ES2625355T3 - Compuestos actúan en múltiples receptores de prostaglandina proporcionando una respuesta anti-inflamatoria general - Google Patents
Compuestos actúan en múltiples receptores de prostaglandina proporcionando una respuesta anti-inflamatoria general Download PDFInfo
- Publication number
- ES2625355T3 ES2625355T3 ES11734222.0T ES11734222T ES2625355T3 ES 2625355 T3 ES2625355 T3 ES 2625355T3 ES 11734222 T ES11734222 T ES 11734222T ES 2625355 T3 ES2625355 T3 ES 2625355T3
- Authority
- ES
- Spain
- Prior art keywords
- chloro
- methyl
- alkyl
- group
- pyrazol
- 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.)
- Active
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 112
- 102000015433 Prostaglandin Receptors Human genes 0.000 title description 4
- 108010050183 Prostaglandin Receptors Proteins 0.000 title description 4
- 230000031990 negative regulation of inflammatory response Effects 0.000 title description 3
- 150000003839 salts Chemical class 0.000 claims abstract description 6
- 238000000034 method Methods 0.000 claims description 68
- 206010061218 Inflammation Diseases 0.000 claims description 21
- 230000004054 inflammatory process Effects 0.000 claims description 21
- 206010046851 Uveitis Diseases 0.000 claims description 11
- 206010010744 Conjunctivitis allergic Diseases 0.000 claims description 2
- 208000002205 allergic conjunctivitis Diseases 0.000 claims description 2
- 208000024998 atopic conjunctivitis Diseases 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 description 101
- -1 hydrocarbyl sulfonamide Chemical class 0.000 description 91
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 65
- 125000003118 aryl group Chemical group 0.000 description 61
- 201000010099 disease Diseases 0.000 description 57
- 125000003545 alkoxy group Chemical group 0.000 description 50
- 229910052739 hydrogen Inorganic materials 0.000 description 42
- 125000001475 halogen functional group Chemical group 0.000 description 39
- 239000002253 acid Substances 0.000 description 36
- 229910052736 halogen Inorganic materials 0.000 description 36
- 150000002367 halogens Chemical class 0.000 description 36
- 125000004093 cyano group Chemical group *C#N 0.000 description 30
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 30
- 125000004104 aryloxy group Chemical group 0.000 description 28
- 102000003938 Thromboxane Receptors Human genes 0.000 description 26
- 108090000300 Thromboxane Receptors Proteins 0.000 description 25
- 210000004027 cell Anatomy 0.000 description 21
- 208000006673 asthma Diseases 0.000 description 19
- 125000005843 halogen group Chemical group 0.000 description 19
- 230000036407 pain Effects 0.000 description 19
- 230000028327 secretion Effects 0.000 description 19
- 125000001188 haloalkyl group Chemical group 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
- 208000002193 Pain Diseases 0.000 description 17
- 239000000203 mixture Substances 0.000 description 17
- 238000011282 treatment Methods 0.000 description 17
- 102100024212 Prostaglandin D2 receptor Human genes 0.000 description 16
- 230000001404 mediated effect Effects 0.000 description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 16
- 102100035842 Prostaglandin E2 receptor EP1 subtype Human genes 0.000 description 15
- 229910052799 carbon Inorganic materials 0.000 description 15
- 230000000694 effects Effects 0.000 description 15
- 101150058615 Ptger1 gene Proteins 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 150000004702 methyl esters Chemical class 0.000 description 14
- 206010039073 rheumatoid arthritis Diseases 0.000 description 14
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 13
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 13
- 101150109738 Ptger4 gene Proteins 0.000 description 13
- 239000000556 agonist Substances 0.000 description 13
- 229910052731 fluorine Inorganic materials 0.000 description 13
- 239000011737 fluorine Substances 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 102000004127 Cytokines Human genes 0.000 description 11
- 108090000695 Cytokines Proteins 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 108050008995 Prostaglandin F receptors Proteins 0.000 description 11
- 108090001097 Transcription Factor DP1 Proteins 0.000 description 11
- 125000000753 cycloalkyl group Chemical group 0.000 description 11
- 238000001356 surgical procedure Methods 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- 201000001320 Atherosclerosis Diseases 0.000 description 10
- 102000006433 Chemokine CCL22 Human genes 0.000 description 10
- 108010083701 Chemokine CCL22 Proteins 0.000 description 10
- 239000005557 antagonist Substances 0.000 description 10
- 210000002540 macrophage Anatomy 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- 208000004454 Hyperalgesia Diseases 0.000 description 9
- 102000004890 Interleukin-8 Human genes 0.000 description 9
- 108090001007 Interleukin-8 Proteins 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 125000004432 carbon atom Chemical group C* 0.000 description 9
- 239000000460 chlorine Substances 0.000 description 9
- 229910052801 chlorine Inorganic materials 0.000 description 9
- 229910052760 oxygen Inorganic materials 0.000 description 9
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 9
- 229910052717 sulfur Inorganic materials 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
- 229910052794 bromium Inorganic materials 0.000 description 8
- 230000003833 cell viability Effects 0.000 description 8
- 208000035475 disorder Diseases 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 8
- 229940096397 interleukin-8 Drugs 0.000 description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 8
- 150000003180 prostaglandins Chemical class 0.000 description 8
- 102000017953 prostanoid receptors Human genes 0.000 description 8
- 108050007059 prostanoid receptors Proteins 0.000 description 8
- 229940124530 sulfonamide Drugs 0.000 description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 7
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 7
- 101001073427 Homo sapiens Prostaglandin E2 receptor EP1 subtype Proteins 0.000 description 7
- 102100024448 Prostaglandin E2 receptor EP2 subtype Human genes 0.000 description 7
- 102100024450 Prostaglandin E2 receptor EP4 subtype Human genes 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- 239000002158 endotoxin Substances 0.000 description 7
- 125000003709 fluoroalkyl group Chemical group 0.000 description 7
- 229920006008 lipopolysaccharide Polymers 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 239000008194 pharmaceutical composition Substances 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 239000003039 volatile agent Substances 0.000 description 7
- 206010027654 Allergic conditions Diseases 0.000 description 6
- 108020004635 Complementary DNA Proteins 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 208000010412 Glaucoma Diseases 0.000 description 6
- 239000007995 HEPES buffer Substances 0.000 description 6
- 208000019695 Migraine disease Diseases 0.000 description 6
- 206010028735 Nasal congestion Diseases 0.000 description 6
- 206010030043 Ocular hypertension Diseases 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 239000012298 atmosphere Substances 0.000 description 6
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 6
- 235000019439 ethyl acetate Nutrition 0.000 description 6
- 125000004494 ethyl ester group Chemical group 0.000 description 6
- 125000001153 fluoro group Chemical group F* 0.000 description 6
- 210000000265 leukocyte Anatomy 0.000 description 6
- 206010027599 migraine Diseases 0.000 description 6
- 210000003097 mucus Anatomy 0.000 description 6
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 230000000770 proinflammatory effect Effects 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 231100000241 scar Toxicity 0.000 description 6
- 208000019116 sleep disease Diseases 0.000 description 6
- 235000002639 sodium chloride Nutrition 0.000 description 6
- KAKQVSNHTBLJCH-UHFFFAOYSA-N trifluoromethanesulfonimidic acid Chemical compound NS(=O)(=O)C(F)(F)F KAKQVSNHTBLJCH-UHFFFAOYSA-N 0.000 description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 6
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 5
- 208000023275 Autoimmune disease Diseases 0.000 description 5
- 206010012438 Dermatitis atopic Diseases 0.000 description 5
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 5
- 101001117509 Homo sapiens Prostaglandin E2 receptor EP4 subtype Proteins 0.000 description 5
- 239000007832 Na2SO4 Substances 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- 208000007950 Ocular Hypotension Diseases 0.000 description 5
- 206010035664 Pneumonia Diseases 0.000 description 5
- 208000003251 Pruritus Diseases 0.000 description 5
- 206010039085 Rhinitis allergic Diseases 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 201000009961 allergic asthma Diseases 0.000 description 5
- 201000010105 allergic rhinitis Diseases 0.000 description 5
- 201000008937 atopic dermatitis Diseases 0.000 description 5
- 230000024279 bone resorption Effects 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 125000000068 chlorophenyl group Chemical group 0.000 description 5
- 231100000673 dose–response relationship Toxicity 0.000 description 5
- 210000003979 eosinophil Anatomy 0.000 description 5
- 230000008595 infiltration Effects 0.000 description 5
- 238000001764 infiltration Methods 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 229910052697 platinum Inorganic materials 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 229940044551 receptor antagonist Drugs 0.000 description 5
- 239000002464 receptor antagonist Substances 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 230000011664 signaling Effects 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- PQHNRODYYLFLRE-UHFFFAOYSA-N 3-(chloromethyl)pentane Chemical compound CCC(CC)CCl PQHNRODYYLFLRE-UHFFFAOYSA-N 0.000 description 4
- NTKCCANMCAOSKM-UHFFFAOYSA-N 3-[1-[[5-chloro-2-(2-ethylbutoxy)phenyl]methyl]-5-methylpyrazol-3-yl]propanoic acid Chemical compound CCC(CC)COC1=CC=C(Cl)C=C1CN1C(C)=CC(CCC(O)=O)=N1 NTKCCANMCAOSKM-UHFFFAOYSA-N 0.000 description 4
- FWLNGQKMSQARPI-UHFFFAOYSA-N 3-[1-[[5-chloro-2-[(4-chlorophenyl)methoxy]phenyl]methyl]-5-methylpyrazol-3-yl]-n-(trifluoromethylsulfonyl)propanamide Chemical compound CC1=CC(CCC(=O)NS(=O)(=O)C(F)(F)F)=NN1CC1=CC(Cl)=CC=C1OCC1=CC=C(Cl)C=C1 FWLNGQKMSQARPI-UHFFFAOYSA-N 0.000 description 4
- 208000025978 Athletic injury Diseases 0.000 description 4
- 208000020084 Bone disease Diseases 0.000 description 4
- 206010007559 Cardiac failure congestive Diseases 0.000 description 4
- 102000019034 Chemokines Human genes 0.000 description 4
- 108010012236 Chemokines Proteins 0.000 description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 4
- 208000032544 Cicatrix Diseases 0.000 description 4
- 206010053567 Coagulopathies Diseases 0.000 description 4
- 206010012689 Diabetic retinopathy Diseases 0.000 description 4
- 206010017711 Gangrene Diseases 0.000 description 4
- 206010019280 Heart failures Diseases 0.000 description 4
- 208000035154 Hyperesthesia Diseases 0.000 description 4
- 206010020741 Hyperpyrexia Diseases 0.000 description 4
- 206010020751 Hypersensitivity Diseases 0.000 description 4
- 208000001953 Hypotension Diseases 0.000 description 4
- 208000002260 Keloid Diseases 0.000 description 4
- 208000000112 Myalgia Diseases 0.000 description 4
- 208000001132 Osteoporosis Diseases 0.000 description 4
- 108091006335 Prostaglandin I receptors Proteins 0.000 description 4
- 206010037368 Pulmonary congestion Diseases 0.000 description 4
- 208000003782 Raynaud disease Diseases 0.000 description 4
- 208000012322 Raynaud phenomenon Diseases 0.000 description 4
- 206010039094 Rhinitis perennial Diseases 0.000 description 4
- 208000036071 Rhinorrhea Diseases 0.000 description 4
- 206010039101 Rhinorrhoea Diseases 0.000 description 4
- 210000001744 T-lymphocyte Anatomy 0.000 description 4
- 206010052779 Transplant rejections Diseases 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 125000002947 alkylene group Chemical group 0.000 description 4
- 208000026935 allergic disease Diseases 0.000 description 4
- 230000000172 allergic effect Effects 0.000 description 4
- 206010053552 allodynia Diseases 0.000 description 4
- 230000023555 blood coagulation Effects 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- VMKJWLXVLHBJNK-UHFFFAOYSA-N cyanuric fluoride Chemical compound FC1=NC(F)=NC(F)=N1 VMKJWLXVLHBJNK-UHFFFAOYSA-N 0.000 description 4
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 210000001035 gastrointestinal tract Anatomy 0.000 description 4
- 230000036543 hypotension Effects 0.000 description 4
- 208000026278 immune system disease Diseases 0.000 description 4
- 239000007943 implant Substances 0.000 description 4
- 208000021267 infertility disease Diseases 0.000 description 4
- 230000004968 inflammatory condition Effects 0.000 description 4
- 208000027866 inflammatory disease Diseases 0.000 description 4
- 208000002551 irritable bowel syndrome Diseases 0.000 description 4
- 230000007803 itching Effects 0.000 description 4
- 210000001117 keloid Anatomy 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- SIGOIUCRXKUEIG-UHFFFAOYSA-N methyl 2-dimethoxyphosphorylacetate Chemical compound COC(=O)CP(=O)(OC)OC SIGOIUCRXKUEIG-UHFFFAOYSA-N 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 4
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 230000011164 ossification Effects 0.000 description 4
- 230000008506 pathogenesis Effects 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 230000002685 pulmonary effect Effects 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 230000000241 respiratory effect Effects 0.000 description 4
- 230000037387 scars Effects 0.000 description 4
- 238000013207 serial dilution Methods 0.000 description 4
- 230000035939 shock Effects 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 230000004614 tumor growth Effects 0.000 description 4
- 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 3
- KVDYESNTWCANOH-UHFFFAOYSA-N 3-[1-[[5-bromo-2-(2-ethylbutoxy)phenyl]methyl]-5-methylpyrazol-3-yl]propanoic acid Chemical compound CCC(CC)COC1=CC=C(Br)C=C1CN1C(C)=CC(CCC(O)=O)=N1 KVDYESNTWCANOH-UHFFFAOYSA-N 0.000 description 3
- 208000019888 Circadian rhythm sleep disease Diseases 0.000 description 3
- 108091006027 G proteins Proteins 0.000 description 3
- 102000030782 GTP binding Human genes 0.000 description 3
- 108091000058 GTP-Binding Proteins 0.000 description 3
- 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 3
- 101001117517 Homo sapiens Prostaglandin E2 receptor EP3 subtype Proteins 0.000 description 3
- 102000000589 Interleukin-1 Human genes 0.000 description 3
- 108010002352 Interleukin-1 Proteins 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 206010028741 Nasal inflammation Diseases 0.000 description 3
- 101150053131 PTGER3 gene Proteins 0.000 description 3
- 102100024447 Prostaglandin E2 receptor EP3 subtype Human genes 0.000 description 3
- 102000000471 Prostaglandin F receptors Human genes 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 125000004422 alkyl sulphonamide group Chemical group 0.000 description 3
- 230000007815 allergy Effects 0.000 description 3
- 230000010100 anticoagulation Effects 0.000 description 3
- 208000010668 atopic eczema Diseases 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 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 3
- 125000004799 bromophenyl group Chemical group 0.000 description 3
- 239000002738 chelating agent Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- NQIIILQXTJXSCA-UHFFFAOYSA-N chloromethylcyclopentane Chemical compound ClCC1CCCC1 NQIIILQXTJXSCA-UHFFFAOYSA-N 0.000 description 3
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 3
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 229960002986 dinoprostone Drugs 0.000 description 3
- 201000006549 dyspepsia Diseases 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 125000005647 linker group Chemical group 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 210000001616 monocyte Anatomy 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 230000002914 neoplasic effect Effects 0.000 description 3
- 210000000440 neutrophil Anatomy 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 230000007115 recruitment Effects 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- 238000000844 transformation Methods 0.000 description 3
- 208000019553 vascular disease Diseases 0.000 description 3
- KQNBRMUBPRGXSL-UHFFFAOYSA-N 1-(bromomethyl)-4-chlorobenzene Chemical compound ClC1=CC=C(CBr)C=C1 KQNBRMUBPRGXSL-UHFFFAOYSA-N 0.000 description 2
- QGPXOZLWJCSAQT-UHFFFAOYSA-N 1-[(5-chloro-2-hydroxyphenyl)methyl]-5-methylpyrazole-3-carboxylic acid Chemical compound CC1=CC(C(O)=O)=NN1CC1=CC(Cl)=CC=C1O QGPXOZLWJCSAQT-UHFFFAOYSA-N 0.000 description 2
- DOJDOCCGHGFTOQ-UHFFFAOYSA-N 1-[(5-chloro-2-phenylmethoxyphenyl)methyl]-5-methylpyrazole-3-carboxylic acid Chemical compound CC1=CC(C(O)=O)=NN1CC1=CC(Cl)=CC=C1OCC1=CC=CC=C1 DOJDOCCGHGFTOQ-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 2
- VKUYLANQOAKALN-UHFFFAOYSA-N 2-[benzyl-(4-methoxyphenyl)sulfonylamino]-n-hydroxy-4-methylpentanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(CC(C)C)C(=O)NO)CC1=CC=CC=C1 VKUYLANQOAKALN-UHFFFAOYSA-N 0.000 description 2
- 125000003858 2-ethylbutoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])O*)C([H])([H])C([H])([H])[H] 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- DCLCBDKYYKUMIP-UHFFFAOYSA-N 3-[1-[[2-(cyclopentylmethoxy)-5-(trifluoromethyl)phenyl]methyl]-5-methylpyrazol-3-yl]propanoic acid Chemical compound CC1=CC(CCC(O)=O)=NN1CC1=CC(C(F)(F)F)=CC=C1OCC1CCCC1 DCLCBDKYYKUMIP-UHFFFAOYSA-N 0.000 description 2
- MSILREZNZDUJJQ-UHFFFAOYSA-N 3-[1-[[5-bromo-2-(cyclopentylmethoxy)phenyl]methyl]-5-methylpyrazol-3-yl]propanoic acid Chemical compound CC1=CC(CCC(O)=O)=NN1CC1=CC(Br)=CC=C1OCC1CCCC1 MSILREZNZDUJJQ-UHFFFAOYSA-N 0.000 description 2
- 208000004998 Abdominal Pain Diseases 0.000 description 2
- 206010003178 Arterial thrombosis Diseases 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 208000002177 Cataract Diseases 0.000 description 2
- 208000002881 Colic Diseases 0.000 description 2
- 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 2
- 206010013082 Discomfort Diseases 0.000 description 2
- 206010063655 Erosive oesophagitis Diseases 0.000 description 2
- 206010019233 Headaches Diseases 0.000 description 2
- 206010019375 Helicobacter infections Diseases 0.000 description 2
- 206010020112 Hirsutism Diseases 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 206010021113 Hypothermia Diseases 0.000 description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 102000008866 Prostaglandin E receptors Human genes 0.000 description 2
- 108010088540 Prostaglandin E receptors Proteins 0.000 description 2
- 102000016611 Proteoglycans Human genes 0.000 description 2
- 108010067787 Proteoglycans Proteins 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- 102100030416 Stromelysin-1 Human genes 0.000 description 2
- 101710108790 Stromelysin-1 Proteins 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- 102100040247 Tumor necrosis factor Human genes 0.000 description 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
- 208000019789 abdominal cramp Diseases 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 208000028004 allergic respiratory disease Diseases 0.000 description 2
- 210000002159 anterior chamber Anatomy 0.000 description 2
- 230000001088 anti-asthma Effects 0.000 description 2
- 239000000924 antiasthmatic agent Substances 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- 230000007214 atherothrombosis Effects 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000036760 body temperature Effects 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000002975 chemoattractant Substances 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 210000001612 chondrocyte Anatomy 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 125000005469 ethylenyl group Chemical group 0.000 description 2
- 206010015907 eye allergy Diseases 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 2
- 231100000869 headache Toxicity 0.000 description 2
- 208000031169 hemorrhagic disease Diseases 0.000 description 2
- 125000001072 heteroaryl group Chemical group 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- 230000002631 hypothermal effect Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 208000011379 keloid formation Diseases 0.000 description 2
- 238000002430 laser surgery Methods 0.000 description 2
- 238000012417 linear regression Methods 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 208000008585 mastocytosis Diseases 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 206010061289 metastatic neoplasm Diseases 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 208000013465 muscle pain Diseases 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000006179 pH buffering agent Substances 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 208000000689 peptic esophagitis Diseases 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229940127557 pharmaceutical product Drugs 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 201000004335 respiratory allergy Diseases 0.000 description 2
- 206010039083 rhinitis Diseases 0.000 description 2
- 125000006413 ring segment Chemical group 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 208000020685 sleep-wake disease Diseases 0.000 description 2
- 210000002460 smooth muscle Anatomy 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 229960004249 sodium acetate Drugs 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- DDMGAAYEUNWXSI-XVSDJDOKSA-M sodium;(5z,8z,11z,14z)-icosa-5,8,11,14-tetraenoate Chemical compound [Na+].CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC([O-])=O DDMGAAYEUNWXSI-XVSDJDOKSA-M 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 150000003456 sulfonamides Chemical class 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000001960 triggered effect Effects 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 238000009736 wetting Methods 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- ZIDQIOZJEJFMOH-JKSUJKDBSA-N (3R,4S)-BW 245C Chemical compound C([C@@H](O)C1CCCCC1)CN1[C@@H](CCCCCCC(O)=O)C(=O)NC1=O ZIDQIOZJEJFMOH-JKSUJKDBSA-N 0.000 description 1
- MEHHSOYPDASCFA-CSKARUKUSA-N (E)-3-[1-[(5-chloro-2-phenylmethoxyphenyl)methyl]-5-methylpyrazol-3-yl]prop-2-enoic acid Chemical compound C(C1=CC=CC=C1)OC1=C(CN2N=C(C=C2C)/C=C/C(=O)O)C=C(C=C1)Cl MEHHSOYPDASCFA-CSKARUKUSA-N 0.000 description 1
- VVEXPDRCGCQELD-CFDZEDGGSA-N (z)-6-[(2s,3r)-2-[[(4-chloro-2-methylphenyl)sulfonylamino]methyl]-3-bicyclo[2.2.2]octanyl]hex-5-enoic acid Chemical compound CC1=CC(Cl)=CC=C1S(=O)(=O)NC[C@@H]1[C@@H](\C=C/CCCC(O)=O)C2CCC1CC2 VVEXPDRCGCQELD-CFDZEDGGSA-N 0.000 description 1
- ICLYJLBTOGPLMC-KVVVOXFISA-N (z)-octadec-9-enoate;tris(2-hydroxyethyl)azanium Chemical compound OCCN(CCO)CCO.CCCCCCCC\C=C/CCCCCCCC(O)=O ICLYJLBTOGPLMC-KVVVOXFISA-N 0.000 description 1
- WPRAXAOJIODQJR-UHFFFAOYSA-N 1-(3,4-dimethylphenyl)ethanone Chemical compound CC(=O)C1=CC=C(C)C(C)=C1 WPRAXAOJIODQJR-UHFFFAOYSA-N 0.000 description 1
- LRHLWQJYGNBUPD-UHFFFAOYSA-N 1-[[5-chloro-2-[(4-chlorophenyl)methoxy]phenyl]methyl]-5-methylpyrazole-3-carboxylic acid Chemical compound CC1=CC(C(O)=O)=NN1CC1=CC(Cl)=CC=C1OCC1=CC=C(Cl)C=C1 LRHLWQJYGNBUPD-UHFFFAOYSA-N 0.000 description 1
- NCWZFTAAWMCXHR-UHFFFAOYSA-N 3-[1-[[5-chloro-2-(cyclopentylmethoxy)phenyl]methyl]-5-methylpyrazol-3-yl]propanoic acid Chemical compound CC1=CC(CCC(O)=O)=NN1CC1=CC(Cl)=CC=C1OCC1CCCC1 NCWZFTAAWMCXHR-UHFFFAOYSA-N 0.000 description 1
- GBEZZDGDKDSKHL-UHFFFAOYSA-N 3-[1-[[5-chloro-2-[(4-chlorophenyl)methoxy]phenyl]methyl]-5-methylpyrazol-3-yl]propanoic acid Chemical compound CC1=CC(CCC(O)=O)=NN1CC1=CC(Cl)=CC=C1OCC1=CC=C(Cl)C=C1 GBEZZDGDKDSKHL-UHFFFAOYSA-N 0.000 description 1
- MKANNUAVWQGDTK-UHFFFAOYSA-N 3-[1-[[5-chloro-2-[(4-chlorophenyl)methoxy]phenyl]methyl]-5-methylpyrazol-3-yl]propanoyl fluoride Chemical compound CC1=CC(CCC(F)=O)=NN1CC1=CC(Cl)=CC=C1OCC1=CC=C(Cl)C=C1 MKANNUAVWQGDTK-UHFFFAOYSA-N 0.000 description 1
- FUGKCSRLAQKUHG-UHFFFAOYSA-N 5-chloro-2-hydroxybenzaldehyde Chemical compound OC1=CC=C(Cl)C=C1C=O FUGKCSRLAQKUHG-UHFFFAOYSA-N 0.000 description 1
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 231100000039 Ames test Toxicity 0.000 description 1
- YZXBAPSDXZZRGB-DOFZRALJSA-M Arachidonate Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC([O-])=O YZXBAPSDXZZRGB-DOFZRALJSA-M 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 208000006386 Bone Resorption Diseases 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 206010006482 Bronchospasm Diseases 0.000 description 1
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 1
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- 102100031151 C-C chemokine receptor type 2 Human genes 0.000 description 1
- 101710149815 C-C chemokine receptor type 2 Proteins 0.000 description 1
- 102000004274 CCR5 Receptors Human genes 0.000 description 1
- 108010017088 CCR5 Receptors Proteins 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical group [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- 201000009273 Endometriosis Diseases 0.000 description 1
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
- 108010008655 Epstein-Barr Virus Nuclear Antigens Proteins 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 206010059024 Gastrointestinal toxicity Diseases 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 101000988802 Homo sapiens Hematopoietic prostaglandin D synthase Proteins 0.000 description 1
- 101000946124 Homo sapiens Lipocalin-1 Proteins 0.000 description 1
- 101001117519 Homo sapiens Prostaglandin E2 receptor EP2 subtype Proteins 0.000 description 1
- 101000836978 Homo sapiens Sperm-associated antigen 11B Proteins 0.000 description 1
- 101000796134 Homo sapiens Thymidine phosphorylase Proteins 0.000 description 1
- 101000666385 Homo sapiens Transcription factor Dp-2 Proteins 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- GRRNUXAQVGOGFE-UHFFFAOYSA-N Hygromycin-B Natural products OC1C(NC)CC(N)C(O)C1OC1C2OC3(C(C(O)C(O)C(C(N)CO)O3)O)OC2C(O)C(CO)O1 GRRNUXAQVGOGFE-UHFFFAOYSA-N 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 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 1
- 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 1
- 229910010084 LiAlH4 Inorganic materials 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- 101710151805 Mitochondrial intermediate peptidase 1 Proteins 0.000 description 1
- 102000014962 Monocyte Chemoattractant Proteins Human genes 0.000 description 1
- 108010064136 Monocyte Chemoattractant Proteins Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 206010030111 Oedema mucosal Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000030852 Parasitic disease Diseases 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 102000012335 Plasminogen Activator Inhibitor 1 Human genes 0.000 description 1
- 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 208000004550 Postoperative Pain Diseases 0.000 description 1
- 102100026476 Prostacyclin receptor Human genes 0.000 description 1
- 102100024218 Prostaglandin D2 receptor 2 Human genes 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 229910019020 PtO2 Inorganic materials 0.000 description 1
- LDXDSHIEDAPSSA-OAHLLOKOSA-N Ramatroban Chemical compound N([C@@H]1CCC=2N(C3=CC=CC=C3C=2C1)CCC(=O)O)S(=O)(=O)C1=CC=C(F)C=C1 LDXDSHIEDAPSSA-OAHLLOKOSA-N 0.000 description 1
- 241000220259 Raphanus Species 0.000 description 1
- 235000006140 Raphanus sativus var sativus Nutrition 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- ZBVKEHDGYSLCCC-UHFFFAOYSA-N Seratrodast Chemical compound O=C1C(C)=C(C)C(=O)C(C(CCCCCC(O)=O)C=2C=CC=CC=2)=C1C ZBVKEHDGYSLCCC-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 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 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 229940099508 TP receptor antagonist Drugs 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 208000036029 Uterine contractions during pregnancy Diseases 0.000 description 1
- 241000289690 Xenarthra Species 0.000 description 1
- YAOVMBSKLAMJJP-UHFFFAOYSA-N [(5-chloro-2-hydroxyphenyl)methylamino]carbamic acid Chemical compound OC(=O)NNCc1cc(Cl)ccc1O YAOVMBSKLAMJJP-UHFFFAOYSA-N 0.000 description 1
- KGDWXFVFPUMIMX-UHFFFAOYSA-N [1-[(5-chloro-2-phenylmethoxyphenyl)methyl]-5-methylpyrazol-3-yl]methanol Chemical compound CC1=CC(CO)=NN1CC1=CC(Cl)=CC=C1OCC1=CC=CC=C1 KGDWXFVFPUMIMX-UHFFFAOYSA-N 0.000 description 1
- CMQBEIHNNVIYBH-UHFFFAOYSA-N [1-[[5-chloro-2-[(4-chlorophenyl)methoxy]phenyl]methyl]-5-methylpyrazol-3-yl]methanol Chemical compound CC1=CC(CO)=NN1CC1=CC(Cl)=CC=C1OCC1=CC=C(Cl)C=C1 CMQBEIHNNVIYBH-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- QOMNQGZXFYNBNG-UHFFFAOYSA-N acetyloxymethyl 2-[2-[2-[5-[3-(acetyloxymethoxy)-2,7-difluoro-6-oxoxanthen-9-yl]-2-[bis[2-(acetyloxymethoxy)-2-oxoethyl]amino]phenoxy]ethoxy]-n-[2-(acetyloxymethoxy)-2-oxoethyl]-4-methylanilino]acetate Chemical compound CC(=O)OCOC(=O)CN(CC(=O)OCOC(C)=O)C1=CC=C(C)C=C1OCCOC1=CC(C2=C3C=C(F)C(=O)C=C3OC3=CC(OCOC(C)=O)=C(F)C=C32)=CC=C1N(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O QOMNQGZXFYNBNG-UHFFFAOYSA-N 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 125000005466 alkylenyl group Chemical group 0.000 description 1
- 230000009285 allergic inflammation Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 239000002870 angiogenesis inducing agent Substances 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 239000003435 antirheumatic agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229940114078 arachidonate Drugs 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 125000005841 biaryl group Chemical group 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 208000034158 bleeding Diseases 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000007885 bronchoconstriction Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 1
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 229920003090 carboxymethyl hydroxyethyl cellulose Polymers 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 230000009084 cardiovascular function Effects 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- ARUGKOZUKWAXDS-SEWALLKFSA-N cicaprost Chemical compound C1\C(=C/COCC(O)=O)C[C@@H]2[C@@H](C#C[C@@H](O)[C@@H](C)CC#CCC)[C@H](O)C[C@@H]21 ARUGKOZUKWAXDS-SEWALLKFSA-N 0.000 description 1
- 229950000634 cicaprost Drugs 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 238000011278 co-treatment Methods 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 229910052681 coesite Inorganic materials 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 229940111134 coxibs Drugs 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229910052906 cristobalite Inorganic materials 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000004981 cycloalkylmethyl group Chemical group 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 201000001981 dermatomyositis Diseases 0.000 description 1
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 230000009266 disease activity Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- CSPJONKOEMIPFY-UHFFFAOYSA-N disulfo sulfate Chemical compound OS(=O)(=O)OS(=O)(=O)OS(O)(=O)=O CSPJONKOEMIPFY-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- OYQVQWIASIXXRT-UHFFFAOYSA-N ethyl 2,4-dioxopentanoate Chemical compound CCOC(=O)C(=O)CC(C)=O OYQVQWIASIXXRT-UHFFFAOYSA-N 0.000 description 1
- HXQVQGWHFRNKMS-UHFFFAOYSA-M ethylmercurithiosalicylic acid Chemical compound CC[Hg]SC1=CC=CC=C1C(O)=O HXQVQGWHFRNKMS-UHFFFAOYSA-M 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 238000011990 functional testing Methods 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 231100000414 gastrointestinal toxicity Toxicity 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 210000005086 glomerual capillary Anatomy 0.000 description 1
- 230000001434 glomerular Effects 0.000 description 1
- 230000024924 glomerular filtration Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 208000024798 heartburn Diseases 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 102000052785 human PTGER1 Human genes 0.000 description 1
- 102000055674 human TFDP2 Human genes 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- GRRNUXAQVGOGFE-NZSRVPFOSA-N hygromycin B Chemical compound O[C@@H]1[C@@H](NC)C[C@@H](N)[C@H](O)[C@H]1O[C@H]1[C@H]2O[C@@]3([C@@H]([C@@H](O)[C@@H](O)[C@@H](C(N)CO)O3)O)O[C@H]2[C@@H](O)[C@@H](CO)O1 GRRNUXAQVGOGFE-NZSRVPFOSA-N 0.000 description 1
- 229940097277 hygromycin b Drugs 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 229960000598 infliximab Drugs 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 230000004410 intraocular pressure 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
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 description 1
- 229960000681 leflunomide Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000003071 memory t lymphocyte Anatomy 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- ISVOVAPTLDWQEY-CSKARUKUSA-N methyl (e)-3-[1-[[5-chloro-2-[(4-chlorophenyl)methoxy]phenyl]methyl]-5-methylpyrazol-3-yl]prop-2-enoate Chemical compound N1=C(/C=C/C(=O)OC)C=C(C)N1CC1=CC(Cl)=CC=C1OCC1=CC=C(Cl)C=C1 ISVOVAPTLDWQEY-CSKARUKUSA-N 0.000 description 1
- NTNUDYROPUKXNA-UHFFFAOYSA-N methyl 2-(triphenyl-$l^{5}-phosphanylidene)acetate Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OC)C1=CC=CC=C1 NTNUDYROPUKXNA-UHFFFAOYSA-N 0.000 description 1
- RZHALQQNIZMQHO-UHFFFAOYSA-N methyl 3-[1-[(5-chloro-2-hydroxyphenyl)methyl]-5-methylpyrazol-3-yl]propanoate Chemical compound N1=C(CCC(=O)OC)C=C(C)N1CC1=CC(Cl)=CC=C1O RZHALQQNIZMQHO-UHFFFAOYSA-N 0.000 description 1
- FIXFZUSSQWFZLZ-UHFFFAOYSA-N methyl 3-[1-[[5-chloro-2-(2-ethylbutoxy)phenyl]methyl]-5-methylpyrazol-3-yl]propanoate Chemical compound CCC(CC)COC1=CC=C(Cl)C=C1CN1C(C)=CC(CCC(=O)OC)=N1 FIXFZUSSQWFZLZ-UHFFFAOYSA-N 0.000 description 1
- OESDPXDFLYFBJA-UHFFFAOYSA-N methyl 3-[1-[[5-chloro-2-[(4-chlorophenyl)methoxy]phenyl]methyl]-5-methylpyrazol-3-yl]propanoate Chemical compound N1=C(CCC(=O)OC)C=C(C)N1CC1=CC(Cl)=CC=C1OCC1=CC=C(Cl)C=C1 OESDPXDFLYFBJA-UHFFFAOYSA-N 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 230000007886 mutagenicity Effects 0.000 description 1
- 231100000299 mutagenicity Toxicity 0.000 description 1
- 230000010309 neoplastic transformation Effects 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000002997 ophthalmic solution Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000008533 pain sensitivity Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000003961 penetration enhancing agent Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000001175 peptic effect Effects 0.000 description 1
- 208000011906 peptic ulcer disease Diseases 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 102000013415 peroxidase activity proteins Human genes 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 238000009522 phase III clinical trial Methods 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- XEBWQGVWTUSTLN-UHFFFAOYSA-M phenylmercury acetate Chemical compound CC(=O)O[Hg]C1=CC=CC=C1 XEBWQGVWTUSTLN-UHFFFAOYSA-M 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 125000004437 phosphorous atom Chemical group 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 230000010118 platelet activation Effects 0.000 description 1
- 208000008423 pleurisy Diseases 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 208000005987 polymyositis Diseases 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 229940124606 potential therapeutic agent Drugs 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- BHMBVRSPMRCCGG-OUTUXVNYSA-N prostaglandin D2 Chemical compound CCCCC[C@H](O)\C=C\[C@@H]1[C@@H](C\C=C/CCCC(O)=O)[C@@H](O)CC1=O BHMBVRSPMRCCGG-OUTUXVNYSA-N 0.000 description 1
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 description 1
- BHMBVRSPMRCCGG-UHFFFAOYSA-N prostaglandine D2 Natural products CCCCCC(O)C=CC1C(CC=CCCCC(O)=O)C(O)CC1=O BHMBVRSPMRCCGG-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 229950004496 ramatroban Drugs 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008085 renal dysfunction Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 238000011808 rodent model Methods 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 229960003090 seratrodast Drugs 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 230000008454 sleep-wake cycle Effects 0.000 description 1
- 230000016160 smooth muscle contraction Effects 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 210000005070 sphincter Anatomy 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 229910052682 stishovite Inorganic materials 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- 210000001258 synovial membrane Anatomy 0.000 description 1
- 210000002437 synoviocyte Anatomy 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 1
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- 229940117013 triethanolamine oleate Drugs 0.000 description 1
- 229960004418 trolamine Drugs 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 210000005167 vascular cell Anatomy 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
- 208000009935 visceral pain Diseases 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P11/02—Nasal agents, e.g. decongestants
-
- 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
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- 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
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- 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
-
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
- A61P33/00—Antiparasitic agents
-
- 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
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Pulmonology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Dermatology (AREA)
- Hematology (AREA)
- Physical Education & Sports Medicine (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Urology & Nephrology (AREA)
- Emergency Medicine (AREA)
- Transplantation (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Child & Adolescent Psychology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Ophthalmology & Optometry (AREA)
- Psychiatry (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US360755P | 2002-03-01 | ||
| US36075510P | 2010-07-01 | 2010-07-01 | |
| PCT/US2011/042729 WO2012003414A1 (en) | 2010-07-01 | 2011-07-01 | Compounds act at multiple prostaglandin receptors giving a general anti-inflammatory response |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2625355T3 true ES2625355T3 (es) | 2017-07-19 |
Family
ID=44514984
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES11734222.0T Active ES2625355T3 (es) | 2010-07-01 | 2011-07-01 | Compuestos actúan en múltiples receptores de prostaglandina proporcionando una respuesta anti-inflamatoria general |
Country Status (18)
| Country | Link |
|---|---|
| US (3) | US8492424B2 (OSRAM) |
| EP (1) | EP2588459B1 (OSRAM) |
| JP (1) | JP5922116B2 (OSRAM) |
| KR (1) | KR20130141434A (OSRAM) |
| CN (1) | CN103038219B (OSRAM) |
| AR (1) | AR082073A1 (OSRAM) |
| AU (1) | AU2011272716B2 (OSRAM) |
| BR (1) | BR112013000065A2 (OSRAM) |
| CA (1) | CA2804194C (OSRAM) |
| CL (1) | CL2013000002A1 (OSRAM) |
| CO (1) | CO6680625A2 (OSRAM) |
| ES (1) | ES2625355T3 (OSRAM) |
| MX (1) | MX2013000170A (OSRAM) |
| PH (1) | PH12013500121A1 (OSRAM) |
| RU (1) | RU2013102967A (OSRAM) |
| SG (1) | SG186886A1 (OSRAM) |
| TW (1) | TW201206891A (OSRAM) |
| WO (1) | WO2012003414A1 (OSRAM) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10206813B2 (en) | 2009-05-18 | 2019-02-19 | Dose Medical Corporation | Implants with controlled drug delivery features and methods of using same |
| US12478503B2 (en) | 2009-05-18 | 2025-11-25 | Glaukos Corporation | Implants with controlled drug delivery features and methods of using same |
| US8859606B2 (en) * | 2010-07-01 | 2014-10-14 | Allergan, Inc. | Compounds act at multiple prostaglandin receptors giving a general anti-inflammatory response |
| US9006450B2 (en) | 2010-07-01 | 2015-04-14 | Boehringer Ingelheim International Gmbh | Compounds, pharmaceutical compositions and uses thereof |
| US8969589B2 (en) * | 2011-12-21 | 2015-03-03 | Allergan, Inc. | Compounds acting at multiple prostaglandin receptors giving a general anti-inflammatory response |
| CA2862263C (en) * | 2011-12-27 | 2016-09-06 | Allergan, Inc. | Compounds acting at multiple prostaglandin receptors giving a general anti-inflammatory response |
| EP2966064A1 (en) * | 2011-12-27 | 2016-01-13 | Allergan, Inc. | Pyrazole-3-carboxylic acid compounds acting at multiple prostaglandin receptors giving a general anti-inflammatory response |
| WO2014028762A1 (en) | 2012-08-15 | 2014-02-20 | University Of Virginia Patent Foundation | Compositions and methods for treating peripheral arterial disease |
| JP6403688B2 (ja) * | 2013-01-21 | 2018-10-10 | アラーガン、インコーポレイテッドＡｌｌｅｒｇａｎ，Ｉｎｃｏｒｐｏｒａｔｅｄ | 全身性抗炎症反応を提供する複数のプロスタグランジン受容体で作用する化合物 |
| EP3063133A1 (en) | 2013-10-31 | 2016-09-07 | Allergan, Inc. | 3-{1-[5-chloro-2-(2-ethylbutoxy)benzyl]-5-methyl-1h-pyrazol-3-yl}propanoic acid in crystalline form and methods for use thereof |
| CN106146400A (zh) * | 2015-03-20 | 2016-11-23 | 四川大学 | 苄基-1h-吡唑、苄基-1h-吡咯衍生物及其制备方法和用途 |
| US10462745B2 (en) | 2016-01-15 | 2019-10-29 | Google Llc | Systems and methods for extending battery life by monitoring device activity |
| CN107723304A (zh) * | 2016-08-10 | 2018-02-23 | 中国科学院上海生命科学研究院 | Prkar2a在炎症消退中的应用 |
| CA3121202A1 (en) | 2018-11-30 | 2020-06-04 | Nuvation Bio Inc. | Pyrrole and pyrazole compounds and methods of use thereof |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4166452A (en) | 1976-05-03 | 1979-09-04 | Generales Constantine D J Jr | Apparatus for testing human responses to stimuli |
| US4256108A (en) | 1977-04-07 | 1981-03-17 | Alza Corporation | Microporous-semipermeable laminated osmotic system |
| US4265874A (en) | 1980-04-25 | 1981-05-05 | Alza Corporation | Method of delivering drug with aid of effervescent activity generated in environment of use |
| US4826868A (en) * | 1986-05-29 | 1989-05-02 | Ortho Pharmaceutical Corporation | 1,5-Diaryl-3-substituted pyrazoles pharmaceutical compositions and use |
| US6511999B2 (en) | 2000-09-14 | 2003-01-28 | Allergan, Inc. | Interheteroaryl 7-oxabicyclic [2.2.1]heptane oxazoles as prostaglandin F2α antagonists |
| US7273883B2 (en) | 2000-09-14 | 2007-09-25 | Allergan, Inc. | Prostaglandin EP4 antagonist |
| US7217725B2 (en) | 2000-09-14 | 2007-05-15 | Allergan, Inc. | Prostaglandin D2 antagonist |
| CA2526013A1 (en) * | 2003-05-20 | 2004-12-02 | Merck Frosst Canada Ltd. | Fluoro-methanesulfonyl-substituted cycloalkanoindoles and their use as prostaglandin d2 antagonists |
| US20070060596A1 (en) | 2003-10-24 | 2007-03-15 | Giblin Gerard M P | Heterocyclyl compounds |
| GB0508472D0 (en) | 2005-04-26 | 2005-06-01 | Glaxo Group Ltd | Compounds |
-
2011
- 2011-06-28 US US13/170,467 patent/US8492424B2/en active Active
- 2011-07-01 PH PH1/2013/500121A patent/PH12013500121A1/en unknown
- 2011-07-01 AU AU2011272716A patent/AU2011272716B2/en not_active Ceased
- 2011-07-01 BR BR112013000065A patent/BR112013000065A2/pt not_active IP Right Cessation
- 2011-07-01 SG SG2013000054A patent/SG186886A1/en unknown
- 2011-07-01 KR KR1020137002639A patent/KR20130141434A/ko not_active Withdrawn
- 2011-07-01 US US13/808,020 patent/US20140121258A1/en not_active Abandoned
- 2011-07-01 AR ARP110102369A patent/AR082073A1/es unknown
- 2011-07-01 WO PCT/US2011/042729 patent/WO2012003414A1/en not_active Ceased
- 2011-07-01 CA CA2804194A patent/CA2804194C/en active Active
- 2011-07-01 CN CN201180038338.0A patent/CN103038219B/zh not_active Expired - Fee Related
- 2011-07-01 ES ES11734222.0T patent/ES2625355T3/es active Active
- 2011-07-01 EP EP11734222.0A patent/EP2588459B1/en active Active
- 2011-07-01 TW TW100123408A patent/TW201206891A/zh unknown
- 2011-07-01 RU RU2013102967/04A patent/RU2013102967A/ru not_active Application Discontinuation
- 2011-07-01 JP JP2013518748A patent/JP5922116B2/ja active Active
- 2011-07-01 MX MX2013000170A patent/MX2013000170A/es active IP Right Grant
-
2013
- 2013-01-02 CL CL2013000002A patent/CL2013000002A1/es unknown
- 2013-01-29 CO CO13016511A patent/CO6680625A2/es unknown
- 2013-05-20 US US13/898,254 patent/US20130253028A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| RU2013102967A (ru) | 2014-08-10 |
| AU2011272716A1 (en) | 2013-02-07 |
| EP2588459B1 (en) | 2017-03-01 |
| BR112013000065A2 (pt) | 2019-09-24 |
| US20140121258A1 (en) | 2014-05-01 |
| US8492424B2 (en) | 2013-07-23 |
| US20130253028A1 (en) | 2013-09-26 |
| EP2588459A1 (en) | 2013-05-08 |
| KR20130141434A (ko) | 2013-12-26 |
| AR082073A1 (es) | 2012-11-07 |
| PH12013500121A1 (en) | 2013-03-11 |
| US20120165382A1 (en) | 2012-06-28 |
| AU2011272716B2 (en) | 2016-05-19 |
| MX2013000170A (es) | 2013-05-28 |
| CA2804194A1 (en) | 2012-01-05 |
| JP2013535424A (ja) | 2013-09-12 |
| TW201206891A (en) | 2012-02-16 |
| CN103038219A (zh) | 2013-04-10 |
| SG186886A1 (en) | 2013-02-28 |
| CA2804194C (en) | 2019-03-05 |
| CL2013000002A1 (es) | 2013-05-31 |
| CN103038219B (zh) | 2016-08-24 |
| WO2012003414A1 (en) | 2012-01-05 |
| CO6680625A2 (es) | 2013-05-31 |
| JP5922116B2 (ja) | 2016-05-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2625355T3 (es) | Compuestos actúan en múltiples receptores de prostaglandina proporcionando una respuesta anti-inflamatoria general | |
| CA2860392C (en) | Compounds acting at multiple prostaglandin receptors giving a general anti-inflammatory response | |
| US9522890B2 (en) | Compounds acting at multiple prostaglandin receptors giving a general anti-inflammatory response | |
| AU2018217252B2 (en) | Compounds act at multiple prostaglandin receptors giving a general anti-inflammatory response | |
| US9394284B2 (en) | Compounds act at multiple prostaglandin receptors giving a general anti-inflammatory response | |
| HK1184441A (en) | Compounds act at multiple prostaglandin receptors giving a general anti-inflammatory respones | |
| HK1184441B (en) | Compounds act at multiple prostaglandin receptors giving a general anti-inflammatory respones |