ES2637009T3 - Nuevos derivados de 1-bencil-3-hidroximetilindazol y su utilización en el tratamiento de enfermedades basadas en la expresión de CX3CR1 y p40 - Google Patents
Nuevos derivados de 1-bencil-3-hidroximetilindazol y su utilización en el tratamiento de enfermedades basadas en la expresión de CX3CR1 y p40 Download PDFInfo
- Publication number
- ES2637009T3 ES2637009T3 ES09717638.2T ES09717638T ES2637009T3 ES 2637009 T3 ES2637009 T3 ES 2637009T3 ES 09717638 T ES09717638 T ES 09717638T ES 2637009 T3 ES2637009 T3 ES 2637009T3
- Authority
- ES
- Spain
- Prior art keywords
- carbon atoms
- group
- acid
- hydrogen
- alkyl group
- 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
- 230000014509 gene expression Effects 0.000 title claims description 46
- 108090000835 CX3C Chemokine Receptor 1 Proteins 0.000 title claims description 37
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 21
- 201000010099 disease Diseases 0.000 title claims description 19
- 102100039196 CX3C chemokine receptor 1 Human genes 0.000 title claims 2
- AKQDXNFPEFHRLS-UHFFFAOYSA-N (1-benzylindazol-3-yl)methanol Chemical class C12=CC=CC=C2C(CO)=NN1CC1=CC=CC=C1 AKQDXNFPEFHRLS-UHFFFAOYSA-N 0.000 title description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 98
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 58
- 150000001875 compounds Chemical class 0.000 claims abstract description 54
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 36
- 239000001257 hydrogen Substances 0.000 claims abstract description 36
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 28
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 15
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 11
- 125000005843 halogen group Chemical group 0.000 claims abstract description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 10
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 5
- 239000000203 mixture Substances 0.000 claims description 69
- 239000008194 pharmaceutical composition Substances 0.000 claims description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 15
- -1 glucamine Chemical compound 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 150000002148 esters Chemical class 0.000 claims description 9
- 201000004681 Psoriasis Diseases 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 5
- 235000011054 acetic acid Nutrition 0.000 claims description 5
- 208000037803 restenosis Diseases 0.000 claims description 5
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 4
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 4
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 4
- 150000007513 acids Chemical class 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 4
- 206010025135 lupus erythematosus Diseases 0.000 claims description 4
- 239000011707 mineral Substances 0.000 claims description 4
- 235000010755 mineral Nutrition 0.000 claims description 4
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 claims description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 4
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 4
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 3
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 3
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 3
- 150000001298 alcohols Chemical class 0.000 claims description 3
- 239000003086 colorant Substances 0.000 claims description 3
- 208000033679 diabetic kidney disease Diseases 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 235000003599 food sweetener Nutrition 0.000 claims description 3
- 229940093915 gynecological organic acid Drugs 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 229910017604 nitric acid Inorganic materials 0.000 claims description 3
- 150000007524 organic acids Chemical class 0.000 claims description 3
- 235000005985 organic acids Nutrition 0.000 claims description 3
- 239000003755 preservative agent Substances 0.000 claims description 3
- 239000003765 sweetening agent Substances 0.000 claims description 3
- 239000003981 vehicle Substances 0.000 claims description 3
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 claims description 2
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 claims description 2
- 229940013085 2-diethylaminoethanol Drugs 0.000 claims description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 2
- HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 claims description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 2
- 206010002383 Angina Pectoris Diseases 0.000 claims description 2
- 239000004475 Arginine Substances 0.000 claims description 2
- 239000005711 Benzoic acid Substances 0.000 claims description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 2
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 claims description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 2
- 239000004472 Lysine Substances 0.000 claims description 2
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 claims description 2
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 claims description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
- 239000002250 absorbent Substances 0.000 claims description 2
- 230000002745 absorbent Effects 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 239000000908 ammonium hydroxide Substances 0.000 claims description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 2
- 235000010323 ascorbic acid Nutrition 0.000 claims description 2
- 239000011668 ascorbic acid Substances 0.000 claims description 2
- 229960005070 ascorbic acid Drugs 0.000 claims description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 2
- 229940092714 benzenesulfonic acid Drugs 0.000 claims description 2
- 235000010233 benzoic acid Nutrition 0.000 claims description 2
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 claims description 2
- PQKHESYTSKMWFP-WZJCLRDWSA-N beta-Funaltrexamine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]1(O)CC[C@H]3NC(=O)/C=C/C(=O)OC)CN2CC1CC1 PQKHESYTSKMWFP-WZJCLRDWSA-N 0.000 claims description 2
- 239000011230 binding agent Substances 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229960001948 caffeine Drugs 0.000 claims description 2
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 claims description 2
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 2
- 239000000920 calcium hydroxide Substances 0.000 claims description 2
- 229910001861 calcium hydroxide Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims description 2
- 229960001231 choline Drugs 0.000 claims description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000007884 disintegrant Substances 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims description 2
- 239000000945 filler Substances 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 229960002442 glucosamine Drugs 0.000 claims description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 2
- 239000003906 humectant Substances 0.000 claims description 2
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 claims description 2
- 239000004310 lactic acid Substances 0.000 claims description 2
- 235000014655 lactic acid Nutrition 0.000 claims description 2
- 239000000314 lubricant Substances 0.000 claims description 2
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims description 2
- 239000001095 magnesium carbonate Substances 0.000 claims description 2
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 2
- 239000011976 maleic acid Substances 0.000 claims description 2
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 2
- 208000010125 myocardial infarction Diseases 0.000 claims description 2
- ACTNHJDHMQSOGL-UHFFFAOYSA-N n',n'-dibenzylethane-1,2-diamine Chemical compound C=1C=CC=CC=1CN(CCN)CC1=CC=CC=C1 ACTNHJDHMQSOGL-UHFFFAOYSA-N 0.000 claims description 2
- 235000006408 oxalic acid Nutrition 0.000 claims description 2
- 239000011736 potassium bicarbonate Substances 0.000 claims description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 2
- 229940086066 potassium hydrogencarbonate Drugs 0.000 claims description 2
- 230000000391 smoking effect Effects 0.000 claims description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 2
- 235000002906 tartaric acid Nutrition 0.000 claims description 2
- 239000011975 tartaric acid Substances 0.000 claims description 2
- 229960004559 theobromine Drugs 0.000 claims description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 2
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 claims description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 2
- 229960000281 trometamol Drugs 0.000 claims description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims 3
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims 1
- 235000015165 citric acid Nutrition 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 93
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 63
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 57
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 49
- 239000000047 product Substances 0.000 description 41
- 239000000243 solution Substances 0.000 description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
- 230000002829 reductive effect Effects 0.000 description 35
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- 238000006243 chemical reaction Methods 0.000 description 33
- 238000000034 method Methods 0.000 description 32
- 229940093499 ethyl acetate Drugs 0.000 description 31
- 235000019439 ethyl acetate Nutrition 0.000 description 31
- 238000002425 crystallisation Methods 0.000 description 30
- 230000008025 crystallization Effects 0.000 description 30
- 210000004027 cell Anatomy 0.000 description 25
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- 239000002904 solvent Substances 0.000 description 24
- 238000002360 preparation method Methods 0.000 description 23
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 22
- 210000001616 monocyte Anatomy 0.000 description 21
- 239000012074 organic phase Substances 0.000 description 20
- 238000005481 NMR spectroscopy Methods 0.000 description 18
- 238000007792 addition Methods 0.000 description 18
- 239000002158 endotoxin Substances 0.000 description 18
- 229920006008 lipopolysaccharide Polymers 0.000 description 18
- 238000004519 manufacturing process Methods 0.000 description 18
- 230000007170 pathology Effects 0.000 description 18
- 102000019034 Chemokines Human genes 0.000 description 17
- 108010012236 Chemokines Proteins 0.000 description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
- 238000005160 1H NMR spectroscopy Methods 0.000 description 16
- 241000282414 Homo sapiens Species 0.000 description 16
- 102000004127 Cytokines Human genes 0.000 description 15
- 108090000695 Cytokines Proteins 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000000725 suspension Substances 0.000 description 14
- 239000003153 chemical reaction reagent Substances 0.000 description 13
- 238000001704 evaporation Methods 0.000 description 13
- 238000010992 reflux Methods 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- 208000011231 Crohn disease Diseases 0.000 description 10
- 238000001816 cooling Methods 0.000 description 10
- 230000002757 inflammatory effect Effects 0.000 description 10
- 229910000104 sodium hydride Inorganic materials 0.000 description 10
- 206010028980 Neoplasm Diseases 0.000 description 9
- 125000001309 chloro group Chemical group Cl* 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- 239000000523 sample Substances 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 102100020997 Fractalkine Human genes 0.000 description 8
- 101000854520 Homo sapiens Fractalkine Proteins 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 229960000583 acetic acid Drugs 0.000 description 8
- 210000001744 T-lymphocyte Anatomy 0.000 description 7
- 239000008346 aqueous phase Substances 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 230000003321 amplification Effects 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 230000004054 inflammatory process Effects 0.000 description 6
- 210000002540 macrophage Anatomy 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 6
- 238000003199 nucleic acid amplification method Methods 0.000 description 6
- 230000008506 pathogenesis Effects 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 description 6
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 5
- PLQWRPKMSGYAKI-UHFFFAOYSA-N 2-[(1-benzyl-5-nitroindazol-3-yl)methoxy]-2-methylpropanoic acid Chemical compound C12=CC=C([N+]([O-])=O)C=C2C(COC(C)(C)C(O)=O)=NN1CC1=CC=CC=C1 PLQWRPKMSGYAKI-UHFFFAOYSA-N 0.000 description 5
- MTHORRSSURHQPZ-UHFFFAOYSA-N 2-[(1-benzylindazol-3-yl)methoxy]-2-methylpropanoic acid Chemical compound C12=CC=CC=C2C(COC(C)(C)C(O)=O)=NN1CC1=CC=CC=C1 MTHORRSSURHQPZ-UHFFFAOYSA-N 0.000 description 5
- JRWUHCYHZPHRIU-UHFFFAOYSA-N 3-[(1-benzylindazol-3-yl)methoxy]propan-1-ol Chemical compound C12=CC=CC=C2C(COCCCO)=NN1CC1=CC=CC=C1 JRWUHCYHZPHRIU-UHFFFAOYSA-N 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 230000000968 intestinal effect Effects 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- ZXDBUZWIMJIMJZ-UHFFFAOYSA-N 2-[(1-benzylindazol-3-yl)methoxy]ethanol Chemical compound C12=CC=CC=C2C(COCCO)=NN1CC1=CC=CC=C1 ZXDBUZWIMJIMJZ-UHFFFAOYSA-N 0.000 description 4
- 201000001320 Atherosclerosis Diseases 0.000 description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 210000002889 endothelial cell Anatomy 0.000 description 4
- 230000002068 genetic effect Effects 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- ITEDNMOIBNOTDT-UHFFFAOYSA-N (1-tritylindazol-3-yl)methanol Chemical compound C12=CC=CC=C2C(CO)=NN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 ITEDNMOIBNOTDT-UHFFFAOYSA-N 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- WUUJVTQUZJCUSE-UHFFFAOYSA-N 1-benzyl-3-(chloromethyl)indazole Chemical compound C12=CC=CC=C2C(CCl)=NN1CC1=CC=CC=C1 WUUJVTQUZJCUSE-UHFFFAOYSA-N 0.000 description 3
- WTBJHNBYEZMVLB-UHFFFAOYSA-N 2-(2h-indazol-3-ylmethoxy)-2-methylpropanoic acid Chemical compound C1=CC=C2C(COC(C)(C)C(O)=O)=NNC2=C1 WTBJHNBYEZMVLB-UHFFFAOYSA-N 0.000 description 3
- QISKNAVPOKUQNP-UHFFFAOYSA-N 2-[2-[(1-benzylindazol-3-yl)methoxy]-2-methylpropoxy]acetic acid Chemical compound C12=CC=CC=C2C(COC(C)(COCC(O)=O)C)=NN1CC1=CC=CC=C1 QISKNAVPOKUQNP-UHFFFAOYSA-N 0.000 description 3
- JRMBACRKARSGCL-UHFFFAOYSA-N 2-[3-[(1-benzylindazol-3-yl)methoxy]propoxy]acetic acid Chemical compound C12=CC=CC=C2C(COCCCOCC(=O)O)=NN1CC1=CC=CC=C1 JRMBACRKARSGCL-UHFFFAOYSA-N 0.000 description 3
- FYCJJJARQZHMFR-UHFFFAOYSA-N 2-[[1-[(4-fluorophenyl)methyl]indazol-3-yl]methoxy]acetic acid Chemical compound C12=CC=CC=C2C(COCC(=O)O)=NN1CC1=CC=C(F)C=C1 FYCJJJARQZHMFR-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 102000000589 Interleukin-1 Human genes 0.000 description 3
- 108010002352 Interleukin-1 Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 238000011530 RNeasy Mini Kit Methods 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 210000000447 Th1 cell Anatomy 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 230000003399 chemotactic effect Effects 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 238000004590 computer program Methods 0.000 description 3
- 210000004443 dendritic cell Anatomy 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- 238000001506 fluorescence spectroscopy Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000008595 infiltration Effects 0.000 description 3
- 238000001764 infiltration Methods 0.000 description 3
- 230000028709 inflammatory response Effects 0.000 description 3
- 208000017169 kidney disease Diseases 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 238000010606 normalization Methods 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 238000010839 reverse transcription Methods 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 210000001258 synovial membrane Anatomy 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- DNIAPMSPPWPWGF-VKHMYHEASA-N (+)-propylene glycol Chemical compound C[C@H](O)CO DNIAPMSPPWPWGF-VKHMYHEASA-N 0.000 description 2
- YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Substances OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 2
- KUVISYTWMYQCGF-UHFFFAOYSA-N 2-[(1-benzoylindazol-3-yl)methoxy]-2-methylpropanoic acid Chemical compound C12=CC=CC=C2C(COC(C)(C)C(O)=O)=NN1C(=O)C1=CC=CC=C1 KUVISYTWMYQCGF-UHFFFAOYSA-N 0.000 description 2
- JPRCKGJDTFIYIG-UHFFFAOYSA-N 2-[(1-benzyl-5-chloroindazol-3-yl)methoxy]-2-methylpropanoic acid Chemical compound C12=CC=C(Cl)C=C2C(COC(C)(C)C(O)=O)=NN1CC1=CC=CC=C1 JPRCKGJDTFIYIG-UHFFFAOYSA-N 0.000 description 2
- YYDKWHIBWKSLBL-UHFFFAOYSA-N 2-[(1-benzylindazol-3-yl)methoxy]-2-methylpropan-1-ol Chemical compound C12=CC=CC=C2C(COC(C)(CO)C)=NN1CC1=CC=CC=C1 YYDKWHIBWKSLBL-UHFFFAOYSA-N 0.000 description 2
- CGNVHBKEPPLLEU-UHFFFAOYSA-N 2-[(5-amino-1-benzylindazol-3-yl)methoxy]-2-methylpropanoic acid Chemical compound C12=CC=C(N)C=C2C(COC(C)(C)C(O)=O)=NN1CC1=CC=CC=C1 CGNVHBKEPPLLEU-UHFFFAOYSA-N 0.000 description 2
- FTGBDVKFMNCIJJ-UHFFFAOYSA-N 2-[2-[(1-benzylindazol-3-yl)methoxy]ethoxy]acetic acid Chemical compound C12=CC=CC=C2C(COCCOCC(=O)O)=NN1CC1=CC=CC=C1 FTGBDVKFMNCIJJ-UHFFFAOYSA-N 0.000 description 2
- BNDFFTXDUHNDBA-UHFFFAOYSA-N 2-[3-[(1-benzylindazol-3-yl)methoxy]propoxy]-2-methylpropanoic acid Chemical compound C12=CC=CC=C2C(COCCCOC(C)(C)C(O)=O)=NN1CC1=CC=CC=C1 BNDFFTXDUHNDBA-UHFFFAOYSA-N 0.000 description 2
- PRHHDAGPIFMZKC-UHFFFAOYSA-N 2-[[1-[(3,4-dichlorophenyl)methyl]indazol-3-yl]methoxy]-2-methylpropanoic acid Chemical compound C12=CC=CC=C2C(COC(C)(C)C(O)=O)=NN1CC1=CC=C(Cl)C(Cl)=C1 PRHHDAGPIFMZKC-UHFFFAOYSA-N 0.000 description 2
- RWSMVRILUVVQLC-UHFFFAOYSA-N 2-methyl-2-[(1-tritylindazol-3-yl)methoxy]propanoic acid Chemical compound C12=CC=CC=C2C(COC(C)(C)C(O)=O)=NN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 RWSMVRILUVVQLC-UHFFFAOYSA-N 0.000 description 2
- HXQOMAWXVVGQMD-UHFFFAOYSA-N 2-methyl-2-[(5-nitro-2h-indazol-3-yl)methoxy]propanoic acid Chemical compound C1=C([N+]([O-])=O)C=C2C(COC(C)(C)C(O)=O)=NNC2=C1 HXQOMAWXVVGQMD-UHFFFAOYSA-N 0.000 description 2
- GMURDZBAVODKTG-UHFFFAOYSA-N 2-methyl-2-[[1-[(4-methylphenyl)methyl]indazol-3-yl]methoxy]propanoic acid Chemical compound C1=CC(C)=CC=C1CN1C2=CC=CC=C2C(COC(C)(C)C(O)=O)=N1 GMURDZBAVODKTG-UHFFFAOYSA-N 0.000 description 2
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 2
- 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 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 102100032367 C-C motif chemokine 5 Human genes 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- 108010055166 Chemokine CCL5 Proteins 0.000 description 2
- 108010078239 Chemokine CX3CL1 Proteins 0.000 description 2
- 108050000299 Chemokine receptor Proteins 0.000 description 2
- 102000009410 Chemokine receptor Human genes 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 2
- 102000013818 Fractalkine Human genes 0.000 description 2
- 102000008070 Interferon-gamma Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- 102000000588 Interleukin-2 Human genes 0.000 description 2
- 208000012659 Joint disease Diseases 0.000 description 2
- 229910010084 LiAlH4 Inorganic materials 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 108700012920 TNF Proteins 0.000 description 2
- KZVMTEGUHIPNEB-UHFFFAOYSA-N [1-[(2,4-dichlorophenyl)methyl]indazol-3-yl]methanol Chemical compound C12=CC=CC=C2C(CO)=NN1CC1=CC=C(Cl)C=C1Cl KZVMTEGUHIPNEB-UHFFFAOYSA-N 0.000 description 2
- GJONLAVHSFDAET-UHFFFAOYSA-N [1-[(3,4-dichlorophenyl)methyl]indazol-3-yl]methanol Chemical compound C12=CC=CC=C2C(CO)=NN1CC1=CC=C(Cl)C(Cl)=C1 GJONLAVHSFDAET-UHFFFAOYSA-N 0.000 description 2
- VTMBFHQWCFTWHC-UHFFFAOYSA-N [1-[(4-fluorophenyl)methyl]indazol-3-yl]methanol Chemical compound C12=CC=CC=C2C(CO)=NN1CC1=CC=C(F)C=C1 VTMBFHQWCFTWHC-UHFFFAOYSA-N 0.000 description 2
- XSTBHDIFRDXZFT-UHFFFAOYSA-N [1-[(4-methylphenyl)methyl]indazol-3-yl]methanol Chemical compound C1=CC(C)=CC=C1CN1C2=CC=CC=C2C(CO)=N1 XSTBHDIFRDXZFT-UHFFFAOYSA-N 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
- 238000003556 assay Methods 0.000 description 2
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 2
- 229940073608 benzyl chloride Drugs 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 229940044627 gamma-interferon Drugs 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 238000012261 overproduction Methods 0.000 description 2
- 230000007310 pathophysiology Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000003880 polar aprotic solvent Substances 0.000 description 2
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 2
- 150000003230 pyrimidines Chemical class 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
- MWDNZMWVENFVHT-UHFFFAOYSA-L (2-decoxy-2-oxoethyl)-[2-[2-[(2-decoxy-2-oxoethyl)-dimethylazaniumyl]ethylsulfanyl]ethyl]-dimethylazanium;dichloride Chemical compound [Cl-].[Cl-].CCCCCCCCCCOC(=O)C[N+](C)(C)CCSCC[N+](C)(C)CC(=O)OCCCCCCCCCC MWDNZMWVENFVHT-UHFFFAOYSA-L 0.000 description 1
- ITOFPJRDSCGOSA-KZLRUDJFSA-N (2s)-2-[[(4r)-4-[(3r,5r,8r,9s,10s,13r,14s,17r)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H](CC[C@]13C)[C@@H]2[C@@H]3CC[C@@H]1[C@H](C)CCC(=O)N[C@H](C(O)=O)CC1=CNC2=CC=CC=C12 ITOFPJRDSCGOSA-KZLRUDJFSA-N 0.000 description 1
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 1
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 1
- WYUIWKFIFOJVKW-UHFFFAOYSA-N 1,2-dichloro-4-methyl-benzene Natural products CC1=CC=C(Cl)C(Cl)=C1 WYUIWKFIFOJVKW-UHFFFAOYSA-N 0.000 description 1
- IZXWCDITFDNEBY-UHFFFAOYSA-N 1-(chloromethyl)-4-fluorobenzene Chemical compound FC1=CC=C(CCl)C=C1 IZXWCDITFDNEBY-UHFFFAOYSA-N 0.000 description 1
- MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 1
- DMHZDOTYAVHSEH-UHFFFAOYSA-N 1-(chloromethyl)-4-methylbenzene Chemical compound CC1=CC=C(CCl)C=C1 DMHZDOTYAVHSEH-UHFFFAOYSA-N 0.000 description 1
- URZAPYFJGQXLKY-UHFFFAOYSA-N 1-chloro-1,2,3,4-tetrahydronaphthalene Chemical compound C1=CC=C2C(Cl)CCCC2=C1 URZAPYFJGQXLKY-UHFFFAOYSA-N 0.000 description 1
- JQZAEUFPPSRDOP-UHFFFAOYSA-N 1-chloro-4-(chloromethyl)benzene Chemical compound ClCC1=CC=C(Cl)C=C1 JQZAEUFPPSRDOP-UHFFFAOYSA-N 0.000 description 1
- IRSVDHPYXFLLDS-UHFFFAOYSA-N 2,4-dichloro-1-(chloromethyl)benzene Chemical compound ClCC1=CC=C(Cl)C=C1Cl IRSVDHPYXFLLDS-UHFFFAOYSA-N 0.000 description 1
- KZTWONRVIPPDKH-UHFFFAOYSA-N 2-(piperidin-1-yl)ethanol Chemical compound OCCN1CCCCC1 KZTWONRVIPPDKH-UHFFFAOYSA-N 0.000 description 1
- XHMPKWZWVAPUSR-UHFFFAOYSA-N 2-[(1-benzyl-5-bromoindazol-3-yl)methoxy]-2-methylpropanoic acid Chemical compound C12=CC=C(Br)C=C2C(COC(C)(C)C(O)=O)=NN1CC1=CC=CC=C1 XHMPKWZWVAPUSR-UHFFFAOYSA-N 0.000 description 1
- NNOCCPLIPKDLFU-UHFFFAOYSA-N 2-[2-[(1-benzylindazol-3-yl)methoxy]ethoxy]-2-methylpropanoic acid Chemical compound C12=CC=CC=C2C(COCCOC(C)(C)C(O)=O)=NN1CC1=CC=CC=C1 NNOCCPLIPKDLFU-UHFFFAOYSA-N 0.000 description 1
- FHDXBJWASQEUTF-UHFFFAOYSA-N 2-[[1-[(2,4-dichlorophenyl)methyl]indazol-3-yl]methoxy]acetic acid Chemical compound C12=CC=CC=C2C(COCC(=O)O)=NN1CC1=CC=C(Cl)C=C1Cl FHDXBJWASQEUTF-UHFFFAOYSA-N 0.000 description 1
- GCKMGZXEHLYNPK-UHFFFAOYSA-N 2-[[1-[(4-chloro-2-methylphenyl)methyl]indazol-3-yl]methoxy]acetic acid Chemical compound CC1=CC(Cl)=CC=C1CN1C2=CC=CC=C2C(COCC(O)=O)=N1 GCKMGZXEHLYNPK-UHFFFAOYSA-N 0.000 description 1
- FZBIMRUNBZRRLO-UHFFFAOYSA-N 2-[[1-[(4-chlorophenyl)methyl]indazol-3-yl]methoxy]-2-methylpropanoic acid Chemical compound C12=CC=CC=C2C(COC(C)(C)C(O)=O)=NN1CC1=CC=C(Cl)C=C1 FZBIMRUNBZRRLO-UHFFFAOYSA-N 0.000 description 1
- SOJYKZHIJUHNFL-UHFFFAOYSA-N 2-[[1-[(4-methoxyphenyl)methyl]indazol-3-yl]methoxy]-2-methylpropanoic acid Chemical compound C1=CC(OC)=CC=C1CN1C2=CC=CC=C2C(COC(C)(C)C(O)=O)=N1 SOJYKZHIJUHNFL-UHFFFAOYSA-N 0.000 description 1
- SLSZSBSLZPDCIM-UHFFFAOYSA-N 2-methylpropyl 1-tritylindazole-3-carboxylate Chemical compound C12=CC=CC=C2C(C(=O)OCC(C)C)=NN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 SLSZSBSLZPDCIM-UHFFFAOYSA-N 0.000 description 1
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 1
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 1
- 208000003200 Adenoma Diseases 0.000 description 1
- 229920001817 Agar Polymers 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
- 241000710929 Alphavirus Species 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
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 102100023702 C-C motif chemokine 13 Human genes 0.000 description 1
- 101710112613 C-C motif chemokine 13 Proteins 0.000 description 1
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 1
- 102100032366 C-C motif chemokine 7 Human genes 0.000 description 1
- 101710155834 C-C motif chemokine 7 Proteins 0.000 description 1
- 102000001902 CC Chemokines Human genes 0.000 description 1
- 108010040471 CC Chemokines Proteins 0.000 description 1
- 108010017312 CCR2 Receptors Proteins 0.000 description 1
- 102000004298 CX3C Chemokine Receptor 1 Human genes 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 229940126657 Compound 17 Drugs 0.000 description 1
- 229940126639 Compound 33 Drugs 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 201000000054 Coronary Restenosis Diseases 0.000 description 1
- 206010056489 Coronary artery restenosis Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 1
- 101100296720 Dictyostelium discoideum Pde4 gene Proteins 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 206010066919 Epidemic polyarthritis Diseases 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 241000206672 Gelidium Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000694288 Homo sapiens 40S ribosomal protein SA Proteins 0.000 description 1
- 101000897480 Homo sapiens C-C motif chemokine 2 Proteins 0.000 description 1
- 101000746022 Homo sapiens CX3C chemokine receptor 1 Proteins 0.000 description 1
- 101001090483 Homo sapiens Glutathione S-transferase LANCL1 Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 101000668058 Infectious salmon anemia virus (isolate Atlantic salmon/Norway/810/9/99) RNA-directed RNA polymerase catalytic subunit Proteins 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 102100036672 Interleukin-23 receptor Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 108090001007 Interleukin-8 Proteins 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
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 208000007117 Oral Ulcer Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 101100082610 Plasmodium falciparum (isolate 3D7) PDEdelta gene Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 241000710942 Ross River virus Species 0.000 description 1
- 229910006074 SO2NH2 Inorganic materials 0.000 description 1
- 235000019485 Safflower oil Nutrition 0.000 description 1
- PNUZDKCDAWUEGK-CYZMBNFOSA-N Sitafloxacin Chemical compound C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1 PNUZDKCDAWUEGK-CYZMBNFOSA-N 0.000 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
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical class [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 206010054094 Tumour necrosis Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 1
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 1
- LRUZZQCLHUEGIQ-UHFFFAOYSA-N [1-[(4-chloro-2-methylphenyl)methyl]indazol-3-yl]methanol Chemical compound CC1=CC(Cl)=CC=C1CN1C2=CC=CC=C2C(CO)=N1 LRUZZQCLHUEGIQ-UHFFFAOYSA-N 0.000 description 1
- VMIOBYYZVPHVJI-UHFFFAOYSA-N [1-[(4-methoxyphenyl)methyl]indazol-3-yl]methanol Chemical compound C1=CC(OC)=CC=C1CN1C2=CC=CC=C2C(CO)=N1 VMIOBYYZVPHVJI-UHFFFAOYSA-N 0.000 description 1
- SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 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 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000006023 anti-tumor response Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 229940054051 antipsychotic indole derivative Drugs 0.000 description 1
- 210000000436 anus Anatomy 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 239000000305 astragalus gummifer gum Substances 0.000 description 1
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 210000003651 basophil Anatomy 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 235000011116 calcium hydroxide Nutrition 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- CFBUZOUXXHZCFB-OYOVHJISSA-N chembl511115 Chemical compound COC1=CC=C([C@@]2(CC[C@H](CC2)C(O)=O)C#N)C=C1OC1CCCC1 CFBUZOUXXHZCFB-OYOVHJISSA-N 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000005482 chemotactic factor Substances 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940125810 compound 20 Drugs 0.000 description 1
- 229940126086 compound 21 Drugs 0.000 description 1
- 229940126208 compound 22 Drugs 0.000 description 1
- 229940125961 compound 24 Drugs 0.000 description 1
- 229940125846 compound 25 Drugs 0.000 description 1
- 229940127204 compound 29 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- XBRDBODLCHKXHI-UHFFFAOYSA-N epolamine Chemical compound OCCN1CCCC1 XBRDBODLCHKXHI-UHFFFAOYSA-N 0.000 description 1
- HKEDUIGHSRRIKD-UHFFFAOYSA-N ethyl 3-hydroxy-3-methylbutanoate Chemical compound CCOC(=O)CC(C)(C)O HKEDUIGHSRRIKD-UHFFFAOYSA-N 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 102000046768 human CCL2 Human genes 0.000 description 1
- 102000051339 human CX3CR1 Human genes 0.000 description 1
- KIUKXJAPPMFGSW-MNSSHETKSA-N hyaluronan Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H](C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-MNSSHETKSA-N 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229940099552 hyaluronan Drugs 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000005550 inflammation mediator Substances 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 108040001844 interleukin-23 receptor activity proteins Proteins 0.000 description 1
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Substances CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000004072 lung Anatomy 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
- 235000014380 magnesium carbonate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 230000008816 organ damage Effects 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 230000000242 pagocytic effect Effects 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000003014 reinforcing effect Effects 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- HJORMJIFDVBMOB-UHFFFAOYSA-N rolipram Chemical compound COC1=CC=C(C2CC(=O)NC2)C=C1OC1CCCC1 HJORMJIFDVBMOB-UHFFFAOYSA-N 0.000 description 1
- 229950005741 rolipram Drugs 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical class [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 239000012730 sustained-release form Substances 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
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000003966 vascular damage Effects 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000001993 wax Substances 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
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- 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
- A61P11/04—Drugs for disorders of the respiratory system for throat disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—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
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Immunology (AREA)
- Oncology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Neurosurgery (AREA)
- Pulmonology (AREA)
- Neurology (AREA)
- Urology & Nephrology (AREA)
- Dermatology (AREA)
- Virology (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Communicable Diseases (AREA)
- Rheumatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Psychiatry (AREA)
- Tropical Medicine & Parasitology (AREA)
- Hospice & Palliative Care (AREA)
- Transplantation (AREA)
- Pain & Pain Management (AREA)
- Emergency Medicine (AREA)
- AIDS & HIV (AREA)
- Child & Adolescent Psychology (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP08425139 | 2008-03-07 | ||
| EP08425139 | 2008-03-07 | ||
| PCT/EP2009/052585 WO2009109613A2 (en) | 2008-03-07 | 2009-03-05 | Novel 1-benzyl-3-hydroxymethylindazole derivatives and use thereof in the treatment of diseases based on the expression of mcp-1, cx3cr1 and p40 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2637009T3 true ES2637009T3 (es) | 2017-10-10 |
Family
ID=39671487
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES09717638.2T Active ES2637009T3 (es) | 2008-03-07 | 2009-03-05 | Nuevos derivados de 1-bencil-3-hidroximetilindazol y su utilización en el tratamiento de enfermedades basadas en la expresión de CX3CR1 y p40 |
| ES09718467.5T Active ES2569330T3 (es) | 2008-03-07 | 2009-03-05 | Derivados del 1-bencil-3-hidroximetilindazol y su utilización en el tratamiento de enfermedades basadas en la expresión de MCP-1, CX3CR1 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES09718467.5T Active ES2569330T3 (es) | 2008-03-07 | 2009-03-05 | Derivados del 1-bencil-3-hidroximetilindazol y su utilización en el tratamiento de enfermedades basadas en la expresión de MCP-1, CX3CR1 |
Country Status (25)
| Country | Link |
|---|---|
| US (3) | US8835481B2 (enExample) |
| EP (3) | EP3181551A1 (enExample) |
| JP (2) | JP5509101B2 (enExample) |
| KR (2) | KR101599867B1 (enExample) |
| CN (2) | CN101945855B (enExample) |
| AR (2) | AR070811A1 (enExample) |
| AU (2) | AU2009221083B2 (enExample) |
| BR (2) | BRPI0907976A2 (enExample) |
| CA (2) | CA2712403C (enExample) |
| CY (2) | CY1117584T1 (enExample) |
| DK (2) | DK2254869T3 (enExample) |
| EA (2) | EA018241B1 (enExample) |
| ES (2) | ES2637009T3 (enExample) |
| GE (2) | GEP20135983B (enExample) |
| HR (2) | HRP20160462T1 (enExample) |
| HU (1) | HUE027098T2 (enExample) |
| IL (3) | IL206893A0 (enExample) |
| LT (1) | LT2254869T (enExample) |
| MX (2) | MX2010009623A (enExample) |
| PL (2) | PL2254869T3 (enExample) |
| PT (1) | PT2254869T (enExample) |
| SG (1) | SG188177A1 (enExample) |
| SI (2) | SI2254869T1 (enExample) |
| UA (2) | UA103605C2 (enExample) |
| WO (2) | WO2009109618A2 (enExample) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101965337B (zh) | 2008-03-07 | 2013-11-06 | 方济各安吉利克化学联合股份有限公司 | 1-苄基-3-羟基甲基吲唑衍生物及其在治疗基于MCP-1、CX3CR1和p40表达的疾病中的用途 |
| PL2254869T3 (pl) * | 2008-03-07 | 2017-10-31 | Acraf | Nowe pochodne 1-benzylo-3-hydroksymetyloindazolu i ich zastosowanie w leczeniu chorób bazujących na ekspresji CX3CR1 i p40 |
| CN101959866B (zh) | 2008-03-07 | 2013-10-02 | 方济各安吉利克化学联合股份有限公司 | 1-苄基-3-羟基甲基吲唑衍生物及其在治疗基于mcp-1和cx3cr1表达的疾病中的用途 |
| CN102471281B (zh) | 2009-08-03 | 2014-10-15 | 方济各安吉利克化学联合股份有限公司 | 1-苄基-3-羟甲基-1h-吲唑及其衍生物以及所需镁中间体的制备方法 |
| UA108742C2 (uk) * | 2009-09-23 | 2015-06-10 | Фармацевтична композиція для лікування запальних захворювань, опосередкованих mcp-1 | |
| US8999292B2 (en) * | 2012-05-01 | 2015-04-07 | Translatum Medicus Inc. | Methods for treating and diagnosing blinding eye diseases |
| CN107050020A (zh) * | 2012-05-01 | 2017-08-18 | 特兰斯拉图姆医学公司 | 用于治疗和诊断致盲性眼病的方法 |
| AU2013261718B2 (en) | 2012-05-18 | 2017-10-19 | Sanofi | Pyrazole derivatives and their use as LPAR5 antagonists |
| EP2850062B1 (en) | 2012-05-18 | 2017-07-19 | Sanofi | Pyridine derivatives and their use in the treatment of conditions associated with pathological thrombus formation |
| US10918588B2 (en) | 2012-11-09 | 2021-02-16 | Colgate-Palmolive Company | Block copolymers for tooth enamel protection |
| JP6625064B2 (ja) * | 2014-05-15 | 2019-12-25 | トランスレイタム メディカス インコーポレイテッド | 眼障害を治療かつ診断するための組成物および方法 |
| BR112017026535B1 (pt) * | 2015-06-12 | 2023-12-19 | Vettore, LLC | Composto e composição farmacêutica |
| EP3310353A4 (en) * | 2015-06-16 | 2019-02-06 | Translatum Medicus, Inc. | COMPOSITIONS AND METHODS OF TREATMENT AND DIAGNOSIS OF EYE DISEASES |
| WO2018111904A1 (en) | 2016-12-12 | 2018-06-21 | Vettore, LLC | Heterocyclic inhibitors of mct4 |
| GB201811169D0 (en) | 2018-07-06 | 2018-08-29 | Kancera Ab | New compounds |
| WO2020026471A1 (ja) * | 2018-07-31 | 2020-02-06 | 株式会社親広産業 | グルコース消費促進剤および解糖系促進剤 |
| JP6612004B1 (ja) * | 2018-07-31 | 2019-11-27 | 株式会社親広産業 | グルコース消費促進剤および解糖系促進剤 |
| EP3990433A4 (en) | 2019-06-25 | 2023-07-26 | Translatum Medicus Inc. | METHODS FOR THE MANUFACTURE OF 2-((1-BENZYL-1H-INDAZOL-3-YL)METHOXY)-2-METHYLPROPANOIC ACID AND ITS DERIVATIVES |
| CN113929627A (zh) * | 2021-10-19 | 2022-01-14 | 吕梁学院 | 一种宾达利的合成方法 |
| WO2024108386A1 (zh) * | 2022-11-22 | 2024-05-30 | 中国科学院深圳先进技术研究院 | 抗mcp1中和抗体在制备治疗神经退行性疾病引起的系统性炎症药物中的应用 |
| EP4662203A1 (en) * | 2023-02-10 | 2025-12-17 | Translatum Medicus Inc. | Bindarit conjugates, compositions and methods for treating ocular diseases or disorders |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US416359A (en) * | 1889-12-03 | Sash-fastener | ||
| US364371A (en) * | 1887-06-07 | peice | ||
| IT1230441B (it) * | 1989-02-07 | 1991-10-23 | Acraf | Eteri della serie dell'indazolo |
| IT1253703B (it) * | 1991-04-22 | 1995-08-23 | Angelini Francesco Ist Ricerca | Uso di acidi metossi alcanoici dell'indazolo per preparare un farmaco attivo nel trattamento di malattie autoimmunitarie |
| IT1293795B1 (it) * | 1997-07-28 | 1999-03-10 | Angelini Ricerche Spa | Farmaco attivo nel ridurre la produzione di proteina mcp-1 |
| JP2003502424A (ja) | 1999-06-17 | 2003-01-21 | シオノギ バイオリサーチ コーポレイション | Ｉｌ−１２産生の阻害物質 |
| EP1199074A1 (en) | 2000-09-15 | 2002-04-24 | Warner-Lambert Company | Pharmaceutical composition for preventing or treating a disease associated with an excess of il-12 production |
| EP1188438A1 (en) | 2000-09-15 | 2002-03-20 | Warner-Lambert Company | Pharmaceutical composition for preventing or treating a disease associated with an excess of Il-12 production |
| US20040097465A1 (en) | 2001-03-15 | 2004-05-20 | Akira Asari | ll-12 expression controlling agents |
| EP1458687B1 (en) | 2001-11-30 | 2012-01-11 | Synta Pharmaceuticals Corporation | Pyrimidine compounds as interleukin-12 (il-12) inhibitors |
| MXPA06003792A (es) | 2003-10-07 | 2006-06-14 | Astrazeneca Ab | Nuevas 4-amino-tiazolo[4,5-d]-pirimidinas 2-sustituidas, utiles como antagonistas del receptor de quimiocina, especialmente cx3cr1. |
| WO2006046739A1 (ja) * | 2004-10-29 | 2006-05-04 | Eisai R & D Management Co., Ltd. | 炎症性疾患治療剤 |
| WO2006053227A2 (en) | 2004-11-10 | 2006-05-18 | Synta Pharmaceuticals Corp. | Il-12 modulatory compounds |
| JP2008520712A (ja) | 2004-11-19 | 2008-06-19 | シンタ ファーマシューティカルズ コーポレーション | ピリミジン化合物及びその使用 |
| AR053347A1 (es) | 2005-04-06 | 2007-05-02 | Astrazeneca Ab | Derivados de [1,3]tiazolo[4,5-d]pirimidin-2(3h)-ona 5,7-sustituidos |
| UA90707C2 (en) | 2005-04-06 | 2010-05-25 | Астразенека Аб | Novel 5-substituted 7-amino-[1,3]thiazolo[4,5-d]pyrimidine derivatives |
| CN101965337B (zh) | 2008-03-07 | 2013-11-06 | 方济各安吉利克化学联合股份有限公司 | 1-苄基-3-羟基甲基吲唑衍生物及其在治疗基于MCP-1、CX3CR1和p40表达的疾病中的用途 |
| PL2254869T3 (pl) | 2008-03-07 | 2017-10-31 | Acraf | Nowe pochodne 1-benzylo-3-hydroksymetyloindazolu i ich zastosowanie w leczeniu chorób bazujących na ekspresji CX3CR1 i p40 |
| CN101959866B (zh) | 2008-03-07 | 2013-10-02 | 方济各安吉利克化学联合股份有限公司 | 1-苄基-3-羟基甲基吲唑衍生物及其在治疗基于mcp-1和cx3cr1表达的疾病中的用途 |
-
2009
- 2009-03-05 PL PL09717638T patent/PL2254869T3/pl unknown
- 2009-03-05 CA CA2712403A patent/CA2712403C/en not_active Expired - Fee Related
- 2009-03-05 KR KR1020107017445A patent/KR101599867B1/ko not_active Expired - Fee Related
- 2009-03-05 HR HRP20160462TT patent/HRP20160462T1/hr unknown
- 2009-03-05 HU HUE09718467A patent/HUE027098T2/en unknown
- 2009-03-05 SI SI200931705T patent/SI2254869T1/sl unknown
- 2009-03-05 SG SG2013013123A patent/SG188177A1/en unknown
- 2009-03-05 MX MX2010009623A patent/MX2010009623A/es active IP Right Grant
- 2009-03-05 AU AU2009221083A patent/AU2009221083B2/en not_active Ceased
- 2009-03-05 DK DK09717638.2T patent/DK2254869T3/en active
- 2009-03-05 JP JP2010549146A patent/JP5509101B2/ja active Active
- 2009-03-05 EP EP17153930.7A patent/EP3181551A1/en not_active Withdrawn
- 2009-03-05 PT PT97176382T patent/PT2254869T/pt unknown
- 2009-03-05 EP EP09717638.2A patent/EP2254869B1/en active Active
- 2009-03-05 EP EP09718467.5A patent/EP2254870B1/en active Active
- 2009-03-05 BR BRPI0907976-9A patent/BRPI0907976A2/pt not_active IP Right Cessation
- 2009-03-05 AU AU2009221089A patent/AU2009221089B2/en not_active Ceased
- 2009-03-05 CA CA2712703A patent/CA2712703C/en not_active Expired - Fee Related
- 2009-03-05 EA EA201071038A patent/EA018241B1/ru not_active IP Right Cessation
- 2009-03-05 BR BRPI0907977-7A patent/BRPI0907977A2/pt not_active IP Right Cessation
- 2009-03-05 SI SI200931404A patent/SI2254870T1/sl unknown
- 2009-03-05 HR HRP20171208TT patent/HRP20171208T1/hr unknown
- 2009-03-05 WO PCT/EP2009/052590 patent/WO2009109618A2/en not_active Ceased
- 2009-03-05 US US12/865,923 patent/US8835481B2/en not_active Expired - Fee Related
- 2009-03-05 MX MX2010009626A patent/MX2010009626A/es active IP Right Grant
- 2009-03-05 US US12/864,767 patent/US7919518B2/en not_active Expired - Fee Related
- 2009-03-05 JP JP2010549143A patent/JP5509099B2/ja active Active
- 2009-03-05 CN CN200980105073.4A patent/CN101945855B/zh not_active Expired - Fee Related
- 2009-03-05 ES ES09717638.2T patent/ES2637009T3/es active Active
- 2009-03-05 PL PL09718467T patent/PL2254870T3/pl unknown
- 2009-03-05 DK DK09718467.5T patent/DK2254870T3/en active
- 2009-03-05 KR KR1020107017806A patent/KR101581828B1/ko not_active Expired - Fee Related
- 2009-03-05 EA EA201071040A patent/EA019711B1/ru not_active IP Right Cessation
- 2009-03-05 ES ES09718467.5T patent/ES2569330T3/es active Active
- 2009-03-05 LT LTEP09717638.2T patent/LT2254869T/lt unknown
- 2009-03-05 WO PCT/EP2009/052585 patent/WO2009109613A2/en not_active Ceased
- 2009-03-05 CN CN200980105556.4A patent/CN101952256B/zh not_active Expired - Fee Related
- 2009-03-05 GE GEAP200911963A patent/GEP20135983B/en unknown
- 2009-03-05 GE GEAP200911965A patent/GEP20135912B/en unknown
- 2009-03-06 AR ARP090100801A patent/AR070811A1/es unknown
- 2009-03-06 AR ARP090100800A patent/AR070810A1/es unknown
- 2009-05-03 UA UAA201008883A patent/UA103605C2/uk unknown
- 2009-05-03 UA UAA201008570A patent/UA105170C2/uk unknown
-
2010
- 2010-07-08 IL IL206893A patent/IL206893A0/en not_active IP Right Cessation
- 2010-07-21 IL IL207131A patent/IL207131A/en not_active IP Right Cessation
-
2011
- 2011-03-07 US US13/041,557 patent/US8283348B2/en not_active Expired - Fee Related
- 2011-10-06 IL IL215579A patent/IL215579A/en not_active IP Right Cessation
-
2016
- 2016-05-13 CY CY20161100406T patent/CY1117584T1/el unknown
-
2017
- 2017-08-09 CY CY20171100858T patent/CY1119252T1/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2637009T3 (es) | Nuevos derivados de 1-bencil-3-hidroximetilindazol y su utilización en el tratamiento de enfermedades basadas en la expresión de CX3CR1 y p40 | |
| ES2753149T3 (es) | Derivados de 1-bencil-3-hidroximetilindazol y utilización de los mismos en el tratamiento de enfermedades basadas en la expresión de MCP-1, CXCR1 y P40 | |
| HK1235053A1 (en) | 1-benzyl-3-hydroxymethylindazole derivatives and use thereof in the treatment of diseases based on the expression of cx3cr1 and p40 | |
| HK1148015B (en) | Novel 1-benzyl-3-hydroxymethylindazole derivatives and use thereof in the treatment of diseases based on the expression of cx3cr1 and p40 | |
| HK1148015A (en) | Novel 1-benzyl-3-hydroxymethylindazole derivatives and use thereof in the treatment of diseases based on the expression of cx3cr1 and p40 | |
| HK1145323B (en) | 1-benzyl-3-hydroxymethylindazole derivatives and use thereof in the treatment of diseases based on the expression of mcp-1, cx3cr1 |