NZ590234A - Fused compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor - Google Patents

Info

Publication number

NZ590234A

NZ590234A NZ590234A NZ59023404A NZ590234A NZ 590234 A NZ590234 A NZ 590234A NZ 590234 A NZ590234 A NZ 590234A NZ 59023404 A NZ59023404 A NZ 59023404A NZ 590234 A NZ590234 A NZ 590234A

Authority

NZ

New Zealand

Prior art keywords

compound

formula

indan

dihydro

inden

Prior art date

2003-06-12

Links

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 561
• 108010025083 TRPV1 receptor Proteins 0.000 title abstract description 23
• 102100029613 Transient receptor potential cation channel subfamily V member 1 Human genes 0.000 title description 17
• 102000005962 receptors Human genes 0.000 title description 14
• 238000000034 method Methods 0.000 claims abstract description 175
• 230000008569 process Effects 0.000 claims abstract description 79
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 62
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 43
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims abstract description 28
• 238000004519 manufacturing process Methods 0.000 claims abstract description 14
• VSTXCZGEEVFJES-UHFFFAOYSA-N 1-cycloundecyl-1,5-diazacycloundec-5-ene Chemical compound C1CCCCCC(CCCC1)N1CCCCCC=NCCC1 VSTXCZGEEVFJES-UHFFFAOYSA-N 0.000 claims abstract 2
• PVFOMCVHYWHZJE-UHFFFAOYSA-N trichloroacetyl chloride Chemical compound ClC(=O)C(Cl)(Cl)Cl PVFOMCVHYWHZJE-UHFFFAOYSA-N 0.000 claims abstract 2
• -1 alkylacarbonyloxy Chemical group 0.000 claims description 154
• 125000000217 alkyl group Chemical group 0.000 claims description 99
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 87
• 229910052739 hydrogen Inorganic materials 0.000 claims description 77
• 239000001257 hydrogen Substances 0.000 claims description 77
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 48
• 150000003839 salts Chemical class 0.000 claims description 46
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 40
• 229910052736 halogen Inorganic materials 0.000 claims description 30
• 150000002367 halogens Chemical class 0.000 claims description 30
• 125000003545 alkoxy group Chemical group 0.000 claims description 28
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 28
• 125000003118 aryl group Chemical group 0.000 claims description 27
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 26
• 125000001188 haloalkyl group Chemical group 0.000 claims description 23
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 23
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 21
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 20
• 125000004966 cyanoalkyl group Chemical group 0.000 claims description 20
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 19
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 19
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 18
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 16
• 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 16
• 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 16
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
• 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 15
• 125000004414 alkyl thio group Chemical group 0.000 claims description 15
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 15
• 125000000623 heterocyclic group Chemical group 0.000 claims description 15
• 125000003342 alkenyl group Chemical group 0.000 claims description 14
• 125000005093 alkyl carbonyl alkyl group Chemical group 0.000 claims description 14
• 125000000304 alkynyl group Chemical group 0.000 claims description 14
• 125000004181 carboxyalkyl group Chemical group 0.000 claims description 14
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
• 125000004995 haloalkylthio group Chemical group 0.000 claims description 14
• 125000005358 mercaptoalkyl group Chemical group 0.000 claims description 14
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 13
• 125000005243 carbonyl alkyl group Chemical group 0.000 claims description 13
• 125000004967 formylalkyl group Chemical group 0.000 claims description 12
• UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 claims description 10
• YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 9
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 7
• 125000001072 heteroaryl group Chemical group 0.000 claims description 6
• PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 4
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
• 125000004429 atom Chemical group 0.000 claims description 3
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 3
• 150000002431 hydrogen Chemical class 0.000 claims 6
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 3
• 241000012481 Xiha Species 0.000 claims 2
• 241000124008 Mammalia Species 0.000 abstract description 17
• 230000036407 pain Effects 0.000 abstract description 12
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 363
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 201
• 238000005481 NMR spectroscopy Methods 0.000 description 111
• 239000000203 mixture Substances 0.000 description 111
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 97
• 229910001868 water Inorganic materials 0.000 description 96
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 88
• 239000000243 solution Substances 0.000 description 88
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 87
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 75
• 239000002904 solvent Substances 0.000 description 68
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 63
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 63
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 63
• 239000007787 solid Substances 0.000 description 62
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 60
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 58
• 238000010511 deprotection reaction Methods 0.000 description 54
• 239000004202 carbamide Substances 0.000 description 48
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 43
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 37
• YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 35
• 239000000047 product Substances 0.000 description 35
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 34
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 34
• 238000006243 chemical reaction Methods 0.000 description 34
• 235000019439 ethyl acetate Nutrition 0.000 description 34
• 125000004435 hydrogen atom Chemical class [H]* 0.000 description 32
• 235000013877 carbamide Nutrition 0.000 description 29
• 239000002253 acid Substances 0.000 description 27
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
• 235000019441 ethanol Nutrition 0.000 description 26
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 26
• 230000002829 reductive effect Effects 0.000 description 26
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 24
• 239000003921 oil Substances 0.000 description 24
• 235000019198 oils Nutrition 0.000 description 24
• 150000001412 amines Chemical class 0.000 description 23
• 229910000069 nitrogen hydride Inorganic materials 0.000 description 23
• 239000000706 filtrate Substances 0.000 description 21
• 239000012044 organic layer Substances 0.000 description 21
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 21
• 239000000651 prodrug Substances 0.000 description 21
• 229940002612 prodrug Drugs 0.000 description 21
• 238000000746 purification Methods 0.000 description 21
• 239000011541 reaction mixture Substances 0.000 description 21
• 229960000583 acetic acid Drugs 0.000 description 20
• IIJPVOVAVTZFRH-UHFFFAOYSA-N 5-tert-butyl-2,3-dihydroinden-1-one Chemical compound CC(C)(C)C1=CC=C2C(=O)CCC2=C1 IIJPVOVAVTZFRH-UHFFFAOYSA-N 0.000 description 18
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 18
• 235000017663 capsaicin Nutrition 0.000 description 17
• 229960002504 capsaicin Drugs 0.000 description 17
• 235000019341 magnesium sulphate Nutrition 0.000 description 17
• 239000012298 atmosphere Substances 0.000 description 16
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 16
• GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 15
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
• 238000010992 reflux Methods 0.000 description 15
• 238000000926 separation method Methods 0.000 description 15
• LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 14
• 238000003756 stirring Methods 0.000 description 14
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 14
• 108020003175 receptors Proteins 0.000 description 13
• RCPFHUXEZIREGX-UHFFFAOYSA-N 5-(1-methoxy-2-methylpropan-2-yl)-2,3-dihydro-1h-inden-1-amine Chemical compound COCC(C)(C)C1=CC=C2C(N)CCC2=C1 RCPFHUXEZIREGX-UHFFFAOYSA-N 0.000 description 12
• 241001465754 Metazoa Species 0.000 description 12
• 239000002585 base Substances 0.000 description 12
• 238000001914 filtration Methods 0.000 description 12
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
• 238000011282 treatment Methods 0.000 description 12
• 150000003672 ureas Chemical class 0.000 description 12
• 238000003556 assay Methods 0.000 description 11
• 150000002148 esters Chemical class 0.000 description 11
• 239000002244 precipitate Substances 0.000 description 11
• QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 11
• 239000000725 suspension Substances 0.000 description 11
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical class CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
• 239000003054 catalyst Substances 0.000 description 10
• 210000004027 cell Anatomy 0.000 description 10
• 238000001816 cooling Methods 0.000 description 10
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
• 208000035475 disorder Diseases 0.000 description 10
• 229940079593 drug Drugs 0.000 description 10
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• 230000002401 inhibitory effect Effects 0.000 description 10
• 239000010410 layer Substances 0.000 description 10
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• 125000003396 thiol group Chemical class [H]S* 0.000 description 10
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
• VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 9
• 150000002473 indoazoles Chemical class 0.000 description 9
• 239000000741 silica gel Substances 0.000 description 9
• 229910002027 silica gel Inorganic materials 0.000 description 9
• 238000005160 1H NMR spectroscopy Methods 0.000 description 8
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 8
• 108091006146 Channels Proteins 0.000 description 8
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 8
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
• 238000002441 X-ray diffraction Methods 0.000 description 8
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
• 238000004128 high performance liquid chromatography Methods 0.000 description 8
• XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 8
• 229910052757 nitrogen Inorganic materials 0.000 description 8
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 8
• YTZKOQUCBOVLHL-UHFFFAOYSA-N tert-butylbenzene Chemical compound CC(C)(C)C1=CC=CC=C1 YTZKOQUCBOVLHL-UHFFFAOYSA-N 0.000 description 8
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 8
• XJEVHMGJSYVQBQ-UHFFFAOYSA-N 2,3-dihydro-1h-inden-1-amine Chemical class C1=CC=C2C(N)CCC2=C1 XJEVHMGJSYVQBQ-UHFFFAOYSA-N 0.000 description 7
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
• 150000004657 carbamic acid derivatives Chemical class 0.000 description 7
• 229910052799 carbon Inorganic materials 0.000 description 7
• 238000000113 differential scanning calorimetry Methods 0.000 description 7
• 239000007924 injection Substances 0.000 description 7
• 238000002347 injection Methods 0.000 description 7
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• 239000008194 pharmaceutical composition Substances 0.000 description 7
• 235000010288 sodium nitrite Nutrition 0.000 description 7
• INUNLMUAPJVRME-UHFFFAOYSA-N 3-chloropropanoyl chloride Chemical compound ClCCC(Cl)=O INUNLMUAPJVRME-UHFFFAOYSA-N 0.000 description 6
• 101150041968 CDC13 gene Proteins 0.000 description 6
• 208000004454 Hyperalgesia Diseases 0.000 description 6
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
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• 238000004821 distillation Methods 0.000 description 6
• 238000010438 heat treatment Methods 0.000 description 6
• PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 6
• 150000004702 methyl esters Chemical class 0.000 description 6
• 238000002156 mixing Methods 0.000 description 6
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• 150000003335 secondary amines Chemical class 0.000 description 6
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 6
• IDWZRJQMSBEVIW-UHFFFAOYSA-N 2-methyl-2-(1-oxo-2,3-dihydroinden-5-yl)propanenitrile Chemical compound N#CC(C)(C)C1=CC=C2C(=O)CCC2=C1 IDWZRJQMSBEVIW-UHFFFAOYSA-N 0.000 description 5
• DTVYNUOOZIKEEX-UHFFFAOYSA-N 5-aminoisoquinoline Chemical class N1=CC=C2C(N)=CC=CC2=C1 DTVYNUOOZIKEEX-UHFFFAOYSA-N 0.000 description 5
• KBHCTNGQJOEDDC-UHFFFAOYSA-N 5-methyl-2,3-dihydroinden-1-one Chemical compound CC1=CC=C2C(=O)CCC2=C1 KBHCTNGQJOEDDC-UHFFFAOYSA-N 0.000 description 5
• JYRVCRJPCWMDQT-UHFFFAOYSA-N 5-tert-butyl-2,3-dihydro-1h-inden-1-amine Chemical compound CC(C)(C)C1=CC=C2C(N)CCC2=C1 JYRVCRJPCWMDQT-UHFFFAOYSA-N 0.000 description 5
• 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 5
• 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 5
• 238000010521 absorption reaction Methods 0.000 description 5
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• 230000003502 anti-nociceptive effect Effects 0.000 description 5
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• 125000004432 carbon atom Chemical group C* 0.000 description 5
• 239000000969 carrier Substances 0.000 description 5
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• DIDJZJDDXQPTLN-UHFFFAOYSA-N indazole-1-carboxylic acid Chemical compound C1=CC=C2N(C(=O)O)N=CC2=C1 DIDJZJDDXQPTLN-UHFFFAOYSA-N 0.000 description 5
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• 231100000252 nontoxic Toxicity 0.000 description 5
• 230000003000 nontoxic effect Effects 0.000 description 5
• 239000000843 powder Substances 0.000 description 5
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• 239000012279 sodium borohydride Substances 0.000 description 5
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• 125000001424 substituent group Chemical group 0.000 description 5
• GNRVWTIJRDMIID-UHFFFAOYSA-N 1-(5-tert-butyl-2-fluoro-2,3-dihydro-1h-inden-1-yl)-3-(1h-indazol-4-yl)urea Chemical compound FC1CC2=CC(C(C)(C)C)=CC=C2C1NC(=O)NC1=CC=CC2=C1C=NN2 GNRVWTIJRDMIID-UHFFFAOYSA-N 0.000 description 4
• NKECRCMIFURWMK-UHFFFAOYSA-N 2-(3-bromophenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)C1=CC=CC(Br)=C1 NKECRCMIFURWMK-UHFFFAOYSA-N 0.000 description 4
• OWIRCRREDNEXTA-UHFFFAOYSA-N 3-nitro-1h-indazole Chemical compound C1=CC=C2C([N+](=O)[O-])=NNC2=C1 OWIRCRREDNEXTA-UHFFFAOYSA-N 0.000 description 4
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 4
• 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 4
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• 229910004373 HOAc Inorganic materials 0.000 description 4
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
• 206010037211 Psychomotor hyperactivity Diseases 0.000 description 4
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
• 206010046543 Urinary incontinence Diseases 0.000 description 4
• 230000003187 abdominal effect Effects 0.000 description 4
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 4
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• 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 description 1
• 229940094989 trimethylsilane Drugs 0.000 description 1
• 238000005292 vacuum distillation Methods 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
• ZQJYTTPJYLKTTI-UHFFFAOYSA-M zinc;2h-pyridin-2-ide;bromide Chemical compound Br[Zn+].C1=CC=N[C-]=C1 ZQJYTTPJYLKTTI-UHFFFAOYSA-M 0.000 description 1