JP2012512178A - リゾホスファチジン酸受容体のアンタゴニスト - Google Patents
リゾホスファチジン酸受容体のアンタゴニスト Download PDFInfo
- Publication number
- JP2012512178A JP2012512178A JP2011540973A JP2011540973A JP2012512178A JP 2012512178 A JP2012512178 A JP 2012512178A JP 2011540973 A JP2011540973 A JP 2011540973A JP 2011540973 A JP2011540973 A JP 2011540973A JP 2012512178 A JP2012512178 A JP 2012512178A
- Authority
- JP
- Japan
- Prior art keywords
- phenyl
- methyl
- compound
- biphenyl
- isoxazol
- Prior art date
- 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.)
- Pending
Links
- 229940123977 Lysophosphatidic acid receptor antagonist Drugs 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 305
- 238000000034 method Methods 0.000 claims abstract description 121
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 39
- 230000001404 mediated effect Effects 0.000 claims abstract description 26
- 230000001419 dependent effect Effects 0.000 claims abstract description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 108
- 241000124008 Mammalia Species 0.000 claims description 90
- 201000010099 disease Diseases 0.000 claims description 85
- -1 4 ′-{3-methyl-4- [1- (3-trifluoromethyl-phenyl) -ethoxycarbonylamino] -isoxazol-5-yl} -biphenyl-4-yl Chemical group 0.000 claims description 78
- 206010016654 Fibrosis Diseases 0.000 claims description 51
- 239000002253 acid Substances 0.000 claims description 47
- 230000004761 fibrosis Effects 0.000 claims description 47
- 229910052739 hydrogen Inorganic materials 0.000 claims description 43
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 34
- 229910052731 fluorine Inorganic materials 0.000 claims description 29
- 229910052801 chlorine Inorganic materials 0.000 claims description 28
- 239000000243 solution Substances 0.000 claims description 27
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 25
- 210000001519 tissue Anatomy 0.000 claims description 24
- 206010028980 Neoplasm Diseases 0.000 claims description 22
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 21
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 21
- 208000006673 asthma Diseases 0.000 claims description 19
- 210000000056 organ Anatomy 0.000 claims description 17
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 16
- 201000011510 cancer Diseases 0.000 claims description 15
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 208000027866 inflammatory disease Diseases 0.000 claims description 13
- 229910052794 bromium Inorganic materials 0.000 claims description 12
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 11
- 208000023504 respiratory system disease Diseases 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 10
- 208000002193 Pain Diseases 0.000 claims description 9
- 239000000499 gel Substances 0.000 claims description 9
- 229910052740 iodine Inorganic materials 0.000 claims description 9
- 201000002793 renal fibrosis Diseases 0.000 claims description 9
- 231100000241 scar Toxicity 0.000 claims description 9
- TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 claims description 8
- 206010027476 Metastases Diseases 0.000 claims description 8
- 229940125851 compound 27 Drugs 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 239000000725 suspension Substances 0.000 claims description 8
- YSGICPNQNJZMCE-UHFFFAOYSA-N 2-[4-[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound C=1C=CC=C(F)C=1C(C)OC(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(CC(O)=O)C=C1 YSGICPNQNJZMCE-UHFFFAOYSA-N 0.000 claims description 7
- 201000001320 Atherosclerosis Diseases 0.000 claims description 7
- 239000003889 eye drop Substances 0.000 claims description 7
- 230000009401 metastasis Effects 0.000 claims description 7
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 6
- NQCJTTBAAFMHFN-UHFFFAOYSA-N 2-[4-[4-[4-[1-(2-methoxyphenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound COC1=CC=CC=C1C(C)OC(=O)NC1=C(C=2C=CC(=CC=2)C=2C=CC(CC(O)=O)=CC=2)ON=C1C NQCJTTBAAFMHFN-UHFFFAOYSA-N 0.000 claims description 6
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 6
- 206010009944 Colon cancer Diseases 0.000 claims description 6
- 206010060862 Prostate cancer Diseases 0.000 claims description 6
- 239000007922 nasal spray Substances 0.000 claims description 6
- 208000004296 neuralgia Diseases 0.000 claims description 6
- 208000021722 neuropathic pain Diseases 0.000 claims description 6
- 208000017520 skin disease Diseases 0.000 claims description 6
- 239000003826 tablet Substances 0.000 claims description 6
- 210000001635 urinary tract Anatomy 0.000 claims description 6
- MRNRJQHRNSENIU-UHFFFAOYSA-N 2-[3-[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]-4-methoxyphenyl]acetic acid Chemical compound COC1=CC=C(CC(O)=O)C=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)OC(C)C=2C(=CC=CC=2)Cl)C=C1 MRNRJQHRNSENIU-UHFFFAOYSA-N 0.000 claims description 5
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 5
- 239000006185 dispersion Substances 0.000 claims description 5
- 208000017169 kidney disease Diseases 0.000 claims description 5
- 208000019423 liver disease Diseases 0.000 claims description 5
- 201000001441 melanoma Diseases 0.000 claims description 5
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 5
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
- 206010033128 Ovarian cancer Diseases 0.000 claims description 4
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 4
- 206010064930 age-related macular degeneration Diseases 0.000 claims description 4
- 239000002775 capsule Substances 0.000 claims description 4
- 206010008118 cerebral infarction Diseases 0.000 claims description 4
- 208000029742 colonic neoplasm Diseases 0.000 claims description 4
- 239000006210 lotion Substances 0.000 claims description 4
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 4
- 229940097496 nasal spray Drugs 0.000 claims description 4
- 239000002674 ointment Substances 0.000 claims description 4
- 201000002528 pancreatic cancer Diseases 0.000 claims description 4
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 4
- 230000001766 physiological effect Effects 0.000 claims description 4
- 239000000829 suppository Substances 0.000 claims description 4
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 3
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 claims description 3
- KLPSKQJHAFYOFX-UHFFFAOYSA-N 2-[4-[4-[3-methyl-4-[1-[2-(trifluoromethyl)phenyl]ethoxycarbonylamino]-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound C=1C=CC=C(C(F)(F)F)C=1C(C)OC(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(CC(O)=O)C=C1 KLPSKQJHAFYOFX-UHFFFAOYSA-N 0.000 claims description 3
- LNDDRUPAICPXIN-GOSISDBHSA-N 2-[4-[4-[3-methyl-4-[[(1r)-1-phenylethoxy]carbonylamino]-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound O([C@H](C)C=1C=CC=CC=1)C(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(CC(O)=O)C=C1 LNDDRUPAICPXIN-GOSISDBHSA-N 0.000 claims description 3
- RCPPMKCYGLGOSN-UHFFFAOYSA-N 2-[4-[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]propanoic acid Chemical compound C=1C=CC=C(Cl)C=1C(C)OC(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(C(C)C(O)=O)C=C1 RCPPMKCYGLGOSN-UHFFFAOYSA-N 0.000 claims description 3
- XTIJUKFPBVYTEE-UHFFFAOYSA-N 2-[4-[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]propanoic acid Chemical compound C=1C=CC=C(F)C=1C(C)OC(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(C(C)C(O)=O)C=C1 XTIJUKFPBVYTEE-UHFFFAOYSA-N 0.000 claims description 3
- WWQTWEWAPUCDDZ-QGZVFWFLSA-N 2-[4-[4-[4-[[(1r)-1-(2-chlorophenyl)ethoxy]carbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound O([C@H](C)C=1C(=CC=CC=1)Cl)C(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(CC(O)=O)C=C1 WWQTWEWAPUCDDZ-QGZVFWFLSA-N 0.000 claims description 3
- 208000031104 Arterial Occlusive disease Diseases 0.000 claims description 3
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 3
- 206010058019 Cancer Pain Diseases 0.000 claims description 3
- 206010008111 Cerebral haemorrhage Diseases 0.000 claims description 3
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 3
- 206010072877 Intestinal fibrosis Diseases 0.000 claims description 3
- 208000016222 Pancreatic disease Diseases 0.000 claims description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 3
- GGBQHSGLUNQRHB-GOSISDBHSA-N [(1r)-1-(2-fluorophenyl)ethyl] n-[5-[4-[4-(cyanomethyl)phenyl]phenyl]-3-methyl-1,2-oxazol-4-yl]carbamate Chemical compound O([C@H](C)C=1C(=CC=CC=1)F)C(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(CC#N)C=C1 GGBQHSGLUNQRHB-GOSISDBHSA-N 0.000 claims description 3
- 208000021328 arterial occlusion Diseases 0.000 claims description 3
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 3
- 206010013990 dysuria Diseases 0.000 claims description 3
- 230000002500 effect on skin Effects 0.000 claims description 3
- 239000000839 emulsion Substances 0.000 claims description 3
- 229940012356 eye drops Drugs 0.000 claims description 3
- 239000005414 inactive ingredient Substances 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 208000020658 intracerebral hemorrhage Diseases 0.000 claims description 3
- 238000010253 intravenous injection Methods 0.000 claims description 3
- 208000002780 macular degeneration Diseases 0.000 claims description 3
- 230000027939 micturition Effects 0.000 claims description 3
- 239000006187 pill Substances 0.000 claims description 3
- 238000010254 subcutaneous injection Methods 0.000 claims description 3
- 238000011200 topical administration Methods 0.000 claims description 3
- ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 claims description 2
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 claims description 2
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 claims description 2
- ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 claims description 2
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 claims description 2
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 claims description 2
- GCTFTMWXZFLTRR-GFCCVEGCSA-N (2r)-2-amino-n-[3-(difluoromethoxy)-4-(1,3-oxazol-5-yl)phenyl]-4-methylpentanamide Chemical compound FC(F)OC1=CC(NC(=O)[C@H](N)CC(C)C)=CC=C1C1=CN=CO1 GCTFTMWXZFLTRR-GFCCVEGCSA-N 0.000 claims description 2
- YJLIKUSWRSEPSM-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CNC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YJLIKUSWRSEPSM-WGQQHEPDSA-N 0.000 claims description 2
- VIJSPAIQWVPKQZ-BLECARSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O VIJSPAIQWVPKQZ-BLECARSGSA-N 0.000 claims description 2
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 claims description 2
- STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 claims description 2
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 claims description 2
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 claims description 2
- UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 claims description 2
- HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 claims description 2
- MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 claims description 2
- YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 claims description 2
- KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 claims description 2
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 claims description 2
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 claims description 2
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 claims description 2
- WGFNXGPBPIJYLI-UHFFFAOYSA-N 2,6-difluoro-3-[(3-fluorophenyl)sulfonylamino]-n-(3-methoxy-1h-pyrazolo[3,4-b]pyridin-5-yl)benzamide Chemical compound C1=C2C(OC)=NNC2=NC=C1NC(=O)C(C=1F)=C(F)C=CC=1NS(=O)(=O)C1=CC=CC(F)=C1 WGFNXGPBPIJYLI-UHFFFAOYSA-N 0.000 claims description 2
- FQMZXMVHHKXGTM-UHFFFAOYSA-N 2-(1-adamantyl)-n-[2-[2-(2-hydroxyethylamino)ethylamino]quinolin-5-yl]acetamide Chemical compound C1C(C2)CC(C3)CC2CC13CC(=O)NC1=CC=CC2=NC(NCCNCCO)=CC=C21 FQMZXMVHHKXGTM-UHFFFAOYSA-N 0.000 claims description 2
- VJIPJEKOMCBQJX-GOSISDBHSA-N 2-[2-[4-[3-methyl-4-[[(1r)-1-phenylethoxy]carbonylamino]-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound O([C@H](C)C=1C=CC=CC=1)C(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=CC=C1CC(O)=O VJIPJEKOMCBQJX-GOSISDBHSA-N 0.000 claims description 2
- CCZZUHHFLVHTAB-UHFFFAOYSA-N 2-[2-[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound C=1C=CC=C(Cl)C=1C(C)OC(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=CC=C1CC(O)=O CCZZUHHFLVHTAB-UHFFFAOYSA-N 0.000 claims description 2
- OQTMCMJPBNCWMD-GOSISDBHSA-N 2-[3-[4-[3-methyl-4-[[(1r)-1-phenylethoxy]carbonylamino]-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound O([C@H](C)C=1C=CC=CC=1)C(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=CC(CC(O)=O)=C1 OQTMCMJPBNCWMD-GOSISDBHSA-N 0.000 claims description 2
- RWWVUWLGZHIANO-UHFFFAOYSA-N 2-[3-[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]-4-fluorophenyl]acetic acid Chemical compound C=1C=CC=C(Cl)C=1C(C)OC(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC(CC(O)=O)=CC=C1F RWWVUWLGZHIANO-UHFFFAOYSA-N 0.000 claims description 2
- SLOKKKUYVRMXAE-UHFFFAOYSA-N 2-[3-[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound C=1C=CC=C(Cl)C=1C(C)OC(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=CC(CC(O)=O)=C1 SLOKKKUYVRMXAE-UHFFFAOYSA-N 0.000 claims description 2
- LNDDRUPAICPXIN-UHFFFAOYSA-N 2-[4-[4-[3-methyl-4-(1-phenylethoxycarbonylamino)-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound C=1C=CC=CC=1C(C)OC(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(CC(O)=O)C=C1 LNDDRUPAICPXIN-UHFFFAOYSA-N 0.000 claims description 2
- GMSKNBNTSXARRC-UHFFFAOYSA-N 2-[4-[4-[4-[1-(2,3-difluorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound C=1C=CC(F)=C(F)C=1C(C)OC(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(CC(O)=O)C=C1 GMSKNBNTSXARRC-UHFFFAOYSA-N 0.000 claims description 2
- NDFWFRRSDCFAHR-UHFFFAOYSA-N 2-[4-[4-[4-[1-(2,4-difluorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound C=1C=C(F)C=C(F)C=1C(C)OC(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(CC(O)=O)C=C1 NDFWFRRSDCFAHR-UHFFFAOYSA-N 0.000 claims description 2
- AHLAPONKKWWKAO-UHFFFAOYSA-N 2-[4-[4-[4-[1-(2,5-difluorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound C=1C(F)=CC=C(F)C=1C(C)OC(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(CC(O)=O)C=C1 AHLAPONKKWWKAO-UHFFFAOYSA-N 0.000 claims description 2
- NYJWRZWLXMLGLM-UHFFFAOYSA-N 2-[4-[4-[4-[1-(2,6-difluorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound FC=1C=CC=C(F)C=1C(C)OC(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(CC(O)=O)C=C1 NYJWRZWLXMLGLM-UHFFFAOYSA-N 0.000 claims description 2
- WWQTWEWAPUCDDZ-UHFFFAOYSA-N 2-[4-[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound C=1C=CC=C(Cl)C=1C(C)OC(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(CC(O)=O)C=C1 WWQTWEWAPUCDDZ-UHFFFAOYSA-N 0.000 claims description 2
- ABYFFZXGUWCMOB-UHFFFAOYSA-N 2-[4-[4-[4-[1-(2-fluoro-4-methoxyphenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound FC1=CC(OC)=CC=C1C(C)OC(=O)NC1=C(C=2C=CC(=CC=2)C=2C=CC(CC(O)=O)=CC=2)ON=C1C ABYFFZXGUWCMOB-UHFFFAOYSA-N 0.000 claims description 2
- SPQJWZXNOFZVCC-UHFFFAOYSA-N 2-[4-[4-[4-[1-(4-chloro-2-fluorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound C=1C=C(Cl)C=C(F)C=1C(C)OC(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(CC(O)=O)C=C1 SPQJWZXNOFZVCC-UHFFFAOYSA-N 0.000 claims description 2
- YSGICPNQNJZMCE-QGZVFWFLSA-N 2-[4-[4-[4-[[(1r)-1-(2-fluorophenyl)ethoxy]carbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound O([C@H](C)C=1C(=CC=CC=1)F)C(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(CC(O)=O)C=C1 YSGICPNQNJZMCE-QGZVFWFLSA-N 0.000 claims description 2
- MPNRGXMWDUQOOR-QGZVFWFLSA-N 2-[4-[4-[4-[[(1r)-1-(3-hydroxyphenyl)ethoxy]carbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound O([C@H](C)C=1C=C(O)C=CC=1)C(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(CC(O)=O)C=C1 MPNRGXMWDUQOOR-QGZVFWFLSA-N 0.000 claims description 2
- YSGICPNQNJZMCE-KRWDZBQOSA-N 2-[4-[4-[4-[[(1s)-1-(2-fluorophenyl)ethoxy]carbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound O([C@@H](C)C=1C(=CC=CC=1)F)C(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(CC(O)=O)C=C1 YSGICPNQNJZMCE-KRWDZBQOSA-N 0.000 claims description 2
- DSRYCYOMZPXIPT-UHFFFAOYSA-N 2-[5-[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]-2-fluorophenyl]acetic acid Chemical compound C=1C=CC=C(Cl)C=1C(C)OC(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(F)C(CC(O)=O)=C1 DSRYCYOMZPXIPT-UHFFFAOYSA-N 0.000 claims description 2
- PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 claims description 2
- FMKGJQHNYMWDFJ-CVEARBPZSA-N 2-[[4-(2,2-difluoropropoxy)pyrimidin-5-yl]methylamino]-4-[[(1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl]amino]pyrimidine-5-carbonitrile Chemical compound FC(COC1=NC=NC=C1CNC1=NC=C(C(=N1)N[C@H]1CC([C@H](CC1)O)(C)C)C#N)(C)F FMKGJQHNYMWDFJ-CVEARBPZSA-N 0.000 claims description 2
- VVCMGAUPZIKYTH-VGHSCWAPSA-N 2-acetyloxybenzoic acid;[(2s,3r)-4-(dimethylamino)-3-methyl-1,2-diphenylbutan-2-yl] propanoate;1,3,7-trimethylpurine-2,6-dione Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C.C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 VVCMGAUPZIKYTH-VGHSCWAPSA-N 0.000 claims description 2
- YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 claims description 2
- NPRYCHLHHVWLQZ-TURQNECASA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynylpurin-8-one Chemical compound NC1=NC=C2N(C(N(C2=N1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C NPRYCHLHHVWLQZ-TURQNECASA-N 0.000 claims description 2
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 claims description 2
- RRVIVMXEZHWCSV-UHFFFAOYSA-N 3-[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]benzoic acid Chemical compound C=1C=CC=C(Cl)C=1C(C)OC(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=CC(C(O)=O)=C1 RRVIVMXEZHWCSV-UHFFFAOYSA-N 0.000 claims description 2
- QJOGQGHFRBEIHS-QGZVFWFLSA-N 4-[4-[3-methyl-4-[[(1r)-1-phenylethoxy]carbonylamino]-1,2-oxazol-5-yl]phenyl]benzoic acid Chemical compound O([C@H](C)C=1C=CC=CC=1)C(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(C(O)=O)C=C1 QJOGQGHFRBEIHS-QGZVFWFLSA-N 0.000 claims description 2
- ZICAQNRRIMPMSM-MRXNPFEDSA-N 4-[4-[4-[[(1r)-1-(2-chlorophenyl)ethoxy]carbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]benzoic acid Chemical compound O([C@H](C)C=1C(=CC=CC=1)Cl)C(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(C(O)=O)C=C1 ZICAQNRRIMPMSM-MRXNPFEDSA-N 0.000 claims description 2
- XFJBGINZIMNZBW-CRAIPNDOSA-N 5-chloro-2-[4-[(1r,2s)-2-[2-(5-methylsulfonylpyridin-2-yl)oxyethyl]cyclopropyl]piperidin-1-yl]pyrimidine Chemical compound N1=CC(S(=O)(=O)C)=CC=C1OCC[C@H]1[C@@H](C2CCN(CC2)C=2N=CC(Cl)=CN=2)C1 XFJBGINZIMNZBW-CRAIPNDOSA-N 0.000 claims description 2
- RSIWALKZYXPAGW-NSHDSACASA-N 6-(3-fluorophenyl)-3-methyl-7-[(1s)-1-(7h-purin-6-ylamino)ethyl]-[1,3]thiazolo[3,2-a]pyrimidin-5-one Chemical compound C=1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)N=C2SC=C(C)N2C(=O)C=1C1=CC=CC(F)=C1 RSIWALKZYXPAGW-NSHDSACASA-N 0.000 claims description 2
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- JQUCWIWWWKZNCS-LESHARBVSA-N C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F Chemical compound C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F JQUCWIWWWKZNCS-LESHARBVSA-N 0.000 claims description 2
- 208000029147 Collagen-vascular disease Diseases 0.000 claims description 2
- 229940126657 Compound 17 Drugs 0.000 claims description 2
- 229940126639 Compound 33 Drugs 0.000 claims description 2
- 229940127007 Compound 39 Drugs 0.000 claims description 2
- 206010057254 Connective tissue inflammation Diseases 0.000 claims description 2
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 2
- 208000005016 Intestinal Neoplasms Diseases 0.000 claims description 2
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 2
- 208000034578 Multiple myelomas Diseases 0.000 claims description 2
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 claims description 2
- QOVYHDHLFPKQQG-NDEPHWFRSA-N N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O Chemical compound N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O QOVYHDHLFPKQQG-NDEPHWFRSA-N 0.000 claims description 2
- PNUZDKCDAWUEGK-CYZMBNFOSA-N Sitafloxacin Chemical compound C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1 PNUZDKCDAWUEGK-CYZMBNFOSA-N 0.000 claims description 2
- QUCHRHVJEVSKLH-GOSISDBHSA-N [(1r)-1-(2-chlorophenyl)ethyl] n-[5-[4-[4-(cyanomethyl)phenyl]phenyl]-3-methyl-1,2-oxazol-4-yl]carbamate Chemical compound O([C@H](C)C=1C(=CC=CC=1)Cl)C(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(CC#N)C=C1 QUCHRHVJEVSKLH-GOSISDBHSA-N 0.000 claims description 2
- LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 claims description 2
- SPXSEZMVRJLHQG-XMMPIXPASA-N [(2R)-1-[[4-[(3-phenylmethoxyphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound C(C1=CC=CC=C1)OC=1C=C(OCC2=CC=C(CN3[C@H](CCC3)CO)C=C2)C=CC=1 SPXSEZMVRJLHQG-XMMPIXPASA-N 0.000 claims description 2
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 claims description 2
- PSLUFJFHTBIXMW-WYEYVKMPSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-5-yl] acetate Chemical compound O([C@@H]1[C@@H]([C@]2(O[C@](C)(CC(=O)[C@]2(O)[C@@]2(C)[C@@H](O)CCC(C)(C)[C@@H]21)C=C)C)OC(=O)C)C(=O)NCCC1=CC=CC=N1 PSLUFJFHTBIXMW-WYEYVKMPSA-N 0.000 claims description 2
- OWJKUWFIJYFRPD-UHFFFAOYSA-N [5-[4-[4-(2-amino-2-iminoethyl)phenyl]phenyl]-3-methyl-1,2-oxazol-4-yl]carbamic acid Chemical compound C(N)(=N)CC1=CC=C(C=C1)C1=CC=C(C=C1)C1=C(C(=NO1)C)NC(=O)O OWJKUWFIJYFRPD-UHFFFAOYSA-N 0.000 claims description 2
- SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 claims description 2
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 claims description 2
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 2
- 239000000084 colloidal system Substances 0.000 claims description 2
- 229940125904 compound 1 Drugs 0.000 claims description 2
- 229940125773 compound 10 Drugs 0.000 claims description 2
- 229940125797 compound 12 Drugs 0.000 claims description 2
- 229940126543 compound 14 Drugs 0.000 claims description 2
- 229940125758 compound 15 Drugs 0.000 claims description 2
- 229940126142 compound 16 Drugs 0.000 claims description 2
- 229940125782 compound 2 Drugs 0.000 claims description 2
- 229940125810 compound 20 Drugs 0.000 claims description 2
- 229940126086 compound 21 Drugs 0.000 claims description 2
- 229940126208 compound 22 Drugs 0.000 claims description 2
- 229940125833 compound 23 Drugs 0.000 claims description 2
- 229940125961 compound 24 Drugs 0.000 claims description 2
- 229940125846 compound 25 Drugs 0.000 claims description 2
- 229940127204 compound 29 Drugs 0.000 claims description 2
- 229940126214 compound 3 Drugs 0.000 claims description 2
- 229940125877 compound 31 Drugs 0.000 claims description 2
- 229940125878 compound 36 Drugs 0.000 claims description 2
- 229940127573 compound 38 Drugs 0.000 claims description 2
- 229940126540 compound 41 Drugs 0.000 claims description 2
- 229940125936 compound 42 Drugs 0.000 claims description 2
- 229940125844 compound 46 Drugs 0.000 claims description 2
- 229940127271 compound 49 Drugs 0.000 claims description 2
- 229940125898 compound 5 Drugs 0.000 claims description 2
- 229940126545 compound 53 Drugs 0.000 claims description 2
- 229940127113 compound 57 Drugs 0.000 claims description 2
- 229940125900 compound 59 Drugs 0.000 claims description 2
- 239000003221 ear drop Substances 0.000 claims description 2
- 208000005017 glioblastoma Diseases 0.000 claims description 2
- 201000010536 head and neck cancer Diseases 0.000 claims description 2
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 2
- 201000002313 intestinal cancer Diseases 0.000 claims description 2
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 claims description 2
- JFGWVKRJIWZNOB-UHFFFAOYSA-N methyl 2-[4-[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)OC(C)C=2C(=CC=CC=2)Cl)C=C1 JFGWVKRJIWZNOB-UHFFFAOYSA-N 0.000 claims description 2
- PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 claims description 2
- 239000007929 subcutaneous injection Substances 0.000 claims description 2
- RZKKQGLZOWGTEY-MRXNPFEDSA-N 2-[4-[4-[4-[[(1r)-1-(2-chlorophenyl)ethoxy]carbonylamino]-3-methyl-1,2-oxazol-5-yl]-2-fluorophenyl]phenyl]acetic acid Chemical compound O([C@H](C)C=1C(=CC=CC=1)Cl)C(=O)NC=1C(C)=NOC=1C(C=C1F)=CC=C1C1=CC=C(CC(O)=O)C=C1 RZKKQGLZOWGTEY-MRXNPFEDSA-N 0.000 claims 2
- DZVNFQGQVPLZCF-MRXNPFEDSA-N 2-[4-[4-[4-[[(1r)-1-(3,5-dibromophenyl)ethoxy]carbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound O([C@H](C)C=1C=C(Br)C=C(Br)C=1)C(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(CC(O)=O)C=C1 DZVNFQGQVPLZCF-MRXNPFEDSA-N 0.000 claims 2
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 claims 1
- OMBVEVHRIQULKW-DNQXCXABSA-M (3r,5r)-7-[3-(4-fluorophenyl)-8-oxo-7-phenyl-1-propan-2-yl-5,6-dihydro-4h-pyrrolo[2,3-c]azepin-2-yl]-3,5-dihydroxyheptanoate Chemical compound O=C1C=2N(C(C)C)C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C(C=3C=CC(F)=CC=3)C=2CCCN1C1=CC=CC=C1 OMBVEVHRIQULKW-DNQXCXABSA-M 0.000 claims 1
- MHSLDASSAFCCDO-UHFFFAOYSA-N 1-(5-tert-butyl-2-methylpyrazol-3-yl)-3-(4-pyridin-4-yloxyphenyl)urea Chemical compound CN1N=C(C(C)(C)C)C=C1NC(=O)NC(C=C1)=CC=C1OC1=CC=NC=C1 MHSLDASSAFCCDO-UHFFFAOYSA-N 0.000 claims 1
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims 1
- DWLVNJWJKNCVGP-MRXNPFEDSA-N 2-[4-[2-chloro-4-[4-[[(1r)-1-(2-chlorophenyl)ethoxy]carbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound O([C@H](C)C=1C(=CC=CC=1)Cl)C(=O)NC=1C(C)=NOC=1C(C=C1Cl)=CC=C1C1=CC=C(CC(O)=O)C=C1 DWLVNJWJKNCVGP-MRXNPFEDSA-N 0.000 claims 1
- GTKGGMLCSHIPEO-UHFFFAOYSA-N 2-[4-[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]-2-methylpropanoic acid Chemical compound C=1C=CC=C(Cl)C=1C(C)OC(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(C(C)(C)C(O)=O)C=C1 GTKGGMLCSHIPEO-UHFFFAOYSA-N 0.000 claims 1
- YNJLAYBFJAQQQI-FKSKYRLFSA-N 2-[4-[4-[4-[[(1r)-1-(2-chlorophenyl)ethoxy]carbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]butanoic acid Chemical compound C1=CC(C(C(O)=O)CC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)O[C@H](C)C=2C(=CC=CC=2)Cl)C=C1 YNJLAYBFJAQQQI-FKSKYRLFSA-N 0.000 claims 1
- UFYLPKMRCFGLPJ-WHCXFUJUSA-N 2-[4-[4-[4-[[(1r)-1-(2-fluorophenyl)ethoxy]carbonylamino]-3-methyl-1,2-oxazol-5-yl]-2-methylphenyl]phenyl]propanoic acid Chemical compound O([C@H](C)C=1C(=CC=CC=1)F)C(=O)NC=1C(C)=NOC=1C(C=C1C)=CC=C1C1=CC=C(C(C)C(O)=O)C=C1 UFYLPKMRCFGLPJ-WHCXFUJUSA-N 0.000 claims 1
- XTIJUKFPBVYTEE-UHUGOGIASA-N 2-[4-[4-[4-[[(1r)-1-(2-fluorophenyl)ethoxy]carbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]propanoic acid Chemical compound O([C@H](C)C=1C(=CC=CC=1)F)C(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(C(C)C(O)=O)C=C1 XTIJUKFPBVYTEE-UHUGOGIASA-N 0.000 claims 1
- WWQTWEWAPUCDDZ-KRWDZBQOSA-N 2-[4-[4-[4-[[(1s)-1-(2-chlorophenyl)ethoxy]carbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound O([C@@H](C)C=1C(=CC=CC=1)Cl)C(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(CC(O)=O)C=C1 WWQTWEWAPUCDDZ-KRWDZBQOSA-N 0.000 claims 1
- 208000009304 Acute Kidney Injury Diseases 0.000 claims 1
- 206010005949 Bone cancer Diseases 0.000 claims 1
- 208000018084 Bone neoplasm Diseases 0.000 claims 1
- 206010048768 Dermatosis Diseases 0.000 claims 1
- 208000033626 Renal failure acute Diseases 0.000 claims 1
- RAOVRZSRZREJIF-GOSISDBHSA-N [(1r)-1-(2-fluorophenyl)ethyl] n-[5-[4-[4-(2-acetylimino-2-aminoethyl)phenyl]phenyl]-3-methyl-1,2-oxazol-4-yl]carbamate Chemical compound O([C@H](C)C=1C(=CC=CC=1)F)C(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(CC(=N)NC(C)=O)C=C1 RAOVRZSRZREJIF-GOSISDBHSA-N 0.000 claims 1
- 201000011040 acute kidney failure Diseases 0.000 claims 1
- KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 claims 1
- 208000020832 chronic kidney disease Diseases 0.000 claims 1
- 208000010643 digestive system disease Diseases 0.000 claims 1
- 125000006627 ethoxycarbonylamino group Chemical group 0.000 claims 1
- 208000018685 gastrointestinal system disease Diseases 0.000 claims 1
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 claims 1
- IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 claims 1
- FDBYIYFVSAHJLY-UHFFFAOYSA-N resmetirom Chemical compound N1C(=O)C(C(C)C)=CC(OC=2C(=CC(=CC=2Cl)N2C(NC(=O)C(C#N)=N2)=O)Cl)=N1 FDBYIYFVSAHJLY-UHFFFAOYSA-N 0.000 claims 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 abstract description 244
- 239000003814 drug Substances 0.000 abstract description 52
- 229940079593 drug Drugs 0.000 abstract description 35
- 239000005557 antagonist Substances 0.000 abstract description 26
- 208000037765 diseases and disorders Diseases 0.000 abstract 1
- XGRLSUFHELJJAB-JGSYTFBMSA-M sodium;[(2r)-2-hydroxy-3-[(z)-octadec-9-enoyl]oxypropyl] hydrogen phosphate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)COP(O)([O-])=O XGRLSUFHELJJAB-JGSYTFBMSA-M 0.000 description 242
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 106
- 239000000203 mixture Substances 0.000 description 93
- 238000003786 synthesis reaction Methods 0.000 description 74
- 230000015572 biosynthetic process Effects 0.000 description 73
- 238000006243 chemical reaction Methods 0.000 description 54
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 52
- 235000019439 ethyl acetate Nutrition 0.000 description 51
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 50
- 210000004027 cell Anatomy 0.000 description 43
- 238000011282 treatment Methods 0.000 description 43
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 42
- 108090000642 Lysophosphatidic Acid Receptors Proteins 0.000 description 42
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- 102000004137 Lysophosphatidic Acid Receptors Human genes 0.000 description 41
- 239000012044 organic layer Substances 0.000 description 34
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 26
- 208000035475 disorder Diseases 0.000 description 22
- 230000000694 effects Effects 0.000 description 22
- 102000005962 receptors Human genes 0.000 description 22
- 108020003175 receptors Proteins 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 241000699670 Mus sp. Species 0.000 description 20
- 125000000217 alkyl group Chemical group 0.000 description 20
- 230000002829 reductive effect Effects 0.000 description 20
- 101000889990 Homo sapiens Apolipoprotein(a) Proteins 0.000 description 19
- 102000045903 human LPA Human genes 0.000 description 19
- 238000010898 silica gel chromatography Methods 0.000 description 19
- RPRBNRDIESZHFL-UHFFFAOYSA-N ethyl 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]acetate Chemical compound C1=CC(CC(=O)OCC)=CC=C1B1OC(C)(C)C(C)(C)O1 RPRBNRDIESZHFL-UHFFFAOYSA-N 0.000 description 18
- 238000009472 formulation Methods 0.000 description 16
- 229940044551 receptor antagonist Drugs 0.000 description 16
- 239000002464 receptor antagonist Substances 0.000 description 16
- 208000024891 symptom Diseases 0.000 description 16
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 15
- 208000036971 interstitial lung disease 2 Diseases 0.000 description 15
- 210000004072 lung Anatomy 0.000 description 15
- 238000002953 preparative HPLC Methods 0.000 description 15
- GFLKZFOUAHOGJF-UHFFFAOYSA-N 5-(4-bromophenyl)-3-methyl-1,2-oxazole-4-carboxylic acid Chemical compound CC1=NOC(C=2C=CC(Br)=CC=2)=C1C(O)=O GFLKZFOUAHOGJF-UHFFFAOYSA-N 0.000 description 13
- 230000002265 prevention Effects 0.000 description 13
- 102000008186 Collagen Human genes 0.000 description 12
- 108010035532 Collagen Proteins 0.000 description 12
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].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 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 12
- 239000012267 brine Substances 0.000 description 12
- 229920001436 collagen Polymers 0.000 description 12
- 125000004494 ethyl ester group Chemical group 0.000 description 12
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
- 206010039710 Scleroderma Diseases 0.000 description 11
- YEEKSTJASNXFCZ-UHFFFAOYSA-N [5-(4-bromophenyl)-3-methyl-1,2-oxazol-4-yl]carbamic acid Chemical compound CC1=NOC(C=2C=CC(Br)=CC=2)=C1NC(O)=O YEEKSTJASNXFCZ-UHFFFAOYSA-N 0.000 description 11
- 239000002299 complementary DNA Substances 0.000 description 11
- 239000010410 layer Substances 0.000 description 11
- 230000035755 proliferation Effects 0.000 description 11
- 229940124597 therapeutic agent Drugs 0.000 description 11
- FEEFNXSBDHQZNO-UHFFFAOYSA-N 5-[4-[4-(2-ethoxy-2-oxoethyl)phenyl]phenyl]-3-methyl-1,2-oxazole-4-carboxylic acid Chemical compound C1=CC(CC(=O)OCC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)C(O)=O)C=C1 FEEFNXSBDHQZNO-UHFFFAOYSA-N 0.000 description 10
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 10
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 238000003556 assay Methods 0.000 description 10
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 10
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 9
- 239000011575 calcium Substances 0.000 description 9
- 239000013058 crude material Substances 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- 230000014509 gene expression Effects 0.000 description 9
- 230000001965 increasing effect Effects 0.000 description 9
- 210000003734 kidney Anatomy 0.000 description 9
- 230000008569 process Effects 0.000 description 9
- 230000004044 response Effects 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 238000010626 work up procedure Methods 0.000 description 9
- 230000029663 wound healing Effects 0.000 description 9
- 102000015225 Connective Tissue Growth Factor Human genes 0.000 description 8
- 108010039419 Connective Tissue Growth Factor Proteins 0.000 description 8
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 8
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 230000008859 change Effects 0.000 description 8
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 8
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 description 8
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 description 8
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 8
- 229940002612 prodrug Drugs 0.000 description 8
- 239000000651 prodrug Substances 0.000 description 8
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
- FMUYWQAVFBVVLU-UHFFFAOYSA-N 1-(2-chlorophenyl)ethyl n-[3-methyl-5-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1,2-oxazol-4-yl]carbamate Chemical compound C=1C=CC=C(Cl)C=1C(C)OC(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1B1OC(C)(C)C(C)(C)O1 FMUYWQAVFBVVLU-UHFFFAOYSA-N 0.000 description 7
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 206010061218 Inflammation Diseases 0.000 description 7
- 208000029523 Interstitial Lung disease Diseases 0.000 description 7
- 239000000556 agonist Substances 0.000 description 7
- 208000026935 allergic disease Diseases 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 230000001684 chronic effect Effects 0.000 description 7
- 230000004054 inflammatory process Effects 0.000 description 7
- 239000003112 inhibitor Substances 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 230000005012 migration Effects 0.000 description 7
- 238000013508 migration Methods 0.000 description 7
- 208000010125 myocardial infarction Diseases 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- 238000001356 surgical procedure Methods 0.000 description 7
- 230000002792 vascular Effects 0.000 description 7
- IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- VMKAFJQFKBASMU-UHFFFAOYSA-N 1-methyl-3,3-diphenyl-3a,4,5,6-tetrahydropyrrolo[1,2-c][1,3,2]oxazaborole Chemical compound C12CCCN2B(C)OC1(C=1C=CC=CC=1)C1=CC=CC=C1 VMKAFJQFKBASMU-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 108010006654 Bleomycin Proteins 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 206010020751 Hypersensitivity Diseases 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 241000283973 Oryctolagus cuniculus Species 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 230000002378 acidificating effect Effects 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 230000033115 angiogenesis Effects 0.000 description 6
- 230000009460 calcium influx Effects 0.000 description 6
- 229940125807 compound 37 Drugs 0.000 description 6
- JMQGGPRJQOQKRT-UHFFFAOYSA-N diphenyl hydrogen phosphate;azide Chemical compound [N-]=[N+]=[N-].C=1C=CC=CC=1OP(=O)(O)OC1=CC=CC=C1 JMQGGPRJQOQKRT-UHFFFAOYSA-N 0.000 description 6
- 210000002950 fibroblast Anatomy 0.000 description 6
- 239000012530 fluid Substances 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 235000019260 propionic acid Nutrition 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 239000012453 solvate Substances 0.000 description 6
- 239000003981 vehicle Substances 0.000 description 6
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 201000004681 Psoriasis Diseases 0.000 description 5
- 208000006011 Stroke Diseases 0.000 description 5
- 208000004608 Ureteral Obstruction Diseases 0.000 description 5
- ZUWQMMFXMFXJEY-GFCCVEGCSA-N [(1r)-1-(2-chlorophenyl)ethyl] n-[5-(4-bromophenyl)-3-methyl-1,2-oxazol-4-yl]carbamate Chemical compound O([C@H](C)C=1C(=CC=CC=1)Cl)C(=O)NC=1C(C)=NOC=1C1=CC=C(Br)C=C1 ZUWQMMFXMFXJEY-GFCCVEGCSA-N 0.000 description 5
- 230000002159 abnormal effect Effects 0.000 description 5
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 5
- 239000012346 acetyl chloride Substances 0.000 description 5
- 230000009471 action Effects 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 229960001561 bleomycin Drugs 0.000 description 5
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 229940098773 bovine serum albumin Drugs 0.000 description 5
- 229910052791 calcium Inorganic materials 0.000 description 5
- 230000007882 cirrhosis Effects 0.000 description 5
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 5
- 239000003246 corticosteroid Substances 0.000 description 5
- 229960001340 histamine Drugs 0.000 description 5
- 230000002757 inflammatory effect Effects 0.000 description 5
- 208000014674 injury Diseases 0.000 description 5
- 229960002725 isoflurane Drugs 0.000 description 5
- 210000004185 liver Anatomy 0.000 description 5
- 210000005228 liver tissue Anatomy 0.000 description 5
- 230000014759 maintenance of location Effects 0.000 description 5
- QAKYFFYZPIPLDN-UHFFFAOYSA-N methyl 3-(methylamino)but-2-enoate Chemical compound CNC(C)=CC(=O)OC QAKYFFYZPIPLDN-UHFFFAOYSA-N 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 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 5
- 230000008506 pathogenesis Effects 0.000 description 5
- 230000002062 proliferating effect Effects 0.000 description 5
- 208000002815 pulmonary hypertension Diseases 0.000 description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 208000011580 syndromic disease Diseases 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- DDUBOVLGCYUYFX-LURJTMIESA-N (1s)-1-(2-chlorophenyl)ethanol Chemical compound C[C@H](O)C1=CC=CC=C1Cl DDUBOVLGCYUYFX-LURJTMIESA-N 0.000 description 4
- ZDOYHCIRUPHUHN-UHFFFAOYSA-N 1-(2-chlorophenyl)ethanone Chemical compound CC(=O)C1=CC=CC=C1Cl ZDOYHCIRUPHUHN-UHFFFAOYSA-N 0.000 description 4
- QMATYTFXDIWACW-UHFFFAOYSA-N 1-(2-fluorophenyl)ethanone Chemical compound CC(=O)C1=CC=CC=C1F QMATYTFXDIWACW-UHFFFAOYSA-N 0.000 description 4
- XVEFRABIRRNWFO-UHFFFAOYSA-N 2-(4-bromophenyl)butanoic acid Chemical compound CCC(C(O)=O)C1=CC=C(Br)C=C1 XVEFRABIRRNWFO-UHFFFAOYSA-N 0.000 description 4
- 206010003445 Ascites Diseases 0.000 description 4
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 208000032544 Cicatrix Diseases 0.000 description 4
- 201000004624 Dermatitis Diseases 0.000 description 4
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 4
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 4
- 206010020772 Hypertension Diseases 0.000 description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 4
- 208000002260 Keloid Diseases 0.000 description 4
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 4
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 4
- 239000012097 Lipofectamine 2000 Substances 0.000 description 4
- 244000062730 Melissa officinalis Species 0.000 description 4
- 235000010654 Melissa officinalis Nutrition 0.000 description 4
- 102000019256 Metalloproteinase inhibitor 1 Human genes 0.000 description 4
- 108050006599 Metalloproteinase inhibitor 1 Proteins 0.000 description 4
- 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 4
- 206010035664 Pneumonia Diseases 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 206010047115 Vasculitis Diseases 0.000 description 4
- 208000027418 Wounds and injury Diseases 0.000 description 4
- YIZLYJGOEIDGMD-CYBMUJFWSA-N [(1r)-1-phenylethyl] n-[5-(4-bromophenyl)-3-methyl-1,2-oxazol-4-yl]carbamate Chemical compound O([C@H](C)C=1C=CC=CC=1)C(=O)NC=1C(C)=NOC=1C1=CC=C(Br)C=C1 YIZLYJGOEIDGMD-CYBMUJFWSA-N 0.000 description 4
- 230000035508 accumulation Effects 0.000 description 4
- 238000009825 accumulation Methods 0.000 description 4
- 150000001242 acetic acid derivatives Chemical class 0.000 description 4
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 4
- 108010022198 alkylglycerophosphoethanolamine phosphodiesterase Proteins 0.000 description 4
- 239000002246 antineoplastic agent Substances 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 208000010668 atopic eczema Diseases 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 210000000170 cell membrane Anatomy 0.000 description 4
- 230000004663 cell proliferation Effects 0.000 description 4
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 4
- 208000023819 chronic asthma Diseases 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 206010012601 diabetes mellitus Diseases 0.000 description 4
- 230000004069 differentiation Effects 0.000 description 4
- 210000002919 epithelial cell Anatomy 0.000 description 4
- XTSCLIBGCPXCLH-UHFFFAOYSA-N ethyl 2-(4-bromophenyl)-2-methylpropanoate Chemical compound CCOC(=O)C(C)(C)C1=CC=C(Br)C=C1 XTSCLIBGCPXCLH-UHFFFAOYSA-N 0.000 description 4
- WHNBIRCJWQMENU-UHFFFAOYSA-N ethyl 2-(4-bromophenyl)propanoate Chemical compound CCOC(=O)C(C)C1=CC=C(Br)C=C1 WHNBIRCJWQMENU-UHFFFAOYSA-N 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 150000002367 halogens Chemical class 0.000 description 4
- 210000002216 heart Anatomy 0.000 description 4
- 208000006454 hepatitis Diseases 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 230000009610 hypersensitivity Effects 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 4
- 210000001117 keloid Anatomy 0.000 description 4
- 239000000865 liniment Substances 0.000 description 4
- 238000004949 mass spectrometry Methods 0.000 description 4
- 230000002503 metabolic effect Effects 0.000 description 4
- 239000002207 metabolite Substances 0.000 description 4
- 238000000386 microscopy Methods 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 4
- 235000011056 potassium acetate Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 230000037387 scars Effects 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 210000003491 skin Anatomy 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 208000037816 tissue injury Diseases 0.000 description 4
- 238000002054 transplantation Methods 0.000 description 4
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 4
- 239000013598 vector Substances 0.000 description 4
- DDUBOVLGCYUYFX-ZCFIWIBFSA-N (1r)-1-(2-chlorophenyl)ethanol Chemical compound C[C@@H](O)C1=CC=CC=C1Cl DDUBOVLGCYUYFX-ZCFIWIBFSA-N 0.000 description 3
- SXFYVXSOEBCFLV-ZCFIWIBFSA-N (1r)-1-(2-fluorophenyl)ethanol Chemical compound C[C@@H](O)C1=CC=CC=C1F SXFYVXSOEBCFLV-ZCFIWIBFSA-N 0.000 description 3
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 3
- VMKAFJQFKBASMU-QGZVFWFLSA-N (r)-2-methyl-cbs-oxazaborolidine Chemical compound C([C@@H]12)CCN1B(C)OC2(C=1C=CC=CC=1)C1=CC=CC=C1 VMKAFJQFKBASMU-QGZVFWFLSA-N 0.000 description 3
- BYCQTFBZUUATPR-UHFFFAOYSA-N 2-[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]benzoic acid Chemical compound C=1C=CC=C(Cl)C=1C(C)OC(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=CC=C1C(O)=O BYCQTFBZUUATPR-UHFFFAOYSA-N 0.000 description 3
- 102100027324 2-hydroxyacyl-CoA lyase 1 Human genes 0.000 description 3
- ZICAQNRRIMPMSM-UHFFFAOYSA-N 4-[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]benzoic acid Chemical compound C=1C=CC=C(Cl)C=1C(C)OC(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(C(O)=O)C=C1 ZICAQNRRIMPMSM-UHFFFAOYSA-N 0.000 description 3
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 3
- 206010002329 Aneurysm Diseases 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 208000005623 Carcinogenesis Diseases 0.000 description 3
- 208000028006 Corneal injury Diseases 0.000 description 3
- 201000003883 Cystic fibrosis Diseases 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- 102100021977 Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 Human genes 0.000 description 3
- 108050004000 Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 Proteins 0.000 description 3
- 102000016359 Fibronectins Human genes 0.000 description 3
- 108010067306 Fibronectins Proteins 0.000 description 3
- 206010018364 Glomerulonephritis Diseases 0.000 description 3
- 101001009252 Homo sapiens 2-hydroxyacyl-CoA lyase 1 Proteins 0.000 description 3
- 108091006905 Human Serum Albumin Proteins 0.000 description 3
- 102000008100 Human Serum Albumin Human genes 0.000 description 3
- 102000004890 Interleukin-8 Human genes 0.000 description 3
- 108090001007 Interleukin-8 Proteins 0.000 description 3
- 206010023330 Keloid scar Diseases 0.000 description 3
- 206010023421 Kidney fibrosis Diseases 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 102000004318 Matrilysin Human genes 0.000 description 3
- 108090000855 Matrilysin Proteins 0.000 description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 208000032056 Radiation Fibrosis Syndrome Diseases 0.000 description 3
- 102000046299 Transforming Growth Factor beta1 Human genes 0.000 description 3
- 101800002279 Transforming growth factor beta-1 Proteins 0.000 description 3
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 3
- 206010047139 Vasoconstriction Diseases 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 208000037883 airway inflammation Diseases 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 229940121363 anti-inflammatory agent Drugs 0.000 description 3
- 239000002260 anti-inflammatory agent Substances 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 230000003305 autocrine Effects 0.000 description 3
- 235000019445 benzyl alcohol Nutrition 0.000 description 3
- 230000027455 binding Effects 0.000 description 3
- 239000000090 biomarker Substances 0.000 description 3
- 230000036772 blood pressure Effects 0.000 description 3
- 210000000988 bone and bone Anatomy 0.000 description 3
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 3
- 230000036952 cancer formation Effects 0.000 description 3
- 231100000504 carcinogenesis Toxicity 0.000 description 3
- 230000035605 chemotaxis Effects 0.000 description 3
- 230000008602 contraction Effects 0.000 description 3
- 229960001334 corticosteroids Drugs 0.000 description 3
- 238000000326 densiometry Methods 0.000 description 3
- 230000008021 deposition Effects 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- CAERSDJFKGMKLY-UHFFFAOYSA-N ethyl 2-(3-bromophenyl)acetate Chemical compound CCOC(=O)CC1=CC=CC(Br)=C1 CAERSDJFKGMKLY-UHFFFAOYSA-N 0.000 description 3
- VYSXNHNLBWPXCZ-UHFFFAOYSA-N ethyl 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propanoate Chemical compound C1=CC(C(C)C(=O)OCC)=CC=C1B1OC(C)(C)C(C)(C)O1 VYSXNHNLBWPXCZ-UHFFFAOYSA-N 0.000 description 3
- 239000013613 expression plasmid Substances 0.000 description 3
- 230000003176 fibrotic effect Effects 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 125000004404 heteroalkyl group Chemical group 0.000 description 3
- 229920002674 hyaluronan Polymers 0.000 description 3
- 229960003160 hyaluronic acid Drugs 0.000 description 3
- 230000001969 hypertrophic effect Effects 0.000 description 3
- 208000026278 immune system disease Diseases 0.000 description 3
- 239000003018 immunosuppressive agent Substances 0.000 description 3
- 230000000977 initiatory effect Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 230000009545 invasion Effects 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 239000007937 lozenge Substances 0.000 description 3
- 206010025135 lupus erythematosus Diseases 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
- 239000008108 microcrystalline cellulose Substances 0.000 description 3
- 201000006417 multiple sclerosis Diseases 0.000 description 3
- 208000031225 myocardial ischemia Diseases 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 210000000440 neutrophil Anatomy 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 125000003729 nucleotide group Chemical group 0.000 description 3
- 201000008482 osteoarthritis Diseases 0.000 description 3
- 229940068196 placebo Drugs 0.000 description 3
- 239000000902 placebo Substances 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 230000002206 pro-fibrotic effect Effects 0.000 description 3
- 238000001959 radiotherapy Methods 0.000 description 3
- 208000037803 restenosis Diseases 0.000 description 3
- 206010039083 rhinitis Diseases 0.000 description 3
- 201000000306 sarcoidosis Diseases 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 238000012163 sequencing technique Methods 0.000 description 3
- 230000003595 spectral effect Effects 0.000 description 3
- 208000020431 spinal cord injury Diseases 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 238000000954 titration curve Methods 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 229940099456 transforming growth factor beta 1 Drugs 0.000 description 3
- 210000000626 ureter Anatomy 0.000 description 3
- 230000025033 vasoconstriction Effects 0.000 description 3
- XOFLBQFBSOEHOG-UUOKFMHZSA-N γS-GTP Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=S)[C@@H](O)[C@H]1O XOFLBQFBSOEHOG-UUOKFMHZSA-N 0.000 description 3
- SDCBYRLJYGORNK-MRVPVSSYSA-N (1r)-1-(2-methylphenyl)ethanol Chemical compound C[C@@H](O)C1=CC=CC=C1C SDCBYRLJYGORNK-MRVPVSSYSA-N 0.000 description 2
- SXFYVXSOEBCFLV-LURJTMIESA-N (1s)-1-(2-fluorophenyl)ethanol Chemical compound C[C@H](O)C1=CC=CC=C1F SXFYVXSOEBCFLV-LURJTMIESA-N 0.000 description 2
- QDLRJDVXXZDDEO-UHFFFAOYSA-N (2-chlorophenyl)methyl n-[5-(4-bromophenyl)-3-methyl-1,2-oxazol-4-yl]carbamate Chemical compound CC1=NOC(C=2C=CC(Br)=CC=2)=C1NC(=O)OCC1=CC=CC=C1Cl QDLRJDVXXZDDEO-UHFFFAOYSA-N 0.000 description 2
- WAPNOHKVXSQRPX-SSDOTTSWSA-N (R)-1-phenylethanol Chemical compound C[C@@H](O)C1=CC=CC=C1 WAPNOHKVXSQRPX-SSDOTTSWSA-N 0.000 description 2
- WAPNOHKVXSQRPX-ZETCQYMHSA-N (S)-1-phenylethanol Chemical compound C[C@H](O)C1=CC=CC=C1 WAPNOHKVXSQRPX-ZETCQYMHSA-N 0.000 description 2
- IWMIWBJLOWDKSQ-UHFFFAOYSA-N 1-(2,3-difluorophenyl)ethanol Chemical compound CC(O)C1=CC=CC(F)=C1F IWMIWBJLOWDKSQ-UHFFFAOYSA-N 0.000 description 2
- RCPAVJXGLFKACE-UHFFFAOYSA-N 1-(2,5-difluorophenyl)ethanol Chemical compound CC(O)C1=CC(F)=CC=C1F RCPAVJXGLFKACE-UHFFFAOYSA-N 0.000 description 2
- SIYWDKQSSDBLOA-UHFFFAOYSA-N 1-(2,6-difluorophenyl)ethanol Chemical compound CC(O)C1=C(F)C=CC=C1F SIYWDKQSSDBLOA-UHFFFAOYSA-N 0.000 description 2
- ZUWQMMFXMFXJEY-UHFFFAOYSA-N 1-(2-chlorophenyl)ethyl n-[5-(4-bromophenyl)-3-methyl-1,2-oxazol-4-yl]carbamate Chemical compound C=1C=CC=C(Cl)C=1C(C)OC(=O)NC=1C(C)=NOC=1C1=CC=C(Br)C=C1 ZUWQMMFXMFXJEY-UHFFFAOYSA-N 0.000 description 2
- SPUCRPMJCHQPRC-UHFFFAOYSA-N 1-(2-fluoro-4-methoxyphenyl)ethanol Chemical compound COC1=CC=C(C(C)O)C(F)=C1 SPUCRPMJCHQPRC-UHFFFAOYSA-N 0.000 description 2
- SXFYVXSOEBCFLV-UHFFFAOYSA-N 1-(2-fluorophenyl)ethanol Chemical compound CC(O)C1=CC=CC=C1F SXFYVXSOEBCFLV-UHFFFAOYSA-N 0.000 description 2
- QYJFVVYIZSTDLE-UHFFFAOYSA-N 1-(2-fluorophenyl)ethyl n-[5-(4-bromophenyl)-3-methyl-1,2-oxazol-4-yl]carbamate Chemical compound C=1C=CC=C(F)C=1C(C)OC(=O)NC=1C(C)=NOC=1C1=CC=C(Br)C=C1 QYJFVVYIZSTDLE-UHFFFAOYSA-N 0.000 description 2
- NHFJDRRYVMJBRJ-UHFFFAOYSA-N 1-(3,5-dibromophenyl)ethanone Chemical compound CC(=O)C1=CC(Br)=CC(Br)=C1 NHFJDRRYVMJBRJ-UHFFFAOYSA-N 0.000 description 2
- YIZLYJGOEIDGMD-UHFFFAOYSA-N 1-phenylethyl n-[5-(4-bromophenyl)-3-methyl-1,2-oxazol-4-yl]carbamate Chemical compound C=1C=CC=CC=1C(C)OC(=O)NC=1C(C)=NOC=1C1=CC=C(Br)C=C1 YIZLYJGOEIDGMD-UHFFFAOYSA-N 0.000 description 2
- ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- ZDFUJDNAQQZONI-UHFFFAOYSA-N 2-[4-[4-[4-[1-(3-bromophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound C=1C=CC(Br)=CC=1C(C)OC(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(CC(O)=O)C=C1 ZDFUJDNAQQZONI-UHFFFAOYSA-N 0.000 description 2
- VQTGHHCIBJNHKB-GOSISDBHSA-N 2-[4-[4-[4-[[(1r)-1-(2-fluorophenyl)ethoxy]carbonylamino]-3-methyl-1,2-oxazol-5-yl]-2-methylphenyl]phenyl]acetic acid Chemical compound O([C@H](C)C=1C(=CC=CC=1)F)C(=O)NC=1C(C)=NOC=1C(C=C1C)=CC=C1C1=CC=C(CC(O)=O)C=C1 VQTGHHCIBJNHKB-GOSISDBHSA-N 0.000 description 2
- COJRWHSKVYUZHQ-ZCFIWIBFSA-N 3-[(1r)-1-hydroxyethyl]phenol Chemical compound C[C@@H](O)C1=CC=CC(O)=C1 COJRWHSKVYUZHQ-ZCFIWIBFSA-N 0.000 description 2
- LUJMEECXHPYQOF-UHFFFAOYSA-N 3-hydroxyacetophenone Chemical compound CC(=O)C1=CC=CC(O)=C1 LUJMEECXHPYQOF-UHFFFAOYSA-N 0.000 description 2
- LZPWAYBEOJRFAX-UHFFFAOYSA-N 4,4,5,5-tetramethyl-1,3,2$l^{2}-dioxaborolane Chemical compound CC1(C)O[B]OC1(C)C LZPWAYBEOJRFAX-UHFFFAOYSA-N 0.000 description 2
- QKNNWDFHKRIYJH-UHFFFAOYSA-N 4-bromo-3-fluorobenzoyl chloride Chemical compound FC1=CC(C(Cl)=O)=CC=C1Br QKNNWDFHKRIYJH-UHFFFAOYSA-N 0.000 description 2
- YUVOENUKSWSTCJ-UHFFFAOYSA-N 5-(4-bromo-2-chlorophenyl)-3-methyl-1,2-oxazole-4-carboxylic acid Chemical compound CC1=NOC(C=2C(=CC(Br)=CC=2)Cl)=C1C(O)=O YUVOENUKSWSTCJ-UHFFFAOYSA-N 0.000 description 2
- BNCPBXVCSXNHJV-UHFFFAOYSA-N 5-(4-bromo-3-chlorophenyl)-3-methyl-1,2-oxazole-4-carboxylic acid Chemical compound CC1=NOC(C=2C=C(Cl)C(Br)=CC=2)=C1C(O)=O BNCPBXVCSXNHJV-UHFFFAOYSA-N 0.000 description 2
- XRKUDBZQTXNKHU-UHFFFAOYSA-N 5-(4-bromo-3-fluorophenyl)-3-methyl-1,2-oxazole-4-carboxylic acid Chemical compound CC1=NOC(C=2C=C(F)C(Br)=CC=2)=C1C(O)=O XRKUDBZQTXNKHU-UHFFFAOYSA-N 0.000 description 2
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
- 102000007469 Actins Human genes 0.000 description 2
- 108010085238 Actins Proteins 0.000 description 2
- 206010001881 Alveolar proteinosis Diseases 0.000 description 2
- 206010003210 Arteriosclerosis Diseases 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 206010003827 Autoimmune hepatitis Diseases 0.000 description 2
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 2
- 208000033222 Biliary cirrhosis primary Diseases 0.000 description 2
- 206010048962 Brain oedema Diseases 0.000 description 2
- 206010006458 Bronchitis chronic Diseases 0.000 description 2
- MWMRJMQGVMFVIA-FRKPEAEDSA-N COC(=O)C(\C(C)=N\C)C(=O)C1=CC=C(Br)C(Cl)=C1 Chemical compound COC(=O)C(\C(C)=N\C)C(=O)C1=CC=C(Br)C(Cl)=C1 MWMRJMQGVMFVIA-FRKPEAEDSA-N 0.000 description 2
- ZOXNGIJTRONSLA-FRKPEAEDSA-N COC(=O)C(\C(C)=N\C)C(=O)C1=CC=C(Br)C(F)=C1 Chemical compound COC(=O)C(\C(C)=N\C)C(=O)C1=CC=C(Br)C(F)=C1 ZOXNGIJTRONSLA-FRKPEAEDSA-N 0.000 description 2
- FITFMNBUKUTOMT-FRKPEAEDSA-N COC(=O)C(\C(C)=N\C)C(=O)C1=CC=C(Br)C=C1Cl Chemical compound COC(=O)C(\C(C)=N\C)C(=O)C1=CC=C(Br)C=C1Cl FITFMNBUKUTOMT-FRKPEAEDSA-N 0.000 description 2
- 229940122444 Chemokine receptor antagonist Drugs 0.000 description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
- 206010010744 Conjunctivitis allergic Diseases 0.000 description 2
- 241000699802 Cricetulus griseus Species 0.000 description 2
- 206010012438 Dermatitis atopic Diseases 0.000 description 2
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 2
- 206010052804 Drug tolerance Diseases 0.000 description 2
- 208000003556 Dry Eye Syndromes Diseases 0.000 description 2
- 206010013774 Dry eye Diseases 0.000 description 2
- 208000001708 Dupuytren contracture Diseases 0.000 description 2
- 206010014561 Emphysema Diseases 0.000 description 2
- 206010014824 Endotoxic shock Diseases 0.000 description 2
- 241000792859 Enema Species 0.000 description 2
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 206010018691 Granuloma Diseases 0.000 description 2
- 239000012981 Hank's balanced salt solution Substances 0.000 description 2
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 2
- 241000711549 Hepacivirus C Species 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 208000010159 IgA glomerulonephritis Diseases 0.000 description 2
- 206010021263 IgA nephropathy Diseases 0.000 description 2
- 208000005615 Interstitial Cystitis Diseases 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
- 201000005099 Langerhans cell histiocytosis Diseases 0.000 description 2
- 208000004852 Lung Injury Diseases 0.000 description 2
- 208000019693 Lung disease Diseases 0.000 description 2
- 206010049459 Lymphangioleiomyomatosis Diseases 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 102100039364 Metalloproteinase inhibitor 1 Human genes 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 208000019695 Migraine disease Diseases 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 208000012902 Nervous system disease Diseases 0.000 description 2
- 208000009905 Neurofibromatoses Diseases 0.000 description 2
- 208000004362 Penile Induration Diseases 0.000 description 2
- 208000020758 Peyronie disease Diseases 0.000 description 2
- 108010064785 Phospholipases Proteins 0.000 description 2
- 102000015439 Phospholipases Human genes 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 206010035600 Pleural fibrosis Diseases 0.000 description 2
- 208000012654 Primary biliary cholangitis Diseases 0.000 description 2
- 208000002158 Proliferative Vitreoretinopathy Diseases 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 206010063837 Reperfusion injury Diseases 0.000 description 2
- 206010038934 Retinopathy proliferative Diseases 0.000 description 2
- 241001303601 Rosacea Species 0.000 description 2
- 206010040070 Septic Shock Diseases 0.000 description 2
- 201000010001 Silicosis Diseases 0.000 description 2
- 208000021386 Sjogren Syndrome Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 208000024770 Thyroid neoplasm Diseases 0.000 description 2
- 108010031374 Tissue Inhibitor of Metalloproteinase-1 Proteins 0.000 description 2
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 2
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 2
- 206010069363 Traumatic lung injury Diseases 0.000 description 2
- 208000026911 Tuberous sclerosis complex Diseases 0.000 description 2
- 208000024780 Urticaria Diseases 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- HQYUGWWMMJJEDM-CYBMUJFWSA-N [(1r)-1-(2-fluorophenyl)ethyl] n-[5-(4-bromo-3-methylphenyl)-3-methyl-1,2-oxazol-4-yl]carbamate Chemical compound O([C@H](C)C=1C(=CC=CC=1)F)C(=O)NC=1C(C)=NOC=1C1=CC=C(Br)C(C)=C1 HQYUGWWMMJJEDM-CYBMUJFWSA-N 0.000 description 2
- JXKLVGFACUFVAI-CQSZACIVSA-N [(1r)-1-(2-methylphenyl)ethyl] n-[5-(4-bromophenyl)-3-methyl-1,2-oxazol-4-yl]carbamate Chemical compound O([C@H](C)C=1C(=CC=CC=1)C)C(=O)NC=1C(C)=NOC=1C1=CC=C(Br)C=C1 JXKLVGFACUFVAI-CQSZACIVSA-N 0.000 description 2
- SWLDVUHLONLEAE-GFCCVEGCSA-N [(1r)-1-(3-hydroxyphenyl)ethyl] n-[5-(4-bromophenyl)-3-methyl-1,2-oxazol-4-yl]carbamate Chemical compound O([C@H](C)C=1C=C(O)C=CC=1)C(=O)NC=1C(C)=NOC=1C1=CC=C(Br)C=C1 SWLDVUHLONLEAE-GFCCVEGCSA-N 0.000 description 2
- YIZLYJGOEIDGMD-ZDUSSCGKSA-N [(1s)-1-phenylethyl] n-[5-(4-bromophenyl)-3-methyl-1,2-oxazol-4-yl]carbamate Chemical compound O([C@@H](C)C=1C=CC=CC=1)C(=O)NC=1C(C)=NOC=1C1=CC=C(Br)C=C1 YIZLYJGOEIDGMD-ZDUSSCGKSA-N 0.000 description 2
- WMUGHFIZEDMJAE-UHFFFAOYSA-N [3-methyl-5-[4-[4-(2h-tetrazol-5-ylmethyl)phenyl]phenyl]-1,2-oxazol-4-yl]carbamic acid Chemical compound CC1=NOC(C=2C=CC(=CC=2)C=2C=CC(CC3=NNN=N3)=CC=2)=C1NC(O)=O WMUGHFIZEDMJAE-UHFFFAOYSA-N 0.000 description 2
- MMZPSFSDYNJFLH-UHFFFAOYSA-N [5-[4-[4-(cyanomethyl)phenyl]phenyl]-3-methyl-1,2-oxazol-4-yl]carbamic acid Chemical compound CC1=NOC(C=2C=CC(=CC=2)C=2C=CC(CC#N)=CC=2)=C1NC(O)=O MMZPSFSDYNJFLH-UHFFFAOYSA-N 0.000 description 2
- 108010016133 acylglycerol kinase Proteins 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 208000002205 allergic conjunctivitis Diseases 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- 150000001413 amino acids Chemical group 0.000 description 2
- 239000002870 angiogenesis inducing agent Substances 0.000 description 2
- 230000000954 anitussive effect Effects 0.000 description 2
- 229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 description 2
- 229940125715 antihistaminic agent Drugs 0.000 description 2
- 239000000739 antihistaminic agent Substances 0.000 description 2
- 239000003434 antitussive agent Substances 0.000 description 2
- 229940124584 antitussives Drugs 0.000 description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 239000010425 asbestos Substances 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- 208000024998 atopic conjunctivitis Diseases 0.000 description 2
- 201000008937 atopic dermatitis Diseases 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 229940124748 beta 2 agonist Drugs 0.000 description 2
- 210000000941 bile Anatomy 0.000 description 2
- 210000000013 bile duct Anatomy 0.000 description 2
- 230000031018 biological processes and functions Effects 0.000 description 2
- 230000008512 biological response Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 208000006752 brain edema Diseases 0.000 description 2
- 206010006451 bronchitis Diseases 0.000 description 2
- 229940124630 bronchodilator Drugs 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 238000012754 cardiac puncture Methods 0.000 description 2
- 230000003915 cell function Effects 0.000 description 2
- 230000012292 cell migration Effects 0.000 description 2
- 239000002559 chemokine receptor antagonist Substances 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 125000000068 chlorophenyl group Chemical group 0.000 description 2
- 239000000812 cholinergic antagonist Substances 0.000 description 2
- 208000007451 chronic bronchitis Diseases 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000002285 corn oil Substances 0.000 description 2
- 235000005687 corn oil Nutrition 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- JCWIWBWXCVGEAN-UHFFFAOYSA-L cyclopentyl(diphenyl)phosphane;dichloropalladium;iron Chemical compound [Fe].Cl[Pd]Cl.[CH]1[CH][CH][CH][C]1P(C=1C=CC=CC=1)C1=CC=CC=C1.[CH]1[CH][CH][CH][C]1P(C=1C=CC=CC=1)C1=CC=CC=C1 JCWIWBWXCVGEAN-UHFFFAOYSA-L 0.000 description 2
- 201000003146 cystitis Diseases 0.000 description 2
- 230000016396 cytokine production Effects 0.000 description 2
- 239000000850 decongestant Substances 0.000 description 2
- 229940124581 decongestants Drugs 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 229910052805 deuterium Inorganic materials 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 239000007920 enema Substances 0.000 description 2
- 229940079360 enema for constipation Drugs 0.000 description 2
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 2
- 210000003979 eosinophil Anatomy 0.000 description 2
- KIWNXKVMDNGRLS-UHFFFAOYSA-N ethyl 2-(3-bromo-4-fluorophenyl)acetate Chemical compound CCOC(=O)CC1=CC=C(F)C(Br)=C1 KIWNXKVMDNGRLS-UHFFFAOYSA-N 0.000 description 2
- SATBRTRSKUDGEQ-UHFFFAOYSA-N ethyl 2-(5-bromo-2-fluorophenyl)acetate Chemical compound CCOC(=O)CC1=CC(Br)=CC=C1F SATBRTRSKUDGEQ-UHFFFAOYSA-N 0.000 description 2
- PHUIZDKLQWKHGE-UHFFFAOYSA-N ethyl 2-[4-[4-[3-methyl-4-[1-[2-(trifluoromethyl)phenyl]ethoxycarbonylamino]-1,2-oxazol-5-yl]phenyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OCC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)OC(C)C=2C(=CC=CC=2)C(F)(F)F)C=C1 PHUIZDKLQWKHGE-UHFFFAOYSA-N 0.000 description 2
- PUCLSBXZYKPZGM-UHFFFAOYSA-N ethyl 2-[4-[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]propanoate Chemical compound C1=CC(C(C)C(=O)OCC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)OC(C)C=2C(=CC=CC=2)F)C=C1 PUCLSBXZYKPZGM-UHFFFAOYSA-N 0.000 description 2
- VPEZPOQOPOEREM-HXUWFJFHSA-N ethyl 2-[4-[4-[4-[[(1r)-1-(2-fluorophenyl)ethoxy]carbonylamino]-3-methyl-1,2-oxazol-5-yl]-2-methylphenyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OCC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)O[C@H](C)C=2C(=CC=CC=2)F)C=C1C VPEZPOQOPOEREM-HXUWFJFHSA-N 0.000 description 2
- KPSKFXBKXLZSNB-UHFFFAOYSA-N ethyl 2-methyl-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propanoate Chemical compound C1=CC(C(C)(C)C(=O)OCC)=CC=C1B1OC(C)(C)C(C)(C)O1 KPSKFXBKXLZSNB-UHFFFAOYSA-N 0.000 description 2
- STMHGPFYLQOGJD-UHFFFAOYSA-N ethyl 3-(4-bromophenyl)propanoate Chemical compound CCOC(=O)CCC1=CC=C(Br)C=C1 STMHGPFYLQOGJD-UHFFFAOYSA-N 0.000 description 2
- KCLNIIVASYXCES-UHFFFAOYSA-N ethyl 4-(4-bromophenyl)butanoate Chemical compound CCOC(=O)CCCC1=CC=C(Br)C=C1 KCLNIIVASYXCES-UHFFFAOYSA-N 0.000 description 2
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000003172 expectorant agent Substances 0.000 description 2
- 230000003419 expectorant effect Effects 0.000 description 2
- 229940066493 expectorants Drugs 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 125000003709 fluoroalkyl group Chemical group 0.000 description 2
- 201000005206 focal segmental glomerulosclerosis Diseases 0.000 description 2
- 231100000854 focal segmental glomerulosclerosis Toxicity 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 230000026781 habituation Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- 231100000283 hepatitis Toxicity 0.000 description 2
- 210000003630 histaminocyte Anatomy 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 230000000642 iatrogenic effect Effects 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 229960003444 immunosuppressant agent Drugs 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 210000004969 inflammatory cell Anatomy 0.000 description 2
- 230000004941 influx Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 230000031146 intracellular signal transduction Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 208000002551 irritable bowel syndrome Diseases 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- 229940043355 kinase inhibitor Drugs 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 239000003199 leukotriene receptor blocking agent Substances 0.000 description 2
- 150000002617 leukotrienes Chemical class 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 231100000515 lung injury Toxicity 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 238000006241 metabolic reaction Methods 0.000 description 2
- NDRIMRILITZPBZ-UHFFFAOYSA-N methyl 2-[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]benzoate Chemical compound COC(=O)C1=CC=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)OC(C)C=2C(=CC=CC=2)Cl)C=C1 NDRIMRILITZPBZ-UHFFFAOYSA-N 0.000 description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
- 206010027599 migraine Diseases 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- TXXHDPDFNKHHGW-UHFFFAOYSA-N muconic acid Chemical compound OC(=O)C=CC=CC(O)=O TXXHDPDFNKHHGW-UHFFFAOYSA-N 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 206010028537 myelofibrosis Diseases 0.000 description 2
- 210000003098 myoblast Anatomy 0.000 description 2
- 210000000651 myofibroblast Anatomy 0.000 description 2
- 208000001491 myopia Diseases 0.000 description 2
- 230000004379 myopia Effects 0.000 description 2
- 239000006199 nebulizer Substances 0.000 description 2
- 208000021971 neovascular inflammatory vitreoretinopathy Diseases 0.000 description 2
- 201000004931 neurofibromatosis Diseases 0.000 description 2
- 230000004766 neurogenesis Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 230000000414 obstructive effect Effects 0.000 description 2
- 239000002997 ophthalmic solution Substances 0.000 description 2
- 229940054534 ophthalmic solution Drugs 0.000 description 2
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 2
- QJPQVXSHYBGQGM-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 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 2
- 230000003076 paracrine Effects 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 239000003358 phospholipase A2 inhibitor Substances 0.000 description 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 2
- 229960003073 pirfenidone Drugs 0.000 description 2
- ISWRGOKTTBVCFA-UHFFFAOYSA-N pirfenidone Chemical compound C1=C(C)C=CC(=O)N1C1=CC=CC=C1 ISWRGOKTTBVCFA-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 230000006785 proliferative vitreoretinopathy Effects 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 238000003753 real-time PCR Methods 0.000 description 2
- 230000007115 recruitment Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 229910052895 riebeckite Inorganic materials 0.000 description 2
- 201000004700 rosacea Diseases 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- 239000008223 sterile water Substances 0.000 description 2
- 210000003518 stress fiber Anatomy 0.000 description 2
- 239000006190 sub-lingual tablet Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 201000002510 thyroid cancer Diseases 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 229940042129 topical gel Drugs 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 208000009999 tuberous sclerosis Diseases 0.000 description 2
- 210000003556 vascular endothelial cell Anatomy 0.000 description 2
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- GCBDPOGOUBGIIC-RXMQYKEDSA-N (1r)-1-(3,5-dibromophenyl)ethanol Chemical compound C[C@@H](O)C1=CC(Br)=CC(Br)=C1 GCBDPOGOUBGIIC-RXMQYKEDSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- ITOFPJRDSCGOSA-KZLRUDJFSA-N (2s)-2-[[(4r)-4-[(3r,5r,8r,9s,10s,13r,14s,17r)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H](CC[C@]13C)[C@@H]2[C@@H]3CC[C@@H]1[C@H](C)CCC(=O)N[C@H](C(O)=O)CC1=CNC2=CC=CC=C12 ITOFPJRDSCGOSA-KZLRUDJFSA-N 0.000 description 1
- ZLNFACCFYUFTLD-UHFFFAOYSA-N (4-ethoxycarbonylphenyl)boronic acid Chemical compound CCOC(=O)C1=CC=C(B(O)O)C=C1 ZLNFACCFYUFTLD-UHFFFAOYSA-N 0.000 description 1
- OCSAUVDNURIBJU-PBTLETOKSA-N (4r,5s)-4-methyl-5-phenyl-3-[2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propanoyl]-1,3-oxazolidin-2-one Chemical compound C1([C@H]2[C@@H](C)N(C(O2)=O)C(=O)C(C)C=2C=CC(=CC=2)B2OC(C)(C)C(C)(C)O2)=CC=CC=C1 OCSAUVDNURIBJU-PBTLETOKSA-N 0.000 description 1
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- PQUXFUBNSYCQAL-UHFFFAOYSA-N 1-(2,3-difluorophenyl)ethanone Chemical compound CC(=O)C1=CC=CC(F)=C1F PQUXFUBNSYCQAL-UHFFFAOYSA-N 0.000 description 1
- XSPFLOHTXTVEJY-UHFFFAOYSA-N 1-(2,3-difluorophenyl)ethyl n-[5-(4-bromophenyl)-3-methyl-1,2-oxazol-4-yl]carbamate Chemical compound C=1C=CC(F)=C(F)C=1C(C)OC(=O)NC=1C(C)=NOC=1C1=CC=C(Br)C=C1 XSPFLOHTXTVEJY-UHFFFAOYSA-N 0.000 description 1
- KUBJARHKXBDGAA-UHFFFAOYSA-N 1-(2,4-difluorophenyl)ethanol Chemical compound CC(O)C1=CC=C(F)C=C1F KUBJARHKXBDGAA-UHFFFAOYSA-N 0.000 description 1
- QEWHNJPLPZOEKU-UHFFFAOYSA-N 1-(2,4-difluorophenyl)ethanone Chemical compound CC(=O)C1=CC=C(F)C=C1F QEWHNJPLPZOEKU-UHFFFAOYSA-N 0.000 description 1
- TYJGVHFPGBVOCC-UHFFFAOYSA-N 1-(2,4-difluorophenyl)ethyl n-[5-(4-bromophenyl)-3-methyl-1,2-oxazol-4-yl]carbamate Chemical compound C=1C=C(F)C=C(F)C=1C(C)OC(=O)NC=1C(C)=NOC=1C1=CC=C(Br)C=C1 TYJGVHFPGBVOCC-UHFFFAOYSA-N 0.000 description 1
- HLAFIZUVVWJAKL-UHFFFAOYSA-N 1-(2,5-difluorophenyl)ethanone Chemical compound CC(=O)C1=CC(F)=CC=C1F HLAFIZUVVWJAKL-UHFFFAOYSA-N 0.000 description 1
- VQZOHBQTRQYJOW-UHFFFAOYSA-N 1-(2,5-difluorophenyl)ethyl n-[5-(4-bromophenyl)-3-methyl-1,2-oxazol-4-yl]carbamate Chemical compound C=1C(F)=CC=C(F)C=1C(C)OC(=O)NC=1C(C)=NOC=1C1=CC=C(Br)C=C1 VQZOHBQTRQYJOW-UHFFFAOYSA-N 0.000 description 1
- VUSOJMQVQGKPNN-UHFFFAOYSA-N 1-(2,6-dichlorophenyl)ethanol Chemical compound CC(O)C1=C(Cl)C=CC=C1Cl VUSOJMQVQGKPNN-UHFFFAOYSA-N 0.000 description 1
- VGIIILXIQLXVLC-UHFFFAOYSA-N 1-(2,6-difluorophenyl)ethanone Chemical compound CC(=O)C1=C(F)C=CC=C1F VGIIILXIQLXVLC-UHFFFAOYSA-N 0.000 description 1
- DNJUYNQPKABAMN-UHFFFAOYSA-N 1-(2,6-difluorophenyl)ethyl n-[5-(4-bromophenyl)-3-methyl-1,2-oxazol-4-yl]carbamate Chemical compound FC=1C=CC=C(F)C=1C(C)OC(=O)NC=1C(C)=NOC=1C1=CC=C(Br)C=C1 DNJUYNQPKABAMN-UHFFFAOYSA-N 0.000 description 1
- DDUBOVLGCYUYFX-UHFFFAOYSA-N 1-(2-chlorophenyl)ethanol Chemical compound CC(O)C1=CC=CC=C1Cl DDUBOVLGCYUYFX-UHFFFAOYSA-N 0.000 description 1
- FHULGPWAFAAOFK-UHFFFAOYSA-N 1-(2-chlorophenyl)ethyl carbamate Chemical compound NC(=O)OC(C)C1=CC=CC=C1Cl FHULGPWAFAAOFK-UHFFFAOYSA-N 0.000 description 1
- OIDIKNFCUCILAH-UHFFFAOYSA-N 1-(2-chlorophenyl)ethyl n-[3-methyl-5-(4-phenylphenyl)-1,2-oxazol-4-yl]carbamate Chemical group C=1C=CC=C(Cl)C=1C(C)OC(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=CC=C1 OIDIKNFCUCILAH-UHFFFAOYSA-N 0.000 description 1
- PIRRWUMTIBFCCW-UHFFFAOYSA-N 1-(2-fluoro-4-methoxyphenyl)ethanone Chemical compound COC1=CC=C(C(C)=O)C(F)=C1 PIRRWUMTIBFCCW-UHFFFAOYSA-N 0.000 description 1
- XRUUBNBLMLFMKF-UHFFFAOYSA-N 1-(2-fluoro-4-methoxyphenyl)ethyl n-[5-(4-bromophenyl)-3-methyl-1,2-oxazol-4-yl]carbamate Chemical compound FC1=CC(OC)=CC=C1C(C)OC(=O)NC1=C(C=2C=CC(Br)=CC=2)ON=C1C XRUUBNBLMLFMKF-UHFFFAOYSA-N 0.000 description 1
- KILNAODKHWDLJW-UHFFFAOYSA-N 1-(2-fluorophenyl)ethyl n-[3-methyl-5-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1,2-oxazol-4-yl]carbamate Chemical compound C=1C=CC=C(F)C=1C(C)OC(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1B1OC(C)(C)C(C)(C)O1 KILNAODKHWDLJW-UHFFFAOYSA-N 0.000 description 1
- DHHGVIOVURMJEA-UHFFFAOYSA-N 1-(2-methoxyphenyl)ethanol Chemical compound COC1=CC=CC=C1C(C)O DHHGVIOVURMJEA-UHFFFAOYSA-N 0.000 description 1
- ULMJQMDYAOJNCC-UHFFFAOYSA-N 1-(3-bromophenyl)ethanol Chemical compound CC(O)C1=CC=CC(Br)=C1 ULMJQMDYAOJNCC-UHFFFAOYSA-N 0.000 description 1
- SFYMSCDTIQQNLH-UHFFFAOYSA-N 1-(4-chloro-2-fluorophenyl)ethanol Chemical compound CC(O)C1=CC=C(Cl)C=C1F SFYMSCDTIQQNLH-UHFFFAOYSA-N 0.000 description 1
- VGHBIJJTMFYTPY-UHFFFAOYSA-N 1-[2-(trifluoromethyl)phenyl]ethanol Chemical compound CC(O)C1=CC=CC=C1C(F)(F)F VGHBIJJTMFYTPY-UHFFFAOYSA-N 0.000 description 1
- YNVXCOKNHXMBQC-UHFFFAOYSA-N 1-[3-(trifluoromethyl)phenyl]ethanol Chemical compound CC(O)C1=CC=CC(C(F)(F)F)=C1 YNVXCOKNHXMBQC-UHFFFAOYSA-N 0.000 description 1
- QXOGPTXQGKQSJT-UHFFFAOYSA-N 1-amino-4-[4-(3,4-dimethylphenyl)sulfanylanilino]-9,10-dioxoanthracene-2-sulfonic acid Chemical compound Cc1ccc(Sc2ccc(Nc3cc(c(N)c4C(=O)c5ccccc5C(=O)c34)S(O)(=O)=O)cc2)cc1C QXOGPTXQGKQSJT-UHFFFAOYSA-N 0.000 description 1
- WAPNOHKVXSQRPX-UHFFFAOYSA-N 1-phenylethanol Chemical compound CC(O)C1=CC=CC=C1 WAPNOHKVXSQRPX-UHFFFAOYSA-N 0.000 description 1
- WAPNOHKVXSQRPX-SPBYTNOZSA-N 1-phenylethanol Chemical class [13CH3][13CH](O)C1=CC=CC=C1 WAPNOHKVXSQRPX-SPBYTNOZSA-N 0.000 description 1
- YXWWHNCQZBVZPV-UHFFFAOYSA-N 2'-methylacetophenone Chemical compound CC(=O)C1=CC=CC=C1C YXWWHNCQZBVZPV-UHFFFAOYSA-N 0.000 description 1
- DWXSYDKEWORWBT-UHFFFAOYSA-N 2-(2-bromophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC=C1Br DWXSYDKEWORWBT-UHFFFAOYSA-N 0.000 description 1
- XXFGIJYSXNXNAU-UHFFFAOYSA-N 2-(3-bromo-4-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(F)C(Br)=C1 XXFGIJYSXNXNAU-UHFFFAOYSA-N 0.000 description 1
- POTVGQUUEQTPNA-UHFFFAOYSA-N 2-(3-bromo-4-methoxyphenyl)acetic acid Chemical compound COC1=CC=C(CC(O)=O)C=C1Br POTVGQUUEQTPNA-UHFFFAOYSA-N 0.000 description 1
- KYNNBXCGXUOREX-UHFFFAOYSA-N 2-(3-bromophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1 KYNNBXCGXUOREX-UHFFFAOYSA-N 0.000 description 1
- PFDBEACWLCHWRZ-UHFFFAOYSA-N 2-(4-bromophenyl)propanoic acid Chemical compound OC(=O)C(C)C1=CC=C(Br)C=C1 PFDBEACWLCHWRZ-UHFFFAOYSA-N 0.000 description 1
- OTVSGUXUQHZGNR-UHFFFAOYSA-N 2-(4-bromophenyl)propanoyl chloride Chemical compound ClC(=O)C(C)C1=CC=C(Br)C=C1 OTVSGUXUQHZGNR-UHFFFAOYSA-N 0.000 description 1
- WSWMCZBGQYAYIS-UHFFFAOYSA-N 2-(5-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC(Br)=CC=C1F WSWMCZBGQYAYIS-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- KHNXTXCADGLVRR-UHFFFAOYSA-N 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethyl acetate Chemical compound C(C)(=O)OCCC1=CC=C(C=C1)B1OC(C(O1)(C)C)(C)C KHNXTXCADGLVRR-UHFFFAOYSA-N 0.000 description 1
- ZWVUBOSDIKCNEB-UHFFFAOYSA-N 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propanoic acid Chemical compound C1=CC(C(C(O)=O)C)=CC=C1B1OC(C)(C)C(C)(C)O1 ZWVUBOSDIKCNEB-UHFFFAOYSA-N 0.000 description 1
- FJLJCFDZORHIGX-UHFFFAOYSA-N 2-[4-[4-[3-methyl-4-[1-[3-(trifluoromethyl)phenyl]ethoxycarbonylamino]-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound C=1C=CC(C(F)(F)F)=CC=1C(C)OC(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(CC(O)=O)C=C1 FJLJCFDZORHIGX-UHFFFAOYSA-N 0.000 description 1
- YFBKQERIZUFBFZ-LJQANCHMSA-N 2-[4-[4-[3-methyl-4-[[(1r)-1-(2-methylphenyl)ethoxy]carbonylamino]-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound O([C@H](C)C=1C(=CC=CC=1)C)C(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(CC(O)=O)C=C1 YFBKQERIZUFBFZ-LJQANCHMSA-N 0.000 description 1
- LNDDRUPAICPXIN-SFHVURJKSA-N 2-[4-[4-[3-methyl-4-[[(1s)-1-phenylethoxy]carbonylamino]-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound O([C@@H](C)C=1C=CC=CC=1)C(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(CC(O)=O)C=C1 LNDDRUPAICPXIN-SFHVURJKSA-N 0.000 description 1
- OTAVOPSDVXBXKW-UHFFFAOYSA-N 2-[4-[4-[4-[(2-chlorophenyl)methoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound CC1=NOC(C=2C=CC(=CC=2)C=2C=CC(CC(O)=O)=CC=2)=C1NC(=O)OCC1=CC=CC=C1Cl OTAVOPSDVXBXKW-UHFFFAOYSA-N 0.000 description 1
- RLDQWMSOMKXUBV-UHFFFAOYSA-N 2-[4-[4-[4-[1-(2,4-dichlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound C=1C=C(Cl)C=C(Cl)C=1C(C)OC(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(CC(O)=O)C=C1 RLDQWMSOMKXUBV-UHFFFAOYSA-N 0.000 description 1
- HLRNONPRSJOLKS-UHFFFAOYSA-N 2-[4-[4-[4-[1-(2,6-dichlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetic acid Chemical compound ClC=1C=CC=C(Cl)C=1C(C)OC(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(CC(O)=O)C=C1 HLRNONPRSJOLKS-UHFFFAOYSA-N 0.000 description 1
- GTKGGMLCSHIPEO-GOSISDBHSA-N 2-[4-[4-[4-[[(1r)-1-(2-chlorophenyl)ethoxy]carbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]-2-methylpropanoic acid Chemical compound O([C@H](C)C=1C(=CC=CC=1)Cl)C(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(C(C)(C)C(O)=O)C=C1 GTKGGMLCSHIPEO-GOSISDBHSA-N 0.000 description 1
- RCPPMKCYGLGOSN-UHUGOGIASA-N 2-[4-[4-[4-[[(1r)-1-(2-chlorophenyl)ethoxy]carbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]propanoic acid Chemical compound O([C@H](C)C=1C(=CC=CC=1)Cl)C(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(C(C)C(O)=O)C=C1 RCPPMKCYGLGOSN-UHUGOGIASA-N 0.000 description 1
- IMDBTLAJSYYCHB-HXUWFJFHSA-N 2-[[2-[4-[4-[3-methyl-4-[[(1r)-1-phenylethoxy]carbonylamino]-1,2-oxazol-5-yl]phenyl]phenyl]acetyl]amino]ethanesulfonic acid Chemical compound O([C@H](C)C=1C=CC=CC=1)C(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(CC(=O)NCCS(O)(=O)=O)C=C1 IMDBTLAJSYYCHB-HXUWFJFHSA-N 0.000 description 1
- IQHSSYROJYPFDV-UHFFFAOYSA-N 2-bromo-1,3-dichloro-5-(trifluoromethyl)benzene Chemical group FC(F)(F)C1=CC(Cl)=C(Br)C(Cl)=C1 IQHSSYROJYPFDV-UHFFFAOYSA-N 0.000 description 1
- LSRTWJCYIWGKCQ-UHFFFAOYSA-N 2-bromo-3-methylbenzoic acid Chemical compound CC1=CC=CC(C(O)=O)=C1Br LSRTWJCYIWGKCQ-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- SFTFNJZWZHASAQ-UHFFFAOYSA-N 3,5-dibromobenzoic acid Chemical compound OC(=O)C1=CC(Br)=CC(Br)=C1 SFTFNJZWZHASAQ-UHFFFAOYSA-N 0.000 description 1
- NCSTWHYWOVZDOC-UHFFFAOYSA-N 3-(4-bromophenyl)propanoic acid Chemical compound OC(=O)CCC1=CC=C(Br)C=C1 NCSTWHYWOVZDOC-UHFFFAOYSA-N 0.000 description 1
- NLAKAZVRTZDIML-UHFFFAOYSA-N 3-[4-[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]propanoic acid Chemical compound C=1C=CC=C(Cl)C=1C(C)OC(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(CCC(O)=O)C=C1 NLAKAZVRTZDIML-UHFFFAOYSA-N 0.000 description 1
- WUIABRMSWOKTOF-OYALTWQYSA-N 3-[[2-[2-[2-[[(2s,3r)-2-[[(2s,3s,4r)-4-[[(2s,3r)-2-[[6-amino-2-[(1s)-3-amino-1-[[(2s)-2,3-diamino-3-oxopropyl]amino]-3-oxopropyl]-5-methylpyrimidine-4-carbonyl]amino]-3-[(2r,3s,4s,5s,6s)-3-[(2r,3s,4s,5r,6r)-4-carbamoyloxy-3,5-dihydroxy-6-(hydroxymethyl)ox Chemical compound OS([O-])(=O)=O.N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1NC=NC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C WUIABRMSWOKTOF-OYALTWQYSA-N 0.000 description 1
- DBVFWZMQJQMJCB-UHFFFAOYSA-N 3-boronobenzoic acid Chemical compound OB(O)C1=CC=CC(C(O)=O)=C1 DBVFWZMQJQMJCB-UHFFFAOYSA-N 0.000 description 1
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- AGIIMNQWNPUJPT-UHFFFAOYSA-N 4-(4-bromophenyl)butanoic acid Chemical compound OC(=O)CCCC1=CC=C(Br)C=C1 AGIIMNQWNPUJPT-UHFFFAOYSA-N 0.000 description 1
- DKBPSHPXVCVGQZ-UHFFFAOYSA-N 4-[4-[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]butanoic acid Chemical compound C=1C=CC=C(Cl)C=1C(C)OC(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C1=CC=C(CCCC(O)=O)C=C1 DKBPSHPXVCVGQZ-UHFFFAOYSA-N 0.000 description 1
- JAVZWSOFJKYSDY-UHFFFAOYSA-N 4-bromo-2-chlorobenzoic acid Chemical compound OC(=O)C1=CC=C(Br)C=C1Cl JAVZWSOFJKYSDY-UHFFFAOYSA-N 0.000 description 1
- IHYXATIWDIHXAA-UHFFFAOYSA-N 4-bromo-2-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Br)C=C1Cl IHYXATIWDIHXAA-UHFFFAOYSA-N 0.000 description 1
- PSKJIHDVFDVNBU-UHFFFAOYSA-N 4-bromo-3-chlorobenzoic acid Chemical compound OC(=O)C1=CC=C(Br)C(Cl)=C1 PSKJIHDVFDVNBU-UHFFFAOYSA-N 0.000 description 1
- OEFADALRZHTONM-UHFFFAOYSA-N 4-bromo-3-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Br)C(Cl)=C1 OEFADALRZHTONM-UHFFFAOYSA-N 0.000 description 1
- KWVXDZLVCISXIB-UHFFFAOYSA-N 4-bromo-3-methylbenzoic acid Chemical compound CC1=CC(C(O)=O)=CC=C1Br KWVXDZLVCISXIB-UHFFFAOYSA-N 0.000 description 1
- PVXGJCNXMPLCJU-UHFFFAOYSA-N 4-bromo-3-methylbenzoyl chloride Chemical compound CC1=CC(C(Cl)=O)=CC=C1Br PVXGJCNXMPLCJU-UHFFFAOYSA-N 0.000 description 1
- TUXYZHVUPGXXQG-UHFFFAOYSA-N 4-bromobenzoic acid Chemical compound OC(=O)C1=CC=C(Br)C=C1 TUXYZHVUPGXXQG-UHFFFAOYSA-N 0.000 description 1
- DENKGPBHLYFNGK-UHFFFAOYSA-N 4-bromobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Br)C=C1 DENKGPBHLYFNGK-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- OBKXEAXTFZPCHS-UHFFFAOYSA-N 4-phenylbutyric acid Chemical compound OC(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-N 0.000 description 1
- 206010000050 Abdominal adhesions Diseases 0.000 description 1
- 208000036065 Airway Remodeling Diseases 0.000 description 1
- 208000022309 Alcoholic Liver disease Diseases 0.000 description 1
- 208000024985 Alport syndrome Diseases 0.000 description 1
- 208000035939 Alveolitis allergic Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 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
- 208000033309 Analgesic asthma syndrome Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 208000003120 Angiofibroma Diseases 0.000 description 1
- 206010059245 Angiopathy Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 200000000007 Arterial disease Diseases 0.000 description 1
- 206010003557 Asthma exercise induced Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 201000001178 Bacterial Pneumonia Diseases 0.000 description 1
- 206010004146 Basal cell carcinoma Diseases 0.000 description 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 206010005042 Bladder fibrosis Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 206010006448 Bronchiolitis Diseases 0.000 description 1
- OJRUSAPKCPIVBY-KQYNXXCUSA-N C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N Chemical compound C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N OJRUSAPKCPIVBY-KQYNXXCUSA-N 0.000 description 1
- KCBAMQOKOLXLOX-BSZYMOERSA-N CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O Chemical compound CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O KCBAMQOKOLXLOX-BSZYMOERSA-N 0.000 description 1
- XCUFEJZAJCDKIO-LJQANCHMSA-N CC1=NOC(=C1NC(=O)O[C@H](C)C2=CC=CC=C2Cl)C3=CC=C(C=C3)C4=CC=C(C=C4)CCOC(=O)C Chemical compound CC1=NOC(=C1NC(=O)O[C@H](C)C2=CC=CC=C2Cl)C3=CC=C(C=C3)C4=CC=C(C=C4)CCOC(=O)C XCUFEJZAJCDKIO-LJQANCHMSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 206010008909 Chronic Hepatitis Diseases 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 102100026735 Coagulation factor VIII Human genes 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 208000027932 Collagen disease Diseases 0.000 description 1
- 206010010996 Corneal degeneration Diseases 0.000 description 1
- 206010011044 Corneal scar Diseases 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
- 206010012441 Dermatitis bullous Diseases 0.000 description 1
- 206010012442 Dermatitis contact Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 206010013654 Drug abuse Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 208000004657 Exercise-Induced Asthma Diseases 0.000 description 1
- 208000027445 Farmer Lung Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 208000001640 Fibromyalgia Diseases 0.000 description 1
- 208000010412 Glaucoma Diseases 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
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 208000001204 Hashimoto Disease Diseases 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 1
- 206010019668 Hepatic fibrosis Diseases 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 208000028782 Hereditary disease Diseases 0.000 description 1
- 241001272567 Hominoidea Species 0.000 description 1
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 description 1
- 101000966782 Homo sapiens Lysophosphatidic acid receptor 1 Proteins 0.000 description 1
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 201000003838 Idiopathic interstitial pneumonia Diseases 0.000 description 1
- 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 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 208000032571 Infant acute respiratory distress syndrome Diseases 0.000 description 1
- 208000003618 Intervertebral Disc Displacement Diseases 0.000 description 1
- 206010050296 Intervertebral disc protrusion Diseases 0.000 description 1
- 208000011200 Kawasaki disease Diseases 0.000 description 1
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 208000000185 Localized scleroderma Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 102000016994 Lysolipids receptors Human genes 0.000 description 1
- 108070000013 Lysolipids receptors Proteins 0.000 description 1
- 102100040607 Lysophosphatidic acid receptor 1 Human genes 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000024556 Mendelian disease Diseases 0.000 description 1
- 208000003250 Mixed connective tissue disease Diseases 0.000 description 1
- TXXHDPDFNKHHGW-CCAGOZQPSA-N Muconic acid Natural products OC(=O)\C=C/C=C\C(O)=O TXXHDPDFNKHHGW-CCAGOZQPSA-N 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 201000002481 Myositis Diseases 0.000 description 1
- LVDRREOUMKACNJ-BKMJKUGQSA-N N-[(2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxoquinolin-7-yl)-6-oxopiperidin-3-yl]-2-methylpropane-1-sulfonamide Chemical compound CC(C)CS(=O)(=O)N[C@H]1CCC(=O)N([C@@H]1c1ccc(Cl)cc1)c1ccc2c(C)cc(=O)n(C)c2c1 LVDRREOUMKACNJ-BKMJKUGQSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- 206010028974 Neonatal respiratory distress syndrome Diseases 0.000 description 1
- 208000000693 Neurogenic Urinary Bladder Diseases 0.000 description 1
- 206010029279 Neurogenic bladder Diseases 0.000 description 1
- 101000578290 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) Nitrogen metabolite repression protein nmr Proteins 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 206010061876 Obstruction Diseases 0.000 description 1
- 208000011623 Obstructive Lung disease Diseases 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 208000022553 Parenchymal lung disease Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 206010034277 Pemphigoid Diseases 0.000 description 1
- 206010035603 Pleural mesothelioma Diseases 0.000 description 1
- 229920005372 Plexiglas® Polymers 0.000 description 1
- 206010035737 Pneumonia viral Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 206010051739 Pulmonary sepsis Diseases 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 206010038687 Respiratory distress Diseases 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 206010039094 Rhinitis perennial Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 206010048908 Seasonal allergy Diseases 0.000 description 1
- 208000019802 Sexually transmitted disease Diseases 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 208000032450 Surgical Shock Diseases 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 206010044541 Traumatic shock Diseases 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 208000026723 Urinary tract disease Diseases 0.000 description 1
- 208000012931 Urologic disease Diseases 0.000 description 1
- 206010046914 Vaginal infection Diseases 0.000 description 1
- 201000008100 Vaginitis Diseases 0.000 description 1
- 208000032594 Vascular Remodeling Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- RSWSOOCDUHOVAX-ADURAZCHSA-N [(1r)-1-(2-chlorophenyl)ethyl] n-[3-methyl-5-[4-[4-[1-[(4r,5s)-4-methyl-2-oxo-5-phenyl-1,3-oxazolidin-3-yl]-1-oxopropan-2-yl]phenyl]phenyl]-1,2-oxazol-4-yl]carbamate Chemical compound C1([C@H]2[C@@H](C)N(C(O2)=O)C(=O)C(C)C2=CC=C(C=C2)C2=CC=C(C=C2)C=2ON=C(C)C=2NC(=O)O[C@H](C)C=2C(=CC=CC=2)Cl)=CC=CC=C1 RSWSOOCDUHOVAX-ADURAZCHSA-N 0.000 description 1
- VXOVXRULOPMNCQ-LLVKDONJSA-N [(1r)-1-(2-chlorophenyl)ethyl] n-[5-(4-bromo-2-chlorophenyl)-3-methyl-1,2-oxazol-4-yl]carbamate Chemical compound O([C@H](C)C=1C(=CC=CC=1)Cl)C(=O)NC=1C(C)=NOC=1C1=CC=C(Br)C=C1Cl VXOVXRULOPMNCQ-LLVKDONJSA-N 0.000 description 1
- AFTCGUZLCPFABC-LLVKDONJSA-N [(1r)-1-(2-chlorophenyl)ethyl] n-[5-(4-bromo-3-chlorophenyl)-3-methyl-1,2-oxazol-4-yl]carbamate Chemical compound O([C@H](C)C=1C(=CC=CC=1)Cl)C(=O)NC=1C(C)=NOC=1C1=CC=C(Br)C(Cl)=C1 AFTCGUZLCPFABC-LLVKDONJSA-N 0.000 description 1
- PRINACLCZCUQJF-LLVKDONJSA-N [(1r)-1-(2-chlorophenyl)ethyl] n-[5-(4-bromo-3-fluorophenyl)-3-methyl-1,2-oxazol-4-yl]carbamate Chemical compound O([C@H](C)C=1C(=CC=CC=1)Cl)C(=O)NC=1C(C)=NOC=1C1=CC=C(Br)C(F)=C1 PRINACLCZCUQJF-LLVKDONJSA-N 0.000 description 1
- QYJFVVYIZSTDLE-GFCCVEGCSA-N [(1r)-1-(2-fluorophenyl)ethyl] n-[5-(4-bromophenyl)-3-methyl-1,2-oxazol-4-yl]carbamate Chemical compound O([C@H](C)C=1C(=CC=CC=1)F)C(=O)NC=1C(C)=NOC=1C1=CC=C(Br)C=C1 QYJFVVYIZSTDLE-GFCCVEGCSA-N 0.000 description 1
- ZUWQMMFXMFXJEY-LBPRGKRZSA-N [(1s)-1-(2-chlorophenyl)ethyl] n-[5-(4-bromophenyl)-3-methyl-1,2-oxazol-4-yl]carbamate Chemical compound O([C@@H](C)C=1C(=CC=CC=1)Cl)C(=O)NC=1C(C)=NOC=1C1=CC=C(Br)C=C1 ZUWQMMFXMFXJEY-LBPRGKRZSA-N 0.000 description 1
- PBNUXNCUNUMZFL-UHFFFAOYSA-N [3-(2-methoxy-2-oxoethyl)phenyl]boronic acid Chemical compound COC(=O)CC1=CC=CC(B(O)O)=C1 PBNUXNCUNUMZFL-UHFFFAOYSA-N 0.000 description 1
- IYYVRMQTAJVSAC-UHFFFAOYSA-N [3-methyl-5-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1,2-oxazol-4-yl]carbamic acid Chemical compound CC1=NOC(C=2C=CC(=CC=2)B2OC(C)(C)C(C)(C)O2)=C1NC(O)=O IYYVRMQTAJVSAC-UHFFFAOYSA-N 0.000 description 1
- RDIRUZGSOKLANG-UHFFFAOYSA-N [4-(2-ethoxy-2-oxoethyl)phenyl]boronic acid Chemical compound CCOC(=O)CC1=CC=C(B(O)O)C=C1 RDIRUZGSOKLANG-UHFFFAOYSA-N 0.000 description 1
- YKVMTTIYBSVPEQ-UHFFFAOYSA-N [4-(cyanomethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=C(CC#N)C=C1 YKVMTTIYBSVPEQ-UHFFFAOYSA-N 0.000 description 1
- KCNPOTRPZJGYSE-UHFFFAOYSA-N [5-[4-[4-(2-acetylimino-2-aminoethyl)phenyl]phenyl]-3-methyl-1,2-oxazol-4-yl]carbamic acid Chemical compound C1=CC(CC(N)=NC(=O)C)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(O)=O)C=C1 KCNPOTRPZJGYSE-UHFFFAOYSA-N 0.000 description 1
- WGRUHEXRUVIOTI-UHFFFAOYSA-M [Li+].[OH-].Cc1noc(c1C(O)=O)-c1ccc(Br)cc1 Chemical compound [Li+].[OH-].Cc1noc(c1C(O)=O)-c1ccc(Br)cc1 WGRUHEXRUVIOTI-UHFFFAOYSA-M 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 210000003489 abdominal muscle Anatomy 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 229960004308 acetylcysteine Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 208000024716 acute asthma Diseases 0.000 description 1
- 231100000354 acute hepatitis Toxicity 0.000 description 1
- 206010069351 acute lung injury Diseases 0.000 description 1
- 208000005298 acute pain Diseases 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 230000011759 adipose tissue development Effects 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 229910001413 alkali metal ion Inorganic materials 0.000 description 1
- 239000013566 allergen Substances 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- XPNGNIFUDRPBFJ-UHFFFAOYSA-N alpha-methylbenzylalcohol Natural products CC1=CC=CC=C1CO XPNGNIFUDRPBFJ-UHFFFAOYSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 230000019552 anatomical structure morphogenesis Effects 0.000 description 1
- 229960004543 anhydrous citric acid Drugs 0.000 description 1
- 239000002518 antifoaming agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 208000007474 aortic aneurysm Diseases 0.000 description 1
- 210000001742 aqueous humor Anatomy 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 208000024744 aspirin-induced respiratory disease Diseases 0.000 description 1
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
- 229960002170 azathioprine Drugs 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 229960004395 bleomycin sulfate Drugs 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 210000000424 bronchial epithelial cell Anatomy 0.000 description 1
- 239000000168 bronchodilator agent Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 210000001054 cardiac fibroblast Anatomy 0.000 description 1
- 230000009787 cardiac fibrosis Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000009087 cell motility Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000031902 chemoattractant activity Effects 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- HEZQRPHEDDAJTF-UHFFFAOYSA-N chloro(phenyl)methanol Chemical compound OC(Cl)C1=CC=CC=C1 HEZQRPHEDDAJTF-UHFFFAOYSA-N 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 230000037319 collagen production Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 208000010247 contact dermatitis Diseases 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 210000003239 corneal fibroblast Anatomy 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 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
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000032459 dedifferentiation Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 201000001981 dermatomyositis Diseases 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- NIJJYAXOARWZEE-UHFFFAOYSA-N di-n-propyl-acetic acid Natural products CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 description 1
- ZOCHARZZJNPSEU-UHFFFAOYSA-N diboron Chemical compound B#B ZOCHARZZJNPSEU-UHFFFAOYSA-N 0.000 description 1
- JGFBRKRYDCGYKD-UHFFFAOYSA-N dibutyl(oxo)tin Chemical compound CCCC[Sn](=O)CCCC JGFBRKRYDCGYKD-UHFFFAOYSA-N 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 238000007907 direct compression Methods 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 101150042537 dld1 gene Proteins 0.000 description 1
- 230000007783 downstream signaling Effects 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000008482 dysregulation Effects 0.000 description 1
- 210000000613 ear canal Anatomy 0.000 description 1
- 229940047652 ear drops Drugs 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000003821 enantio-separation Methods 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 239000006274 endogenous ligand Substances 0.000 description 1
- 210000004696 endometrium Anatomy 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 210000000871 endothelium corneal Anatomy 0.000 description 1
- 231100000284 endotoxic Toxicity 0.000 description 1
- 230000002346 endotoxic effect Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000003248 enzyme activator Substances 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical compound CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
- YMZZEMPQYJBPFT-UHFFFAOYSA-N ethyl 2-(3-bromo-4-methoxyphenyl)acetate Chemical compound CCOC(=O)CC1=CC=C(OC)C(Br)=C1 YMZZEMPQYJBPFT-UHFFFAOYSA-N 0.000 description 1
- HPGZZDGRCJGYFU-UHFFFAOYSA-N ethyl 2-[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]acetate Chemical compound CCOC(=O)CC1=CC=CC=C1B1OC(C)(C)C(C)(C)O1 HPGZZDGRCJGYFU-UHFFFAOYSA-N 0.000 description 1
- YVUVXTATGINEQL-HXUWFJFHSA-N ethyl 2-[2-[4-[3-methyl-4-[[(1r)-1-phenylethoxy]carbonylamino]-1,2-oxazol-5-yl]phenyl]phenyl]acetate Chemical compound CCOC(=O)CC1=CC=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)O[C@H](C)C=2C=CC=CC=2)C=C1 YVUVXTATGINEQL-HXUWFJFHSA-N 0.000 description 1
- QZCVHKSHHLVLNZ-UHFFFAOYSA-N ethyl 2-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]acetate Chemical compound CCOC(=O)CC1=CC=CC(B2OC(C)(C)C(C)(C)O2)=C1 QZCVHKSHHLVLNZ-UHFFFAOYSA-N 0.000 description 1
- HAVRRGBWUHZEOU-HXUWFJFHSA-N ethyl 2-[3-[4-[3-methyl-4-[[(1r)-1-phenylethoxy]carbonylamino]-1,2-oxazol-5-yl]phenyl]phenyl]acetate Chemical compound CCOC(=O)CC1=CC=CC(C=2C=CC(=CC=2)C2=C(C(C)=NO2)NC(=O)O[C@H](C)C=2C=CC=CC=2)=C1 HAVRRGBWUHZEOU-HXUWFJFHSA-N 0.000 description 1
- SBONIQJLVRKLEZ-UHFFFAOYSA-N ethyl 2-[3-[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]-4-fluorophenyl]acetate Chemical compound CCOC(=O)CC1=CC=C(F)C(C=2C=CC(=CC=2)C2=C(C(C)=NO2)NC(=O)OC(C)C=2C(=CC=CC=2)Cl)=C1 SBONIQJLVRKLEZ-UHFFFAOYSA-N 0.000 description 1
- AQENJBCMTJOPJW-UHFFFAOYSA-N ethyl 2-[3-[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]-4-methoxyphenyl]acetate Chemical compound CCOC(=O)CC1=CC=C(OC)C(C=2C=CC(=CC=2)C2=C(C(C)=NO2)NC(=O)OC(C)C=2C(=CC=CC=2)Cl)=C1 AQENJBCMTJOPJW-UHFFFAOYSA-N 0.000 description 1
- JBDKWZIYWDHNER-UHFFFAOYSA-N ethyl 2-[3-[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetate Chemical compound CCOC(=O)CC1=CC=CC(C=2C=CC(=CC=2)C2=C(C(C)=NO2)NC(=O)OC(C)C=2C(=CC=CC=2)Cl)=C1 JBDKWZIYWDHNER-UHFFFAOYSA-N 0.000 description 1
- QGPQAZHGXUJBRV-UHFFFAOYSA-N ethyl 2-[4-[4-[3-methyl-4-(1-phenylethoxycarbonylamino)-1,2-oxazol-5-yl]phenyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OCC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)OC(C)C=2C=CC=CC=2)C=C1 QGPQAZHGXUJBRV-UHFFFAOYSA-N 0.000 description 1
- FIVDVSFCXYBWLZ-UHFFFAOYSA-N ethyl 2-[4-[4-[3-methyl-4-[1-[3-(trifluoromethyl)phenyl]ethoxycarbonylamino]-1,2-oxazol-5-yl]phenyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OCC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)OC(C)C=2C=C(C=CC=2)C(F)(F)F)C=C1 FIVDVSFCXYBWLZ-UHFFFAOYSA-N 0.000 description 1
- JCLSDHFXEDGZHP-OAQYLSRUSA-N ethyl 2-[4-[4-[3-methyl-4-[[(1r)-1-(2-methylphenyl)ethoxy]carbonylamino]-1,2-oxazol-5-yl]phenyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OCC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)O[C@H](C)C=2C(=CC=CC=2)C)C=C1 JCLSDHFXEDGZHP-OAQYLSRUSA-N 0.000 description 1
- QGPQAZHGXUJBRV-HXUWFJFHSA-N ethyl 2-[4-[4-[3-methyl-4-[[(1r)-1-phenylethoxy]carbonylamino]-1,2-oxazol-5-yl]phenyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OCC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)O[C@H](C)C=2C=CC=CC=2)C=C1 QGPQAZHGXUJBRV-HXUWFJFHSA-N 0.000 description 1
- QGPQAZHGXUJBRV-FQEVSTJZSA-N ethyl 2-[4-[4-[3-methyl-4-[[(1s)-1-phenylethoxy]carbonylamino]-1,2-oxazol-5-yl]phenyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OCC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)O[C@@H](C)C=2C=CC=CC=2)C=C1 QGPQAZHGXUJBRV-FQEVSTJZSA-N 0.000 description 1
- GDTQKNLLWZQTLD-UHFFFAOYSA-N ethyl 2-[4-[4-[4-[1-(2,3-difluorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OCC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)OC(C)C=2C(=C(F)C=CC=2)F)C=C1 GDTQKNLLWZQTLD-UHFFFAOYSA-N 0.000 description 1
- FRKADXJXPHBBCY-UHFFFAOYSA-N ethyl 2-[4-[4-[4-[1-(2,4-dichlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OCC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)OC(C)C=2C(=CC(Cl)=CC=2)Cl)C=C1 FRKADXJXPHBBCY-UHFFFAOYSA-N 0.000 description 1
- GNXSYYPQUWZCND-UHFFFAOYSA-N ethyl 2-[4-[4-[4-[1-(2,4-difluorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OCC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)OC(C)C=2C(=CC(F)=CC=2)F)C=C1 GNXSYYPQUWZCND-UHFFFAOYSA-N 0.000 description 1
- KEVXXADHJKDRKN-UHFFFAOYSA-N ethyl 2-[4-[4-[4-[1-(2,5-difluorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OCC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)OC(C)C=2C(=CC=C(F)C=2)F)C=C1 KEVXXADHJKDRKN-UHFFFAOYSA-N 0.000 description 1
- DINCLUPZPILQKJ-UHFFFAOYSA-N ethyl 2-[4-[4-[4-[1-(2,6-dichlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OCC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)OC(C)C=2C(=CC=CC=2Cl)Cl)C=C1 DINCLUPZPILQKJ-UHFFFAOYSA-N 0.000 description 1
- VOKBZVDYTJHXAB-UHFFFAOYSA-N ethyl 2-[4-[4-[4-[1-(2,6-difluorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OCC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)OC(C)C=2C(=CC=CC=2F)F)C=C1 VOKBZVDYTJHXAB-UHFFFAOYSA-N 0.000 description 1
- KRIPPPZOZVFRKW-UHFFFAOYSA-N ethyl 2-[4-[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]-2-methylpropanoate Chemical compound C1=CC(C(C)(C)C(=O)OCC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)OC(C)C=2C(=CC=CC=2)Cl)C=C1 KRIPPPZOZVFRKW-UHFFFAOYSA-N 0.000 description 1
- OCERXKCDEKVLKY-UHFFFAOYSA-N ethyl 2-[4-[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OCC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)OC(C)C=2C(=CC=CC=2)Cl)C=C1 OCERXKCDEKVLKY-UHFFFAOYSA-N 0.000 description 1
- VEMIIHZKQDTIRQ-UHFFFAOYSA-N ethyl 2-[4-[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]propanoate Chemical compound C1=CC(C(C)C(=O)OCC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)OC(C)C=2C(=CC=CC=2)Cl)C=C1 VEMIIHZKQDTIRQ-UHFFFAOYSA-N 0.000 description 1
- IUZIGPGHFOQDDZ-UHFFFAOYSA-N ethyl 2-[4-[4-[4-[1-(2-fluoro-4-methoxyphenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OCC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)OC(C)C=2C(=CC(OC)=CC=2)F)C=C1 IUZIGPGHFOQDDZ-UHFFFAOYSA-N 0.000 description 1
- QIBQPZQKWFJMGB-UHFFFAOYSA-N ethyl 2-[4-[4-[4-[1-(2-fluorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]-2-methylpropanoate Chemical compound C1=CC(C(C)(C)C(=O)OCC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)OC(C)C=2C(=CC=CC=2)F)C=C1 QIBQPZQKWFJMGB-UHFFFAOYSA-N 0.000 description 1
- GJXYYJCPNGTLCD-LJQANCHMSA-N ethyl 2-[4-[4-[4-[[(1r)-1-(2-fluorophenyl)ethoxy]carbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OCC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)O[C@H](C)C=2C(=CC=CC=2)F)C=C1 GJXYYJCPNGTLCD-LJQANCHMSA-N 0.000 description 1
- PUCLSBXZYKPZGM-ROPPNANJSA-N ethyl 2-[4-[4-[4-[[(1r)-1-(2-fluorophenyl)ethoxy]carbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]propanoate Chemical compound C1=CC(C(C)C(=O)OCC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)O[C@H](C)C=2C(=CC=CC=2)F)C=C1 PUCLSBXZYKPZGM-ROPPNANJSA-N 0.000 description 1
- JEGXHQSMHGOKIV-LJQANCHMSA-N ethyl 2-[4-[4-[4-[[(1r)-1-(3-hydroxyphenyl)ethoxy]carbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OCC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)O[C@H](C)C=2C=C(O)C=CC=2)C=C1 JEGXHQSMHGOKIV-LJQANCHMSA-N 0.000 description 1
- OCERXKCDEKVLKY-IBGZPJMESA-N ethyl 2-[4-[4-[4-[[(1s)-1-(2-chlorophenyl)ethoxy]carbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OCC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)O[C@@H](C)C=2C(=CC=CC=2)Cl)C=C1 OCERXKCDEKVLKY-IBGZPJMESA-N 0.000 description 1
- GJXYYJCPNGTLCD-IBGZPJMESA-N ethyl 2-[4-[4-[4-[[(1s)-1-(2-fluorophenyl)ethoxy]carbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OCC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)O[C@@H](C)C=2C(=CC=CC=2)F)C=C1 GJXYYJCPNGTLCD-IBGZPJMESA-N 0.000 description 1
- XBSUKMMUZUPEQR-UHFFFAOYSA-N ethyl 2-[4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]acetate Chemical compound CCOC(=O)CC1=CC=C(OC)C(B2OC(C)(C)C(C)(C)O2)=C1 XBSUKMMUZUPEQR-UHFFFAOYSA-N 0.000 description 1
- OIAWRONFYVUKEY-UHFFFAOYSA-N ethyl 2-[5-[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]-2-fluorophenyl]acetate Chemical compound C1=C(F)C(CC(=O)OCC)=CC(C=2C=CC(=CC=2)C2=C(C(C)=NO2)NC(=O)OC(C)C=2C(=CC=CC=2)Cl)=C1 OIAWRONFYVUKEY-UHFFFAOYSA-N 0.000 description 1
- KXOOGXIFYDHHGS-UHFFFAOYSA-N ethyl 3-[4-[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]propanoate Chemical compound C1=CC(CCC(=O)OCC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)OC(C)C=2C(=CC=CC=2)Cl)C=C1 KXOOGXIFYDHHGS-UHFFFAOYSA-N 0.000 description 1
- VMBJUIGVKXLDIR-LJQANCHMSA-N ethyl 4-[4-[3-methyl-4-[[(1r)-1-phenylethoxy]carbonylamino]-1,2-oxazol-5-yl]phenyl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)O[C@H](C)C=2C=CC=CC=2)C=C1 VMBJUIGVKXLDIR-LJQANCHMSA-N 0.000 description 1
- ORXBMONZYFTECK-UHFFFAOYSA-N ethyl 4-[4-[4-[4-[1-(2-chlorophenyl)ethoxycarbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]phenyl]butanoate Chemical compound C1=CC(CCCC(=O)OCC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)OC(C)C=2C(=CC=CC=2)Cl)C=C1 ORXBMONZYFTECK-UHFFFAOYSA-N 0.000 description 1
- ZLPHBJNBOXGTJU-GOSISDBHSA-N ethyl 4-[4-[4-[[(1r)-1-(2-chlorophenyl)ethoxy]carbonylamino]-3-methyl-1,2-oxazol-5-yl]phenyl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1C1=CC=C(C2=C(C(C)=NO2)NC(=O)O[C@H](C)C=2C(=CC=CC=2)Cl)C=C1 ZLPHBJNBOXGTJU-GOSISDBHSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- WDAXFOBOLVPGLV-UHFFFAOYSA-N ethyl isobutyrate Chemical compound CCOC(=O)C(C)C WDAXFOBOLVPGLV-UHFFFAOYSA-N 0.000 description 1
- 208000024695 exercise-induced bronchoconstriction Diseases 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 208000022195 farmer lung disease Diseases 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000019305 fibroblast migration Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 125000001207 fluorophenyl group Chemical group 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
- 239000012458 free base Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 206010061989 glomerulosclerosis Diseases 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 150000002366 halogen compounds Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 210000002837 heart atrium Anatomy 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 210000005003 heart tissue Anatomy 0.000 description 1
- 208000018578 heart valve disease Diseases 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 210000004024 hepatic stellate cell Anatomy 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 208000003215 hereditary nephritis Diseases 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000007489 histopathology method Methods 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 208000000069 hyperpigmentation Diseases 0.000 description 1
- 230000003810 hyperpigmentation Effects 0.000 description 1
- 208000000122 hyperventilation Diseases 0.000 description 1
- 230000000870 hyperventilation Effects 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 229940060367 inert ingredients Drugs 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 210000000876 intercostal muscle Anatomy 0.000 description 1
- 230000021995 interleukin-8 production Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 208000037906 ischaemic injury Diseases 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 210000001503 joint Anatomy 0.000 description 1
- 230000006651 lactation Effects 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 210000000867 larynx Anatomy 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 229940065725 leukotriene receptor antagonists for obstructive airway diseases Drugs 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- RENRQMCACQEWFC-UGKGYDQZSA-N lnp023 Chemical compound C1([C@H]2N(CC=3C=4C=CNC=4C(C)=CC=3OC)CC[C@@H](C2)OCC)=CC=C(C(O)=O)C=C1 RENRQMCACQEWFC-UGKGYDQZSA-N 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- 229910052749 magnesium Inorganic materials 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
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- SYPJDLNUUCJWMV-UHFFFAOYSA-N methanol;propanoic acid Chemical compound OC.CCC(O)=O SYPJDLNUUCJWMV-UHFFFAOYSA-N 0.000 description 1
- DDAGPKPTZSVHAO-UHFFFAOYSA-N methyl 2-(4-bromobenzoyl)-3-oxobutanoate Chemical compound COC(=O)C(C(C)=O)C(=O)C1=CC=C(Br)C=C1 DDAGPKPTZSVHAO-UHFFFAOYSA-N 0.000 description 1
- BLPDNEGFSINGPV-UHFFFAOYSA-N methyl 2-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]acetate Chemical compound COC(=O)CC1=CC=CC(B2OC(C)(C)C(C)(C)O2)=C1 BLPDNEGFSINGPV-UHFFFAOYSA-N 0.000 description 1
- LTUHVFMVKKPLII-UHFFFAOYSA-N methyl 5-(4-bromo-2-chlorophenyl)-3-methyl-1,2-oxazole-4-carboxylate Chemical compound CC1=NOC(C=2C(=CC(Br)=CC=2)Cl)=C1C(=O)OC LTUHVFMVKKPLII-UHFFFAOYSA-N 0.000 description 1
- SSLOQIONIWWFRT-UHFFFAOYSA-N methyl 5-(4-bromo-3-chlorophenyl)-3-methyl-1,2-oxazole-4-carboxylate Chemical compound CC1=NOC(C=2C=C(Cl)C(Br)=CC=2)=C1C(=O)OC SSLOQIONIWWFRT-UHFFFAOYSA-N 0.000 description 1
- ROPKPDMIAFXXIA-UHFFFAOYSA-N methyl 5-(4-bromo-3-fluorophenyl)-3-methyl-1,2-oxazole-4-carboxylate Chemical compound CC1=NOC(C=2C=C(F)C(Br)=CC=2)=C1C(=O)OC ROPKPDMIAFXXIA-UHFFFAOYSA-N 0.000 description 1
- YVWJQDKQALEQHO-UHFFFAOYSA-N methyl 5-(4-bromophenyl)-3-methyl-1,2-oxazole-4-carboxylate Chemical compound CC1=NOC(C=2C=CC(Br)=CC=2)=C1C(=O)OC YVWJQDKQALEQHO-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 229940105902 mint extract Drugs 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 208000001725 mucocutaneous lymph node syndrome Diseases 0.000 description 1
- 201000006938 muscular dystrophy Diseases 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 201000000050 myeloid neoplasm Diseases 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- FSGYTLFCOYYZKG-UHFFFAOYSA-N n,n-dichloroformamide Chemical compound ClN(Cl)C=O FSGYTLFCOYYZKG-UHFFFAOYSA-N 0.000 description 1
- YCJZWBZJSYLMPB-UHFFFAOYSA-N n-(2-chloropyrimidin-4-yl)-2,5-dimethyl-1-phenylimidazole-4-carboxamide Chemical compound CC=1N(C=2C=CC=CC=2)C(C)=NC=1C(=O)NC1=CC=NC(Cl)=N1 YCJZWBZJSYLMPB-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 201000009240 nasopharyngitis Diseases 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 210000002241 neurite Anatomy 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 201000002652 newborn respiratory distress syndrome Diseases 0.000 description 1
- 230000003040 nociceptive effect Effects 0.000 description 1
- 208000024696 nocturnal asthma Diseases 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 210000001331 nose Anatomy 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 208000007892 occupational asthma Diseases 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
- 239000008203 oral pharmaceutical composition Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N p-menthan-3-ol Chemical compound CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 201000005675 papillary conjunctivitis Diseases 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 208000022719 perennial allergic rhinitis Diseases 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 201000002513 peritoneal mesothelioma Diseases 0.000 description 1
- 210000004303 peritoneum Anatomy 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 210000003800 pharynx Anatomy 0.000 description 1
- 208000001297 phlebitis Diseases 0.000 description 1
- 210000001127 pigmented epithelial cell Anatomy 0.000 description 1
- 229940023488 pill Drugs 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 230000010118 platelet activation Effects 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 208000007232 portal hypertension Diseases 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 208000003476 primary myelofibrosis Diseases 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 208000026526 progressive weakness Diseases 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000004088 pulmonary circulation Effects 0.000 description 1
- 230000009325 pulmonary function Effects 0.000 description 1
- 238000009613 pulmonary function test Methods 0.000 description 1
- 201000003651 pulmonary sarcoidosis Diseases 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 210000003370 receptor cell Anatomy 0.000 description 1
- 229940041666 rectal gel Drugs 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 210000002254 renal artery Anatomy 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 208000032253 retinal ischemia Diseases 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 238000007790 scraping Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000001932 seasonal effect Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 239000002453 shampoo Substances 0.000 description 1
- 206010040560 shock Diseases 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 102000034285 signal transducing proteins Human genes 0.000 description 1
- 108091006024 signal transducing proteins Proteins 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 201000009890 sinusitis Diseases 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 230000016160 smooth muscle contraction Effects 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000006104 solid solution Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 206010062261 spinal cord neoplasm Diseases 0.000 description 1
- 208000005198 spinal stenosis Diseases 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 229940098466 sublingual tablet Drugs 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 206010043778 thyroiditis Diseases 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000009772 tissue formation Effects 0.000 description 1
- 230000008467 tissue growth Effects 0.000 description 1
- 230000007838 tissue remodeling Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 239000006211 transdermal dosage form Substances 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 208000037999 tubulointerstitial fibrosis Diseases 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000005740 tumor formation Effects 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 230000036967 uncompetitive effect Effects 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 208000014001 urinary system disease Diseases 0.000 description 1
- 201000002327 urinary tract obstruction Diseases 0.000 description 1
- MSRILKIQRXUYCT-UHFFFAOYSA-M valproate semisodium Chemical compound [Na+].CCCC(C(O)=O)CCC.CCCC(C([O-])=O)CCC MSRILKIQRXUYCT-UHFFFAOYSA-M 0.000 description 1
- 229960000604 valproic acid Drugs 0.000 description 1
- 230000006496 vascular abnormality Effects 0.000 description 1
- 230000000982 vasogenic effect Effects 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 208000009421 viral pneumonia Diseases 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D261/14—Nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
-
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/12—Antidiuretics, e.g. drugs for diabetes insipidus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Dermatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Vascular Medicine (AREA)
- Physical Education & Sports Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Gastroenterology & Hepatology (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12256808P | 2008-12-15 | 2008-12-15 | |
| US61/122,568 | 2008-12-15 | ||
| PCT/US2009/068106 WO2010077883A2 (en) | 2008-12-15 | 2009-12-15 | Antagonists of lysophosphatidic acid receptors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2012512178A true JP2012512178A (ja) | 2012-05-31 |
| JP2012512178A5 JP2012512178A5 (enExample) | 2013-02-14 |
Family
ID=41666879
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011540973A Pending JP2012512178A (ja) | 2008-12-15 | 2009-12-15 | リゾホスファチジン酸受容体のアンタゴニスト |
Country Status (18)
| Country | Link |
|---|---|
| US (4) | US20110301142A1 (enExample) |
| EP (1) | EP2358688B1 (enExample) |
| JP (1) | JP2012512178A (enExample) |
| KR (1) | KR101323054B1 (enExample) |
| CN (1) | CN102245584A (enExample) |
| AR (1) | AR074676A1 (enExample) |
| AU (1) | AU2009333275B2 (enExample) |
| BR (1) | BRPI0923512A2 (enExample) |
| CA (1) | CA2744221C (enExample) |
| EA (1) | EA201100691A1 (enExample) |
| GB (1) | GB2466121B (enExample) |
| IL (1) | IL212779A (enExample) |
| MX (1) | MX2011006407A (enExample) |
| SG (1) | SG172163A1 (enExample) |
| TW (1) | TWI415841B (enExample) |
| UY (1) | UY32327A (enExample) |
| WO (2) | WO2010077882A2 (enExample) |
| ZA (1) | ZA201103945B (enExample) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013506695A (ja) * | 2009-10-01 | 2013-02-28 | アミラ ファーマシューティカルス，インコーポレーテッド | リゾホスファチジン酸受容体アンタゴニストとしての化合物 |
| WO2017086430A1 (ja) * | 2015-11-20 | 2017-05-26 | 宇部興産株式会社 | Ｎａｓｈの治療又は予防のための医薬組成物 |
| JP2023544476A (ja) * | 2020-08-11 | 2023-10-24 | ビバ スター バイオサイエンシズ リミテッド | Ｌｐａ受容体アンタゴニストとしてのトリアゾール－ピリジニル置換アザシクロヘキシル酢酸化合物 |
Families Citing this family (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010016590A1 (ja) | 2008-08-07 | 2010-02-11 | 国立大学法人 長崎大学 | 全身性疼痛症候群の治療または予防薬 |
| US8455499B2 (en) | 2008-12-11 | 2013-06-04 | Amira Pharmaceuticals, Inc. | Alkyne antagonists of lysophosphatidic acid receptors |
| GB2466121B (en) | 2008-12-15 | 2010-12-08 | Amira Pharmaceuticals Inc | Antagonists of lysophosphatidic acid receptors |
| GB2470833B (en) * | 2009-06-03 | 2011-06-01 | Amira Pharmaceuticals Inc | Polycyclic antagonists of lysophosphatidic acid receptors |
| EP2462128B1 (en) | 2009-08-04 | 2016-09-21 | Amira Pharmaceuticals, Inc. | Compounds as lysophosphatidic acid receptor antagonists |
| GB2474748B (en) * | 2009-10-01 | 2011-10-12 | Amira Pharmaceuticals Inc | Polycyclic compounds as lysophosphatidic acid receptor antagonists |
| ES2530345T3 (es) | 2010-09-02 | 2015-03-02 | Merck Patent Gmbh | Derivados de pirazolopiridinona como antagonistas del receptor del LPA |
| US9556133B2 (en) * | 2010-12-07 | 2017-01-31 | Bristol-Myers Squibb Company | Polycyclic LPA1 antagonist and uses thereof |
| CA2820817A1 (en) * | 2010-12-07 | 2012-06-14 | Amira Pharmaceuticals, Inc. | Lysophosphatidic acid receptor antagonists and uses thereof |
| WO2012100436A1 (en) * | 2011-01-30 | 2012-08-02 | Curegenix Inc. | Compound as antagonist of lysophosphatidic acid receptor, composition, and use thereof |
| EP2694496A1 (en) | 2011-04-05 | 2014-02-12 | Amira Pharmaceuticals, Inc. | 3- or 5 - bi phenyl - 4 - ylisoxazole - based compounds useful for the treatment of fibrosis, pain, cancer and respiratory, allergic, nervous system or cardiovascular disorders |
| PH12014500355A1 (en) | 2011-08-15 | 2014-03-31 | Intermune Inc | Lysophosphatidic acid receptor antagonists |
| WO2013070879A1 (en) * | 2011-11-10 | 2013-05-16 | Bristol-Myers Squibb Company | Methods for treating spinal cord injury with lpa receptor antagonists |
| MX2014006130A (es) | 2011-11-22 | 2015-04-13 | Intermune Inc | Metodos de diagnostico y tratamiento de la fibrosis pulmonar idiopatica. |
| US20140329871A1 (en) * | 2011-12-04 | 2014-11-06 | Angion Biomedica Corp. | Small molecule anti-fibrotic compounds and uses thereof |
| CA2869602A1 (en) * | 2012-06-20 | 2013-12-27 | F. Hoffmann-La Roche Ag | Substituted pyrazole compounds as lpar antagonists |
| JP2015520202A (ja) * | 2012-06-20 | 2015-07-16 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | Ｌｐａｒ拮抗薬としてのｎ−アルキルトリアゾール化合物 |
| WO2014104372A1 (ja) * | 2012-12-28 | 2014-07-03 | 宇部興産株式会社 | ハロゲン置換へテロ環化合物 |
| PT3929207T (pt) | 2013-03-15 | 2024-10-21 | Univ Texas | Utilização do péptido fttftvt no tratamento de fibrose |
| BR112015023267B1 (pt) | 2013-03-15 | 2023-01-31 | Epigen Biosciences, Inc | Composto, e medicamento para tratar um indivíduo com doença ou condição lisofosfatídica dependente de ácido |
| EP3089986B1 (en) * | 2013-12-30 | 2019-06-26 | Rxbio Inc. | Crystalline salts of (z)-o-octadec-9-en-1-yl o,o-dihydrogen phosphorothioate |
| ES2824801T3 (es) * | 2014-06-27 | 2021-05-13 | Ube Industries | Sal de compuesto heterocíclico sustituido con halógeno |
| AU2016270373A1 (en) | 2015-06-05 | 2018-01-04 | Vertex Pharmaceuticals Incorporated | Triazoles for the treatment of demyelinating diseases |
| WO2018106641A1 (en) | 2016-12-06 | 2018-06-14 | Vertex Pharmaceuticals Incorporated | Pyrazoles for the treatment of demyelinating diseases |
| WO2018106643A1 (en) | 2016-12-06 | 2018-06-14 | Vertex Pharmaceuticals Incorporated | Heterocyclic azoles for the treatment of demyelinating diseases |
| WO2018106646A1 (en) | 2016-12-06 | 2018-06-14 | Vertex Pharmaceuticals Incorporated | Aminotriazoles for the treatment of demyelinating diseases |
| WO2019041340A1 (en) | 2017-09-04 | 2019-03-07 | Eli Lilly And Company | LYSOPHOSPHATIDE ACID RECEPTOR 1 RECEPTOR INHIBITORS (LPAR1) |
| JP7301840B2 (ja) | 2017-12-19 | 2023-07-03 | ブリストル－マイヤーズ スクイブ カンパニー | Ｌｐａアンタゴニストとしてのイソキサゾールｎ結合カルバモイルシクロヘキシル酸 |
| EP3849580A4 (en) | 2018-09-10 | 2022-06-15 | Lung Therapeutics, Inc. | Modified peptide fragments of cav-1 protein and the use thereof in the treatment of fibrosis |
| EP4058144A1 (en) | 2019-11-15 | 2022-09-21 | Gilead Sciences, Inc. | Triazole carbamate pyridyl sulfonamides as lpa receptor antagonists and uses thereof |
| TWI838626B (zh) | 2020-06-03 | 2024-04-11 | 美商基利科學股份有限公司 | Lpa受體拮抗劑及其用途 |
| AU2021282986B2 (en) | 2020-06-03 | 2024-03-07 | Gilead Sciences, Inc. | LPA receptor antagonists and uses thereof |
| WO2022006470A1 (en) | 2020-07-01 | 2022-01-06 | Vanderbilt University | Methods of treatment for a kidney disease |
| AU2022273631B2 (en) | 2021-05-11 | 2025-04-17 | Gilead Sciences, Inc. | Lpa receptor antagonists and uses thereof |
| KR20240007233A (ko) | 2021-05-13 | 2024-01-16 | 길리애드 사이언시즈, 인코포레이티드 | Lpa 수용체 길항제 및 이의 용도 |
| JP7709612B2 (ja) | 2021-12-08 | 2025-07-16 | ギリアード サイエンシーズ， インコーポレイテッド | Ｌｐａ受容体アンタゴニスト及びそれらの使用 |
| AR128613A1 (es) | 2022-02-25 | 2024-05-29 | Lhotse Bio Inc | Compuestos y composiciones para el tratamiento de afecciones asociadas con la actividad del receptor de lpa |
| CN115181069B (zh) * | 2022-07-15 | 2023-04-11 | 天津医科大学眼科医院 | 一种防治近视的化合物 |
| CN116236486B (zh) * | 2023-03-30 | 2024-03-22 | 复旦大学附属中山医院 | 髓过氧化物酶抑制剂在制备心脏保护药物中的应用 |
| CN117562896B (zh) * | 2023-11-23 | 2024-04-26 | 中国人民解放军海军军医大学第二附属医院 | Lpar拮抗剂在制备多发性骨髓瘤car t细胞联合治疗药物中的应用 |
| WO2025235487A1 (en) * | 2024-05-06 | 2025-11-13 | Ohio State Innovation Foundation | Lpa receptor antagonist-derived lipid compounds and uses thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001060819A1 (en) * | 2000-02-18 | 2001-08-23 | Kirin Beer Kabushiki Kaisha | Novel isoxazole and thiazole compounds and use thereof as drugs |
| WO2004031118A1 (ja) * | 2002-10-03 | 2004-04-15 | Ono Pharmaceutical Co., Ltd. | Ｌｐａ受容体拮抗剤 |
| WO2005012269A1 (ja) * | 2003-08-05 | 2005-02-10 | Ajinomoto Co., Inc. | 新規アゾール化合物 |
| WO2005058790A1 (ja) * | 2003-12-19 | 2005-06-30 | Ono Pharmaceutical Co., Ltd. | リゾホスファチジン酸受容体拮抗作用を有する化合物およびその用途 |
| WO2008014286A1 (en) * | 2006-07-24 | 2008-01-31 | University Of Virginia Patent Foundation | Vinyl phosphonate lysophosphatidic acid receptor antagonists |
Family Cites Families (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5612359A (en) * | 1994-08-26 | 1997-03-18 | Bristol-Myers Squibb Company | Substituted biphenyl isoxazole sulfonamides |
| US5861359A (en) | 1995-07-25 | 1999-01-19 | Fmc Corporation | Herbicidal phenylmethoxphenyl heterocycles |
| JP2001500482A (ja) | 1996-08-27 | 2001-01-16 | ノバルティス アクチェンゲゼルシャフト | 除草性ｓ置換１，２，４，６―チアトリアジン類 |
| WO1998028282A2 (en) | 1996-12-23 | 1998-07-02 | Du Pont Pharmaceuticals Company | OXYGEN OR SULFUR CONTAINING 5-MEMBERED HETEROAROMATICS AS FACTOR Xa INHIBITORS |
| JP3237608B2 (ja) * | 1997-04-21 | 2001-12-10 | 住友製薬株式会社 | イソキサゾール誘導体 |
| US20050119332A1 (en) | 1998-03-12 | 2005-06-02 | Lone Jeppesen | Substituted thiophene compounds as modulators of protein tyrosine phosphatases (PTPases) |
| US6413997B1 (en) | 1998-10-23 | 2002-07-02 | Dow Agrosciences Llc | 3-(substituted phenyl)-5-(substituted heterocyclyl)-1,2,4-triazole compounds |
| ATE241621T1 (de) | 1999-04-02 | 2003-06-15 | Bristol Myers Squibb Pharma Co | Arylsulfonyle als faktor xa inhibitoren |
| WO2002000651A2 (en) | 2000-06-27 | 2002-01-03 | Bristol-Myers Squibb Pharma Company | Factor xa inhibitors |
| WO2002062389A1 (en) | 2001-02-08 | 2002-08-15 | Ono Pharmaceutical Co., Ltd. | Remedies for urinary diseases comprising lpa receptor controlling agents |
| US7521192B2 (en) | 2001-04-18 | 2009-04-21 | Rigel Pharmaceuticals, Inc. | EDG: modulators of lymphocyte activation and migration |
| JPWO2003007991A1 (ja) | 2001-07-17 | 2004-11-04 | 小野薬品工業株式会社 | Ｌｐａ受容体調節剤からなる膵液分泌制御剤 |
| MY151199A (en) | 2001-11-02 | 2014-04-30 | Rigel Pharmaceuticals Inc | Substituted diphenyl heterocycles useful for treating hcv infection |
| WO2003055481A1 (en) | 2001-12-25 | 2003-07-10 | Ajinomoto Co., Inc. | Organ fibrosis inhibitors |
| US20050261298A1 (en) | 2002-01-18 | 2005-11-24 | David Solow-Cordero | Methods of treating conditions associated with an Edg-7 receptor |
| CA2473740A1 (en) | 2002-01-18 | 2003-07-31 | David Solow-Cordero | Methods of treating conditions associated with an edg receptor |
| US20050101518A1 (en) | 2002-01-18 | 2005-05-12 | David Solow-Cordero | Methods of treating conditions associated with an EDG-2 receptor |
| US20050113283A1 (en) | 2002-01-18 | 2005-05-26 | David Solow-Cordero | Methods of treating conditions associated with an EDG-4 receptor |
| US20040014662A1 (en) | 2002-05-08 | 2004-01-22 | Per Lindquist | Modulation of neural stem cells and neural progenitor cells |
| US7229987B2 (en) | 2002-05-13 | 2007-06-12 | Eli Lilly And Company | Multicyclic compounds for use as melanin concentrating hormone antagonists in the treatment of obesity and diabetes |
| WO2003099765A1 (en) | 2002-05-28 | 2003-12-04 | Ono Pharmaceutical Co., Ltd. | β-ALANINE DERIVATIVE AND USE THEREOF |
| AU2003241834A1 (en) * | 2002-06-26 | 2004-01-19 | Ono Pharmaceutical Co., Ltd. | Remedy for chronic disease |
| EP1570081A4 (en) | 2002-11-19 | 2006-05-31 | Amgen Inc | AMPLIFIED GENES INVOLVED IN CANCER |
| US20040192739A1 (en) | 2003-01-16 | 2004-09-30 | David Solow-Cordero | Methods of treating conditions associated with an Edg-2 receptor |
| US20040167132A1 (en) | 2003-01-16 | 2004-08-26 | Geetha Shankar | Methods of treating conditions associted with an Edg-2 receptor |
| US20050065194A1 (en) | 2003-01-16 | 2005-03-24 | Geetha Shankar | Methods of treating conditions associated with an Edg-2 receptor |
| US7135469B2 (en) | 2003-03-18 | 2006-11-14 | Bristol Myers Squibb, Co. | Linear chain substituted monocyclic and bicyclic derivatives as factor Xa inhibitors |
| US7115642B2 (en) * | 2003-05-02 | 2006-10-03 | Rigel Pharmaceuticals, Inc. | Substituted diphenyl isoxazoles, pyrazoles and oxadiazoles useful for treating HCV infection |
| DE10360369A1 (de) | 2003-12-22 | 2005-07-14 | Bayer Cropscience Ag | Amide |
| JP5544503B2 (ja) * | 2004-05-24 | 2014-07-09 | 独立行政法人物質・材料研究機構 | マリモカーボン及びその製造方法並びにその製造装置 |
| JP2006096712A (ja) | 2004-09-30 | 2006-04-13 | Senju Pharmaceut Co Ltd | Ｌｐａ受容体拮抗剤を含有する角膜知覚改善剤 |
| DE102005018389A1 (de) * | 2005-04-20 | 2006-10-26 | Sanofi-Aventis Deutschland Gmbh | Azolderivate als Inhibitoren von Lipasen und Phospholipasen |
| JP2008545767A (ja) | 2005-06-08 | 2008-12-18 | ノバルティス アクチエンゲゼルシャフト | 多環式オキサジアゾールまたはイソキサゾールおよびｓｉｐ受容体リガンドとしてのそれらの使用 |
| WO2007007588A1 (ja) | 2005-07-08 | 2007-01-18 | Ono Pharmaceutical Co., Ltd. | 平面性を有する環状基を母核とする化合物 |
| US20090221547A1 (en) | 2005-08-23 | 2009-09-03 | Irm Llc | Immunosuppressant Compounds and Compositions |
| CA2643670A1 (en) | 2006-02-27 | 2007-08-30 | Sterix Limited | Diaryl compounds as non-steroidal inhibitors of 17-beta hydroxysteroid dehydrogenase and/or steroid sulphatase for the treatment of oestrogen-related diseases such as hormone dependent breast cancer |
| US20090029949A1 (en) | 2006-05-25 | 2009-01-29 | Parrill-Baker Abby L | GPCR Ligands Identified by Computational Modeling |
| US20080051372A1 (en) | 2006-08-24 | 2008-02-28 | The Scripps Research Institute | Methods utilizing cell-signaling lysophospholipids |
| WO2008024979A2 (en) | 2006-08-24 | 2008-02-28 | The Scripps Research Institute | Methods utilizing cell-signaling lysophospholipids |
| US20100143381A1 (en) | 2007-03-12 | 2010-06-10 | Andrew Tager | Lysophosphatidic acid receptor targeting for lung disease |
| US20090069288A1 (en) | 2007-07-16 | 2009-03-12 | Breinlinger Eric C | Novel therapeutic compounds |
| NZ588807A (en) | 2008-05-05 | 2011-07-29 | Sanofi Aventis | Acylamino-substituted fused cyclopentanecarboxylic acid derivatives and their use as pharmaceuticals |
| US8455499B2 (en) * | 2008-12-11 | 2013-06-04 | Amira Pharmaceuticals, Inc. | Alkyne antagonists of lysophosphatidic acid receptors |
| GB2466121B (en) | 2008-12-15 | 2010-12-08 | Amira Pharmaceuticals Inc | Antagonists of lysophosphatidic acid receptors |
| GB2470833B (en) | 2009-06-03 | 2011-06-01 | Amira Pharmaceuticals Inc | Polycyclic antagonists of lysophosphatidic acid receptors |
| EP2462128B1 (en) | 2009-08-04 | 2016-09-21 | Amira Pharmaceuticals, Inc. | Compounds as lysophosphatidic acid receptor antagonists |
| GB2474748B (en) | 2009-10-01 | 2011-10-12 | Amira Pharmaceuticals Inc | Polycyclic compounds as lysophosphatidic acid receptor antagonists |
| GB2474120B (en) | 2009-10-01 | 2011-12-21 | Amira Pharmaceuticals Inc | Compounds as Lysophosphatidic acid receptor antagonists |
-
2009
- 2009-12-10 GB GB0921606A patent/GB2466121B/en not_active Expired - Fee Related
- 2009-12-15 AU AU2009333275A patent/AU2009333275B2/en not_active Ceased
- 2009-12-15 SG SG2011043627A patent/SG172163A1/en unknown
- 2009-12-15 US US13/139,271 patent/US20110301142A1/en not_active Abandoned
- 2009-12-15 UY UY0001032327A patent/UY32327A/es not_active Application Discontinuation
- 2009-12-15 EA EA201100691A patent/EA201100691A1/ru unknown
- 2009-12-15 CA CA2744221A patent/CA2744221C/en not_active Expired - Fee Related
- 2009-12-15 TW TW098142946A patent/TWI415841B/zh not_active IP Right Cessation
- 2009-12-15 EP EP09836853.3A patent/EP2358688B1/en active Active
- 2009-12-15 US US13/139,260 patent/US20110301211A1/en not_active Abandoned
- 2009-12-15 CN CN2009801506164A patent/CN102245584A/zh active Pending
- 2009-12-15 US US12/638,702 patent/US8048902B2/en active Active
- 2009-12-15 MX MX2011006407A patent/MX2011006407A/es active IP Right Grant
- 2009-12-15 AR ARP090104891A patent/AR074676A1/es not_active Application Discontinuation
- 2009-12-15 KR KR1020117013405A patent/KR101323054B1/ko not_active Expired - Fee Related
- 2009-12-15 WO PCT/US2009/068105 patent/WO2010077882A2/en not_active Ceased
- 2009-12-15 JP JP2011540973A patent/JP2012512178A/ja active Pending
- 2009-12-15 BR BRPI0923512A patent/BRPI0923512A2/pt not_active IP Right Cessation
- 2009-12-15 WO PCT/US2009/068106 patent/WO2010077883A2/en not_active Ceased
-
2011
- 2011-04-22 US US13/092,860 patent/US8440707B2/en active Active
- 2011-05-09 IL IL212779A patent/IL212779A/en not_active IP Right Cessation
- 2011-05-27 ZA ZA2011/03945A patent/ZA201103945B/en unknown
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001060819A1 (en) * | 2000-02-18 | 2001-08-23 | Kirin Beer Kabushiki Kaisha | Novel isoxazole and thiazole compounds and use thereof as drugs |
| WO2004031118A1 (ja) * | 2002-10-03 | 2004-04-15 | Ono Pharmaceutical Co., Ltd. | Ｌｐａ受容体拮抗剤 |
| WO2005012269A1 (ja) * | 2003-08-05 | 2005-02-10 | Ajinomoto Co., Inc. | 新規アゾール化合物 |
| WO2005058790A1 (ja) * | 2003-12-19 | 2005-06-30 | Ono Pharmaceutical Co., Ltd. | リゾホスファチジン酸受容体拮抗作用を有する化合物およびその用途 |
| WO2008014286A1 (en) * | 2006-07-24 | 2008-01-31 | University Of Virginia Patent Foundation | Vinyl phosphonate lysophosphatidic acid receptor antagonists |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013506695A (ja) * | 2009-10-01 | 2013-02-28 | アミラ ファーマシューティカルス，インコーポレーテッド | リゾホスファチジン酸受容体アンタゴニストとしての化合物 |
| WO2017086430A1 (ja) * | 2015-11-20 | 2017-05-26 | 宇部興産株式会社 | Ｎａｓｈの治療又は予防のための医薬組成物 |
| CN108348610A (zh) * | 2015-11-20 | 2018-07-31 | 宇部兴产株式会社 | 用于治疗或预防nash的医药组合物 |
| JP2023544476A (ja) * | 2020-08-11 | 2023-10-24 | ビバ スター バイオサイエンシズ リミテッド | Ｌｐａ受容体アンタゴニストとしてのトリアゾール－ピリジニル置換アザシクロヘキシル酢酸化合物 |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2012512178A (ja) | リゾホスファチジン酸受容体のアンタゴニスト | |
| TWI401082B (zh) | 作為溶血磷脂酸受體拮抗劑之化合物 | |
| US10000456B2 (en) | Polycyclic compounds as lysophosphatidic acid receptor antagonists | |
| TWI405757B (zh) | 溶血磷脂酸受體之多環拮抗劑 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20121213 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20121213 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140217 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20140804 |