Cl)(=O)=O HUNUAFNLLYVTQD-UHFFFAOYSA-N 0.000 description 2
238000002156 mixing Methods 0.000 description 2
210000001616 monocyte Anatomy 0.000 description 2
OFCCYDUUBNUJIB-UHFFFAOYSA-N n,n-diethylcarbamoyl chloride Chemical compound CCN(CC)C(Cl)=O OFCCYDUUBNUJIB-UHFFFAOYSA-N 0.000 description 2
OPECTNGATDYLSS-UHFFFAOYSA-N naphthalene-2-sulfonyl chloride Chemical compound C1=CC=CC2=CC(S(=O)(=O)Cl)=CC=C21 OPECTNGATDYLSS-UHFFFAOYSA-N 0.000 description 2
125000001624 naphthyl group Chemical group 0.000 description 2
AKRYBBWYDSDZHG-UHFFFAOYSA-N nitrosobis(2-oxopropyl)amine Chemical compound CC(=O)CN(N=O)CC(C)=O AKRYBBWYDSDZHG-UHFFFAOYSA-N 0.000 description 2
239000002674 ointment Substances 0.000 description 2
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
239000007800 oxidant agent Substances 0.000 description 2
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 2
239000012188 paraffin wax Substances 0.000 description 2
230000005298 paramagnetic effect Effects 0.000 description 2
230000001575 pathological effect Effects 0.000 description 2
229960003330 pentetic acid Drugs 0.000 description 2
229940124531 pharmaceutical excipient Drugs 0.000 description 2
RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthridine Chemical compound C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 description 2
HXEACLLIILLPRG-UHFFFAOYSA-N pipecolic acid Chemical compound OC(=O)C1CCCCN1 HXEACLLIILLPRG-UHFFFAOYSA-N 0.000 description 2
230000036470 plasma concentration Effects 0.000 description 2
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
229910003446 platinum oxide Inorganic materials 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
239000011591 potassium Substances 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
239000000651 prodrug Substances 0.000 description 2
229940002612 prodrug Drugs 0.000 description 2
125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
235000018102 proteins Nutrition 0.000 description 2
102000004169 proteins and genes Human genes 0.000 description 2
108090000623 proteins and genes Proteins 0.000 description 2
239000000376 reactant Substances 0.000 description 2
102000005962 receptors Human genes 0.000 description 2
108020003175 receptors Proteins 0.000 description 2
238000006268 reductive amination reaction Methods 0.000 description 2
230000000241 respiratory effect Effects 0.000 description 2
102220240796 rs553605556 Human genes 0.000 description 2
FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
230000037390 scarring Effects 0.000 description 2
238000013207 serial dilution Methods 0.000 description 2
210000003491 skin Anatomy 0.000 description 2
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
239000004299 sodium benzoate Substances 0.000 description 2
235000010234 sodium benzoate Nutrition 0.000 description 2
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
239000008247 solid mixture Substances 0.000 description 2
239000007858 starting material Substances 0.000 description 2
230000036262 stenosis Effects 0.000 description 2
208000037804 stenosis Diseases 0.000 description 2
239000011550 stock solution Substances 0.000 description 2
UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
239000000758 substrate Substances 0.000 description 2
NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 2
150000003457 sulfones Chemical class 0.000 description 2
238000001356 surgical procedure Methods 0.000 description 2
230000002459 sustained effect Effects 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
125000001984 thiazolidinyl group Chemical group 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
125000000464 thioxo group Chemical group S=* 0.000 description 2
230000000451 tissue damage Effects 0.000 description 2
231100000827 tissue damage Toxicity 0.000 description 2
LMYRWZFENFIFIT-UHFFFAOYSA-N toluene-4-sulfonamide Chemical compound CC1=CC=C(S(N)(=O)=O)C=C1 LMYRWZFENFIFIT-UHFFFAOYSA-N 0.000 description 2
238000007070 tosylation reaction Methods 0.000 description 2
WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
239000001993 wax Substances 0.000 description 2
239000000230 xanthan gum Substances 0.000 description 2
235000010493 xanthan gum Nutrition 0.000 description 2
229920001285 xanthan gum Polymers 0.000 description 2
229940082509 xanthan gum Drugs 0.000 description 2
GSQBIOQCECCMOQ-UHFFFAOYSA-N β-alanine ethyl ester Chemical compound CCOC(=O)CCN GSQBIOQCECCMOQ-UHFFFAOYSA-N 0.000 description 2
WMSUFWLPZLCIHP-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 9h-fluoren-9-ylmethyl carbonate Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1COC(=O)ON1C(=O)CCC1=O WMSUFWLPZLCIHP-UHFFFAOYSA-N 0.000 description 1
IADUEWIQBXOCDZ-UHFFFAOYSA-N (2S)-azetidine-2-carboxylic acid Natural products OC(=O)C1CCN1 IADUEWIQBXOCDZ-UHFFFAOYSA-N 0.000 description 1
QNRXNRGSOJZINA-QMMMGPOBSA-N (2s)-2,3-dihydro-1h-indole-2-carboxylic acid Chemical compound C1=CC=C2N[C@H](C(=O)O)CC2=C1 QNRXNRGSOJZINA-QMMMGPOBSA-N 0.000 description 1
PECGVEGMRUZOML-AWEZNQCLSA-N (2s)-2-amino-3,3-diphenylpropanoic acid Chemical compound C=1C=CC=CC=1C([C@H](N)C(O)=O)C1=CC=CC=C1 PECGVEGMRUZOML-AWEZNQCLSA-N 0.000 description 1
DFZVZEMNPGABKO-ZETCQYMHSA-N (2s)-2-amino-3-pyridin-3-ylpropanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=CN=C1 DFZVZEMNPGABKO-ZETCQYMHSA-N 0.000 description 1
GTVVZTAFGPQSPC-QMMMGPOBSA-N (2s)-2-azaniumyl-3-(4-nitrophenyl)propanoate Chemical class OC(=O)[C@@H](N)CC1=CC=C([N+]([O-])=O)C=C1 GTVVZTAFGPQSPC-QMMMGPOBSA-N 0.000 description 1
FQFVANSXYKWQOT-ZETCQYMHSA-N (2s)-2-azaniumyl-3-pyridin-4-ylpropanoate Chemical compound OC(=O)[C@@H](N)CC1=CC=NC=C1 FQFVANSXYKWQOT-ZETCQYMHSA-N 0.000 description 1
MXWMFBYWXMXRPD-YFKPBYRVSA-N (2s)-2-azaniumyl-4-[(2-methylpropan-2-yl)oxy]-4-oxobutanoate Chemical compound CC(C)(C)OC(=O)C[C@H](N)C(O)=O MXWMFBYWXMXRPD-YFKPBYRVSA-N 0.000 description 1
KHZVLGLEHBZEPO-QMMMGPOBSA-N (2s)-2-hydrazinyl-3-phenylpropanoic acid Chemical class NN[C@H](C(O)=O)CC1=CC=CC=C1 KHZVLGLEHBZEPO-QMMMGPOBSA-N 0.000 description 1
RRONHWAVOYADJL-HNNXBMFYSA-N (2s)-3-phenyl-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC=1C=CC=CC=1)C1=CC=CC=C1 RRONHWAVOYADJL-HNNXBMFYSA-N 0.000 description 1
ZIWHMENIDGOELV-BKLSDQPFSA-N (2s)-4-fluoropyrrolidine-2-carboxylic acid Chemical class OC(=O)[C@@H]1CC(F)CN1 ZIWHMENIDGOELV-BKLSDQPFSA-N 0.000 description 1
OYNANFOWNSGDJL-BKLSDQPFSA-N (2s)-4-sulfanylpyrrolidine-2-carboxylic acid Chemical group OC(=O)[C@@H]1CC(S)CN1 OYNANFOWNSGDJL-BKLSDQPFSA-N 0.000 description 1
PIRXUBXPDYOLBL-SJORKVTESA-N (2s,3r)-1-(4-methylphenyl)sulfonyl-3-phenylpyrrolidine-2-carboxylic acid Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1[C@H](C(O)=O)[C@@H](C=2C=CC=CC=2)CC1 PIRXUBXPDYOLBL-SJORKVTESA-N 0.000 description 1
NXLNNXIXOYSCMB-UHFFFAOYSA-N (4-nitrophenyl) carbonochloridate Chemical compound [O-][N+](=O)C1=CC=C(OC(Cl)=O)C=C1 NXLNNXIXOYSCMB-UHFFFAOYSA-N 0.000 description 1
XJLSEXAGTJCILF-RXMQYKEDSA-N (R)-nipecotic acid zwitterion Chemical compound OC(=O)[C@@H]1CCCNC1 XJLSEXAGTJCILF-RXMQYKEDSA-N 0.000 description 1
IADUEWIQBXOCDZ-VKHMYHEASA-N (S)-azetidine-2-carboxylic acid Chemical group OC(=O)[C@@H]1CCN1 IADUEWIQBXOCDZ-VKHMYHEASA-N 0.000 description 1
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 1
HYJQWMUBCRPGDS-UHFFFAOYSA-N 1,3-thiazole-2-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=NC=CS1 HYJQWMUBCRPGDS-UHFFFAOYSA-N 0.000 description 1
OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
XHOCKWIJWIXZQZ-UHFFFAOYSA-N 1,4-bis(3-chlorophenyl)piperazine Chemical compound ClC1=CC=CC(N2CCN(CC2)C=2C=C(Cl)C=CC=2)=C1 XHOCKWIJWIXZQZ-UHFFFAOYSA-N 0.000 description 1
FUVZDXDCPRQZSQ-UHFFFAOYSA-N 1,5,6,7-tetrahydroindazol-4-one Chemical compound O=C1CCCC2=C1C=NN2 FUVZDXDCPRQZSQ-UHFFFAOYSA-N 0.000 description 1
FVTVMQPGKVHSEY-UHFFFAOYSA-N 1-AMINOCYCLOBUTANE CARBOXYLIC ACID Chemical compound OC(=O)C1(N)CCC1 FVTVMQPGKVHSEY-UHFFFAOYSA-N 0.000 description 1
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
WKBPZYKAUNRMKP-UHFFFAOYSA-N 1-[2-(2,4-dichlorophenyl)pentyl]1,2,4-triazole Chemical compound C=1C=C(Cl)C=C(Cl)C=1C(CCC)CN1C=NC=N1 WKBPZYKAUNRMKP-UHFFFAOYSA-N 0.000 description 1
WOXWUZCRWJWTRT-UHFFFAOYSA-N 1-amino-1-cyclohexanecarboxylic acid Chemical class OC(=O)C1(N)CCCCC1 WOXWUZCRWJWTRT-UHFFFAOYSA-N 0.000 description 1
CRRUGYDDEMGVDY-UHFFFAOYSA-N 1-bromoethylbenzene Chemical compound CC(Br)C1=CC=CC=C1 CRRUGYDDEMGVDY-UHFFFAOYSA-N 0.000 description 1
WSNFKVVZSAMWRX-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrochloride Chemical group Cl.C1=CC=C2N(O)N=NC2=C1 WSNFKVVZSAMWRX-UHFFFAOYSA-N 0.000 description 1
NPOVTGVGOBJZPY-UHFFFAOYSA-N 1-isocyanato-3-methoxybenzene Chemical compound COC1=CC=CC(N=C=O)=C1 NPOVTGVGOBJZPY-UHFFFAOYSA-N 0.000 description 1
OQURWGJAWSLGQG-UHFFFAOYSA-N 1-isocyanatopropane Chemical compound CCCN=C=O OQURWGJAWSLGQG-UHFFFAOYSA-N 0.000 description 1
HCKNAJXCHMACDN-UHFFFAOYSA-N 1-methylpiperidine-4-carboxylic acid Chemical compound CN1CCC(C(O)=O)CC1 HCKNAJXCHMACDN-UHFFFAOYSA-N 0.000 description 1
RDAVKKQKMLINOH-UHFFFAOYSA-N 1-methylpyrazole-4-sulfonyl chloride Chemical compound CN1C=C(S(Cl)(=O)=O)C=N1 RDAVKKQKMLINOH-UHFFFAOYSA-N 0.000 description 1
PKDPUENCROCRCH-UHFFFAOYSA-N 1-piperazin-1-ylethanone Chemical compound CC(=O)N1CCNCC1 PKDPUENCROCRCH-UHFFFAOYSA-N 0.000 description 1
WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 description 1
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
MXCZCMCHRWGSBX-UHFFFAOYSA-N 1h-imidazole-5-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CN=CN1 MXCZCMCHRWGSBX-UHFFFAOYSA-N 0.000 description 1
JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 description 1
PVJZBZSCGJAWNG-UHFFFAOYSA-N 2,4,6-trimethylbenzenesulfonyl chloride Chemical compound CC1=CC(C)=C(S(Cl)(=O)=O)C(C)=C1 PVJZBZSCGJAWNG-UHFFFAOYSA-N 0.000 description 1
JJKSHSHZJOWSEC-UHFFFAOYSA-N 2,5-dichlorothiophene-3-sulfonyl chloride Chemical compound ClC1=CC(S(Cl)(=O)=O)=C(Cl)S1 JJKSHSHZJOWSEC-UHFFFAOYSA-N 0.000 description 1
FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 1
MXIUWSYTQJLIKE-UHFFFAOYSA-N 2-(trifluoromethyl)benzoyl chloride Chemical compound FC(F)(F)C1=CC=CC=C1C(Cl)=O MXIUWSYTQJLIKE-UHFFFAOYSA-N 0.000 description 1
FUOOLUPWFVMBKG-UHFFFAOYSA-N 2-Aminoisobutyric acid Chemical compound CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 description 1
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
UTYWQAMTLPMQHB-WMXJXTQLSA-N 2-[(1-methylpyridin-1-ium-3-carbonyl)amino]ethyl (2s)-2-[[(2s)-1-(4-methylphenyl)sulfonylpyrrolidine-2-carbonyl]amino]-3-phenylpropanoate;iodide Chemical compound [I-].C1=CC(C)=CC=C1S(=O)(=O)N1[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)OCCNC(=O)C=2C=[N+](C)C=CC=2)CCC1 UTYWQAMTLPMQHB-WMXJXTQLSA-N 0.000 description 1
PDRJLZDUOULRHE-ZETCQYMHSA-N 2-aza-L-phenylalanine Natural products OC(=O)[C@@H](N)CC1=CC=CC=N1 PDRJLZDUOULRHE-ZETCQYMHSA-N 0.000 description 1
NZCKTGCKFJDGFD-UHFFFAOYSA-N 2-bromobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1Br NZCKTGCKFJDGFD-UHFFFAOYSA-N 0.000 description 1
UORPZQUQDLLNGR-UHFFFAOYSA-N 2-chloro-n-(6-chlorohexyl)ethanimine Chemical compound ClCCCCCCN=CCCl UORPZQUQDLLNGR-UHFFFAOYSA-N 0.000 description 1
ZRWICZHXYMHBDP-UHFFFAOYSA-N 2-chlorosulfonylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1S(Cl)(=O)=O ZRWICZHXYMHBDP-UHFFFAOYSA-N 0.000 description 1
AUVALWUPUHHNQV-UHFFFAOYSA-N 2-hydroxy-3-propylbenzoic acid Chemical class CCCC1=CC=CC(C(O)=O)=C1O AUVALWUPUHHNQV-UHFFFAOYSA-N 0.000 description 1
NQVMZRZWNPTCJC-UHFFFAOYSA-N 2-methyl-1,3-thiazole-4-sulfonyl chloride Chemical compound CC1=NC(S(Cl)(=O)=O)=CS1 NQVMZRZWNPTCJC-UHFFFAOYSA-N 0.000 description 1
GPZXFICWCMCQPF-UHFFFAOYSA-N 2-methylbenzoyl chloride Chemical compound CC1=CC=CC=C1C(Cl)=O GPZXFICWCMCQPF-UHFFFAOYSA-N 0.000 description 1
VLRSADZEDXVUPG-UHFFFAOYSA-N 2-naphthalen-1-ylpyridine Chemical compound N1=CC=CC=C1C1=CC=CC2=CC=CC=C12 VLRSADZEDXVUPG-UHFFFAOYSA-N 0.000 description 1
VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 1
LKFNLHZZPHHFEC-UHFFFAOYSA-N 2-phenylethanesulfonyl chloride Chemical compound ClS(=O)(=O)CCC1=CC=CC=C1 LKFNLHZZPHHFEC-UHFFFAOYSA-N 0.000 description 1
HACRKYQRZABURO-UHFFFAOYSA-N 2-phenylethyl isocyanate Chemical compound O=C=NCCC1=CC=CC=C1 HACRKYQRZABURO-UHFFFAOYSA-N 0.000 description 1
HUKWNFVGBRDJIM-UHFFFAOYSA-N 2-phenylethyl thiocyanate Chemical compound N#CSCCC1=CC=CC=C1 HUKWNFVGBRDJIM-UHFFFAOYSA-N 0.000 description 1
VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
NYIBPWGZGSXURD-UHFFFAOYSA-N 3,4-dichlorobenzenesulfonyl chloride Chemical compound ClC1=CC=C(S(Cl)(=O)=O)C=C1Cl NYIBPWGZGSXURD-UHFFFAOYSA-N 0.000 description 1
BTRCVKADYDVSLI-UHFFFAOYSA-N 3,5-bis(trifluoromethyl)benzenesulfonyl chloride Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(S(Cl)(=O)=O)=C1 BTRCVKADYDVSLI-UHFFFAOYSA-N 0.000 description 1
LPQRCJYLQYGWFT-UHFFFAOYSA-N 3-(diethylamino)propyl thiocyanate Chemical compound CCN(CC)CCCSC#N LPQRCJYLQYGWFT-UHFFFAOYSA-N 0.000 description 1
MKKYNXOZXDQGFF-HDJSMCDHSA-N 3-[[2-[(4-methylphenyl)sulfonylamino]-3-[1-[(2S)-pyrrolidine-2-carbonyl]cyclohexa-2,4-dien-1-yl]propanoyl]amino]propanoic acid Chemical compound C1(=CC=C(C=C1)S(=O)(=O)NC(CC1(CC=CC=C1)C([C@H]1NCCC1)=O)C(=O)NCCC(=O)O)C MKKYNXOZXDQGFF-HDJSMCDHSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical group NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
CYLQTKJROAUTJA-UHFFFAOYSA-N 3-isocyanatosulfanylpyridine Chemical compound O=C=NSC1=CC=CN=C1 CYLQTKJROAUTJA-UHFFFAOYSA-N 0.000 description 1
IBNOJEJGCXPGSO-UHFFFAOYSA-N 3-phenylpropyl thiocyanate Chemical compound N#CSCCCC1=CC=CC=C1 IBNOJEJGCXPGSO-UHFFFAOYSA-N 0.000 description 1
CBKDCOKSXCTDAA-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1-benzothiophene Chemical compound C1CCCC2=C1C=CS2 CBKDCOKSXCTDAA-UHFFFAOYSA-N 0.000 description 1
ZAPMTSHEXFEPSD-UHFFFAOYSA-N 4-(2-chloroethyl)morpholine Chemical compound ClCCN1CCOCC1 ZAPMTSHEXFEPSD-UHFFFAOYSA-N 0.000 description 1
SXDPPADZILPFLK-UHFFFAOYSA-N 4-(4-methylphenyl)sulfonylthiomorpholine-3-carboxylic acid Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1C(C(O)=O)CSCC1 SXDPPADZILPFLK-UHFFFAOYSA-N 0.000 description 1
UHCDBMIOLNKDHG-UHFFFAOYSA-N 4-(trifluoromethoxy)benzenesulfonyl chloride Chemical compound FC(F)(F)OC1=CC=C(S(Cl)(=O)=O)C=C1 UHCDBMIOLNKDHG-UHFFFAOYSA-N 0.000 description 1
OZDCZHDOIBUGAJ-UHFFFAOYSA-N 4-(trifluoromethyl)benzenesulfonyl chloride Chemical compound FC(F)(F)C1=CC=C(S(Cl)(=O)=O)C=C1 OZDCZHDOIBUGAJ-UHFFFAOYSA-N 0.000 description 1
KMMHZIBWCXYAAH-UHFFFAOYSA-N 4-bromobenzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C(Br)C=C1 KMMHZIBWCXYAAH-UHFFFAOYSA-N 0.000 description 1
UVGFHUNOQIVABI-UHFFFAOYSA-N 4-carbamimidoylbenzenesulfonyl chloride Chemical compound NC(=N)C1=CC=C(S(Cl)(=O)=O)C=C1 UVGFHUNOQIVABI-UHFFFAOYSA-N 0.000 description 1
AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 1
125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 1
229960000549 4-dimethylaminophenol Drugs 0.000 description 1
BFXHJFKKRGVUMU-UHFFFAOYSA-N 4-fluorobenzenesulfonyl chloride Chemical compound FC1=CC=C(S(Cl)(=O)=O)C=C1 BFXHJFKKRGVUMU-UHFFFAOYSA-N 0.000 description 1
125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 description 1
TVSXDZNUTPLDKY-UHFFFAOYSA-N 4-isocyanatobenzonitrile Chemical compound O=C=NC1=CC=C(C#N)C=C1 TVSXDZNUTPLDKY-UHFFFAOYSA-N 0.000 description 1
JXRGUPLJCCDGKG-UHFFFAOYSA-N 4-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC=C(S(Cl)(=O)=O)C=C1 JXRGUPLJCCDGKG-UHFFFAOYSA-N 0.000 description 1
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
YEZADZMMVHWFIY-UHFFFAOYSA-N 4-tert-butylbenzenesulfonyl chloride Chemical compound CC(C)(C)C1=CC=C(S(Cl)(=O)=O)C=C1 YEZADZMMVHWFIY-UHFFFAOYSA-N 0.000 description 1
125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 description 1
MHIJWYNLXIPTFB-UHFFFAOYSA-N 5,5-dichlorocyclohexa-1,3-diene-1-sulfonyl chloride Chemical group ClC1(Cl)CC(S(Cl)(=O)=O)=CC=C1 MHIJWYNLXIPTFB-UHFFFAOYSA-N 0.000 description 1
HWGVUNSKAPCFNF-UHFFFAOYSA-N 5-chloro-1,3-dimethylpyrazole-4-sulfonyl chloride Chemical compound CC1=NN(C)C(Cl)=C1S(Cl)(=O)=O HWGVUNSKAPCFNF-UHFFFAOYSA-N 0.000 description 1
FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
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 1
244000215068 Acacia senegal Species 0.000 description 1
235000006491 Acacia senegal Nutrition 0.000 description 1
240000005020 Acaciella glauca Species 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
208000000884 Airway Obstruction Diseases 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
239000005695 Ammonium acetate Substances 0.000 description 1
241001156002 Anthonomus pomorum Species 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
208000023275 Autoimmune disease Diseases 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
UFAGLHQDCZGQMV-OKFDZGCWSA-N CCOC(=O)CCNC(=O)C(CC1(CC=CC=C1)C(=O)[C@@H]2CCCN2)NS(=O)(=O)C3=CC=C(C=C3)C Chemical compound CCOC(=O)CCNC(=O)C(CC1(CC=CC=C1)C(=O)[C@@H]2CCCN2)NS(=O)(=O)C3=CC=C(C=C3)C UFAGLHQDCZGQMV-OKFDZGCWSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
241001247986 Calotropis procera Species 0.000 description 1
241000283707 Capra Species 0.000 description 1
CKDWPUIZGOQOOM-UHFFFAOYSA-N Carbamyl chloride Chemical compound NC(Cl)=O CKDWPUIZGOQOOM-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
241000700198 Cavia Species 0.000 description 1
241000700199 Cavia porcellus Species 0.000 description 1
206010051288 Central nervous system inflammation Diseases 0.000 description 1
208000022306 Cerebral injury Diseases 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
102000008186 Collagen Human genes 0.000 description 1
108010035532 Collagen Proteins 0.000 description 1
206010009944 Colon cancer Diseases 0.000 description 1
241000557626 Corvus corax Species 0.000 description 1
108090000695 Cytokines Proteins 0.000 description 1
102000004127 Cytokines Human genes 0.000 description 1
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 1
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 1
ONIBWKKTOPOVIA-SCSAIBSYSA-N D-Proline Chemical compound OC(=O)[C@H]1CCCN1 ONIBWKKTOPOVIA-SCSAIBSYSA-N 0.000 description 1
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 1
RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
YIIMEMSDCNDGTB-UHFFFAOYSA-N Dimethylcarbamoyl chloride Chemical compound CN(C)C(Cl)=O YIIMEMSDCNDGTB-UHFFFAOYSA-N 0.000 description 1
238000004435 EPR spectroscopy Methods 0.000 description 1
241000196324 Embryophyta Species 0.000 description 1
206010014612 Encephalitis viral Diseases 0.000 description 1
208000001836 Firesetting Behavior Diseases 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
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 1
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
229920000084 Gum arabic Polymers 0.000 description 1
229910004373 HOAc Inorganic materials 0.000 description 1
101000994375 Homo sapiens Integrin alpha-4 Proteins 0.000 description 1
101000935043 Homo sapiens Integrin beta-1 Proteins 0.000 description 1
101000635799 Homo sapiens Run domain Beclin-1-interacting and cysteine-rich domain-containing protein Proteins 0.000 description 1
101000879758 Homo sapiens Sjoegren syndrome nuclear autoantigen 1 Proteins 0.000 description 1
108010020056 Hydrogenase Proteins 0.000 description 1
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
206010020751 Hypersensitivity Diseases 0.000 description 1
206010020880 Hypertrophy Diseases 0.000 description 1
WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
108060003951 Immunoglobulin Proteins 0.000 description 1
102100032818 Integrin alpha-4 Human genes 0.000 description 1
108010041012 Integrin alpha4 Proteins 0.000 description 1
102100025304 Integrin beta-1 Human genes 0.000 description 1
PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
239000005909 Kieselgur Substances 0.000 description 1
150000008575 L-amino acids Chemical class 0.000 description 1
ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
102000007547 Laminin Human genes 0.000 description 1
108010085895 Laminin Proteins 0.000 description 1
NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
206010025323 Lymphomas Diseases 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical class OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
206010027260 Meningitis viral Diseases 0.000 description 1
238000006751 Mitsunobu reaction Methods 0.000 description 1
241001529936 Murinae Species 0.000 description 1
241000699666 Mus <mouse, genus> Species 0.000 description 1
102000006386 Myelin Proteins Human genes 0.000 description 1
108010083674 Myelin Proteins Proteins 0.000 description 1
235000009421 Myristica fragrans Nutrition 0.000 description 1
RKOTXQYWCBGZLP-UHFFFAOYSA-N N-[(2,4-difluorophenyl)methyl]-2-ethyl-9-hydroxy-3-methoxy-1,8-dioxospiro[3H-pyrido[1,2-a]pyrazine-4,3'-oxolane]-7-carboxamide Chemical compound CCN1C(OC)C2(CCOC2)N2C=C(C(=O)NCC3=C(F)C=C(F)C=C3)C(=O)C(O)=C2C1=O RKOTXQYWCBGZLP-UHFFFAOYSA-N 0.000 description 1
230000006181 N-acylation Effects 0.000 description 1
PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
238000010934 O-alkylation reaction Methods 0.000 description 1
RZXVCUCQBFNUNV-RSAXXLAASA-N OS(=O)(=O)Cc1ccccc1.N[C@@H](Cc1ccccc1)C(=O)OCc1ccccc1 Chemical compound OS(=O)(=O)Cc1ccccc1.N[C@@H](Cc1ccccc1)C(=O)OCc1ccccc1 RZXVCUCQBFNUNV-RSAXXLAASA-N 0.000 description 1
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
229930182555 Penicillin Natural products 0.000 description 1
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
102000035195 Peptidases Human genes 0.000 description 1
108091005804 Peptidases Proteins 0.000 description 1
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
108010004729 Phycoerythrin Proteins 0.000 description 1
241000288906 Primates Species 0.000 description 1
IWIANZLCJVYEFX-RYUDHWBXSA-N Pro-Phe Chemical compound C([C@@H](C(=O)O)NC(=O)[C@H]1NCCC1)C1=CC=CC=C1 IWIANZLCJVYEFX-RYUDHWBXSA-N 0.000 description 1
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
239000012980 RPMI-1640 medium Substances 0.000 description 1
102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
208000002200 Respiratory Hypersensitivity Diseases 0.000 description 1
208000025747 Rheumatic disease Diseases 0.000 description 1
108010077895 Sarcosine Proteins 0.000 description 1
229920001800 Shellac Polymers 0.000 description 1
102100037330 Sjoegren syndrome nuclear autoantigen 1 Human genes 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 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
229920001615 Tragacanth Polymers 0.000 description 1
208000025865 Ulcer Diseases 0.000 description 1
208000024248 Vascular System injury Diseases 0.000 description 1
208000012339 Vascular injury Diseases 0.000 description 1
UAYWVJHJZHQCIE-UHFFFAOYSA-L Zinc iodide Inorganic materials I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 description 1
DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
PMWJQPMSEVSRQX-UHFFFAOYSA-M [I-].COC(=O)C1=CC=CC=C1[Zn+] Chemical compound [I-].COC(=O)C1=CC=CC=C1[Zn+] PMWJQPMSEVSRQX-UHFFFAOYSA-M 0.000 description 1
XOLMUIRYZDCSKR-UHFFFAOYSA-N [S]N1CCOCC1 Chemical compound [S]N1CCOCC1 XOLMUIRYZDCSKR-UHFFFAOYSA-N 0.000 description 1
210000000683 abdominal cavity Anatomy 0.000 description 1
235000010489 acacia gum Nutrition 0.000 description 1
238000009825 accumulation Methods 0.000 description 1
229940081735 acetylcellulose Drugs 0.000 description 1
230000003213 activating effect Effects 0.000 description 1
208000038016 acute inflammation Diseases 0.000 description 1
230000006022 acute inflammation Effects 0.000 description 1
230000010062 adhesion mechanism Effects 0.000 description 1
102000019997 adhesion receptor Human genes 0.000 description 1
108010013985 adhesion receptor Proteins 0.000 description 1
230000036428 airway hyperreactivity Effects 0.000 description 1
230000010085 airway hyperresponsiveness Effects 0.000 description 1
230000008369 airway response Effects 0.000 description 1
150000001294 alanine derivatives Chemical class 0.000 description 1
229940072056 alginate Drugs 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
150000001342 alkaline earth metals Chemical class 0.000 description 1
150000001348 alkyl chlorides Chemical class 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
ZGUNAGUHMKGQNY-UHFFFAOYSA-N alpha-phenylglycine Chemical compound OC(=O)C(N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-UHFFFAOYSA-N 0.000 description 1
229910052782 aluminium Chemical group 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical group [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
210000001132 alveolar macrophage Anatomy 0.000 description 1
229940043376 ammonium acetate Drugs 0.000 description 1
235000019257 ammonium acetate Nutrition 0.000 description 1
125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
230000003110 anti-inflammatory effect Effects 0.000 description 1
210000000436 anus Anatomy 0.000 description 1
206010002906 aortic stenosis Diseases 0.000 description 1
239000008365 aqueous carrier Substances 0.000 description 1
239000003125 aqueous solvent Substances 0.000 description 1
210000001367 artery Anatomy 0.000 description 1
206010003246 arthritis Diseases 0.000 description 1
210000000544 articulatio talocruralis Anatomy 0.000 description 1
238000002820 assay format Methods 0.000 description 1
238000000376 autoradiography Methods 0.000 description 1
XEXFVRMLYUDDJY-UHFFFAOYSA-N azane;hydrate;hydrochloride Chemical compound [NH4+].[NH4+].[OH-].[Cl-] XEXFVRMLYUDDJY-UHFFFAOYSA-N 0.000 description 1
125000002393 azetidinyl group Chemical group 0.000 description 1
150000001540 azides Chemical class 0.000 description 1
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
210000003719 b-lymphocyte Anatomy 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
UENWRTRMUIOCKN-UHFFFAOYSA-N benzyl thiol Chemical group SCC1=CC=CC=C1 UENWRTRMUIOCKN-UHFFFAOYSA-N 0.000 description 1
WTOFYLAWDLQMBZ-LURJTMIESA-N beta(2-thienyl)alanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CS1 WTOFYLAWDLQMBZ-LURJTMIESA-N 0.000 description 1
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 1
239000003124 biologic agent Substances 0.000 description 1
230000017531 blood circulation Effects 0.000 description 1
210000004204 blood vessel Anatomy 0.000 description 1
210000005013 brain tissue Anatomy 0.000 description 1
210000000621 bronchi Anatomy 0.000 description 1
230000005587 bubbling Effects 0.000 description 1
239000000872 buffer Substances 0.000 description 1
WEDIIKBPDQQQJU-UHFFFAOYSA-N butane-1-sulfonyl chloride Chemical compound CCCCS(Cl)(=O)=O WEDIIKBPDQQQJU-UHFFFAOYSA-N 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
229960001714 calcium phosphate Drugs 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
239000000378 calcium silicate Substances 0.000 description 1
229910052918 calcium silicate Inorganic materials 0.000 description 1
229960003340 calcium silicate Drugs 0.000 description 1
235000012241 calcium silicate Nutrition 0.000 description 1
OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical compound [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 description 1
229960004484 carbachol Drugs 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
VWPHTOATEPXMCB-UHFFFAOYSA-N carbamoyl chloride;hydrochloride Chemical class Cl.NC(Cl)=O VWPHTOATEPXMCB-UHFFFAOYSA-N 0.000 description 1
150000007942 carboxylates Chemical class 0.000 description 1
150000001733 carboxylic acid esters Chemical class 0.000 description 1
239000000969 carrier Substances 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
210000004970 cd4 cell Anatomy 0.000 description 1
230000004663 cell proliferation Effects 0.000 description 1
230000017455 cell-cell adhesion Effects 0.000 description 1
229920002301 cellulose acetate Polymers 0.000 description 1
208000015114 central nervous system disease Diseases 0.000 description 1
230000002490 cerebral effect Effects 0.000 description 1
206010008118 cerebral infarction Diseases 0.000 description 1
208000026106 cerebrovascular disease Diseases 0.000 description 1
229960000541 cetyl alcohol Drugs 0.000 description 1
230000008859 change Effects 0.000 description 1
239000002738 chelating agent Substances 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
239000005482 chemotactic factor Substances 0.000 description 1
238000010568 chiral column chromatography Methods 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
229940089960 chloroacetate Drugs 0.000 description 1
HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 1
KQDDQXNVESLJNO-UHFFFAOYSA-N chloromethanesulfonyl chloride Chemical compound ClCS(Cl)(=O)=O KQDDQXNVESLJNO-UHFFFAOYSA-N 0.000 description 1
208000037976 chronic inflammation Diseases 0.000 description 1
230000006020 chronic inflammation Effects 0.000 description 1
230000004087 circulation Effects 0.000 description 1
238000000576 coating method Methods 0.000 description 1
239000003240 coconut oil Substances 0.000 description 1
235000019864 coconut oil Nutrition 0.000 description 1
229920001436 collagen Polymers 0.000 description 1
229940075614 colloidal silicon dioxide Drugs 0.000 description 1
239000003086 colorant Substances 0.000 description 1
239000002299 complementary DNA Substances 0.000 description 1
238000010276 construction Methods 0.000 description 1
UWCHSDIUMBNDLT-UHFFFAOYSA-L copper;methylsulfanylmethane;dibromide Chemical compound CSC.Br[Cu]Br UWCHSDIUMBNDLT-UHFFFAOYSA-L 0.000 description 1
235000012343 cottonseed oil Nutrition 0.000 description 1
239000002385 cottonseed oil Substances 0.000 description 1
230000009260 cross reactivity Effects 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([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
230000006196 deacetylation Effects 0.000 description 1
238000003381 deacetylation reaction Methods 0.000 description 1
238000006114 decarboxylation reaction Methods 0.000 description 1
230000001934 delay Effects 0.000 description 1
238000001514 detection method Methods 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
KZNICNPSHKQLFF-UHFFFAOYSA-N dihydromaleimide Natural products O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 1
229940043279 diisopropylamine Drugs 0.000 description 1
208000037765 diseases and disorders Diseases 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
239000002612 dispersion medium Substances 0.000 description 1
239000006196 drop Substances 0.000 description 1
229940112141 dry powder inhaler Drugs 0.000 description 1
210000001198 duodenum Anatomy 0.000 description 1
239000008157 edible vegetable oil Substances 0.000 description 1
210000001513 elbow Anatomy 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000002702 enteric coating Substances 0.000 description 1
239000002532 enzyme inhibitor Substances 0.000 description 1
238000006345 epimerization reaction Methods 0.000 description 1
210000003238 esophagus Anatomy 0.000 description 1
LJQKCYFTNDAAPC-UHFFFAOYSA-N ethanol;ethyl acetate Chemical compound CCO.CCOC(C)=O LJQKCYFTNDAAPC-UHFFFAOYSA-N 0.000 description 1
SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 1
CJGXMNONHNZEQQ-JTQLQIEISA-N ethyl (2s)-2-amino-3-phenylpropanoate Chemical compound CCOC(=O)[C@@H](N)CC1=CC=CC=C1 CJGXMNONHNZEQQ-JTQLQIEISA-N 0.000 description 1
HLBORWSSRVPMNT-KBPBESRZSA-N ethyl (2s,3s)-1-acetyl-3-phenylpyrrolidine-2-carboxylate Chemical compound C1CN(C(C)=O)[C@H](C(=O)OCC)[C@@H]1C1=CC=CC=C1 HLBORWSSRVPMNT-KBPBESRZSA-N 0.000 description 1
229960003750 ethyl chloride Drugs 0.000 description 1
WUDNUHPRLBTKOJ-UHFFFAOYSA-N ethyl isocyanate Chemical compound CCN=C=O WUDNUHPRLBTKOJ-UHFFFAOYSA-N 0.000 description 1
WFCLYEAZTHWNEH-UHFFFAOYSA-N ethylthiocyanate Chemical compound CCSC#N WFCLYEAZTHWNEH-UHFFFAOYSA-N 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
210000003414 extremity Anatomy 0.000 description 1
235000019197 fats Nutrition 0.000 description 1
239000012091 fetal bovine serum Substances 0.000 description 1
239000012894 fetal calf serum Substances 0.000 description 1
239000000835 fiber Substances 0.000 description 1
210000002950 fibroblast Anatomy 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
239000013305 flexible fiber Substances 0.000 description 1
239000006260 foam Substances 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
229940014259 gelatin Drugs 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
238000007429 general method Methods 0.000 description 1
230000001434 glomerular Effects 0.000 description 1
235000013922 glutamic acid Nutrition 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
229960002743 glutamine Drugs 0.000 description 1
230000036541 health Effects 0.000 description 1
210000005003 heart tissue Anatomy 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
238000009775 high-speed stirring Methods 0.000 description 1
208000010726 hind limb paralysis Diseases 0.000 description 1
229960001340 histamine Drugs 0.000 description 1
210000003630 histaminocyte Anatomy 0.000 description 1
229960002885 histidine Drugs 0.000 description 1
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
239000008240 homogeneous mixture Substances 0.000 description 1
238000000265 homogenisation Methods 0.000 description 1
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
229910000041 hydrogen chloride Inorganic materials 0.000 description 1
229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
238000007327 hydrogenolysis reaction Methods 0.000 description 1
XNXVOSBNFZWHBV-UHFFFAOYSA-N hydron;o-methylhydroxylamine;chloride Chemical compound Cl.CON XNXVOSBNFZWHBV-UHFFFAOYSA-N 0.000 description 1
239000000819 hypertonic solution Substances 0.000 description 1
210000003405 ileum Anatomy 0.000 description 1
238000003384 imaging method Methods 0.000 description 1
MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
230000006058 immune tolerance Effects 0.000 description 1
238000003018 immunoassay Methods 0.000 description 1
102000018358 immunoglobulin Human genes 0.000 description 1
238000005462 in vivo assay Methods 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
229940055742 indium-111 Drugs 0.000 description 1
APFVFJFRJDLVQX-AHCXROLUSA-N indium-111 Chemical compound [111In] APFVFJFRJDLVQX-AHCXROLUSA-N 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 description 1
HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 1
125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
239000011261 inert gas Substances 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
230000008595 infiltration Effects 0.000 description 1
238000001764 infiltration Methods 0.000 description 1
230000006749 inflammatory damage Effects 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
230000000968 intestinal effect Effects 0.000 description 1
210000004347 intestinal mucosa Anatomy 0.000 description 1
238000001361 intraarterial administration Methods 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
230000009545 invasion Effects 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
208000028867 ischemia Diseases 0.000 description 1
229960002725 isoflurane Drugs 0.000 description 1
SRJOCJYGOFTFLH-UHFFFAOYSA-N isonipecotic acid Chemical compound OC(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-N 0.000 description 1
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
208000017169 kidney disease Diseases 0.000 description 1
210000003127 knee Anatomy 0.000 description 1
238000011005 laboratory method Methods 0.000 description 1
230000003902 lesion Effects 0.000 description 1
150000002617 leukotrienes Chemical class 0.000 description 1
238000011694 lewis rat Methods 0.000 description 1
229960004194 lidocaine Drugs 0.000 description 1
208000027905 limb weakness Diseases 0.000 description 1
231100000861 limb weakness Toxicity 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
239000011344 liquid material Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
210000003141 lower extremity Anatomy 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
210000004072 lung Anatomy 0.000 description 1
239000001115 mace Substances 0.000 description 1
229920002521 macromolecule Polymers 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
229910000000 metal hydroxide Inorganic materials 0.000 description 1
150000004692 metal hydroxides Chemical class 0.000 description 1
229910021645 metal ion Inorganic materials 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
KCUNTYMNJVXYKZ-JTQLQIEISA-N methyl (2s)-2-amino-3-(1h-indol-3-yl)propanoate Chemical compound C1=CC=C2C(C[C@H](N)C(=O)OC)=CNC2=C1 KCUNTYMNJVXYKZ-JTQLQIEISA-N 0.000 description 1
XNFNGGQRDXFYMM-PPHPATTJSA-N methyl (2s)-2-amino-3-(1h-indol-3-yl)propanoate;hydrochloride Chemical compound Cl.C1=CC=C2C(C[C@H](N)C(=O)OC)=CNC2=C1 XNFNGGQRDXFYMM-PPHPATTJSA-N 0.000 description 1
JOTSVOSIVDVLQL-FJXQXJEOSA-N methyl (2s)-2-amino-3-thiophen-2-ylpropanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)CC1=CC=CS1 JOTSVOSIVDVLQL-FJXQXJEOSA-N 0.000 description 1
VCZANKJSRYTJDN-STQMWFEESA-N methyl (2s)-3-phenyl-2-[[(2s)-pyrrolidine-2-carbonyl]amino]propanoate Chemical compound C([C@@H](C(=O)OC)NC(=O)[C@H]1NCCC1)C1=CC=CC=C1 VCZANKJSRYTJDN-STQMWFEESA-N 0.000 description 1
QZRKHEWOZOUBLM-UHFFFAOYSA-N methyl 2-amino-3-(1h-1,2,4-triazol-5-yl)propanoate Chemical compound COC(=O)C(N)CC1=NC=NN1 QZRKHEWOZOUBLM-UHFFFAOYSA-N 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
229940050176 methyl chloride Drugs 0.000 description 1
VYHVQEYOFIYNJP-UHFFFAOYSA-N methyl thiocyanate Chemical compound CSC#N VYHVQEYOFIYNJP-UHFFFAOYSA-N 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
230000005012 migration Effects 0.000 description 1
238000013508 migration Methods 0.000 description 1
238000003801 milling Methods 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
230000000116 mitigating effect Effects 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
210000004877 mucosa Anatomy 0.000 description 1
210000005012 myelin Anatomy 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
210000004165 myocardium Anatomy 0.000 description 1
GSLWSSUWNCJILM-UHFFFAOYSA-N n,n-dibenzyl-2-chloroethanamine Chemical compound C=1C=CC=CC=1CN(CCCl)CC1=CC=CC=C1 GSLWSSUWNCJILM-UHFFFAOYSA-N 0.000 description 1
JFCHSQDLLFJHOA-UHFFFAOYSA-N n,n-dimethylsulfamoyl chloride Chemical compound CN(C)S(Cl)(=O)=O JFCHSQDLLFJHOA-UHFFFAOYSA-N 0.000 description 1
DBDNQNARCHWMSP-UHFFFAOYSA-N n-(2-chloroethyl)-n-ethylaniline Chemical compound ClCCN(CC)C1=CC=CC=C1 DBDNQNARCHWMSP-UHFFFAOYSA-N 0.000 description 1
XOVAMNMHLZQZJL-UHFFFAOYSA-N n-benzyl-3-chloro-n-methylpropan-1-amine Chemical compound ClCCCN(C)CC1=CC=CC=C1 XOVAMNMHLZQZJL-UHFFFAOYSA-N 0.000 description 1
125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
KCXYZMFPZHYUFO-UHFFFAOYSA-N n-methyl-n-phosphanylmethanamine Chemical compound CN(C)P KCXYZMFPZHYUFO-UHFFFAOYSA-N 0.000 description 1
DASJFYAPNPUBGG-UHFFFAOYSA-N naphthalene-1-sulfonyl chloride Chemical compound C1=CC=C2C(S(=O)(=O)Cl)=CC=CC2=C1 DASJFYAPNPUBGG-UHFFFAOYSA-N 0.000 description 1
210000004126 nerve fiber Anatomy 0.000 description 1
230000000926 neurological effect Effects 0.000 description 1
210000000440 neutrophil Anatomy 0.000 description 1
230000003448 neutrophilic effect Effects 0.000 description 1
238000010534 nucleophilic substitution reaction Methods 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
238000005457 optimization Methods 0.000 description 1
210000004789 organ system Anatomy 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
LVSJDHGRKAEGLX-UHFFFAOYSA-N oxolane;2,2,2-trifluoroacetic acid Chemical compound C1CCOC1.OC(=O)C(F)(F)F LVSJDHGRKAEGLX-UHFFFAOYSA-N 0.000 description 1
229940094443 oxytocics prostaglandins Drugs 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
210000000496 pancreas Anatomy 0.000 description 1
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
230000001314 paroxysmal effect Effects 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
229940049954 penicillin Drugs 0.000 description 1
HGBOYTHUEUWSSQ-UHFFFAOYSA-N pentanal Chemical compound CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
210000005259 peripheral blood Anatomy 0.000 description 1
239000011886 peripheral blood Substances 0.000 description 1
230000002572 peristaltic effect Effects 0.000 description 1
239000008063 pharmaceutical solvent Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
229950000688 phenothiazine Drugs 0.000 description 1
YXCDJKQYFBEAOU-UHFFFAOYSA-N phenyl thiocyanate Chemical compound N#CSC1=CC=CC=C1 YXCDJKQYFBEAOU-UHFFFAOYSA-N 0.000 description 1
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
OAHKWDDSKCRNFE-UHFFFAOYSA-N phenylmethanesulfonyl chloride Chemical compound ClS(=O)(=O)CC1=CC=CC=C1 OAHKWDDSKCRNFE-UHFFFAOYSA-N 0.000 description 1
125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
239000004033 plastic Substances 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
239000013641 positive control Substances 0.000 description 1
239000012286 potassium permanganate Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002265 prevention Effects 0.000 description 1
150000003141 primary amines Chemical group 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
238000012545 processing Methods 0.000 description 1
230000000750 progressive effect Effects 0.000 description 1
JPWDURLJLRNJAT-NSHDSACASA-N propan-2-yl (2s)-2-amino-3-phenylpropanoate Chemical compound CC(C)OC(=O)[C@@H](N)CC1=CC=CC=C1 JPWDURLJLRNJAT-NSHDSACASA-N 0.000 description 1
DRINJBFRTLBHNF-UHFFFAOYSA-N propane-2-sulfonyl chloride Chemical compound CC(C)S(Cl)(=O)=O DRINJBFRTLBHNF-UHFFFAOYSA-N 0.000 description 1
150000003180 prostaglandins Chemical class 0.000 description 1
235000019833 protease Nutrition 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
238000003521 protein stability assay Methods 0.000 description 1
CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
230000000541 pulsatile effect Effects 0.000 description 1
239000008213 purified water Substances 0.000 description 1
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
PSAYJRPASWETSH-UHFFFAOYSA-N pyridine-2-carbonyl chloride Chemical compound ClC(=O)C1=CC=CC=N1 PSAYJRPASWETSH-UHFFFAOYSA-N 0.000 description 1
ATBIAJXSKNPHEI-UHFFFAOYSA-N pyridine-3-carbonyl chloride Chemical compound ClC(=O)C1=CC=CN=C1 ATBIAJXSKNPHEI-UHFFFAOYSA-N 0.000 description 1
CDRNYKLYADJTMN-UHFFFAOYSA-N pyridine-3-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CN=C1 CDRNYKLYADJTMN-UHFFFAOYSA-N 0.000 description 1
RVQZKNOMKUSGCI-UHFFFAOYSA-N pyridine-4-carbonyl chloride Chemical compound ClC(=O)C1=CC=NC=C1 RVQZKNOMKUSGCI-UHFFFAOYSA-N 0.000 description 1
CULAGHAXBSYDOC-UHFFFAOYSA-N pyrimidine-2-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=NC=CC=N1 CULAGHAXBSYDOC-UHFFFAOYSA-N 0.000 description 1
HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
238000011084 recovery Methods 0.000 description 1
235000003499 redwood Nutrition 0.000 description 1
210000002345 respiratory system Anatomy 0.000 description 1
230000004043 responsiveness Effects 0.000 description 1
238000012552 review Methods 0.000 description 1
230000000552 rheumatic effect Effects 0.000 description 1
JWHOQZUREKYPBY-UHFFFAOYSA-N rubonic acid Natural products CC1(C)CCC2(CCC3(C)C(=CCC4C5(C)CCC(=O)C(C)(C)C5CC(=O)C34C)C2C1)C(=O)O JWHOQZUREKYPBY-UHFFFAOYSA-N 0.000 description 1
238000003118 sandwich ELISA Methods 0.000 description 1
229940043230 sarcosine Drugs 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
239000012056 semi-solid material Substances 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
229960001153 serine Drugs 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
239000004208 shellac Substances 0.000 description 1
229940113147 shellac Drugs 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
235000013874 shellac Nutrition 0.000 description 1
210000000329 smooth muscle myocyte Anatomy 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
235000009518 sodium iodide Nutrition 0.000 description 1
239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
XBMGRDWEYMVTOS-UHFFFAOYSA-M sodium;2-iodobenzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1I XBMGRDWEYMVTOS-UHFFFAOYSA-M 0.000 description 1
JBJWASZNUJCEKT-UHFFFAOYSA-M sodium;hydroxide;hydrate Chemical compound O.[OH-].[Na+] JBJWASZNUJCEKT-UHFFFAOYSA-M 0.000 description 1
239000011343 solid material Substances 0.000 description 1
239000012265 solid product Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
235000010356 sorbitol Nutrition 0.000 description 1
241000894007 species Species 0.000 description 1
230000009870 specific binding Effects 0.000 description 1
210000000278 spinal cord Anatomy 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
238000004659 sterilization and disinfection Methods 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
229960005322 streptomycin Drugs 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
229940014800 succinic anhydride Drugs 0.000 description 1
229960002317 succinimide Drugs 0.000 description 1
229960004793 sucrose Drugs 0.000 description 1
QAHVHSLSRLSVGS-UHFFFAOYSA-N sulfamoyl chloride Chemical compound NS(Cl)(=O)=O QAHVHSLSRLSVGS-UHFFFAOYSA-N 0.000 description 1
229940124530 sulfonamide Drugs 0.000 description 1
150000003456 sulfonamides Chemical class 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
150000003871 sulfonates Chemical class 0.000 description 1
NBNBICNWNFQDDD-UHFFFAOYSA-N sulfuryl dibromide Chemical compound BrS(Br)(=O)=O NBNBICNWNFQDDD-UHFFFAOYSA-N 0.000 description 1
OBTWBSRJZRCYQV-UHFFFAOYSA-N sulfuryl difluoride Chemical compound FS(F)(=O)=O OBTWBSRJZRCYQV-UHFFFAOYSA-N 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
230000005062 synaptic transmission Effects 0.000 description 1
210000002437 synoviocyte Anatomy 0.000 description 1
238000001308 synthesis method Methods 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
239000007916 tablet composition Substances 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
210000004876 tela submucosa Anatomy 0.000 description 1
CQGINQHLCKTOMH-VXKWHMMOSA-N tert-butyl (2S)-2-[[(2S)-1-oxo-3-phenyl-1-phenylmethoxypropan-2-yl]carbamoyl]pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)OCc1ccccc1 CQGINQHLCKTOMH-VXKWHMMOSA-N 0.000 description 1
QOISWWBTZMFUEL-NSHDSACASA-N tert-butyl (2s)-2-amino-3-phenylpropanoate Chemical compound CC(C)(C)OC(=O)[C@@H](N)CC1=CC=CC=C1 QOISWWBTZMFUEL-NSHDSACASA-N 0.000 description 1
XJJBXZIKXFOMLP-ZETCQYMHSA-N tert-butyl (2s)-pyrrolidine-2-carboxylate Chemical compound CC(C)(C)OC(=O)[C@@H]1CCCN1 XJJBXZIKXFOMLP-ZETCQYMHSA-N 0.000 description 1
BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
NPDBDJFLKKQMCM-UHFFFAOYSA-N tert-butylglycine Chemical compound CC(C)(C)C(N)C(O)=O NPDBDJFLKKQMCM-UHFFFAOYSA-N 0.000 description 1
125000001302 tertiary amino group Chemical group 0.000 description 1
125000005207 tetraalkylammonium group Chemical group 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
238000011287 therapeutic dose Methods 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
150000003568 thioethers Chemical class 0.000 description 1
BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
125000004568 thiomorpholinyl group Chemical group 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
150000003585 thioureas Chemical class 0.000 description 1
239000011031 topaz Substances 0.000 description 1
229910052853 topaz Inorganic materials 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
238000002691 topical anesthesia Methods 0.000 description 1
125000005490 tosylate group Chemical group 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
230000037317 transdermal delivery Effects 0.000 description 1
238000012546 transfer Methods 0.000 description 1
238000011269 treatment regimen Methods 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
UFXIRMVZNARBDL-UHFFFAOYSA-N trifluoro(morpholin-4-yl)-$l^{4}-sulfane Chemical compound FS(F)(F)N1CCOCC1 UFXIRMVZNARBDL-UHFFFAOYSA-N 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
210000003606 umbilical vein Anatomy 0.000 description 1
150000003672 ureas Chemical class 0.000 description 1
230000002792 vascular Effects 0.000 description 1
210000003556 vascular endothelial cell Anatomy 0.000 description 1
210000005166 vasculature Anatomy 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
201000002498 viral encephalitis Diseases 0.000 description 1
201000010044 viral meningitis Diseases 0.000 description 1
238000005303 weighing Methods 0.000 description 1
230000004580 weight loss Effects 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
210000000707 wrist Anatomy 0.000 description 1
239000008096 xylene Substances 0.000 description 1
229910052727 yttrium Inorganic materials 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
- C07K5/06165—Dipeptides with the first amino acid being heterocyclic and Pro-amino acid; Derivatives thereof
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Biophysics (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Molecular Biology (AREA)
Genetics & Genomics (AREA)
Biochemistry (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Pulmonology (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Hospice & Palliative Care (AREA)
Psychiatry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Thiazole And Isothizaole Compounds (AREA)
Pyrrole Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

JP2000505191A 1997-07-31 1998-07-31 Ｖｌａ−４が介在する白血球付着を阻害するベンジル化合物 Withdrawn JP2001512138A (ja)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US90358597A	1997-07-31	1997-07-31
US08/903,585		1997-07-31
PCT/US1998/015327 WO1999006436A1 (fr)	1997-07-31	1998-07-31	Composes de benzyle inhibant une adhesion de leucocytes regulee par vla-4

Publications (1)

Publication Number	Publication Date
JP2001512138A true JP2001512138A (ja)	2001-08-21

Family

ID=25417733

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP2000505191A Withdrawn JP2001512138A (ja)	1997-07-31	1998-07-31	Ｖｌａ−４が介在する白血球付着を阻害するベンジル化合物

Country Status (12)

Country	Link
EP (1)	EP1001975A1 (fr)
JP (1)	JP2001512138A (fr)
KR (1)	KR20010022413A (fr)
CN (1)	CN1265675A (fr)
AU (1)	AU8585198A (fr)
BR (1)	BR9811573A (fr)
CA (1)	CA2291473A1 (fr)
HU (1)	HUP0002680A3 (fr)
IL (1)	IL133635A0 (fr)
NO (1)	NO20000414L (fr)
PL (1)	PL338510A1 (fr)
WO (1)	WO1999006436A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP2002523493A (ja) *	1998-08-31	2002-07-30	アストラゼネカ・アクチエボラーグ	アリールピペラジン類および金属プロテイナーゼ阻害剤（ｍｍｐ）としてのそれらの用途
JP2005531524A (ja) *	2002-03-28	2005-10-20	アプライドリサーチシステムズエーアールエスホールディングナームロゼフェンノートシャップ	プロスタグランジンｆ受容体のモジュレーターとしてのチアゾリジンカルボキサミド誘導体
JP2008505077A (ja) *	2004-06-29	2008-02-21	アベンティス・ファーマスーティカルズ・インコーポレイテツド	Ｆｋｂｐ結合組成物及びその医薬上の使用

Families Citing this family (55)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6903075B1 (en)	1997-05-29	2005-06-07	Merck & Co., Inc.	Heterocyclic amide compounds as cell adhesion inhibitors
US6093696A (en) *	1997-05-30	2000-07-25	Celltech Therapeutics, Limited	Tyrosine derivatives
GB2365338B (en) *	1997-06-14	2002-04-03	Enzacta R & D Ltd	Therapeutic systems
WO1998058902A1 (fr)	1997-06-23	1998-12-30	Tanabe Seiyaku Co., Ltd.	INHIBITEURS D'ADHERENCE CELLULAIRE INDUITE PAR α4β¿1?
US6492421B1 (en)	1997-07-31	2002-12-10	Athena Neurosciences, Inc.	Substituted phenylalanine type compounds which inhibit leukocyte adhesion mediated by VLA-4
US6423688B1 (en)	1997-07-31	2002-07-23	Athena Neurosciences, Inc.	Dipeptide and related compounds which inhibit leukocyte adhesion mediated by VLA-4
US6583139B1 (en)	1997-07-31	2003-06-24	Eugene D. Thorsett	Compounds which inhibit leukocyte adhesion mediated by VLA-4
US6489300B1 (en)	1997-07-31	2002-12-03	Eugene D. Thorsett	Carbamyloxy compounds which inhibit leukocyte adhesion mediated by VLA-4
US6559127B1 (en)	1997-07-31	2003-05-06	Athena Neurosciences, Inc.	Compounds which inhibit leukocyte adhesion mediated by VLA-4
US6362341B1 (en)	1997-07-31	2002-03-26	Athena Neurosciences, Inc.	Benzyl compounds which inhibit leukocyte adhesion mediated by VLA-4
US7030114B1 (en)	1997-07-31	2006-04-18	Elan Pharmaceuticals, Inc.	Compounds which inhibit leukocyte adhesion mediated by VLA-4
US6939855B2 (en)	1997-07-31	2005-09-06	Elan Pharmaceuticals, Inc.	Anti-inflammatory compositions and method
US6197794B1 (en) *	1998-01-08	2001-03-06	Celltech Therapeutics Limited	Phenylalanine derivatives
MY153569A (en)	1998-01-20	2015-02-27	Mitsubishi Tanabe Pharma Corp	Inhibitors of ?4 mediated cell adhesion
US6329372B1 (en)	1998-01-27	2001-12-11	Celltech Therapeutics Limited	Phenylalanine derivatives
JP2002504534A (ja)	1998-02-26	2002-02-12	セルテック・セラピューティクス・リミテッド	α４インテグリンの阻害剤としてのフェニルアラニン誘導体
US6521626B1 (en)	1998-03-24	2003-02-18	Celltech R&D Limited	Thiocarboxamide derivatives
GB9811159D0 (en) *	1998-05-22	1998-07-22	Celltech Therapeutics Ltd	Chemical compounds
GB9811969D0 (en) *	1998-06-03	1998-07-29	Celltech Therapeutics Ltd	Chemical compounds
US6685617B1 (en)	1998-06-23	2004-02-03	Pharmacia & Upjohn Company	Inhibitors of α4β1 mediated cell adhesion
GB9814414D0 (en)	1998-07-03	1998-09-02	Celltech Therapeutics Ltd	Chemical compounds
US6333340B1 (en) *	1998-08-14	2001-12-25	Gpi Nil Holdings, Inc.	Small molecule sulfonamides for vision and memory disorders
US6339101B1 (en) *	1998-08-14	2002-01-15	Gpi Nil Holdings, Inc.	N-linked sulfonamides of N-heterocyclic carboxylic acids or isosteres for vision and memory disorders
GB9821061D0 (en)	1998-09-28	1998-11-18	Celltech Therapeutics Ltd	Chemical compounds
GB9821222D0 (en)	1998-09-30	1998-11-25	Celltech Therapeutics Ltd	Chemical compounds
GB9825652D0 (en)	1998-11-23	1999-01-13	Celltech Therapeutics Ltd	Chemical compounds
GB9826174D0 (en)	1998-11-30	1999-01-20	Celltech Therapeutics Ltd	Chemical compounds
US6407066B1 (en)	1999-01-26	2002-06-18	Elan Pharmaceuticals, Inc.	Pyroglutamic acid derivatives and related compounds which inhibit leukocyte adhesion mediated by VLA-4
US6518283B1 (en)	1999-05-28	2003-02-11	Celltech R&D Limited	Squaric acid derivatives
US6534513B1 (en)	1999-09-29	2003-03-18	Celltech R&D Limited	Phenylalkanoic acid derivatives
ATE447969T1 (de) *	1999-12-16	2009-11-15	Biogen Idec Inc	Verfahren zur behandlung der schädigung des zentralnervensystems durch ischämie oder durch hämorrhagie mit antagonisten von alpha4 integrin
US6455539B2 (en)	1999-12-23	2002-09-24	Celltech R&D Limited	Squaric acid derivates
AU2018301A (en)	1999-12-28	2001-07-24	Pfizer Products Inc.	Non-peptidyl inhibitors of vla-4 dependent cell binding useful in treating inflammatory, autoimmune, and respiratory diseases
ATE375330T1 (de)	2000-04-17	2007-10-15	Ucb Pharma Sa	Enamin-derivate als zell-adhäsionsmoleküle
US6545013B2 (en)	2000-05-30	2003-04-08	Celltech R&D Limited	2,7-naphthyridine derivatives
US6403608B1 (en)	2000-05-30	2002-06-11	Celltech R&D, Ltd.	3-Substituted isoquinolin-1-yl derivatives
US6960597B2 (en) *	2000-06-30	2005-11-01	Orth-Mcneil Pharmaceutical, Inc.	Aza-bridged-bicyclic amino acid derivatives as α4 integrin antagonists
JP2004502762A (ja)	2000-07-07	2004-01-29	セルテック　アール　アンド　ディ　リミテッド	二環性ヘテロ芳香環を含有するインテグリンアンタゴニストとしてのスクエア酸誘導体
WO2002010136A1 (fr)	2000-08-02	2002-02-07	Celltech R & D Limited	Derives d'isoquinoline-1-yl substitues en 3
MY129000A (en)	2000-08-31	2007-03-30	Tanabe Seiyaku Co	INHIBITORS OF a4 MEDIATED CELL ADHESION
JP2005022976A (ja) *	2001-07-18	2005-01-27	Ajinomoto Co Inc	カルボン酸誘導体
MY140707A (en)	2002-02-28	2010-01-15	Mitsubishi Tanabe Pharma Corp	Process for preparing a phenylalanine derivative and intermediates thereof
KR101260497B1 (ko) *	2003-01-24	2013-09-12	엘란 파마슈티칼스, 인크.	수초재생제의 투여에 의한 탈수초성 질환 및 마비의 치료 및 조성물
CA2561858A1 (fr) *	2004-04-20	2005-12-15	Amgen Inc.	Arylsulfonamides et leurs utilisations
CA2714335A1 (fr)	2007-02-20	2008-08-28	Merrimack Pharmaceuticals, Inc.	Methodes de traitement de la sclerose en plaques par administration d'une alpha-foetoproteine combinee a un antagoniste de l'integrine
NZ589086A (en)	2008-04-11	2012-09-28	Merrimack Pharmaceuticals Inc	Human serum albumin (HSA) linkers and conjugates thereof
EP4032912B1 (fr)	2010-04-16	2025-05-28	Biogen MA Inc.	Anticorps anti-vla-4
CN102675244B (zh) *	2011-03-16	2016-03-30	中国人民解放军军事医学科学院毒物药物研究所	噻嗪酰胺衍生物及其在制备神经退行性疾病防治药物的用途
KR20170052526A (ko)	2014-03-13	2017-05-12	프로테나 바이오사이언시즈 리미티드	다발성 경화증에 대한 병용 치료
CN112867394B9 (zh)	2018-06-04	2024-12-06	马萨诸塞州渤健公司	具有降低的效应功能的抗vla-4抗体
CN112969504B (zh)	2018-10-30	2024-04-09	吉利德科学公司	用于抑制α4β7整合素的化合物
WO2020092375A1 (fr)	2018-10-30	2020-05-07	Gilead Sciences, Inc.	Dérivés de quinoléine utilisés en tant qu'inhibiteurs de l'intégrine alpha4bêta7
PL3873900T3 (pl)	2018-10-30	2025-06-02	Gilead Sciences, Inc.	Imidazo[1,2-a]pirydynowe pochodne jako inhibitory integryny alpha4beta7 do leczenia chorób zapalnych
WO2020092383A1 (fr)	2018-10-30	2020-05-07	Gilead Sciences, Inc.	Composés pour l'inhibition de l'intégrine alpha 4 bêta 7
CA3148613A1 (fr)	2019-08-14	2021-02-18	Gilead Sciences, Inc.	Composes derives de la phenylalanine et utilisation comme inhibiteurs del'integrine alpha-4 beta-7

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPH04154732A (ja) *	1990-10-18	1992-05-27	Nippon Kayaku Co Ltd	光学分割法
WO1995015973A1 (fr) *	1993-12-06	1995-06-15	Cytel Corporation	Peptidomimetiques cs-1, compositions et procedes pour les utiliser
US6306840B1 (en) *	1995-01-23	2001-10-23	Biogen, Inc.	Cell adhesion inhibitors

1998
- 1998-07-31 EP EP98937054A patent/EP1001975A1/fr not_active Withdrawn
- 1998-07-31 CN CN98807764A patent/CN1265675A/zh active Pending
- 1998-07-31 PL PL98338510A patent/PL338510A1/xx unknown
- 1998-07-31 HU HU0002680A patent/HUP0002680A3/hu unknown
- 1998-07-31 AU AU85851/98A patent/AU8585198A/en not_active Abandoned
- 1998-07-31 WO PCT/US1998/015327 patent/WO1999006436A1/fr not_active Application Discontinuation
- 1998-07-31 IL IL13363598A patent/IL133635A0/xx unknown
- 1998-07-31 BR BR9811573-1A patent/BR9811573A/pt not_active Application Discontinuation
- 1998-07-31 JP JP2000505191A patent/JP2001512138A/ja not_active Withdrawn
- 1998-07-31 CA CA002291473A patent/CA2291473A1/fr not_active Abandoned
- 1998-07-31 KR KR1020007000993A patent/KR20010022413A/ko not_active Withdrawn
2000
- 2000-01-27 NO NO20000414A patent/NO20000414L/no not_active Application Discontinuation

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP2002523493A (ja) *	1998-08-31	2002-07-30	アストラゼネカ・アクチエボラーグ	アリールピペラジン類および金属プロテイナーゼ阻害剤（ｍｍｐ）としてのそれらの用途
JP4776778B2 (ja) *	1998-08-31	2011-09-21	アストラゼネカ・アクチエボラーグ	アリールピペラジン類および金属プロテイナーゼ阻害剤（ｍｍｐ）としてのそれらの用途
JP2005531524A (ja) *	2002-03-28	2005-10-20	アプライドリサーチシステムズエーアールエスホールディングナームロゼフェンノートシャップ	プロスタグランジンｆ受容体のモジュレーターとしてのチアゾリジンカルボキサミド誘導体
JP2008505077A (ja) *	2004-06-29	2008-02-21	アベンティス・ファーマスーティカルズ・インコーポレイテツド	Ｆｋｂｐ結合組成物及びその医薬上の使用
JP4812758B2 (ja) *	2004-06-29	2011-11-09	アベンティス・ファーマスーティカルズ・インコーポレイテツド	Ｆｋｂｐ結合組成物及びその医薬上の使用

Also Published As

Publication number	Publication date
NO20000414L (no)	2000-03-28
HUP0002680A3 (en)	2001-12-28
KR20010022413A (ko)	2001-03-15
HUP0002680A2 (hu)	2001-07-30
WO1999006436A1 (fr)	1999-02-11
CA2291473A1 (fr)	1999-02-11
AU8585198A (en)	1999-02-22
CN1265675A (zh)	2000-09-06
BR9811573A (pt)	2000-09-19
NO20000414D0 (no)	2000-01-27
EP1001975A1 (fr)	2000-05-24
PL338510A1 (en)	2000-11-06
IL133635A0 (en)	2001-04-30

Publication	Publication Date	Title
JP2001512138A (ja)	2001-08-21	Ｖｌａ−４が介在する白血球付着を阻害するベンジル化合物
EP1001974B1 (fr)	2006-05-24	Composes de type 4-amino-phenylalanine inhibant une adhesion de leucocytes regulee par vla-4
JP2001512139A (ja)	2001-08-21	Ｖｌａ−４が介在する白血球接着を阻害するスルホニル化ジペプチド化合物
JP2001512135A (ja)	2001-08-21	Ｖｌａ−４によって媒介された白血球接着を阻害するジペプチドおよび関連化合物
JP2001512136A (ja)	2001-08-21	Ｖｌａ−４により仲介される白血球接着を抑制する化合物
JP2001512134A (ja)	2001-08-21	Ｖｌａ−４仲介性白血球付着を阻害する置換フェニルアラニン型化合物
US7320960B2 (en)	2008-01-22	Carbamyloxy compounds which inhibit leukocyte adhesion mediated by VLA-4
JP2001512114A (ja)	2001-08-21	Ｖｌａ−４に媒介される白血球接着を阻害するカルバミルオキシ化合物
KR20010022412A (ko)	2001-03-15	Ｖｌａ-4에 의해 매개되는 백혈구 유착을 억제하는디펩티드 화합물
US7288526B2 (en)	2007-10-30	Dipeptide and related compounds which inhibit leukocyte adhesion mediated by VLA-4
US6586602B2 (en)	2003-07-01	Benzyl compounds which inhibit leukocyte adhesion mediated by VLA-4
JP2002535341A (ja)	2002-10-22	Ｖｌａ−４により媒介される白血球接着を阻害するピログルタミン酸誘導体および関連化合物
US6291453B1 (en)	2001-09-18	4-amino-phenylalanine type compounds which inhibit leukocyte adhesion mediated by VLA-4
US7166580B2 (en)	2007-01-23	Compounds which inhibit leukocyte adhesion mediated by VLA-4
JP2002539080A (ja)	2002-11-19	Ｖｌａ−４によって媒介される白血球接着を阻害する化合物
US20040006093A1 (en)	2004-01-08	Compounds which inhibit leukocyte adhesion mediated by VLA-4
MXPA00000708A (en)	2001-11-21	Benzyl compounds which inhibit leukocyte adhesion mediated by vla-4
MXPA00000706A (en)	2001-11-21	Dipeptide and related compounds which inhibit leukocyte adhesion mediated by vla-4

Legal Events

Date	Code	Title	Description
2005-10-04	A300	Application deemed to be withdrawn because no request for examination was validly filed	Free format text: JAPANESE INTERMEDIATE CODE: A300 Effective date: 20051004

Date

Code

Title

Description

2005-10-04

A300

Application deemed to be withdrawn because no request for examination was validly filed

Free format text: JAPANESE INTERMEDIATE CODE: A300

Effective date: 20051004