AU2016257025A1 - Selective modulators of the activity of the GPR55 receptor: chromenopyrazole derivatives - Google Patents
Selective modulators of the activity of the GPR55 receptor: chromenopyrazole derivatives Download PDFInfo
- Publication number
- AU2016257025A1 AU2016257025A1 AU2016257025A AU2016257025A AU2016257025A1 AU 2016257025 A1 AU2016257025 A1 AU 2016257025A1 AU 2016257025 A AU2016257025 A AU 2016257025A AU 2016257025 A AU2016257025 A AU 2016257025A AU 2016257025 A1 AU2016257025 A1 AU 2016257025A1
- Authority
- AU
- Australia
- Prior art keywords
- methoxy
- pyrazole
- dihydro
- dimethylchromeno
- compound according
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 102100033061 G-protein coupled receptor 55 Human genes 0.000 title claims abstract description 37
- 101000871151 Homo sapiens G-protein coupled receptor 55 Proteins 0.000 title claims abstract description 37
- 230000000694 effects Effects 0.000 title description 13
- 150000001875 compounds Chemical class 0.000 claims abstract description 103
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 16
- 239000003814 drug Substances 0.000 claims abstract description 13
- 208000004296 neuralgia Diseases 0.000 claims abstract description 6
- 208000021722 neuropathic pain Diseases 0.000 claims abstract description 6
- 206010006187 Breast cancer Diseases 0.000 claims abstract description 5
- 208000026310 Breast neoplasm Diseases 0.000 claims abstract description 5
- 201000009030 Carcinoma Diseases 0.000 claims abstract description 5
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 5
- 206010033128 Ovarian cancer Diseases 0.000 claims abstract description 5
- 206010061535 Ovarian neoplasm Diseases 0.000 claims abstract description 5
- 208000018737 Parkinson disease Diseases 0.000 claims abstract description 5
- 206010060862 Prostate cancer Diseases 0.000 claims abstract description 5
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims abstract description 5
- 208000006990 cholangiocarcinoma Diseases 0.000 claims abstract description 5
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 5
- 208000005017 glioblastoma Diseases 0.000 claims abstract description 5
- 201000006417 multiple sclerosis Diseases 0.000 claims abstract description 5
- 150000003839 salts Chemical class 0.000 claims description 26
- 239000012453 solvate Substances 0.000 claims description 17
- 125000003118 aryl group Chemical group 0.000 claims description 13
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 208000035475 disorder Diseases 0.000 claims description 8
- 125000002947 alkylene group Chemical group 0.000 claims description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 238000004166 bioassay Methods 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- YCDKBLKJPZTRIS-UHFFFAOYSA-N 2-[4-(2,3-dimethylphenyl)piperazin-1-yl]-N-[(7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazol-1-yl)methyl]acetamide Chemical compound CC1=C(C=CC=C1C)N1CCN(CC1)CC(=O)NCN1N=CC2=C1C=1C=CC(=CC=1OC2(C)C)OC YCDKBLKJPZTRIS-UHFFFAOYSA-N 0.000 claims description 3
- RSHFORFJBYLIHA-UHFFFAOYSA-N N-[(7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazol-1-yl)methyl]-2-[4-(2-methoxyphenyl)piperazin-1-yl]acetamide Chemical compound COc1ccc2-c3c(cnn3CNC(=O)CN3CCN(CC3)c3ccccc3OC)C(C)(C)Oc2c1 RSHFORFJBYLIHA-UHFFFAOYSA-N 0.000 claims description 3
- MUGFMAHJBSPZPI-UHFFFAOYSA-N N-[(7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazol-2-yl)methyl]-2-(4-phenylpiperazin-1-yl)acetamide Chemical compound COC=1C=CC2=C(C=1)OC(C=1C2=NN(C=1)CNC(CN1CCN(CC1)C1=CC=CC=C1)=O)(C)C MUGFMAHJBSPZPI-UHFFFAOYSA-N 0.000 claims description 3
- ZKLZJXGGGOMHIM-UHFFFAOYSA-N N-[(7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazol-2-yl)methyl]-2-[4-(2-methoxyphenyl)piperazin-1-yl]acetamide Chemical compound COC=1C=CC2=C(C=1)OC(C=1C2=NN(C=1)CNC(CN1CCN(CC1)C1=C(C=CC=C1)OC)=O)(C)C ZKLZJXGGGOMHIM-UHFFFAOYSA-N 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 3
- 230000002611 ovarian Effects 0.000 claims description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 2
- 239000005977 Ethylene Substances 0.000 claims description 2
- DPOYJPWOCHCMJG-UHFFFAOYSA-N N-[(7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazol-1-yl)methyl]-2-(4-phenylpiperazin-1-yl)acetamide Chemical compound COC=1C=CC2=C(C=1)OC(C1=C2N(N=C1)CNC(CN1CCN(CC1)C1=CC=CC=C1)=O)(C)C DPOYJPWOCHCMJG-UHFFFAOYSA-N 0.000 claims description 2
- OGCYKMRKHKZCCI-UHFFFAOYSA-N N-[(7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazol-1-yl)methyl]-2-[4-(4-methoxyphenyl)piperazin-1-yl]acetamide Chemical compound COC=1C=CC2=C(C=1)OC(C1=C2N(N=C1)CNC(CN1CCN(CC1)C1=CC=C(C=C1)OC)=O)(C)C OGCYKMRKHKZCCI-UHFFFAOYSA-N 0.000 claims description 2
- 125000003107 substituted aryl group Chemical group 0.000 claims description 2
- 229930192474 thiophene Chemical group 0.000 claims description 2
- 201000010099 disease Diseases 0.000 abstract description 8
- 229930003827 cannabinoid Natural products 0.000 abstract description 4
- 239000003557 cannabinoid Substances 0.000 abstract description 4
- 229940065144 cannabinoids Drugs 0.000 abstract description 2
- 102000005962 receptors Human genes 0.000 abstract description 2
- 108020003175 receptors Proteins 0.000 abstract description 2
- 206010028980 Neoplasm Diseases 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 description 32
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 22
- 238000005160 1H NMR spectroscopy Methods 0.000 description 22
- 238000000034 method Methods 0.000 description 21
- UOXRPRZMAROFPH-IESLQMLBSA-N lysophosphatidylinositol Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](O)COP(O)(=O)OC1[C@H](O)[C@@H](O)C(O)[C@@H](O)[C@H]1O UOXRPRZMAROFPH-IESLQMLBSA-N 0.000 description 15
- 239000007787 solid Substances 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 11
- 239000000203 mixture Substances 0.000 description 11
- -1 1 -(2-(4-(2-furoyl)piperazinyl)ethyl)-1,4-dihydro-7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazole - 2-(2-(4-furoylpiperazinyl)ethyl)-2,4-dihydro-7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazole Chemical compound 0.000 description 10
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 10
- PTHGSQDDSZQCSI-UHFFFAOYSA-N BrCCN1NC2=C(C1)C(OC=1C=C(C=CC=12)OC)(C)C Chemical compound BrCCN1NC2=C(C1)C(OC=1C=C(C=CC=12)OC)(C)C PTHGSQDDSZQCSI-UHFFFAOYSA-N 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 10
- 229910052739 hydrogen Inorganic materials 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 150000003217 pyrazoles Chemical class 0.000 description 8
- XPHOXWMXDVPPHC-UHFFFAOYSA-N 7-methoxy-4,4-dimethyl-1H-chromeno[4,3-c]pyrazole Chemical compound COC1=CC2=C(C=C1)C=1NN=CC1C(O2)(C)C XPHOXWMXDVPPHC-UHFFFAOYSA-N 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 125000000217 alkyl group Chemical group 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- JOTSHAINQGFQEC-UHFFFAOYSA-N 1-(2-bromoethyl)-7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazole Chemical compound BrCCN1N=CC2=C1C=1C=CC(=CC=1OC2(C)C)OC JOTSHAINQGFQEC-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000010779 crude oil Substances 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 150000002367 halogens Chemical class 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 125000004193 piperazinyl group Chemical group 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 108010073366 CB1 Cannabinoid Receptor Proteins 0.000 description 3
- 102000009132 CB1 Cannabinoid Receptor Human genes 0.000 description 3
- 108010073376 CB2 Cannabinoid Receptor Proteins 0.000 description 3
- 102000009135 CB2 Cannabinoid Receptor Human genes 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- QLDARMIUQUXWPN-UHFFFAOYSA-N N-(hydroxymethyl)-2-(4-phenylpiperazin-1-yl)acetamide Chemical compound OCNC(CN1CCN(CC1)C1=CC=CC=C1)=O QLDARMIUQUXWPN-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 235000019439 ethyl acetate Nutrition 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- VUNXBQRNMNVUMV-UHFFFAOYSA-N phenyl(piperazin-1-yl)methanone Chemical class C=1C=CC=CC=1C(=O)N1CCNCC1 VUNXBQRNMNVUMV-UHFFFAOYSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- UKESBLFBQANJHH-UHFFFAOYSA-N 1-(Tetrahydro-2-furoyl)piperazine Chemical compound C1CNCCN1C(=O)C1CCCO1 UKESBLFBQANJHH-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical class NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- QRPBGMJWBJNCHY-UHFFFAOYSA-N 2-[4-(2,3-dimethylphenyl)piperazin-1-yl]-N-[(7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazol-2-yl)methyl]acetamide Chemical compound CC1=C(C=CC=C1C)N1CCN(CC1)CC(=O)NCN1N=C2C(=C1)C(OC=1C=C(C=CC=12)OC)(C)C QRPBGMJWBJNCHY-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- 102000018208 Cannabinoid Receptor Human genes 0.000 description 2
- 108050007331 Cannabinoid receptor Proteins 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 229940101165 GPR55 agonist Drugs 0.000 description 2
- 229940093505 GPR55 antagonist Drugs 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 238000000126 in silico method Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical compound C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 description 2
- BLRUMSYYHSFSKQ-UHFFFAOYSA-N piperazin-1-yl(thiophen-2-yl)methanone;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C=CSC=1C(=O)N1CCNCC1 BLRUMSYYHSFSKQ-UHFFFAOYSA-N 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
- HESSNIBRKZKEDT-UHFFFAOYSA-N 1,4-dihydrochromeno[4,3-c]pyrazole Chemical compound C1OC2=CC=CC=C2C2=C1C=NN2 HESSNIBRKZKEDT-UHFFFAOYSA-N 0.000 description 1
- BDZJIXFHXRVQQJ-UHFFFAOYSA-N 1-[4-[2-(7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazol-2-yl)ethyl]piperazin-1-yl]-2-phenoxyethanone Chemical compound COC=1C=CC2=C(C=1)OC(C=1C2=NN(C=1)CCN1CCN(CC1)C(COC1=CC=CC=C1)=O)(C)C BDZJIXFHXRVQQJ-UHFFFAOYSA-N 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- XZCPXUCNSORUCQ-UHFFFAOYSA-N 2-phenoxy-1-piperazin-1-ylethanone Chemical compound C1CNCCN1C(=O)COC1=CC=CC=C1 XZCPXUCNSORUCQ-UHFFFAOYSA-N 0.000 description 1
- ABEAQECASHOMNW-UHFFFAOYSA-N 3-(hydroxymethylidene)-7-methoxy-2,2-dimethylchromen-4-one Chemical compound O=C1C(=CO)C(C)(C)OC2=CC(OC)=CC=C21 ABEAQECASHOMNW-UHFFFAOYSA-N 0.000 description 1
- QXKXYXNEOUCMIY-UHFFFAOYSA-N 7-methoxy-2,2-dimethyl-3h-chromen-4-one Chemical compound O=C1CC(C)(C)OC2=CC(OC)=CC=C21 QXKXYXNEOUCMIY-UHFFFAOYSA-N 0.000 description 1
- ARCLGOHQIXNBRP-UHFFFAOYSA-N 7-methoxy-4,4-dimethyl-2,3-dihydrochromene Chemical compound O1CCC(C)(C)C=2C1=CC(OC)=CC=2 ARCLGOHQIXNBRP-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 101000894524 Bos taurus Transforming growth factor-beta-induced protein ig-h3 Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-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
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 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
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical class NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 101001047090 Homo sapiens Potassium voltage-gated channel subfamily H member 2 Proteins 0.000 description 1
- 101000798717 Homo sapiens Transmembrane 9 superfamily member 1 Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 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
- 206010065390 Inflammatory pain Diseases 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
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 102000019149 MAP kinase activity proteins Human genes 0.000 description 1
- 108040008097 MAP kinase activity proteins Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 150000001200 N-acyl ethanolamides Chemical class 0.000 description 1
- 238000007126 N-alkylation reaction Methods 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- UILPJVPSNHJFIK-UHFFFAOYSA-N Paeonol Chemical compound COC1=CC=C(C(C)=O)C(O)=C1 UILPJVPSNHJFIK-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 102100022807 Potassium voltage-gated channel subfamily H member 2 Human genes 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 102100032463 Transmembrane 9 superfamily member 1 Human genes 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- VNHMVXGWVQNAGP-UHFFFAOYSA-N [4-[2-(7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazol-1-yl)ethyl]piperazin-1-yl]-phenylmethanone Chemical compound C(C1=CC=CC=C1)(=O)N1CCN(CC1)CCN1N=CC2=C1C=1C=CC(=CC=1OC2(C)C)OC VNHMVXGWVQNAGP-UHFFFAOYSA-N 0.000 description 1
- OMNFAFXJJUAYRX-UHFFFAOYSA-N [4-[2-(7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazol-1-yl)ethyl]piperazin-1-yl]-thiophen-2-ylmethanone Chemical compound COC=1C=CC2=C(C=1)OC(C1=C2N(N=C1)CCN1CCN(CC1)C(C1=CC=CS1)=O)(C)C OMNFAFXJJUAYRX-UHFFFAOYSA-N 0.000 description 1
- UBONXKDRGHQECY-UHFFFAOYSA-N [4-[2-(7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazol-2-yl)ethyl]piperazin-1-yl]-(oxolan-2-yl)methanone Chemical compound COC=1C=CC2=C(C=1)OC(C=1C2=NN(C=1)CCN1CCN(CC1)C(=O)C1OCCC1)(C)C UBONXKDRGHQECY-UHFFFAOYSA-N 0.000 description 1
- YYSZFBQTFOSIAL-UHFFFAOYSA-N [4-[2-(7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazol-2-yl)ethyl]piperazin-1-yl]-phenylmethanone Chemical compound C(C1=CC=CC=C1)(=O)N1CCN(CC1)CCN1N=C2C(=C1)C(OC=1C=C(C=CC=12)OC)(C)C YYSZFBQTFOSIAL-UHFFFAOYSA-N 0.000 description 1
- VPTROEDHDNXYHP-UHFFFAOYSA-N [4-[2-(7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazol-2-yl)ethyl]piperazin-1-yl]-thiophen-2-ylmethanone Chemical compound COC=1C=CC2=C(C=1)OC(C=1C2=NN(C=1)CCN1CCN(CC1)C(C1=CC=CS1)=O)(C)C VPTROEDHDNXYHP-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000003869 acetamides Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 150000001408 amides Chemical group 0.000 description 1
- 150000001412 amines Chemical group 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 150000005840 aryl radicals Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 102000000072 beta-Arrestins Human genes 0.000 description 1
- 108010080367 beta-Arrestins Proteins 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 125000006267 biphenyl group Chemical group 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 230000014461 bone development Effects 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- XZWHYCOUQRVXMF-UHFFFAOYSA-N cyclohexyl-[4-[2-(7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazol-2-yl)ethyl]piperazin-1-yl]methanone Chemical compound C1(CCCCC1)C(=O)N1CCN(CC1)CCN1N=C2C(=C1)C(OC=1C=C(C=CC=12)OC)(C)C XZWHYCOUQRVXMF-UHFFFAOYSA-N 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 229960002887 deanol Drugs 0.000 description 1
- 239000011903 deuterated solvents Substances 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000012972 dimethylethanolamine Substances 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000002621 endocannabinoid Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 238000006170 formylation reaction Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- SADPINFEWFPMEA-UHFFFAOYSA-N furan-2-yl(piperazin-1-yl)methanone Chemical compound C=1C=COC=1C(=O)N1CCNCC1 SADPINFEWFPMEA-UHFFFAOYSA-N 0.000 description 1
- AQWDNHQURKZWRU-UHFFFAOYSA-N furan-2-yl-[4-[2-(7-methoxy-4,4-dimethylchromeno[4,3-c]pyrazol-2-yl)ethyl]piperazin-1-yl]methanone Chemical compound O1C(=CC=C1)C(=O)N1CCN(CC1)CCN1N=C2C(=C1)C(OC=1C=C(C=CC=12)OC)(C)C AQWDNHQURKZWRU-UHFFFAOYSA-N 0.000 description 1
- 125000002541 furyl group Chemical group 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
- 238000007429 general method Methods 0.000 description 1
- 230000002650 habitual effect Effects 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 238000003919 heteronuclear multiple bond coherence Methods 0.000 description 1
- 238000005570 heteronuclear single quantum coherence Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000002847 impedance measurement Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000000302 molecular modelling Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Chemical group 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 239000004031 partial agonist Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000008180 pharmaceutical surfactant Substances 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 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
- 238000003566 phosphorylation assay Methods 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 238000012113 quantitative test Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229910052717 sulfur Chemical group 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 102000027257 transmembrane receptors Human genes 0.000 description 1
- 108091008578 transmembrane receptors Proteins 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/052—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered
-
- 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
- A61K31/4162—1,2-Diazoles condensed with heterocyclic ring systems
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Physical Education & Sports Medicine (AREA)
- Neurosurgery (AREA)
- Diabetes (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Psychology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES201530608A ES2593057B1 (es) | 2015-05-05 | 2015-05-05 | Moduladores selectivos de la actividad del receptor GPR55: derivados de cromenopirazol |
| ESP201530608 | 2015-05-05 | ||
| PCT/ES2016/070314 WO2016177922A1 (es) | 2015-05-05 | 2016-04-27 | Moduladores selectivos de la actividad del receptor gpr55: derivados de cromenopirazol |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2016257025A1 true AU2016257025A1 (en) | 2017-11-30 |
Family
ID=57217626
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2016257025A Abandoned AU2016257025A1 (en) | 2015-05-05 | 2016-04-27 | Selective modulators of the activity of the GPR55 receptor: chromenopyrazole derivatives |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US10435412B2 (https=) |
| EP (1) | EP3305794B1 (https=) |
| JP (1) | JP2018515499A (https=) |
| KR (1) | KR20180002717A (https=) |
| CN (1) | CN107735397A (https=) |
| AU (1) | AU2016257025A1 (https=) |
| BR (1) | BR112017023834A2 (https=) |
| CA (1) | CA2985021A1 (https=) |
| ES (1) | ES2593057B1 (https=) |
| IL (1) | IL255420A0 (https=) |
| MX (1) | MX2017014145A (https=) |
| RU (1) | RU2017138563A (https=) |
| WO (1) | WO2016177922A1 (https=) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109420174B (zh) * | 2017-08-31 | 2021-07-13 | 清华大学 | Gpr18及其调节剂在防治免疫系统疾病中的应用 |
| CN109420173B (zh) * | 2017-08-31 | 2021-07-13 | 清华大学 | Gpr55及其调节剂在防治免疫系统疾病中的应用 |
| EP4472947A1 (en) * | 2022-03-07 | 2024-12-11 | Firmenich Incorporated | Sweetener compositions |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3624102A (en) * | 1969-05-21 | 1971-11-30 | Warner Lambert Co | Substituted benzopyranopyrazoles |
| GB0010960D0 (en) | 2000-05-05 | 2000-06-28 | Glaxo Group Ltd | Assay |
| WO2004074844A1 (en) * | 2003-02-18 | 2004-09-02 | Astrazeneca Ab | Screening assays for cannabinoid-ligand-type modulators of gpr55 |
| EP2079736B1 (en) * | 2006-12-29 | 2017-10-18 | Rigel Pharmaceuticals, Inc. | Substituted triazoles useful as axl inhibitors |
| WO2009010824A1 (en) * | 2007-07-13 | 2009-01-22 | Glenmark Pharmaceuticals, S.A. | Dihydrochromenopyrazole derivatives as vanilloid receptor ligands |
| ES2345592B1 (es) * | 2009-03-24 | 2011-07-21 | Consejo Superior De Investigaciones Cientificas (Csic), 70% | Derivados de cromenopirazoles como ligandos de receptores de cannabinoides. |
| WO2014013117A1 (es) * | 2012-07-18 | 2014-01-23 | Consejo Superior De Investigaciones Científicas (Csic) | Cromenopirazoldionas como derivados cannabinoides de quinonas con actividad antitumoral |
| ES2548789B1 (es) | 2014-03-18 | 2016-08-08 | Consejo Superior De Investigaciones Científicas (Csic) | Nuevas cromenoquinonas moduladoras de receptores cannabinoidescb2 con actividad antitumoral |
-
2015
- 2015-05-05 ES ES201530608A patent/ES2593057B1/es not_active Expired - Fee Related
-
2016
- 2016-04-27 RU RU2017138563A patent/RU2017138563A/ru not_active Application Discontinuation
- 2016-04-27 WO PCT/ES2016/070314 patent/WO2016177922A1/es not_active Ceased
- 2016-04-27 AU AU2016257025A patent/AU2016257025A1/en not_active Abandoned
- 2016-04-27 BR BR112017023834-9A patent/BR112017023834A2/pt not_active Application Discontinuation
- 2016-04-27 MX MX2017014145A patent/MX2017014145A/es unknown
- 2016-04-27 EP EP16789355.1A patent/EP3305794B1/en active Active
- 2016-04-27 US US15/571,671 patent/US10435412B2/en active Active
- 2016-04-27 KR KR1020177034239A patent/KR20180002717A/ko not_active Withdrawn
- 2016-04-27 CN CN201680039783.1A patent/CN107735397A/zh active Pending
- 2016-04-27 JP JP2017557942A patent/JP2018515499A/ja active Pending
- 2016-04-27 CA CA2985021A patent/CA2985021A1/en not_active Abandoned
-
2017
- 2017-11-05 IL IL255420A patent/IL255420A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US20180201620A1 (en) | 2018-07-19 |
| JP2018515499A (ja) | 2018-06-14 |
| EP3305794A1 (en) | 2018-04-11 |
| ES2593057A1 (es) | 2016-12-05 |
| WO2016177922A1 (es) | 2016-11-10 |
| EP3305794B1 (en) | 2020-02-05 |
| EP3305794A4 (en) | 2018-11-07 |
| IL255420A0 (en) | 2017-12-31 |
| RU2017138563A3 (https=) | 2019-06-06 |
| BR112017023834A2 (pt) | 2018-07-31 |
| MX2017014145A (es) | 2018-06-20 |
| CA2985021A1 (en) | 2016-11-10 |
| KR20180002717A (ko) | 2018-01-08 |
| RU2017138563A (ru) | 2019-06-05 |
| ES2593057B1 (es) | 2017-09-12 |
| US10435412B2 (en) | 2019-10-08 |
| CN107735397A (zh) | 2018-02-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2020353984B2 (en) | 2-isoindol-1,3,4-oxadiazole derivatives useful as HDAC6 inhibitors | |
| EP2445340B1 (en) | Substituted hydroxamic acids and uses thereof | |
| KR102925479B1 (ko) | Ret 키나제 억제제로서의 방향족 헤테로고리 화합물 및 그 제조와 응용 | |
| WO2016055479A1 (en) | Tetrahydroisoquinoline derivatives | |
| EP3184520B1 (en) | Salt of monocyclic pyridine derivative and crystal thereof | |
| CN117050062A (zh) | Egfr抑制剂及其制备和应用 | |
| SK278553B6 (en) | Azaheterocyclymethyl-chromates, manufacturing process thereof and pharmaceutical composition containing same | |
| JP2010505851A (ja) | ヒスタミン−３アンタゴニストとしてのｎ−置換−アザシクリルアミン | |
| CA2943778A1 (en) | 4-[(1s)-1-({[4-bromo-1-(isoquinolin-3-ylmethyl)-3-methyl-1 h-pyrazol-5yl]carbonyl}amino)ethyl]benzoic acid for the treatment of chronic renal failure and/or diabetic nephropathy | |
| US10435412B2 (en) | Selective modulators of the activity of the GPR55 receptor: chromenopyrazole derivatives | |
| JP2011515359A (ja) | 治療用トリアゾールアミド誘導体 | |
| JP2022511287A (ja) | ｃ－ＭＹＣ標的剤としての置換複素環化合物 | |
| EP4043457A1 (en) | Aromatic heterocyclic compound having tricyclic structure, and preparation method therefor and application thereof | |
| EP2896613B1 (en) | Sulfonamide compound | |
| TW201504227A (zh) | 環狀胺基甲基嘧啶衍生物 | |
| AU2008330653B2 (en) | Fused indane compound | |
| CN103328446B (zh) | 用于治疗癌症的新的4-氨基-n-羟基-苯甲酰胺 | |
| CN109305969A (zh) | 哌嗪-2,5-二酮类衍生物、其制备方法及其在医药上的应用 | |
| CN117986249A (zh) | 吡唑类衍生物抑制剂、其制备方法和应用 | |
| HK40057478B (zh) | Hpk1抑制剂及其使用方法 | |
| CN121342804A (zh) | 一种二酮哌嗪类化合物、合成方法、药物组合物及用途 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK4 | Application lapsed section 142(2)(d) - no continuation fee paid for the application |