AU2007227274A1 - S1P receptor modulating compounds - Google Patents
S1P receptor modulating compounds Download PDFInfo
- Publication number
- AU2007227274A1 AU2007227274A1 AU2007227274A AU2007227274A AU2007227274A1 AU 2007227274 A1 AU2007227274 A1 AU 2007227274A1 AU 2007227274 A AU2007227274 A AU 2007227274A AU 2007227274 A AU2007227274 A AU 2007227274A AU 2007227274 A1 AU2007227274 A1 AU 2007227274A1
- Authority
- AU
- Australia
- Prior art keywords
- compound
- alkyl
- halo
- alkoxy
- oxoimidazolidin
- 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.)
- Abandoned
Links
- 150000001875 compounds Chemical class 0.000 title claims description 181
- 102000011011 Sphingosine 1-phosphate receptors Human genes 0.000 title description 7
- 108050001083 Sphingosine 1-phosphate receptors Proteins 0.000 title description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 82
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 62
- -1 C2-6 alkeπyl Chemical group 0.000 claims description 60
- 125000003545 alkoxy group Chemical group 0.000 claims description 51
- 125000003118 aryl group Chemical group 0.000 claims description 43
- 102000005962 receptors Human genes 0.000 claims description 40
- 108020003175 receptors Proteins 0.000 claims description 40
- 229910052739 hydrogen Inorganic materials 0.000 claims description 35
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 34
- 238000000034 method Methods 0.000 claims description 34
- GFZWHAAOIVMHOI-UHFFFAOYSA-N azetidine-3-carboxylic acid Chemical compound OC(=O)C1CNC1 GFZWHAAOIVMHOI-UHFFFAOYSA-N 0.000 claims description 31
- 239000001257 hydrogen Substances 0.000 claims description 31
- 125000001072 heteroaryl group Chemical group 0.000 claims description 30
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 22
- 125000004414 alkyl thio group Chemical group 0.000 claims description 21
- 229910052799 carbon Inorganic materials 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- 150000002367 halogens Chemical group 0.000 claims description 19
- 229910052717 sulfur Inorganic materials 0.000 claims description 19
- 229910052760 oxygen Inorganic materials 0.000 claims description 18
- 239000003937 drug carrier Substances 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 17
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 14
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 13
- 239000001301 oxygen Substances 0.000 claims description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- 125000004429 atom Chemical group 0.000 claims description 11
- 230000001404 mediated effect Effects 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 125000003282 alkyl amino group Chemical group 0.000 claims description 9
- 125000001769 aryl amino group Chemical group 0.000 claims description 9
- 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 claims description 8
- 125000002947 alkylene group Chemical group 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- 208000023275 Autoimmune disease Diseases 0.000 claims description 6
- 230000001154 acute effect Effects 0.000 claims description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
- 239000011734 sodium Substances 0.000 claims description 6
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 5
- 229940044601 receptor agonist Drugs 0.000 claims description 5
- 239000000018 receptor agonist Substances 0.000 claims description 5
- VRCMDIJUDHBXJY-UHFFFAOYSA-N 1-[[4-[3-(4-benzylphenyl)-2-oxoimidazolidin-1-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(N2C(N(CC2)C=2C=CC(CC=3C=CC=CC=3)=CC=2)=O)C=C1 VRCMDIJUDHBXJY-UHFFFAOYSA-N 0.000 claims description 4
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 4
- 208000011231 Crohn disease Diseases 0.000 claims description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 4
- 206010028980 Neoplasm Diseases 0.000 claims description 4
- 201000004681 Psoriasis Diseases 0.000 claims description 4
- 206010052779 Transplant rejections Diseases 0.000 claims description 4
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 4
- 201000006417 multiple sclerosis Diseases 0.000 claims description 4
- 229940044551 receptor antagonist Drugs 0.000 claims description 4
- 239000002464 receptor antagonist Substances 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- BIPVZXIAFMRKRN-UHFFFAOYSA-N 1-[[4-[2-oxo-3-[3-(trifluoromethyl)phenyl]imidazolidin-1-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(N2C(N(CC2)C=2C=C(C=CC=2)C(F)(F)F)=O)C=C1 BIPVZXIAFMRKRN-UHFFFAOYSA-N 0.000 claims description 3
- BIXKOKIZYRGKIF-UHFFFAOYSA-N 1-[[4-[3-(3-tert-butylphenyl)-2-oxoimidazolidin-1-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound CC(C)(C)C1=CC=CC(N2C(N(CC2)C=2C=CC(CN3CC(C3)C(O)=O)=CC=2)=O)=C1 BIXKOKIZYRGKIF-UHFFFAOYSA-N 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- 125000001188 haloalkyl group Chemical group 0.000 claims description 3
- 208000027866 inflammatory disease Diseases 0.000 claims description 3
- 206010025323 Lymphomas Diseases 0.000 claims description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- 125000005241 heteroarylamino group Chemical group 0.000 claims description 2
- 206010025135 lupus erythematosus Diseases 0.000 claims description 2
- 239000011777 magnesium Substances 0.000 claims description 2
- 229910052749 magnesium Inorganic materials 0.000 claims description 2
- 239000004031 partial agonist Substances 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 1
- 159000000007 calcium salts Chemical class 0.000 claims 1
- IPZJQDSFZGZEOY-UHFFFAOYSA-N dimethylmethylene Chemical compound C[C]C IPZJQDSFZGZEOY-UHFFFAOYSA-N 0.000 claims 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims 1
- 239000002469 receptor inverse agonist Substances 0.000 claims 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 126
- 239000000126 substance Substances 0.000 description 68
- 239000000243 solution Substances 0.000 description 53
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- 238000005481 NMR spectroscopy Methods 0.000 description 36
- 238000009472 formulation Methods 0.000 description 36
- 239000003814 drug Substances 0.000 description 33
- 101001062098 Homo sapiens RNA-binding protein 14 Proteins 0.000 description 32
- 229940125904 compound 1 Drugs 0.000 description 32
- 102100022888 KN motif and ankyrin repeat domain-containing protein 2 Human genes 0.000 description 31
- 239000003795 chemical substances by application Substances 0.000 description 31
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 238000002360 preparation method Methods 0.000 description 30
- 239000004480 active ingredient Substances 0.000 description 29
- 230000000694 effects Effects 0.000 description 27
- 239000002775 capsule Substances 0.000 description 26
- 235000002639 sodium chloride Nutrition 0.000 description 26
- 125000000304 alkynyl group Chemical group 0.000 description 24
- 239000003826 tablet Substances 0.000 description 24
- 239000007787 solid Substances 0.000 description 23
- 239000002904 solvent Substances 0.000 description 23
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 22
- 125000003342 alkenyl group Chemical group 0.000 description 22
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 21
- 238000011282 treatment Methods 0.000 description 21
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 20
- 239000007788 liquid Substances 0.000 description 20
- 229940124597 therapeutic agent Drugs 0.000 description 20
- 210000001519 tissue Anatomy 0.000 description 19
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 18
- 125000000623 heterocyclic group Chemical group 0.000 description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
- 239000004615 ingredient Substances 0.000 description 17
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 15
- 239000000843 powder Substances 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- 201000010099 disease Diseases 0.000 description 13
- 239000011780 sodium chloride Substances 0.000 description 13
- 230000001225 therapeutic effect Effects 0.000 description 13
- 239000006185 dispersion Substances 0.000 description 12
- 239000002552 dosage form Substances 0.000 description 12
- 125000005843 halogen group Chemical group 0.000 description 12
- 238000002347 injection Methods 0.000 description 12
- 239000007924 injection Substances 0.000 description 12
- 238000001990 intravenous administration Methods 0.000 description 12
- 208000028867 ischemia Diseases 0.000 description 12
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 12
- 239000000546 pharmaceutical excipient Substances 0.000 description 12
- 239000006187 pill Substances 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 239000000556 agonist Substances 0.000 description 11
- 239000000969 carrier Substances 0.000 description 11
- 238000002648 combination therapy Methods 0.000 description 11
- 150000002431 hydrogen Chemical class 0.000 description 11
- 238000007918 intramuscular administration Methods 0.000 description 11
- 108010010803 Gelatin Proteins 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- 239000013543 active substance Substances 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- 150000007942 carboxylates Chemical class 0.000 description 10
- 238000000576 coating method Methods 0.000 description 10
- 239000002612 dispersion medium Substances 0.000 description 10
- 239000008273 gelatin Substances 0.000 description 10
- 229920000159 gelatin Polymers 0.000 description 10
- 229940014259 gelatin Drugs 0.000 description 10
- 235000019322 gelatine Nutrition 0.000 description 10
- 235000011852 gelatine desserts Nutrition 0.000 description 10
- 239000003446 ligand Substances 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
- 229910019142 PO4 Inorganic materials 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 230000006378 damage Effects 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- 210000000056 organ Anatomy 0.000 description 9
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 9
- 239000010452 phosphate Substances 0.000 description 9
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 8
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 8
- 208000002193 Pain Diseases 0.000 description 8
- 230000009471 action Effects 0.000 description 8
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 8
- 229940121375 antifungal agent Drugs 0.000 description 8
- 125000004658 aryl carbonyl amino group Chemical group 0.000 description 8
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 8
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 8
- 208000035475 disorder Diseases 0.000 description 8
- 235000011187 glycerol Nutrition 0.000 description 8
- 125000005842 heteroatom Chemical group 0.000 description 8
- 239000008101 lactose Substances 0.000 description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 8
- 238000007911 parenteral administration Methods 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 238000007920 subcutaneous administration Methods 0.000 description 8
- 239000000829 suppository Substances 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- 229920002261 Corn starch Polymers 0.000 description 7
- 108091006027 G proteins Proteins 0.000 description 7
- 102000030782 GTP binding Human genes 0.000 description 7
- 108091000058 GTP-Binding Proteins 0.000 description 7
- 208000027418 Wounds and injury Diseases 0.000 description 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 7
- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 description 7
- 125000004947 alkyl aryl amino group Chemical group 0.000 description 7
- 125000002877 alkyl aryl group Chemical group 0.000 description 7
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 7
- 125000004691 alkyl thio carbonyl group Chemical group 0.000 description 7
- 125000005199 aryl carbonyloxy group Chemical group 0.000 description 7
- 125000005110 aryl thio group Chemical group 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 239000008120 corn starch Substances 0.000 description 7
- 229940099112 cornstarch Drugs 0.000 description 7
- 125000004663 dialkyl amino group Chemical group 0.000 description 7
- 125000004986 diarylamino group Chemical group 0.000 description 7
- 238000007912 intraperitoneal administration Methods 0.000 description 7
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 7
- 150000003467 sulfuric acid derivatives Chemical group 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- 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 6
- 241001465754 Metazoa Species 0.000 description 6
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 6
- 229930006000 Sucrose Natural products 0.000 description 6
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
- 125000004442 acylamino group Chemical group 0.000 description 6
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 6
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 description 6
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 6
- 239000005557 antagonist Substances 0.000 description 6
- 230000000844 anti-bacterial effect Effects 0.000 description 6
- 125000005129 aryl carbonyl group Chemical group 0.000 description 6
- 125000005200 aryloxy carbonyloxy group Chemical group 0.000 description 6
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 6
- 230000004071 biological effect Effects 0.000 description 6
- 208000014674 injury Diseases 0.000 description 6
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 6
- 239000007951 isotonicity adjuster Substances 0.000 description 6
- 235000019359 magnesium stearate Nutrition 0.000 description 6
- 244000005700 microbiome Species 0.000 description 6
- 231100000252 nontoxic Toxicity 0.000 description 6
- 230000003000 nontoxic effect Effects 0.000 description 6
- 229920001223 polyethylene glycol Polymers 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 239000003755 preservative agent Substances 0.000 description 6
- 230000002265 prevention Effects 0.000 description 6
- 239000003381 stabilizer Substances 0.000 description 6
- 239000005720 sucrose Substances 0.000 description 6
- 125000004434 sulfur atom Chemical group 0.000 description 6
- 238000002054 transplantation Methods 0.000 description 6
- 239000003981 vehicle Substances 0.000 description 6
- DFISRMXKVKAKMB-UHFFFAOYSA-N 1-[[4-[3-(4-tert-butylphenyl)-2-oxoimidazolidin-1-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1=CC(C(C)(C)C)=CC=C1N1C(=O)N(C=2C=CC(CN3CC(C3)C(O)=O)=CC=2)CC1 DFISRMXKVKAKMB-UHFFFAOYSA-N 0.000 description 5
- 102000013446 GTP Phosphohydrolases Human genes 0.000 description 5
- 108091006109 GTPases Proteins 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- 239000003242 anti bacterial agent Substances 0.000 description 5
- 239000003429 antifungal agent Substances 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 125000000392 cycloalkenyl group Chemical group 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 description 5
- 238000001802 infusion Methods 0.000 description 5
- 238000010253 intravenous injection Methods 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 230000010410 reperfusion Effects 0.000 description 5
- 239000008107 starch Substances 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- 239000011593 sulfur Substances 0.000 description 5
- WRGQSWVCFNIUNZ-GDCKJWNLSA-N 1-oleoyl-sn-glycerol 3-phosphate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)COP(O)(O)=O WRGQSWVCFNIUNZ-GDCKJWNLSA-N 0.000 description 4
- FZWBNHMXJMCXLU-UHFFFAOYSA-N 2,3,4,5-tetrahydroxy-6-[3,4,5-trihydroxy-6-[[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]oxan-2-yl]oxyhexanal Chemical compound OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OCC(O)C(O)C(O)C(O)C=O)O1 FZWBNHMXJMCXLU-UHFFFAOYSA-N 0.000 description 4
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 4
- 241000416162 Astragalus gummifer Species 0.000 description 4
- 241000167854 Bourreria succulenta Species 0.000 description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 4
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 4
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 206010021143 Hypoxia Diseases 0.000 description 4
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 4
- 240000007472 Leucaena leucocephala Species 0.000 description 4
- 229930195725 Mannitol Natural products 0.000 description 4
- LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 4
- 235000019483 Peanut oil Nutrition 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical group C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- 229920001800 Shellac Polymers 0.000 description 4
- 229920001615 Tragacanth Polymers 0.000 description 4
- 239000003070 absorption delaying agent Substances 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 125000002252 acyl group Chemical group 0.000 description 4
- 235000010443 alginic acid Nutrition 0.000 description 4
- 229920000615 alginic acid Polymers 0.000 description 4
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 4
- 125000000129 anionic group Chemical group 0.000 description 4
- 239000012736 aqueous medium Substances 0.000 description 4
- 208000006673 asthma Diseases 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 239000001768 carboxy methyl cellulose Substances 0.000 description 4
- 230000036755 cellular response Effects 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 235000019693 cherries Nutrition 0.000 description 4
- 229960004926 chlorobutanol Drugs 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 229940119744 dextran 40 Drugs 0.000 description 4
- 229940119743 dextran 70 Drugs 0.000 description 4
- 235000005911 diet Nutrition 0.000 description 4
- 230000037213 diet Effects 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 239000012055 enteric layer Substances 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 235000003599 food sweetener Nutrition 0.000 description 4
- 238000004108 freeze drying Methods 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 4
- 230000001146 hypoxic effect Effects 0.000 description 4
- 210000000987 immune system Anatomy 0.000 description 4
- 229960003444 immunosuppressant agent Drugs 0.000 description 4
- 239000003018 immunosuppressive agent Substances 0.000 description 4
- 238000010255 intramuscular injection Methods 0.000 description 4
- 239000007927 intramuscular injection Substances 0.000 description 4
- 210000004153 islets of langerhan Anatomy 0.000 description 4
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 4
- 239000006193 liquid solution Substances 0.000 description 4
- 239000006194 liquid suspension Substances 0.000 description 4
- 239000006210 lotion Substances 0.000 description 4
- 239000000594 mannitol Substances 0.000 description 4
- 235000010355 mannitol Nutrition 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 4
- JJEJWKYMXZCGPN-UHFFFAOYSA-N methyl 4-(2-oxoimidazolidin-1-yl)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1N1C(=O)NCC1 JJEJWKYMXZCGPN-UHFFFAOYSA-N 0.000 description 4
- 229920000609 methyl cellulose Polymers 0.000 description 4
- 235000010981 methylcellulose Nutrition 0.000 description 4
- 239000001923 methylcellulose Substances 0.000 description 4
- 239000002324 mouth wash Substances 0.000 description 4
- 239000000312 peanut oil Substances 0.000 description 4
- 230000035515 penetration Effects 0.000 description 4
- 239000008196 pharmacological composition Substances 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 229920001592 potato starch Polymers 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000002035 prolonged effect Effects 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 239000008159 sesame oil Substances 0.000 description 4
- 235000011803 sesame oil Nutrition 0.000 description 4
- 239000004208 shellac Substances 0.000 description 4
- 229940113147 shellac Drugs 0.000 description 4
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 4
- 235000013874 shellac Nutrition 0.000 description 4
- 235000015424 sodium Nutrition 0.000 description 4
- 239000008247 solid mixture Substances 0.000 description 4
- 230000001954 sterilising effect Effects 0.000 description 4
- 238000004659 sterilization and disinfection Methods 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- 239000003765 sweetening agent Substances 0.000 description 4
- 235000020357 syrup Nutrition 0.000 description 4
- 239000006188 syrup Substances 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- 229940033134 talc Drugs 0.000 description 4
- 235000012222 talc Nutrition 0.000 description 4
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 4
- 229940033663 thimerosal Drugs 0.000 description 4
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 4
- 238000001291 vacuum drying Methods 0.000 description 4
- BIWMVMWKMBGRFU-UHFFFAOYSA-N 1-[[4-[3-(3-cyclohexylphenyl)-2-oxoimidazolidin-1-yl]-3-fluorophenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC(C=C1F)=CC=C1N1C(=O)N(C=2C=C(C=CC=2)C2CCCCC2)CC1 BIWMVMWKMBGRFU-UHFFFAOYSA-N 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- 102000009027 Albumins Human genes 0.000 description 3
- 108010088751 Albumins Proteins 0.000 description 3
- 208000000094 Chronic Pain Diseases 0.000 description 3
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 3
- 206010018364 Glomerulonephritis Diseases 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 3
- 125000002723 alicyclic group Chemical group 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 230000003466 anti-cipated effect Effects 0.000 description 3
- 230000000843 anti-fungal effect Effects 0.000 description 3
- 239000007900 aqueous suspension Substances 0.000 description 3
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 3
- 239000001506 calcium phosphate Substances 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 3
- 229940038472 dicalcium phosphate Drugs 0.000 description 3
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 3
- 235000019439 ethyl acetate Nutrition 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 208000006454 hepatitis Diseases 0.000 description 3
- 231100000283 hepatitis Toxicity 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 230000002519 immonomodulatory effect Effects 0.000 description 3
- 230000028993 immune response Effects 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- 210000004379 membrane Anatomy 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- XWCBIWVBFMGMMH-UHFFFAOYSA-N methyl 4-(2-chloroethylcarbamoylamino)benzoate Chemical compound COC(=O)C1=CC=C(NC(=O)NCCCl)C=C1 XWCBIWVBFMGMMH-UHFFFAOYSA-N 0.000 description 3
- 125000004430 oxygen atom Chemical group O* 0.000 description 3
- 125000004437 phosphorous atom Chemical group 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- DUYSYHSSBDVJSM-KRWOKUGFSA-N sphingosine 1-phosphate Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)COP(O)(O)=O DUYSYHSSBDVJSM-KRWOKUGFSA-N 0.000 description 3
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 3
- 125000003107 substituted aryl group Chemical group 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 230000002459 sustained effect Effects 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- AJDUQFGDOSVMJF-UHFFFAOYSA-N 1-(4-tert-butylphenyl)-3-[4-(hydroxymethyl)phenyl]imidazolidin-2-one Chemical compound C1=CC(C(C)(C)C)=CC=C1N1C(=O)N(C=2C=CC(CO)=CC=2)CC1 AJDUQFGDOSVMJF-UHFFFAOYSA-N 0.000 description 2
- IPRHNYQOAGIGMI-UHFFFAOYSA-N 1-[[4-[3-(3-benzylphenyl)-2-oxoimidazolidin-1-yl]-3-fluorophenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC(C=C1F)=CC=C1N1C(=O)N(C=2C=C(CC=3C=CC=CC=3)C=CC=2)CC1 IPRHNYQOAGIGMI-UHFFFAOYSA-N 0.000 description 2
- VDCOAFQPTCADQT-UHFFFAOYSA-N 1-[[4-[3-(4-butylphenyl)-2-oxoimidazolidin-1-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1=CC(CCCC)=CC=C1N1C(=O)N(C=2C=CC(CN3CC(C3)C(O)=O)=CC=2)CC1 VDCOAFQPTCADQT-UHFFFAOYSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- LCZKVTRNMXQDSZ-UHFFFAOYSA-N 4-[3-(4-tert-butylphenyl)-2-oxoimidazolidin-1-yl]benzaldehyde Chemical compound C1=CC(C(C)(C)C)=CC=C1N1C(=O)N(C=2C=CC(C=O)=CC=2)CC1 LCZKVTRNMXQDSZ-UHFFFAOYSA-N 0.000 description 2
- ZDRVLAOYDGQLFI-UHFFFAOYSA-N 4-[[4-(4-chlorophenyl)-1,3-thiazol-2-yl]amino]phenol;hydrochloride Chemical compound Cl.C1=CC(O)=CC=C1NC1=NC(C=2C=CC(Cl)=CC=2)=CS1 ZDRVLAOYDGQLFI-UHFFFAOYSA-N 0.000 description 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- 235000006491 Acacia senegal Nutrition 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 101100156448 Caenorhabditis elegans vps-33.1 gene Proteins 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 2
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 2
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 2
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 2
- 108010036949 Cyclosporine Proteins 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 206010016654 Fibrosis Diseases 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- 206010018691 Granuloma Diseases 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 101001038001 Homo sapiens Lysophosphatidic acid receptor 2 Proteins 0.000 description 2
- 101001038006 Homo sapiens Lysophosphatidic acid receptor 3 Proteins 0.000 description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 108010076876 Keratins Proteins 0.000 description 2
- 102000011782 Keratins Human genes 0.000 description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 2
- 239000004166 Lanolin Substances 0.000 description 2
- 239000004367 Lipase Substances 0.000 description 2
- 102000004882 Lipase Human genes 0.000 description 2
- 108090001060 Lipase Proteins 0.000 description 2
- 208000019693 Lung disease Diseases 0.000 description 2
- 102100040387 Lysophosphatidic acid receptor 2 Human genes 0.000 description 2
- 102100040388 Lysophosphatidic acid receptor 3 Human genes 0.000 description 2
- 244000246386 Mentha pulegium Species 0.000 description 2
- 235000016257 Mentha pulegium Nutrition 0.000 description 2
- 235000004357 Mentha x piperita Nutrition 0.000 description 2
- FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 101100189356 Mus musculus Papolb gene Proteins 0.000 description 2
- 241000238367 Mya arenaria Species 0.000 description 2
- 101710143583 Na(+)/H(+) exchange regulatory cofactor NHE-RF2 Proteins 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 206010028851 Necrosis Diseases 0.000 description 2
- 208000001294 Nociceptive Pain Diseases 0.000 description 2
- 208000001132 Osteoporosis Diseases 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- 102000035195 Peptidases Human genes 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 239000004264 Petrolatum Substances 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- 206010063837 Reperfusion injury Diseases 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
- 102100025747 Sphingosine 1-phosphate receptor 3 Human genes 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 208000025865 Ulcer Diseases 0.000 description 2
- 206010046851 Uveitis Diseases 0.000 description 2
- 102100028458 Zinc finger E-box-binding homeobox 2 Human genes 0.000 description 2
- 230000001594 aberrant effect Effects 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 229940081735 acetylcellulose Drugs 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 229960000552 alclometasone Drugs 0.000 description 2
- FJXOGVLKCZQRDN-PHCHRAKRSA-N alclometasone Chemical compound C([C@H]1Cl)C2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O FJXOGVLKCZQRDN-PHCHRAKRSA-N 0.000 description 2
- 229940072056 alginate Drugs 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 150000004781 alginic acids Chemical class 0.000 description 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 230000001363 autoimmune Effects 0.000 description 2
- 229960000686 benzalkonium chloride Drugs 0.000 description 2
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 2
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 2
- 229960001950 benzethonium chloride Drugs 0.000 description 2
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 2
- 229960002537 betamethasone Drugs 0.000 description 2
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-DVTGEIKXSA-N 0.000 description 2
- 229960000074 biopharmaceutical Drugs 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002301 cellulose acetate Polymers 0.000 description 2
- 229960000541 cetyl alcohol Drugs 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000007958 cherry flavor Substances 0.000 description 2
- 229960001265 ciclosporin Drugs 0.000 description 2
- 239000008395 clarifying agent Substances 0.000 description 2
- 238000005345 coagulation Methods 0.000 description 2
- 230000015271 coagulation Effects 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 239000003240 coconut oil Substances 0.000 description 2
- 235000019864 coconut oil Nutrition 0.000 description 2
- 239000008119 colloidal silica Substances 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 229940124301 concurrent medication Drugs 0.000 description 2
- 229960004544 cortisone Drugs 0.000 description 2
- 235000012343 cottonseed oil Nutrition 0.000 description 2
- 239000002385 cottonseed oil Substances 0.000 description 2
- 229960004397 cyclophosphamide Drugs 0.000 description 2
- 229930182912 cyclosporin Natural products 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 229960003662 desonide Drugs 0.000 description 2
- WBGKWQHBNHJJPZ-LECWWXJVSA-N desonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O WBGKWQHBNHJJPZ-LECWWXJVSA-N 0.000 description 2
- 229960002593 desoximetasone Drugs 0.000 description 2
- VWVSBHGCDBMOOT-IIEHVVJPSA-N desoximetasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@H](C(=O)CO)[C@@]1(C)C[C@@H]2O VWVSBHGCDBMOOT-IIEHVVJPSA-N 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 102000038379 digestive enzymes Human genes 0.000 description 2
- 108091007734 digestive enzymes Proteins 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- GXGAKHNRMVGRPK-UHFFFAOYSA-N dimagnesium;dioxido-bis[[oxido(oxo)silyl]oxy]silane Chemical compound [Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O GXGAKHNRMVGRPK-UHFFFAOYSA-N 0.000 description 2
- LNGNZSMIUVQZOX-UHFFFAOYSA-L disodium;dioxido(sulfanylidene)-$l^{4}-sulfane Chemical compound [Na+].[Na+].[O-]S([O-])=S LNGNZSMIUVQZOX-UHFFFAOYSA-L 0.000 description 2
- 210000001198 duodenum Anatomy 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 238000005538 encapsulation Methods 0.000 description 2
- 239000002702 enteric coating Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 230000004761 fibrosis Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000020375 flavoured syrup Nutrition 0.000 description 2
- 229960000676 flunisolide Drugs 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 230000002538 fungal effect Effects 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 229960005150 glycerol Drugs 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 239000008240 homogeneous mixture Substances 0.000 description 2
- 235000001050 hortel pimenta Nutrition 0.000 description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 2
- 229940071826 hydroxyethyl cellulose Drugs 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 239000002955 immunomodulating agent Substances 0.000 description 2
- 229940121354 immunomodulator Drugs 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000003701 inert diluent Substances 0.000 description 2
- 239000011261 inert gas Substances 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000036512 infertility Effects 0.000 description 2
- 239000007972 injectable composition Substances 0.000 description 2
- 229910052816 inorganic phosphate Inorganic materials 0.000 description 2
- 235000019388 lanolin Nutrition 0.000 description 2
- 229940039717 lanolin Drugs 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 2
- 235000019421 lipase Nutrition 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 2
- 239000001095 magnesium carbonate Substances 0.000 description 2
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 2
- 239000000391 magnesium silicate Substances 0.000 description 2
- 229940099273 magnesium trisilicate Drugs 0.000 description 2
- 229910000386 magnesium trisilicate Inorganic materials 0.000 description 2
- 235000019793 magnesium trisilicate Nutrition 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 229960000485 methotrexate Drugs 0.000 description 2
- PDORUEYAZSSTSF-UHFFFAOYSA-N methyl 4-[3-(3-iodophenyl)-2-oxoimidazolidin-1-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1N1C(=O)N(C=2C=C(I)C=CC=2)CC1 PDORUEYAZSSTSF-UHFFFAOYSA-N 0.000 description 2
- YUNGQODCORUULZ-UHFFFAOYSA-N methyl 4-[3-(4-benzylphenyl)-2-oxoimidazolidin-1-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(CC=3C=CC=CC=3)=CC=2)CC1 YUNGQODCORUULZ-UHFFFAOYSA-N 0.000 description 2
- XJRFFCVTJBDUHQ-UHFFFAOYSA-N methyl 4-[3-(4-tert-butylphenyl)-2-oxoimidazolidin-1-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C(C)(C)C)CC1 XJRFFCVTJBDUHQ-UHFFFAOYSA-N 0.000 description 2
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- 229960004584 methylprednisolone Drugs 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 235000019799 monosodium phosphate Nutrition 0.000 description 2
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 2
- 206010028417 myasthenia gravis Diseases 0.000 description 2
- 229920001206 natural gum Polymers 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 230000001338 necrotic effect Effects 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 239000012053 oil suspension Substances 0.000 description 2
- 229940054534 ophthalmic solution Drugs 0.000 description 2
- 239000002997 ophthalmic solution Substances 0.000 description 2
- 239000006186 oral dosage form Substances 0.000 description 2
- 239000008203 oral pharmaceutical composition Substances 0.000 description 2
- 239000007968 orange flavor Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 229940112824 paste Drugs 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000002304 perfume Substances 0.000 description 2
- 230000010412 perfusion Effects 0.000 description 2
- 230000002085 persistent effect Effects 0.000 description 2
- 235000019271 petrolatum Nutrition 0.000 description 2
- 229940066842 petrolatum Drugs 0.000 description 2
- 239000008024 pharmaceutical diluent Substances 0.000 description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229960003742 phenol Drugs 0.000 description 2
- 229960000502 poloxamer Drugs 0.000 description 2
- 229920001983 poloxamer Polymers 0.000 description 2
- 229920001515 polyalkylene glycol Polymers 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 229940068977 polysorbate 20 Drugs 0.000 description 2
- 229940068968 polysorbate 80 Drugs 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 2
- 239000011736 potassium bicarbonate Substances 0.000 description 2
- 235000011181 potassium carbonates Nutrition 0.000 description 2
- 235000011164 potassium chloride Nutrition 0.000 description 2
- 239000001103 potassium chloride Substances 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 229940116317 potato starch Drugs 0.000 description 2
- 229960005205 prednisolone Drugs 0.000 description 2
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 2
- 229960004618 prednisone Drugs 0.000 description 2
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
- 235000013772 propylene glycol Nutrition 0.000 description 2
- 235000019833 protease Nutrition 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000002510 pyrogen Substances 0.000 description 2
- MIXMJCQRHVAJIO-TZHJZOAOSA-N qk4dys664x Chemical compound O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O MIXMJCQRHVAJIO-TZHJZOAOSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 229940075993 receptor modulator Drugs 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000000241 respiratory effect Effects 0.000 description 2
- 230000029058 respiratory gaseous exchange Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 229940081974 saccharin Drugs 0.000 description 2
- 235000019204 saccharin Nutrition 0.000 description 2
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 238000003345 scintillation counting Methods 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 2
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 2
- 229940001584 sodium metabisulfite Drugs 0.000 description 2
- 235000010262 sodium metabisulphite Nutrition 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 230000003381 solubilizing effect Effects 0.000 description 2
- 235000010199 sorbic acid Nutrition 0.000 description 2
- 239000004334 sorbic acid Substances 0.000 description 2
- 229940075582 sorbic acid Drugs 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 108010035597 sphingosine kinase Proteins 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 125000005017 substituted alkenyl group Chemical group 0.000 description 2
- 125000005415 substituted alkoxy group Chemical group 0.000 description 2
- 125000000547 substituted alkyl group Chemical group 0.000 description 2
- 125000004426 substituted alkynyl group Chemical group 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 2
- 229960001967 tacrolimus Drugs 0.000 description 2
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000008719 thickening Effects 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 150000003568 thioethers Chemical class 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 235000010487 tragacanth Nutrition 0.000 description 2
- 239000000196 tragacanth Substances 0.000 description 2
- 229940116362 tragacanth Drugs 0.000 description 2
- 150000003626 triacylglycerols Chemical class 0.000 description 2
- 229960005294 triamcinolone Drugs 0.000 description 2
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- WUUHFRRPHJEEKV-UHFFFAOYSA-N tripotassium borate Chemical class [K+].[K+].[K+].[O-]B([O-])[O-] WUUHFRRPHJEEKV-UHFFFAOYSA-N 0.000 description 2
- 229920001664 tyloxapol Polymers 0.000 description 2
- MDYZKJNTKZIUSK-UHFFFAOYSA-N tyloxapol Chemical compound O=C.C1CO1.CC(C)(C)CC(C)(C)C1=CC=C(O)C=C1 MDYZKJNTKZIUSK-UHFFFAOYSA-N 0.000 description 2
- 229960004224 tyloxapol Drugs 0.000 description 2
- 231100000397 ulcer Toxicity 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 235000012431 wafers Nutrition 0.000 description 2
- 238000009736 wetting Methods 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 239000009637 wintergreen oil Substances 0.000 description 2
- WWUZIQQURGPMPG-UHFFFAOYSA-N (-)-D-erythro-Sphingosine Natural products CCCCCCCCCCCCCC=CC(O)C(N)CO WWUZIQQURGPMPG-UHFFFAOYSA-N 0.000 description 1
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
- MIBKFRFQBLWUBU-UHFFFAOYSA-N 1-(3-benzylphenyl)-3-[2-fluoro-4-(hydroxymethyl)phenyl]imidazolidin-2-one Chemical compound FC1=CC(CO)=CC=C1N1C(=O)N(C=2C=C(CC=3C=CC=CC=3)C=CC=2)CC1 MIBKFRFQBLWUBU-UHFFFAOYSA-N 0.000 description 1
- VGWLJGHHQNGPHI-UHFFFAOYSA-N 1-(3-cyclohexylphenyl)-3-[2-fluoro-4-(hydroxymethyl)phenyl]imidazolidin-2-one Chemical compound FC1=CC(CO)=CC=C1N1C(=O)N(C=2C=C(C=CC=2)C2CCCCC2)CC1 VGWLJGHHQNGPHI-UHFFFAOYSA-N 0.000 description 1
- YPEVUNQJCGBBAY-UHFFFAOYSA-N 1-(3-cyclohexylphenyl)-3-[4-(hydroxymethyl)phenyl]imidazolidin-2-one Chemical compound C1=CC(CO)=CC=C1N1C(=O)N(C=2C=C(C=CC=2)C2CCCCC2)CC1 YPEVUNQJCGBBAY-UHFFFAOYSA-N 0.000 description 1
- ZSPKRZMBDBLOLS-UHFFFAOYSA-N 1-(3-cyclohexylphenyl)-3-[4-[[3-(2h-tetrazol-5-yl)azetidin-1-yl]methyl]phenyl]imidazolidin-2-one Chemical compound O=C1N(C=2C=CC(CN3CC(C3)C3=NNN=N3)=CC=2)CCN1C(C=1)=CC=CC=1C1CCCCC1 ZSPKRZMBDBLOLS-UHFFFAOYSA-N 0.000 description 1
- SGAYXXFSBBWSRD-UHFFFAOYSA-N 1-(4-benzylphenyl)-3-[4-(hydroxymethyl)phenyl]imidazolidin-2-one Chemical compound C1=CC(CO)=CC=C1N1C(=O)N(C=2C=CC(CC=3C=CC=CC=3)=CC=2)CC1 SGAYXXFSBBWSRD-UHFFFAOYSA-N 0.000 description 1
- USEYKQLDYOTBGT-UHFFFAOYSA-N 1-(4-butylphenyl)-3-[4-(hydroxymethyl)phenyl]imidazolidin-2-one Chemical compound C1=CC(CCCC)=CC=C1N1C(=O)N(C=2C=CC(CO)=CC=2)CC1 USEYKQLDYOTBGT-UHFFFAOYSA-N 0.000 description 1
- QZNQSIHCDAGZIA-UHFFFAOYSA-N 1-(bromomethyl)-4-tert-butylbenzene Chemical compound CC(C)(C)C1=CC=C(CBr)C=C1 QZNQSIHCDAGZIA-UHFFFAOYSA-N 0.000 description 1
- VEWIIQISVHXUTR-UHFFFAOYSA-N 1-[(4-tert-butylphenyl)methyl]-3-[4-(hydroxymethyl)phenyl]imidazolidin-2-one Chemical compound C1=CC(C(C)(C)C)=CC=C1CN1C(=O)N(C=2C=CC(CO)=CC=2)CC1 VEWIIQISVHXUTR-UHFFFAOYSA-N 0.000 description 1
- BZCVJXNIROWPHJ-UHFFFAOYSA-N 1-[4-(hydroxymethyl)phenyl]-3-(4-phenylphenyl)imidazolidin-2-one Chemical compound C1=CC(CO)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C=2C=CC=CC=2)CC1 BZCVJXNIROWPHJ-UHFFFAOYSA-N 0.000 description 1
- KXIXJJLXHDLLBC-UHFFFAOYSA-N 1-[4-(hydroxymethyl)phenyl]-3-[3-(trifluoromethyl)phenyl]imidazolidin-2-one Chemical compound C1=CC(CO)=CC=C1N1C(=O)N(C=2C=C(C=CC=2)C(F)(F)F)CC1 KXIXJJLXHDLLBC-UHFFFAOYSA-N 0.000 description 1
- POINNTRJUKLOHL-UHFFFAOYSA-N 1-[[4-[2-oxo-3-(3-phenoxyphenyl)imidazolidin-1-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(N2C(N(CC2)C=2C=C(OC=3C=CC=CC=3)C=CC=2)=O)C=C1 POINNTRJUKLOHL-UHFFFAOYSA-N 0.000 description 1
- RMWBESYOLPVMCM-UHFFFAOYSA-N 1-[[4-[2-oxo-3-(3-phenylsulfanylphenyl)imidazolidin-1-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(N2C(N(CC2)C=2C=C(SC=3C=CC=CC=3)C=CC=2)=O)C=C1 RMWBESYOLPVMCM-UHFFFAOYSA-N 0.000 description 1
- NBRRKSUNPWKYMB-UHFFFAOYSA-N 1-[[4-[2-oxo-3-(4-phenylphenyl)imidazolidin-1-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(N2C(N(CC2)C=2C=CC(=CC=2)C=2C=CC=CC=2)=O)C=C1 NBRRKSUNPWKYMB-UHFFFAOYSA-N 0.000 description 1
- WQISRBBFHBZVEC-UHFFFAOYSA-N 1-[[4-[2-oxo-3-[3-(1-phenylethyl)phenyl]imidazolidin-1-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C=1C=CC(N2C(N(CC2)C=2C=CC(CN3CC(C3)C(O)=O)=CC=2)=O)=CC=1C(C)C1=CC=CC=C1 WQISRBBFHBZVEC-UHFFFAOYSA-N 0.000 description 1
- KBZXMFBQAOJLGF-UHFFFAOYSA-N 1-[[4-[3-(2-cyclohexylpyridin-4-yl)-2-oxoimidazolidin-1-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(N2C(N(CC2)C=2C=C(N=CC=2)C2CCCCC2)=O)C=C1 KBZXMFBQAOJLGF-UHFFFAOYSA-N 0.000 description 1
- JXFCNVXTCJUKEB-UHFFFAOYSA-N 1-[[4-[3-(3-benzoylphenyl)-2-oxoimidazolidin-1-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(N2C(N(CC2)C=2C=C(C=CC=2)C(=O)C=2C=CC=CC=2)=O)C=C1 JXFCNVXTCJUKEB-UHFFFAOYSA-N 0.000 description 1
- MGXVMRKBBOUXHK-UHFFFAOYSA-N 1-[[4-[3-(3-cyclohexyl-1,2,4-thiadiazol-5-yl)-2-oxoimidazolidin-1-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(N2C(N(CC2)C=2SN=C(N=2)C2CCCCC2)=O)C=C1 MGXVMRKBBOUXHK-UHFFFAOYSA-N 0.000 description 1
- WFVNKBVQNUXWBA-UHFFFAOYSA-N 1-[[4-[3-(3-cyclohexylphenyl)-2-oxo-5-(trifluoromethyl)imidazolidin-1-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(N2C(N(CC2C(F)(F)F)C=2C=C(C=CC=2)C2CCCCC2)=O)C=C1 WFVNKBVQNUXWBA-UHFFFAOYSA-N 0.000 description 1
- ZJVQVJSFSUISRT-UHFFFAOYSA-N 1-[[4-[3-(3-cyclohexylphenyl)-2-oxoimidazolidin-1-yl]-2-fluorophenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(N2C(N(CC2)C=2C=C(C=CC=2)C2CCCCC2)=O)C=C1F ZJVQVJSFSUISRT-UHFFFAOYSA-N 0.000 description 1
- WYNYAOHOGJSNEH-UHFFFAOYSA-N 1-[[4-[3-(3-cyclohexylphenyl)-2-oxoimidazolidin-1-yl]-3-(trifluoromethyl)phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC(C=C1C(F)(F)F)=CC=C1N1C(=O)N(C=2C=C(C=CC=2)C2CCCCC2)CC1 WYNYAOHOGJSNEH-UHFFFAOYSA-N 0.000 description 1
- NAYXKNCRBHYVFB-UHFFFAOYSA-N 1-[[4-[3-(3-cyclohexylphenyl)-2-oxoimidazolidin-1-yl]-3-methoxyphenyl]methyl]azetidine-3-carboxylic acid Chemical compound C=1C=C(N2C(N(CC2)C=2C=C(C=CC=2)C2CCCCC2)=O)C(OC)=CC=1CN1CC(C(O)=O)C1 NAYXKNCRBHYVFB-UHFFFAOYSA-N 0.000 description 1
- ZHZQPXSDQDSSTF-UHFFFAOYSA-N 1-[[4-[3-(3-cyclohexylphenyl)-2-oxoimidazolidin-1-yl]phenyl]methyl]-3-hydroxyazetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)(O)CN1CC1=CC=C(N2C(N(CC2)C=2C=C(C=CC=2)C2CCCCC2)=O)C=C1 ZHZQPXSDQDSSTF-UHFFFAOYSA-N 0.000 description 1
- IECFFHSWNKHBPJ-UHFFFAOYSA-N 1-[[4-[3-(3-cyclohexylphenyl)-2-oxoimidazolidin-1-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(N2C(N(CC2)C=2C=C(C=CC=2)C2CCCCC2)=O)C=C1 IECFFHSWNKHBPJ-UHFFFAOYSA-N 0.000 description 1
- MJPIHEUKBNDZOE-UHFFFAOYSA-N 1-[[4-[3-(3-cyclohexylphenyl)-2-oxoimidazolidin-1-yl]phenyl]methyl]piperidine-4-carboxylic acid Chemical compound C1CC(C(=O)O)CCN1CC1=CC=C(N2C(N(CC2)C=2C=C(C=CC=2)C2CCCCC2)=O)C=C1 MJPIHEUKBNDZOE-UHFFFAOYSA-N 0.000 description 1
- CLDZCGFAJVJCRS-UHFFFAOYSA-N 1-[[4-[3-(3-cyclohexylphenyl)-2-oxoimidazolidin-1-yl]phenyl]methyl]pyrrolidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CCN1CC1=CC=C(N2C(N(CC2)C=2C=C(C=CC=2)C2CCCCC2)=O)C=C1 CLDZCGFAJVJCRS-UHFFFAOYSA-N 0.000 description 1
- YWLMYEGVXAZINO-UHFFFAOYSA-N 1-[[4-[3-(3-cyclohexylphenyl)-5,5-dimethyl-2-oxoimidazolidin-1-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound CC1(C)CN(C=2C=C(C=CC=2)C2CCCCC2)C(=O)N1C(C=C1)=CC=C1CN1CC(C(O)=O)C1 YWLMYEGVXAZINO-UHFFFAOYSA-N 0.000 description 1
- CTBAXAAQFWVFJV-UHFFFAOYSA-N 1-[[4-[3-(3-cyclohexylphenyl)-5-methyl-2-oxoimidazolidin-1-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound CC1CN(C=2C=C(C=CC=2)C2CCCCC2)C(=O)N1C(C=C1)=CC=C1CN1CC(C(O)=O)C1 CTBAXAAQFWVFJV-UHFFFAOYSA-N 0.000 description 1
- PSZJHPPCEAHFLJ-UHFFFAOYSA-N 1-[[4-[3-(4-cyclohexyl-1,3-oxazol-2-yl)-2-oxoimidazolidin-1-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(N2C(N(CC2)C=2OC=C(N=2)C2CCCCC2)=O)C=C1 PSZJHPPCEAHFLJ-UHFFFAOYSA-N 0.000 description 1
- IFKDLWCVXDUZES-UHFFFAOYSA-N 1-[[4-[3-(5-cyclohexylpyridin-3-yl)-2-oxoimidazolidin-1-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(N2C(N(CC2)C=2C=C(C=NC=2)C2CCCCC2)=O)C=C1 IFKDLWCVXDUZES-UHFFFAOYSA-N 0.000 description 1
- BAIMBZHFMPOTBE-UHFFFAOYSA-N 1-[[4-[3-[3-(benzenesulfinyl)phenyl]-2-oxoimidazolidin-1-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(N2C(N(CC2)C=2C=C(C=CC=2)S(=O)C=2C=CC=CC=2)=O)C=C1 BAIMBZHFMPOTBE-UHFFFAOYSA-N 0.000 description 1
- IIEBFHDSNYQRGE-UHFFFAOYSA-N 1-[[4-[3-[3-(benzenesulfonyl)phenyl]-2-oxoimidazolidin-1-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(N2C(N(CC2)C=2C=C(C=CC=2)S(=O)(=O)C=2C=CC=CC=2)=O)C=C1 IIEBFHDSNYQRGE-UHFFFAOYSA-N 0.000 description 1
- PUOLORCRSJQSNR-UHFFFAOYSA-N 1-[[4-[3-[3-(cyclobutylmethoxy)phenyl]-2-oxoimidazolidin-1-yl]-3-fluorophenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC(C=C1F)=CC=C1N1C(=O)N(C=2C=C(OCC3CCC3)C=CC=2)CC1 PUOLORCRSJQSNR-UHFFFAOYSA-N 0.000 description 1
- URFYPGQMTYWZDJ-UHFFFAOYSA-N 1-[[4-[3-[3-(cyclohexyloxymethyl)phenyl]-2-oxoimidazolidin-1-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(N2C(N(CC2)C=2C=C(COC3CCCCC3)C=CC=2)=O)C=C1 URFYPGQMTYWZDJ-UHFFFAOYSA-N 0.000 description 1
- OGUSGOJXCNWYHB-UHFFFAOYSA-N 1-[[4-[3-[3-(cyclopropylmethoxy)phenyl]-2-oxoimidazolidin-1-yl]-3-fluorophenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC(C=C1F)=CC=C1N1C(=O)N(C=2C=C(OCC3CC3)C=CC=2)CC1 OGUSGOJXCNWYHB-UHFFFAOYSA-N 0.000 description 1
- FKGOMKZLLJNLBX-UHFFFAOYSA-N 1-[[4-[3-[3-[(3-fluorophenyl)methyl]phenyl]-2-oxoimidazolidin-1-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(N2C(N(CC2)C=2C=C(CC=3C=C(F)C=CC=3)C=CC=2)=O)C=C1 FKGOMKZLLJNLBX-UHFFFAOYSA-N 0.000 description 1
- PHAWMWXTAMOELL-UHFFFAOYSA-N 1-[[4-[3-[3-[(4-fluorophenyl)methyl]phenyl]-2-oxoimidazolidin-1-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(N2C(N(CC2)C=2C=C(CC=3C=CC(F)=CC=3)C=CC=2)=O)C=C1 PHAWMWXTAMOELL-UHFFFAOYSA-N 0.000 description 1
- JOYYZADDOIBEOK-UHFFFAOYSA-N 1-[[4-[3-[3-cyclohexyl-4-(trifluoromethyl)phenyl]-2-oxoimidazolidin-1-yl]phenyl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(N2C(N(CC2)C=2C=C(C(=CC=2)C(F)(F)F)C2CCCCC2)=O)C=C1 JOYYZADDOIBEOK-UHFFFAOYSA-N 0.000 description 1
- QYBJVHSHCXVFLI-UHFFFAOYSA-N 1-[[5-[3-(3-cyclohexylphenyl)-2-oxoimidazolidin-1-yl]-1,3,4-oxadiazol-2-yl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=NN=C(N2C(N(CC2)C=2C=C(C=CC=2)C2CCCCC2)=O)O1 QYBJVHSHCXVFLI-UHFFFAOYSA-N 0.000 description 1
- PXKHQKPEDMOWKK-UHFFFAOYSA-N 1-[[5-[3-(3-cyclohexylphenyl)-2-oxoimidazolidin-1-yl]-1,3-benzothiazol-2-yl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=NC2=CC(N3C(N(CC3)C=3C=C(C=CC=3)C3CCCCC3)=O)=CC=C2S1 PXKHQKPEDMOWKK-UHFFFAOYSA-N 0.000 description 1
- ZTMJNBWEXPGQPK-UHFFFAOYSA-N 1-[[5-[3-(3-cyclohexylphenyl)-2-oxoimidazolidin-1-yl]-1,3-thiazol-2-yl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=NC=C(N2C(N(CC2)C=2C=C(C=CC=2)C2CCCCC2)=O)S1 ZTMJNBWEXPGQPK-UHFFFAOYSA-N 0.000 description 1
- PYFKSNXNFWBSLR-UHFFFAOYSA-N 1-[[5-[3-(3-cyclohexylphenyl)-2-oxoimidazolidin-1-yl]-1-benzofuran-2-yl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC2=CC(N3C(N(CC3)C=3C=C(C=CC=3)C3CCCCC3)=O)=CC=C2O1 PYFKSNXNFWBSLR-UHFFFAOYSA-N 0.000 description 1
- NUPZJQNDPOQGOD-UHFFFAOYSA-N 1-[[5-[3-(3-cyclohexylphenyl)-2-oxoimidazolidin-1-yl]furo[2,3-b]pyridin-2-yl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC2=CC(N3C(N(CC3)C=3C=C(C=CC=3)C3CCCCC3)=O)=CN=C2O1 NUPZJQNDPOQGOD-UHFFFAOYSA-N 0.000 description 1
- BLUATXPSVIBTDE-UHFFFAOYSA-N 1-[[6-[3-(3-cyclohexylphenyl)-2-oxoimidazolidin-1-yl]-[1,3]thiazolo[5,4-b]pyridin-2-yl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=NC2=CC(N3C(N(CC3)C=3C=C(C=CC=3)C3CCCCC3)=O)=CN=C2S1 BLUATXPSVIBTDE-UHFFFAOYSA-N 0.000 description 1
- SAECCIPJEOKLAP-UHFFFAOYSA-N 1-[[6-[3-(3-cyclohexylphenyl)-2-oxoimidazolidin-1-yl]pyridin-3-yl]methyl]azetidine-3-carboxylic acid Chemical compound C1C(C(=O)O)CN1CC1=CC=C(N2C(N(CC2)C=2C=C(C=CC=2)C2CCCCC2)=O)N=C1 SAECCIPJEOKLAP-UHFFFAOYSA-N 0.000 description 1
- FCUNNMLRHRWXAM-UHFFFAOYSA-N 1-benzyl-4-iodobenzene Chemical compound C1=CC(I)=CC=C1CC1=CC=CC=C1 FCUNNMLRHRWXAM-UHFFFAOYSA-N 0.000 description 1
- HHKXBMVLTDSVCG-UHFFFAOYSA-N 1-tert-butyl-2,4-diiodobenzene Chemical compound CC(C)(C)C1=CC=C(I)C=C1I HHKXBMVLTDSVCG-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- 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 1
- YAHKFRAQTSUEOC-UHFFFAOYSA-N 2-[[4-[3-(3-cyclohexylphenyl)-2-oxoimidazolidin-1-yl]phenyl]methylamino]butanedioic acid Chemical compound C1=CC(CNC(CC(=O)O)C(O)=O)=CC=C1N1C(=O)N(C=2C=C(C=CC=2)C2CCCCC2)CC1 YAHKFRAQTSUEOC-UHFFFAOYSA-N 0.000 description 1
- VLPDWYJGYLBHCI-UHFFFAOYSA-N 2-amino-3-[[4-[3-(3-cyclohexylphenyl)-2-oxoimidazolidin-1-yl]phenyl]methylamino]propanoic acid Chemical compound C1=CC(CNCC(N)C(O)=O)=CC=C1N1C(=O)N(C=2C=C(C=CC=2)C2CCCCC2)CC1 VLPDWYJGYLBHCI-UHFFFAOYSA-N 0.000 description 1
- JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 1
- GORCPHCEVNFULF-UHFFFAOYSA-N 3-[4-[3-(3-cyclohexylphenyl)-2-oxoimidazolidin-1-yl]phenyl]propanoic acid Chemical compound C1=CC(CCC(=O)O)=CC=C1N1C(=O)N(C=2C=C(C=CC=2)C2CCCCC2)CC1 GORCPHCEVNFULF-UHFFFAOYSA-N 0.000 description 1
- CKPMVHBJKIZVJV-UHFFFAOYSA-N 3-[4-[[4-[3-(3-cyclohexylphenyl)-2-oxoimidazolidin-1-yl]phenyl]methyl]piperidin-1-yl]propanoic acid Chemical compound C1CN(CCC(=O)O)CCC1CC1=CC=C(N2C(N(CC2)C=2C=C(C=CC=2)C2CCCCC2)=O)C=C1 CKPMVHBJKIZVJV-UHFFFAOYSA-N 0.000 description 1
- DEYHLGKVEPENCR-UHFFFAOYSA-N 3-[6-[3-(3-cyclohexylphenyl)-2-oxoimidazolidin-1-yl]-3,4-dihydro-1h-isoquinolin-2-yl]propanoic acid Chemical compound C=1C=C2CN(CCC(=O)O)CCC2=CC=1N(C1=O)CCN1C(C=1)=CC=CC=1C1CCCCC1 DEYHLGKVEPENCR-UHFFFAOYSA-N 0.000 description 1
- GIXWYEMZQWUMIR-UHFFFAOYSA-N 3-[[4-[3-(3-cyclohexylphenyl)-2-oxoimidazolidin-1-yl]phenyl]methylamino]propanoic acid Chemical compound C1=CC(CNCCC(=O)O)=CC=C1N1C(=O)N(C=2C=C(C=CC=2)C2CCCCC2)CC1 GIXWYEMZQWUMIR-UHFFFAOYSA-N 0.000 description 1
- PEPBFCOIJRULGJ-UHFFFAOYSA-N 3h-1,2,3-benzodioxazole Chemical compound C1=CC=C2NOOC2=C1 PEPBFCOIJRULGJ-UHFFFAOYSA-N 0.000 description 1
- NVCDDBLGCUBTHG-UHFFFAOYSA-N 4-[2-oxo-3-(4-phenylphenyl)imidazolidin-1-yl]benzaldehyde Chemical compound C1=CC(C=O)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C=2C=CC=CC=2)CC1 NVCDDBLGCUBTHG-UHFFFAOYSA-N 0.000 description 1
- YHRCDJSBAQMAPI-UHFFFAOYSA-N 4-[2-oxo-3-[3-(trifluoromethyl)phenyl]imidazolidin-1-yl]benzaldehyde Chemical compound FC(F)(F)C1=CC=CC(N2C(N(CC2)C=2C=CC(C=O)=CC=2)=O)=C1 YHRCDJSBAQMAPI-UHFFFAOYSA-N 0.000 description 1
- OYBFEPUHSRVSBE-UHFFFAOYSA-N 4-[3-(3-benzylphenyl)-2-oxoimidazolidin-1-yl]-3-fluorobenzaldehyde Chemical compound FC1=CC(C=O)=CC=C1N1C(=O)N(C=2C=C(CC=3C=CC=CC=3)C=CC=2)CC1 OYBFEPUHSRVSBE-UHFFFAOYSA-N 0.000 description 1
- KQCVKHXHYHRNAF-UHFFFAOYSA-N 4-[3-(3-cyclohexylphenyl)-2-oxoimidazolidin-1-yl]-3-fluorobenzaldehyde Chemical compound FC1=CC(C=O)=CC=C1N1C(=O)N(C=2C=C(C=CC=2)C2CCCCC2)CC1 KQCVKHXHYHRNAF-UHFFFAOYSA-N 0.000 description 1
- RWIZAYPSGYDYLA-UHFFFAOYSA-N 4-[3-(3-tert-butylphenyl)-2-oxoimidazolidin-1-yl]benzaldehyde Chemical compound CC(C)(C)C1=CC=CC(N2C(N(CC2)C=2C=CC(C=O)=CC=2)=O)=C1 RWIZAYPSGYDYLA-UHFFFAOYSA-N 0.000 description 1
- FOURHFTTYLWAOL-UHFFFAOYSA-N 4-[3-(4-benzylphenyl)-2-oxoimidazolidin-1-yl]benzaldehyde Chemical compound C1=CC(C=O)=CC=C1N1C(=O)N(C=2C=CC(CC=3C=CC=CC=3)=CC=2)CC1 FOURHFTTYLWAOL-UHFFFAOYSA-N 0.000 description 1
- BNUDRBWWXMBJFB-UHFFFAOYSA-N 4-[3-[(4-tert-butylphenyl)methyl]-2-oxoimidazolidin-1-yl]benzaldehyde Chemical compound C1=CC(C(C)(C)C)=CC=C1CN1C(=O)N(C=2C=CC(C=O)=CC=2)CC1 BNUDRBWWXMBJFB-UHFFFAOYSA-N 0.000 description 1
- MBDLZVDWAYMCCZ-UHFFFAOYSA-N 4-[[4-[3-(3-cyclohexylphenyl)-2-oxoimidazolidin-1-yl]phenyl]methylamino]-4-oxobutanoic acid Chemical compound C1=CC(CNC(=O)CCC(=O)O)=CC=C1N1C(=O)N(C=2C=C(C=CC=2)C2CCCCC2)CC1 MBDLZVDWAYMCCZ-UHFFFAOYSA-N 0.000 description 1
- AUBFVGCCACBFTQ-UHFFFAOYSA-N 4-[[4-[3-(3-cyclohexylphenyl)-2-oxoimidazolidin-1-yl]phenyl]methylamino]butanoic acid Chemical compound C1=CC(CNCCCC(=O)O)=CC=C1N1C(=O)N(C=2C=C(C=CC=2)C2CCCCC2)CC1 AUBFVGCCACBFTQ-UHFFFAOYSA-N 0.000 description 1
- ZMGMDXCADSRNCX-UHFFFAOYSA-N 5,6-dihydroxy-1,3-diazepan-2-one Chemical compound OC1CNC(=O)NCC1O ZMGMDXCADSRNCX-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 201000005670 Anovulation Diseases 0.000 description 1
- 206010002659 Anovulatory cycle Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 206010003827 Autoimmune hepatitis Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 208000020925 Bipolar disease Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 208000032841 Bulimia Diseases 0.000 description 1
- 206010006550 Bulimia nervosa Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 206010007556 Cardiac failure acute Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010008909 Chronic Hepatitis Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 206010012218 Delirium Diseases 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 1
- 101000966782 Homo sapiens Lysophosphatidic acid receptor 1 Proteins 0.000 description 1
- 101000864393 Homo sapiens Protein BUD31 homolog Proteins 0.000 description 1
- 101000693269 Homo sapiens Sphingosine 1-phosphate receptor 3 Proteins 0.000 description 1
- 101000653759 Homo sapiens Sphingosine 1-phosphate receptor 5 Proteins 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029523 Interstitial Lung disease Diseases 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- 208000034693 Laceration Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010025327 Lymphopenia Diseases 0.000 description 1
- 102100040607 Lysophosphatidic acid receptor 1 Human genes 0.000 description 1
- 206010025538 Malignant ascites Diseases 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 102000006386 Myelin Proteins Human genes 0.000 description 1
- 108010083674 Myelin Proteins Proteins 0.000 description 1
- 208000013901 Nephropathies and tubular disease Diseases 0.000 description 1
- 206010029164 Nephrotic syndrome Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 241000005308 Orsa Species 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 1
- 208000004210 Pressure Ulcer Diseases 0.000 description 1
- 108091006335 Prostaglandin I receptors Proteins 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 102100030160 Protein BUD31 homolog Human genes 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 208000010362 Protozoan Infections Diseases 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 206010038687 Respiratory distress Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 208000036623 Severe mental retardation Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 102100025750 Sphingosine 1-phosphate receptor 1 Human genes 0.000 description 1
- 101710155454 Sphingosine 1-phosphate receptor 1 Proteins 0.000 description 1
- 101710155457 Sphingosine 1-phosphate receptor 3 Proteins 0.000 description 1
- 102100029803 Sphingosine 1-phosphate receptor 4 Human genes 0.000 description 1
- 101710155458 Sphingosine 1-phosphate receptor 4 Proteins 0.000 description 1
- 102100029802 Sphingosine 1-phosphate receptor 5 Human genes 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 208000002847 Surgical Wound Diseases 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 1
- 206010043561 Thrombocytopenic purpura Diseases 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 206010046555 Urinary retention Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 206010047700 Vomiting 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
- 208000005298 acute pain Diseases 0.000 description 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000005090 alkenylcarbonyl group Chemical group 0.000 description 1
- 125000000278 alkyl amino alkyl group Chemical group 0.000 description 1
- 125000005157 alkyl carboxy group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 231100000552 anovulation Toxicity 0.000 description 1
- 230000003527 anti-angiogenesis Effects 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 125000005125 aryl alkyl amino carbonyl group Chemical group 0.000 description 1
- 125000005099 aryl alkyl carbonyl group Chemical group 0.000 description 1
- 125000005135 aryl sulfinyl group Chemical group 0.000 description 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 1
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 1
- 239000012752 auxiliary agent Substances 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
- MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical class O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 208000028683 bipolar I disease Diseases 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 235000010338 boric acid Nutrition 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- OKTJSMMVPCPJKN-YPZZEJLDSA-N carbon-10 atom Chemical group [10C] OKTJSMMVPCPJKN-YPZZEJLDSA-N 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 210000001627 cerebral artery Anatomy 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 210000004246 corpus luteum Anatomy 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000011262 co‐therapy Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([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
- 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 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
- 125000000298 cyclopropenyl group Chemical group [H]C1=C([H])C1([H])* 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 125000003493 decenyl group Chemical group [H]C([*])=C([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005070 decynyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C#C* 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000026721 endothelial cell chemotaxis Effects 0.000 description 1
- 230000009762 endothelial cell differentiation Effects 0.000 description 1
- 208000037888 epithelial cell injury Diseases 0.000 description 1
- RSOJSFYJLQADDM-UHFFFAOYSA-N ethanesulfonamide Chemical compound [CH2]CS(N)(=O)=O RSOJSFYJLQADDM-UHFFFAOYSA-N 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- GTMNGHGYEHCPPO-UHFFFAOYSA-N ethyl 4-[3-(3-bromophenyl)-2-oxoimidazolidin-1-yl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1N1C(=O)N(C=2C=C(Br)C=CC=2)CC1 GTMNGHGYEHCPPO-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 208000024711 extrinsic asthma Diseases 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000004175 fluorobenzyl group Chemical group 0.000 description 1
- 125000004785 fluoromethoxy group Chemical group [H]C([H])(F)O* 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 230000001434 glomerular Effects 0.000 description 1
- 206010061989 glomerulosclerosis Diseases 0.000 description 1
- 208000007475 hemolytic anemia Diseases 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000002390 heteroarenes Chemical class 0.000 description 1
- 125000006038 hexenyl group Chemical group 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
- 125000005980 hexynyl group Chemical group 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- DOUHZFSGSXMPIE-UHFFFAOYSA-N hydroxidooxidosulfur(.) Chemical compound [O]SO DOUHZFSGSXMPIE-UHFFFAOYSA-N 0.000 description 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 230000005965 immune activity Effects 0.000 description 1
- 230000008629 immune suppression Effects 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 208000012947 ischemia reperfusion injury Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 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
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical group C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 238000005567 liquid scintillation counting Methods 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- 231100001023 lymphopenia Toxicity 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- ROPRIFLKCBEZDO-UHFFFAOYSA-N methyl 3-fluoro-4-(2-oxoimidazolidin-1-yl)benzoate Chemical compound FC1=CC(C(=O)OC)=CC=C1N1C(=O)NCC1 ROPRIFLKCBEZDO-UHFFFAOYSA-N 0.000 description 1
- CSINTCQZMJYRGG-UHFFFAOYSA-N methyl 3-fluoro-4-[3-(3-iodophenyl)-2-oxoimidazolidin-1-yl]benzoate Chemical compound FC1=CC(C(=O)OC)=CC=C1N1C(=O)N(C=2C=C(I)C=CC=2)CC1 CSINTCQZMJYRGG-UHFFFAOYSA-N 0.000 description 1
- KLSYPAYVJDPCQV-UHFFFAOYSA-N methyl 4-[2-oxo-3-(4-phenylphenyl)imidazolidin-1-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1N1C(=O)N(C=2C=CC(=CC=2)C=2C=CC=CC=2)CC1 KLSYPAYVJDPCQV-UHFFFAOYSA-N 0.000 description 1
- LZZQCYDUURCQII-UHFFFAOYSA-N methyl 4-[3-(3-benzylphenyl)-2-oxoimidazolidin-1-yl]-3-fluorobenzoate Chemical compound FC1=CC(C(=O)OC)=CC=C1N1C(=O)N(C=2C=C(CC=3C=CC=CC=3)C=CC=2)CC1 LZZQCYDUURCQII-UHFFFAOYSA-N 0.000 description 1
- QOIDEAVXDOFOHA-UHFFFAOYSA-N methyl 4-[3-(3-cyclohexylphenyl)-2-oxoimidazolidin-1-yl]-3-fluorobenzoate Chemical compound FC1=CC(C(=O)OC)=CC=C1N1C(=O)N(C=2C=C(C=CC=2)C2CCCCC2)CC1 QOIDEAVXDOFOHA-UHFFFAOYSA-N 0.000 description 1
- UCNDEAZESDTJEU-UHFFFAOYSA-N methyl 4-[3-(3-cyclohexylphenyl)-2-oxoimidazolidin-1-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1N1C(=O)N(C=2C=C(C=CC=2)C2CCCCC2)CC1 UCNDEAZESDTJEU-UHFFFAOYSA-N 0.000 description 1
- FKMIUHNSZBJADW-UHFFFAOYSA-N methyl 4-[3-(3-tert-butylphenyl)-2-oxoimidazolidin-1-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1N1C(=O)N(C=2C=C(C=CC=2)C(C)(C)C)CC1 FKMIUHNSZBJADW-UHFFFAOYSA-N 0.000 description 1
- VDTDIVSCYULKSU-UHFFFAOYSA-N methyl 4-[3-[(4-tert-butylphenyl)methyl]-2-oxoimidazolidin-1-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1N1C(=O)N(CC=2C=CC(=CC=2)C(C)(C)C)CC1 VDTDIVSCYULKSU-UHFFFAOYSA-N 0.000 description 1
- LZXXNPOYQCLXRS-UHFFFAOYSA-N methyl 4-aminobenzoate Chemical compound COC(=O)C1=CC=C(N)C=C1 LZXXNPOYQCLXRS-UHFFFAOYSA-N 0.000 description 1
- 229960002900 methylcellulose Drugs 0.000 description 1
- PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000005012 myelin Anatomy 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 208000009928 nephrosis Diseases 0.000 description 1
- 231100001027 nephrosis Toxicity 0.000 description 1
- 210000004126 nerve fiber Anatomy 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 230000003955 neuronal function Effects 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 230000003040 nociceptive effect Effects 0.000 description 1
- 238000013546 non-drug therapy Methods 0.000 description 1
- 125000005187 nonenyl group Chemical group C(=CCCCCCCC)* 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000005071 nonynyl group Chemical group C(#CCCCCCCC)* 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 125000004365 octenyl group Chemical group C(=CCCCCCC)* 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000005069 octynyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C#C* 0.000 description 1
- 230000009210 ongoing activation Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000001148 pentyloxycarbonyl group Chemical group 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 201000002628 peritoneum cancer Diseases 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- ACVYVLVWPXVTIT-UHFFFAOYSA-M phosphinate Chemical compound [O-][PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-M 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 230000001107 psychogenic effect Effects 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 150000004040 pyrrolidinones Chemical class 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 235000019615 sensations Nutrition 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 230000007781 signaling event Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 101150101769 sip5 gene Proteins 0.000 description 1
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
- 229960002930 sirolimus Drugs 0.000 description 1
- 201000002314 small intestine cancer Diseases 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 230000003238 somatosensory effect Effects 0.000 description 1
- WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 description 1
- 150000003410 sphingosines Chemical class 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 150000008053 sultones Chemical class 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 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
- 238000012360 testing method Methods 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- 125000005300 thiocarboxy group Chemical group C(=S)(O)* 0.000 description 1
- 229930192474 thiophene Chemical group 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 150000003852 triazoles Chemical group 0.000 description 1
- 125000004784 trichloromethoxy group Chemical group ClC(O*)(Cl)Cl 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 208000009935 visceral pain Diseases 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 230000037314 wound repair Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic 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
- 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
- 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
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Diabetes (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Dermatology (AREA)
- Rheumatology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Oncology (AREA)
- Emergency Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Psychiatry (AREA)
- Obesity (AREA)
- Heart & Thoracic Surgery (AREA)
- Endocrinology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US78454806P | 2006-03-21 | 2006-03-21 | |
| US60/784,548 | 2006-03-21 | ||
| PCT/US2007/007037 WO2007109330A2 (en) | 2006-03-21 | 2007-03-21 | S1p receptor modulating compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2007227274A1 true AU2007227274A1 (en) | 2007-09-27 |
Family
ID=38421478
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2007227274A Abandoned AU2007227274A1 (en) | 2006-03-21 | 2007-03-21 | S1P receptor modulating compounds |
Country Status (9)
| Country | Link |
|---|---|
| US (2) | US7790707B2 (https=) |
| EP (1) | EP2010524A2 (https=) |
| JP (1) | JP2009530389A (https=) |
| AR (1) | AR060050A1 (https=) |
| AU (1) | AU2007227274A1 (https=) |
| CA (1) | CA2646469A1 (https=) |
| CL (1) | CL2007000742A1 (https=) |
| TW (1) | TW200806633A (https=) |
| WO (1) | WO2007109330A2 (https=) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006081332A1 (en) * | 2005-01-25 | 2006-08-03 | Epix Delaware, Inc. | Substituted arylamine compounds and their use as 5-ht6 modulators |
| EP1965807A4 (en) * | 2005-11-23 | 2010-10-27 | Epix Delaware Inc | S1P RECEPTOR MODULATING COMPOUNDS AND THEIR USE |
| US7919519B2 (en) | 2005-11-23 | 2011-04-05 | Epix Pharmaceuticals Inc. | S1P receptor modulating compounds and use thereof |
| JP2009530389A (ja) | 2006-03-21 | 2009-08-27 | エピックス デラウェア， インコーポレイテッド | Ｓ１ｐ受容体調節化合物及びその使用 |
| ES2360929T3 (es) * | 2007-09-20 | 2011-06-10 | Amgen Inc. | Derivados del ácido 1-(4-(4-bencilbenzamido)-bencil)azetidin-3-carboxílico y compuestos relacionados como moduladores del receptor s1p para el tratamiento de trastornos inmunitarios. |
| TW201000099A (en) * | 2008-06-20 | 2010-01-01 | Amgen Inc | S1P1 receptor agonists and use thereof |
| EA019252B1 (ru) | 2008-07-23 | 2014-02-28 | Арена Фармасьютикалз, Инк. | ЗАМЕЩЕННЫЕ ПРОИЗВОДНЫЕ (1,2,3,4-ТЕТРАГИДРОЦИКЛОПЕНТА[b]ИНДОЛ-3-ИЛ)УКСУСНОЙ КИСЛОТЫ, ПРИМЕНИМЫЕ В ЛЕЧЕНИИ АУТОИММУННЫХ И ВОСПАЛИТЕЛЬНЫХ РАССТРОЙСТВ |
| SI2342205T1 (sl) | 2008-08-27 | 2016-09-30 | Arena Pharmaceuticals, Inc. | Substituirani triciklični kislinski derivati kot agonisti S1P1 receptorja, uporabni v zdravljenju avtoimunskih in vnetnih obolenj |
| UY32730A (es) | 2009-06-26 | 2011-01-31 | Novartis Ag | Inhibidores de cyp17 |
| US8399451B2 (en) * | 2009-08-07 | 2013-03-19 | Bristol-Myers Squibb Company | Heterocyclic compounds |
| JP5728487B2 (ja) | 2009-10-29 | 2015-06-03 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | 三環式ヘテロ環化合物 |
| SG10201906876PA (en) | 2010-01-27 | 2019-09-27 | Arena Pharm Inc | Processes for the preparation of (r)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid and salts thereof |
| SG183416A1 (en) | 2010-03-03 | 2012-09-27 | Arena Pharm Inc | Processes for the preparation of s1p1 receptor modulators and crystalline forms thereof |
| WO2011133734A1 (en) | 2010-04-23 | 2011-10-27 | Bristol-Myers Squibb Company | 4 - (5 - isoxazolyl or 5 - pyrrazolyl -1,2,4- oxadiazol - 3 - yl) -mandelic acid amides as sphingosin- 1 - phosphate 1 rreceptor agonists |
| JP5788507B2 (ja) * | 2010-07-20 | 2015-09-30 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | 置換３−フェニル−１，２，４−オキサジアゾール化合物 |
| EP2619190B1 (en) | 2010-09-24 | 2015-08-12 | Bristol-Myers Squibb Company | Substituted oxadiazole compounds and their use as s1p1 agonists |
| WO2012061459A1 (en) | 2010-11-03 | 2012-05-10 | Bristol-Myers Squibb Company | Heterocyclic compounds as s1p1 agonists for the treatment of autoimmune and vascular diseases |
| AU2012249421B9 (en) | 2011-04-28 | 2015-10-22 | Novartis Ag | 17alpha-hydroxylase/C17,20-lyase inhibitors |
| TWI613182B (zh) | 2013-02-21 | 2018-02-01 | 必治妥美雅史谷比公司 | 雙環化合物 |
| TWI689487B (zh) | 2014-08-20 | 2020-04-01 | 美商必治妥美雅史谷比公司 | 經取代雙環化合物 |
| MX386419B (es) | 2015-01-06 | 2025-03-18 | Arena Pharm Inc | Metodos de condiciones de tratamiento relacionadas con el receptor s1p1. |
| EP3939965A1 (en) | 2015-06-22 | 2022-01-19 | Arena Pharmaceuticals, Inc. | Crystalline l-arginine salt of (r)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclo-penta[b]indol-3-yl)acetic acid for use in sipi receptor-associated disorders |
| ES2859478T3 (es) | 2016-09-02 | 2021-10-04 | Bristol Myers Squibb Co | Compuestos heterocíclicos tricíclicos sustituidos |
| WO2018151834A1 (en) | 2017-02-16 | 2018-08-23 | Arena Pharmaceuticals, Inc. | Compounds and methods for treatment of inflammatory bowel disease with extra-intestinal manifestations |
| MA47504A (fr) | 2017-02-16 | 2019-12-25 | Arena Pharm Inc | Composés et méthodes de traitement de l'angiocholite biliaire primitive |
| WO2019032631A1 (en) | 2017-08-09 | 2019-02-14 | Bristol-Myers Squibb Company | Oxime ether compounds |
| US11046646B2 (en) | 2017-08-09 | 2021-06-29 | Bristol-Myers Squibb Company | Alkylphenyl compounds |
| ES2987794T3 (es) | 2018-06-06 | 2024-11-18 | Arena Pharm Inc | Procedimientos de tratamiento de afecciones relacionadas con el receptor S1P1 |
| CN112955431A (zh) | 2018-09-06 | 2021-06-11 | 艾尼纳制药公司 | 可用于治疗自身免疫性病症和炎性病症的化合物 |
| WO2022212638A1 (en) * | 2021-04-02 | 2022-10-06 | Jiangsu Hengrui Pharmaceuticals Co., Ltd. | Prodrugs of adamts inhibitors, preparation methods and medicinal uses thereof |
| WO2022265993A1 (en) | 2021-06-14 | 2022-12-22 | Scorpion Therapeutics, Inc. | Urea derivatives which can be used to treat cancer |
| US11919879B2 (en) * | 2021-06-16 | 2024-03-05 | Celgene Corporation | Carboxylic acid containing azetidinyl compounds for the treatment of neurodegenerative diseases |
Family Cites Families (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3329781A (en) * | 1965-07-06 | 1967-07-04 | Mallory & Co Inc P R | Sequential timing device |
| US4767896A (en) * | 1985-09-03 | 1988-08-30 | Molex Incorporated | Stamped circuitry assembly |
| DE69025418T2 (de) * | 1989-04-19 | 1996-11-14 | Otsuka Pharma Co Ltd | Phenylcarbonsäurederivate mit einem Heterocyclus |
| SK94393A3 (en) * | 1992-09-11 | 1994-08-10 | Thomae Gmbh Dr K | Cyclic derivatives of urea, process for their production and their pharmaceutical agents with the content of those |
| DE4405378A1 (de) * | 1994-02-19 | 1995-08-24 | Merck Patent Gmbh | Adhäsionsrezeptor-Antagonisten |
| JPH10204059A (ja) | 1997-01-22 | 1998-08-04 | Ono Pharmaceut Co Ltd | フェニルスルホンアミド誘導体 |
| JP3802653B2 (ja) * | 1997-05-21 | 2006-07-26 | オリンパス株式会社 | 立体画像表示装置 |
| US6384061B1 (en) * | 1997-07-26 | 2002-05-07 | Lg Chemical Ltd. | Hydantoin compounds and methods related thereto |
| US7064217B2 (en) | 2001-01-30 | 2006-06-20 | University Of Virginia Patent Foundation | Agonists and antagonists of sphingosine-1-phosphate receptors |
| MXPA01013326A (es) * | 2001-02-14 | 2002-08-26 | Warner Lambert Co | Bifenil sulfonamidas utiles como inhibisdores de metaloproteinasa de matriz. |
| US20020183519A1 (en) * | 2001-03-13 | 2002-12-05 | Herbert Nar | Antithrombotic carboxylic acid amides |
| US20050070506A1 (en) | 2002-01-18 | 2005-03-31 | Doherty George A. | Selective s1p1/edg1 receptor agonists |
| US20050113283A1 (en) * | 2002-01-18 | 2005-05-26 | David Solow-Cordero | Methods of treating conditions associated with an EDG-4 receptor |
| US7479504B2 (en) * | 2002-01-18 | 2009-01-20 | Merck & Co., Inc. | Edg receptor agonists |
| JP2005533058A (ja) | 2002-06-17 | 2005-11-04 | メルク エンド カムパニー インコーポレーテッド | Ｅｄｇ受容体アゴニストとしての１−（（５−アリール−１，２，４−オキサジアゾール−３−イル）ベンジル）アゼチジン−３−カルボキシラートおよび１−（（５−アリール−１，２，４−オキサジアゾール−３−イル）ベンジル）ピロリジン−３−カルボキシラート |
| JP4691988B2 (ja) | 2002-10-03 | 2011-06-01 | 小野薬品工業株式会社 | Ｌｐａ受容体拮抗剤 |
| CA2506799A1 (en) | 2002-11-21 | 2004-06-10 | Eli Lilly And Company | Mixed lineage kinase modulators |
| DE10300398A1 (de) | 2003-01-09 | 2004-07-22 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verwendung von substituierten 2-Phenylbenzimidazolen als Arzneimittel |
| BRPI0410439A (pt) * | 2003-05-19 | 2006-06-06 | Irm Llc | compostos e composições imunossupressoras |
| ES2558761T3 (es) | 2003-05-19 | 2016-02-08 | Novartis Ag | Compuestos y composiciones inmunosupresores |
| EP1661881B1 (en) | 2003-08-29 | 2014-12-17 | Ono Pharmaceutical Co., Ltd. | Compound capable of binding s1p receptor and pharmaceutical use thereof |
| WO2005063704A1 (ja) * | 2003-12-25 | 2005-07-14 | Ono Pharmaceutical Co., Ltd. | アゼチジン環化合物およびその医薬 |
| MX2007001661A (es) | 2004-08-13 | 2007-04-23 | Praecis Pharm Inc | Metodos y composiciones para modular la actividad del receptor de esfingosina -1 fosfato (sip). |
| EP2592066B1 (en) * | 2004-12-13 | 2014-12-03 | Ono Pharmaceutical Co., Ltd. | Aminocarboxylic acid derivative and medical use thereof |
| US7919519B2 (en) * | 2005-11-23 | 2011-04-05 | Epix Pharmaceuticals Inc. | S1P receptor modulating compounds and use thereof |
| EP1965807A4 (en) * | 2005-11-23 | 2010-10-27 | Epix Delaware Inc | S1P RECEPTOR MODULATING COMPOUNDS AND THEIR USE |
| JP2009530389A (ja) | 2006-03-21 | 2009-08-27 | エピックス デラウェア， インコーポレイテッド | Ｓ１ｐ受容体調節化合物及びその使用 |
| MX2009010060A (es) | 2007-03-21 | 2010-01-20 | Epix Pharm Inc | Compuestos moduladores del receptor de esfingosin-1-fosfato y uso de los mismos. |
| ES2360929T3 (es) | 2007-09-20 | 2011-06-10 | Amgen Inc. | Derivados del ácido 1-(4-(4-bencilbenzamido)-bencil)azetidin-3-carboxílico y compuestos relacionados como moduladores del receptor s1p para el tratamiento de trastornos inmunitarios. |
-
2007
- 2007-03-21 JP JP2009501545A patent/JP2009530389A/ja active Pending
- 2007-03-21 TW TW096109748A patent/TW200806633A/zh unknown
- 2007-03-21 AU AU2007227274A patent/AU2007227274A1/en not_active Abandoned
- 2007-03-21 US US11/726,356 patent/US7790707B2/en not_active Expired - Fee Related
- 2007-03-21 WO PCT/US2007/007037 patent/WO2007109330A2/en not_active Ceased
- 2007-03-21 AR ARP070101166A patent/AR060050A1/es unknown
- 2007-03-21 CA CA002646469A patent/CA2646469A1/en not_active Abandoned
- 2007-03-21 CL CL2007000742A patent/CL2007000742A1/es unknown
- 2007-03-21 EP EP07753647A patent/EP2010524A2/en not_active Withdrawn
-
2010
- 2010-08-24 US US12/862,631 patent/US20100317649A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20100317649A1 (en) | 2010-12-16 |
| JP2009530389A (ja) | 2009-08-27 |
| US20080015177A1 (en) | 2008-01-17 |
| TW200806633A (en) | 2008-02-01 |
| WO2007109330A2 (en) | 2007-09-27 |
| WO2007109330A3 (en) | 2007-11-22 |
| AR060050A1 (es) | 2008-05-21 |
| CL2007000742A1 (es) | 2008-01-11 |
| CA2646469A1 (en) | 2007-09-27 |
| US7790707B2 (en) | 2010-09-07 |
| EP2010524A2 (en) | 2009-01-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7790707B2 (en) | S1P receptor modulating compounds and use thereof | |
| EP2188252B1 (en) | 1-(4-(4-benzylbenzamido)-benzyl)azetidine-3-carboxylic acid derivatives and related compounds as s1p receptor modulators for the treatment of immune disorders | |
| AU2006317689B2 (en) | S1P receptor modulating compounds and use thereof | |
| EP1991544B1 (en) | Substituted imidazole derivatives and their use as ptpase inhibitors | |
| EP2364976B1 (en) | S1P receptor modulating compounds and use thereof | |
| JP2010540438A5 (https=) | ||
| US5162326A (en) | Pyrimidinedione derivatives, their production and use | |
| US7919519B2 (en) | S1P receptor modulating compounds and use thereof | |
| JP3116256B2 (ja) | （チオ）ウレア誘導体 | |
| MX2008006603A (en) | S1p receptor modulating compounds and use thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK4 | Application lapsed section 142(2)(d) - no continuation fee paid for the application |