AU2012212088B2

AU2012212088B2 - Alpha-ketoheterocycles and methods of making and using

Alpha-ketoheterocycles and methods of making and using

Info

Publication number: AU2012212088B2
Authority: AU; Australia
Prior art keywords: compound; mhz; nmr; heteroaryl; mmol
Prior art date: 2011-02-04
Legal status : Ceased

Application number

AU2012212088A

Other languages

English (en)

Other versions

AU2012212088A1 (en

Inventor

Dale L. Boger

Current Assignee

Scripps Research Institute

Original Assignee

Scripps Research Institute

Priority date

2011-02-04

Filing date

2012-02-03

Publication date

2016-07-14

2012-02-03 Application filed by Scripps Research Institute filed Critical Scripps Research Institute

2013-08-08 Publication of AU2012212088A1 publication Critical patent/AU2012212088A1/en

2016-07-14 Application granted granted Critical

2016-07-14 Publication of AU2012212088B2 publication Critical patent/AU2012212088B2/en

Status Ceased legal-status Critical Current

2032-02-03 Anticipated expiration legal-status Critical

Links

238000000034 method Methods 0.000 title claims abstract description 129
150000001875 compounds Chemical class 0.000 claims abstract description 409
230000000202 analgesic effect Effects 0.000 claims abstract description 23
-1 -Z-aryl Chemical group 0.000 claims description 224
239000000203 mixture Substances 0.000 claims description 105
125000003118 aryl group Chemical group 0.000 claims description 69
125000001072 heteroaryl group Chemical group 0.000 claims description 58
125000000623 heterocyclic group Chemical group 0.000 claims description 54
229910052739 hydrogen Inorganic materials 0.000 claims description 49
125000002252 acyl group Chemical group 0.000 claims description 43
229910052799 carbon Inorganic materials 0.000 claims description 43
150000003839 salts Chemical class 0.000 claims description 39
125000001424 substituent group Chemical group 0.000 claims description 39
125000000217 alkyl group Chemical group 0.000 claims description 37
125000004432 carbon atom Chemical group C* 0.000 claims description 37
208000002193 Pain Diseases 0.000 claims description 29
230000036407 pain Effects 0.000 claims description 28
125000004433 nitrogen atom Chemical group N* 0.000 claims description 27
238000011282 treatment Methods 0.000 claims description 27
125000000753 cycloalkyl group Chemical group 0.000 claims description 26
239000001257 hydrogen Substances 0.000 claims description 24
229910052757 nitrogen Inorganic materials 0.000 claims description 24
125000004429 atom Chemical group 0.000 claims description 23
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
229910052760 oxygen Inorganic materials 0.000 claims description 17
125000005843 halogen group Chemical group 0.000 claims description 16
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 16
238000001727 in vivo Methods 0.000 claims description 16
229910052740 iodine Inorganic materials 0.000 claims description 16
125000003710 aryl alkyl group Chemical group 0.000 claims description 15
239000003814 drug Substances 0.000 claims description 15
229910052794 bromium Inorganic materials 0.000 claims description 13
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
150000001732 carboxylic acid derivatives Chemical group 0.000 claims description 11
150000002825 nitriles Chemical class 0.000 claims description 11
229910052717 sulfur Inorganic materials 0.000 claims description 10
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
229910052736 halogen Inorganic materials 0.000 claims description 9
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 9
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 8
230000003110 anti-inflammatory effect Effects 0.000 claims description 7
230000009286 beneficial effect Effects 0.000 claims description 7
125000004093 cyano group Chemical group *C#N 0.000 claims description 7
208000019116 sleep disease Diseases 0.000 claims description 7
125000002947 alkylene group Chemical group 0.000 claims description 6
229910052731 fluorine Inorganic materials 0.000 claims description 6
125000001188 haloalkyl group Chemical group 0.000 claims description 6
150000002367 halogens Chemical class 0.000 claims description 6
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 5
229930003827 cannabinoid Natural products 0.000 claims description 5
239000003557 cannabinoid Substances 0.000 claims description 5
229940127240 opiate Drugs 0.000 claims description 5
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
229940111134 coxibs Drugs 0.000 claims description 4
239000003255 cyclooxygenase 2 inhibitor Substances 0.000 claims description 4
230000002401 inhibitory effect Effects 0.000 claims description 4
230000005923 long-lasting effect Effects 0.000 claims description 4
230000000631 nonopiate Effects 0.000 claims description 4
239000000546 pharmaceutical excipient Substances 0.000 claims description 4
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 3
102000004157 Hydrolases Human genes 0.000 claims description 3
108090000604 Hydrolases Proteins 0.000 claims description 3
125000005518 carboxamido group Chemical group 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
238000000338 in vitro Methods 0.000 claims description 2
125000003003 spiro group Chemical group 0.000 claims description 2
102100027297 Fatty acid 2-hydroxylase Human genes 0.000 claims 3
101000937693 Homo sapiens Fatty acid 2-hydroxylase Proteins 0.000 claims 3
101000918494 Homo sapiens Fatty-acid amide hydrolase 1 Proteins 0.000 claims 3
125000004453 alkoxycarbonyl group Chemical group 0.000 claims 1
208000020685 sleep-wake disease Diseases 0.000 claims 1
230000002557 soporific effect Effects 0.000 claims 1
108010046094 fatty-acid amide hydrolase Proteins 0.000 abstract description 75
102100029111 Fatty-acid amide hydrolase 1 Human genes 0.000 abstract description 49
230000000694 effects Effects 0.000 abstract description 41
LGEQQWMQCRIYKG-DOFZRALJSA-N anandamide Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)NCCO LGEQQWMQCRIYKG-DOFZRALJSA-N 0.000 abstract description 21
LGEQQWMQCRIYKG-UHFFFAOYSA-N arachidonic acid ethanolamide Natural products CCCCCC=CCC=CCC=CCC=CCCCC(=O)NCCO LGEQQWMQCRIYKG-UHFFFAOYSA-N 0.000 abstract description 19
230000005764 inhibitory process Effects 0.000 abstract description 16
238000002360 preparation method Methods 0.000 abstract description 14
102000004190 Enzymes Human genes 0.000 abstract description 13
108090000790 Enzymes Proteins 0.000 abstract description 13
230000001939 inductive effect Effects 0.000 abstract description 6
230000015556 catabolic process Effects 0.000 abstract description 2
YZAZOMTZCPDGBK-UHFFFAOYSA-N bis(1,3-oxazol-2-yl)methanone Chemical class N=1C=COC=1C(=O)C1=NC=CO1 YZAZOMTZCPDGBK-UHFFFAOYSA-N 0.000 abstract 1
239000002621 endocannabinoid Substances 0.000 abstract 1
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 248
238000005481 NMR spectroscopy Methods 0.000 description 177
VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 160
238000003818 flash chromatography Methods 0.000 description 145
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 141
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 139
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 136
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 133
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 125
229910052681 coesite Inorganic materials 0.000 description 124
229910052906 cristobalite Inorganic materials 0.000 description 124
229910052682 stishovite Inorganic materials 0.000 description 124
229910052905 tridymite Inorganic materials 0.000 description 124
239000000243 solution Substances 0.000 description 106
229920006395 saturated elastomer Polymers 0.000 description 86
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 76
239000012230 colorless oil Substances 0.000 description 74
239000003112 inhibitor Substances 0.000 description 71
239000011541 reaction mixture Substances 0.000 description 71
235000019439 ethyl acetate Nutrition 0.000 description 68
239000007787 solid Substances 0.000 description 64
239000002904 solvent Substances 0.000 description 63
239000011780 sodium chloride Substances 0.000 description 60
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 59
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 56
230000002829 reductive effect Effects 0.000 description 56
239000012044 organic layer Substances 0.000 description 51
238000005160 1H NMR spectroscopy Methods 0.000 description 46
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 46
229910001868 water Inorganic materials 0.000 description 39
239000012071 phase Substances 0.000 description 37
238000004128 high performance liquid chromatography Methods 0.000 description 35
239000011734 sodium Substances 0.000 description 35
229910052943 magnesium sulfate Inorganic materials 0.000 description 31
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 30
239000003921 oil Substances 0.000 description 29
235000019198 oils Nutrition 0.000 description 29
238000001704 evaporation Methods 0.000 description 27
230000008020 evaporation Effects 0.000 description 27
125000005842 heteroatom Chemical group 0.000 description 26
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
239000002253 acid Substances 0.000 description 23
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
210000004556 brain Anatomy 0.000 description 20
JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 20
238000004587 chromatography analysis Methods 0.000 description 18
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
241000699670 Mus sp. Species 0.000 description 17
NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 17
125000004304 oxazol-5-yl group Chemical group O1C=NC=C1* 0.000 description 17
SIOXPEMLGUPBBT-UHFFFAOYSA-M picolinate Chemical compound [O-]C(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-M 0.000 description 17
CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 17
RCRCTBLIHCHWDZ-UHFFFAOYSA-N 2-Arachidonoyl Glycerol Chemical compound CCCCCC=CCC=CCC=CCC=CCCCC(=O)OC(CO)CO RCRCTBLIHCHWDZ-UHFFFAOYSA-N 0.000 description 16
150000001721 carbon Chemical group 0.000 description 16
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
208000004454 Hyperalgesia Diseases 0.000 description 15
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 15
239000003940 fatty acid amidase inhibitor Substances 0.000 description 15
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 14
230000015572 biosynthetic process Effects 0.000 description 14
239000012043 crude product Substances 0.000 description 14
238000007912 intraperitoneal administration Methods 0.000 description 14
WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 14
BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 14
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 13
241001465754 Metazoa Species 0.000 description 13
235000014113 dietary fatty acids Nutrition 0.000 description 13
239000000194 fatty acid Substances 0.000 description 13
229930195729 fatty acid Natural products 0.000 description 13
239000000543 intermediate Substances 0.000 description 13
150000002576 ketones Chemical class 0.000 description 13
150000004702 methyl esters Chemical class 0.000 description 13
125000004287 oxazol-2-yl group Chemical group [H]C1=C([H])N=C(*)O1 0.000 description 13
230000003389 potentiating effect Effects 0.000 description 13
238000003786 synthesis reaction Methods 0.000 description 13
238000012360 testing method Methods 0.000 description 13
PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 12
239000003981 vehicle Substances 0.000 description 12
150000001412 amines Chemical class 0.000 description 11
238000010992 reflux Methods 0.000 description 11
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
125000003545 alkoxy group Chemical group 0.000 description 10
238000004458 analytical method Methods 0.000 description 10
238000003556 assay Methods 0.000 description 10
239000013078 crystal Substances 0.000 description 10
150000004665 fatty acids Chemical class 0.000 description 10
IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 description 9
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 9
CDXSJGDDABYYJV-UHFFFAOYSA-N acetic acid;ethanol Chemical compound CCO.CC(O)=O CDXSJGDDABYYJV-UHFFFAOYSA-N 0.000 description 9
206010053552 allodynia Diseases 0.000 description 9
230000003502 anti-nociceptive effect Effects 0.000 description 9
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
150000002431 hydrogen Chemical class 0.000 description 9
150000002632 lipids Chemical class 0.000 description 9
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
GCTFWCDSFPMHHS-UHFFFAOYSA-M Tributyltin chloride Chemical compound CCCC[Sn](Cl)(CCCC)CCCC GCTFWCDSFPMHHS-UHFFFAOYSA-M 0.000 description 8
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
125000004130 indan-2-yl group Chemical group [H]C1=C([H])C([H])=C2C(=C1[H])C([H])([H])C([H])(*)C2([H])[H] 0.000 description 8
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 8
230000008447 perception Effects 0.000 description 8
239000000758 substrate Substances 0.000 description 8
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 8
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 7
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
230000003213 activating effect Effects 0.000 description 7
229940114079 arachidonic acid Drugs 0.000 description 7
235000021342 arachidonic acid Nutrition 0.000 description 7
239000000460 chlorine Substances 0.000 description 7
125000004122 cyclic group Chemical group 0.000 description 7
239000002552 dosage form Substances 0.000 description 7
238000009472 formulation Methods 0.000 description 7
150000002500 ions Chemical class 0.000 description 7
210000004185 liver Anatomy 0.000 description 7
229960005181 morphine Drugs 0.000 description 7
230000003287 optical effect Effects 0.000 description 7
125000004076 pyridyl group Chemical group 0.000 description 7
229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
238000001356 surgical procedure Methods 0.000 description 7
238000003419 tautomerization reaction Methods 0.000 description 7
MXNFUCNDPLBTMF-UHFFFAOYSA-N 1,3-oxazole-5-carboxamide Chemical compound NC(=O)C1=CN=CO1 MXNFUCNDPLBTMF-UHFFFAOYSA-N 0.000 description 6
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
241000124008 Mammalia Species 0.000 description 6
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
208000027418 Wounds and injury Diseases 0.000 description 6
UGAPHEBNTGUMBB-UHFFFAOYSA-N acetic acid;ethyl acetate Chemical compound CC(O)=O.CCOC(C)=O UGAPHEBNTGUMBB-UHFFFAOYSA-N 0.000 description 6
230000009471 action Effects 0.000 description 6
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 6
239000002585 base Substances 0.000 description 6
150000003857 carboxamides Chemical class 0.000 description 6
201000010099 disease Diseases 0.000 description 6
230000001965 increasing effect Effects 0.000 description 6
239000007924 injection Substances 0.000 description 6
238000002347 injection Methods 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
SGNCOKUHMXLGAH-UHFFFAOYSA-N methyl 6-bromopyridine-2-carboxylate Chemical compound COC(=O)C1=CC=CC(Br)=N1 SGNCOKUHMXLGAH-UHFFFAOYSA-N 0.000 description 6
239000001301 oxygen Substances 0.000 description 6
125000004430 oxygen atom Chemical group O* 0.000 description 6
230000009467 reduction Effects 0.000 description 6
239000000126 substance Substances 0.000 description 6
125000000335 thiazolyl group Chemical group 0.000 description 6
IDFPQEHZYBXIFO-GFCCVEGCSA-N (R)-(4-fluoro-2-propylphenyl)-(1H-imidazol-2-yl)methanol Chemical compound CCCc1cc(F)ccc1[C@@H](O)c1ncc[nH]1 IDFPQEHZYBXIFO-GFCCVEGCSA-N 0.000 description 5
229910020489 SiO3 Inorganic materials 0.000 description 5
150000001299 aldehydes Chemical class 0.000 description 5
125000003342 alkenyl group Chemical group 0.000 description 5
125000000304 alkynyl group Chemical group 0.000 description 5
239000002775 capsule Substances 0.000 description 5
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 5
150000001768 cations Chemical class 0.000 description 5
230000008859 change Effects 0.000 description 5
238000012512 characterization method Methods 0.000 description 5
238000006243 chemical reaction Methods 0.000 description 5
229910052801 chlorine Inorganic materials 0.000 description 5
229940125782 compound 2 Drugs 0.000 description 5
230000006378 damage Effects 0.000 description 5
238000010511 deprotection reaction Methods 0.000 description 5
239000003085 diluting agent Substances 0.000 description 5
208000014674 injury Diseases 0.000 description 5
230000003993 interaction Effects 0.000 description 5
239000007788 liquid Substances 0.000 description 5
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 5
BOWVQLFMWHZBEF-KTKRTIGZSA-N oleoyl ethanolamide Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)NCCO BOWVQLFMWHZBEF-KTKRTIGZSA-N 0.000 description 5
125000002971 oxazolyl group Chemical group 0.000 description 5
230000003647 oxidation Effects 0.000 description 5
238000007254 oxidation reaction Methods 0.000 description 5
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 5
125000003367 polycyclic group Chemical group 0.000 description 5
239000000651 prodrug Substances 0.000 description 5
229940002612 prodrug Drugs 0.000 description 5
239000000047 product Substances 0.000 description 5
238000000746 purification Methods 0.000 description 5
238000000926 separation method Methods 0.000 description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 4
NTAGXJQHJQUOOA-UHFFFAOYSA-N 1,2,3,4-tetrahydronaphthalene-2-carboxylic acid Chemical compound C1=CC=C2CC(C(=O)O)CCC2=C1 NTAGXJQHJQUOOA-UHFFFAOYSA-N 0.000 description 4
FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 description 4
BSNIXNVMYNRRMG-UHFFFAOYSA-N 1,3-oxazole-5-carbonitrile Chemical compound N#CC1=CN=CO1 BSNIXNVMYNRRMG-UHFFFAOYSA-N 0.000 description 4
RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
229920002556 Polyethylene Glycol 300 Polymers 0.000 description 4
150000001298 alcohols Chemical class 0.000 description 4
150000001408 amides Chemical class 0.000 description 4
150000001413 amino acids Chemical class 0.000 description 4
125000003277 amino group Chemical group 0.000 description 4
150000001450 anions Chemical class 0.000 description 4
230000002238 attenuated effect Effects 0.000 description 4
CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 4
150000001540 azides Chemical class 0.000 description 4
230000003197 catalytic effect Effects 0.000 description 4
210000004027 cell Anatomy 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
230000001684 chronic effect Effects 0.000 description 4
229940125797 compound 12 Drugs 0.000 description 4
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 4
230000002255 enzymatic effect Effects 0.000 description 4
150000002148 esters Chemical class 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 4
125000001153 fluoro group Chemical group F* 0.000 description 4
210000002683 foot Anatomy 0.000 description 4
230000014509 gene expression Effects 0.000 description 4
125000001475 halogen functional group Chemical group 0.000 description 4
125000004404 heteroalkyl group Chemical group 0.000 description 4
230000002209 hydrophobic effect Effects 0.000 description 4
230000001976 improved effect Effects 0.000 description 4
230000000155 isotopic effect Effects 0.000 description 4
239000003446 ligand Substances 0.000 description 4
238000006138 lithiation reaction Methods 0.000 description 4
YIHFTASGYLUZRL-UHFFFAOYSA-N methyl 5-hydroxy-2,3-dihydro-1h-indene-2-carboxylate Chemical compound C1=C(O)C=C2CC(C(=O)OC)CC2=C1 YIHFTASGYLUZRL-UHFFFAOYSA-N 0.000 description 4
OBWFJXLKRAFEDI-UHFFFAOYSA-N methyl cyanoformate Chemical compound COC(=O)C#N OBWFJXLKRAFEDI-UHFFFAOYSA-N 0.000 description 4
238000003032 molecular docking Methods 0.000 description 4
208000004296 neuralgia Diseases 0.000 description 4
208000021722 neuropathic pain Diseases 0.000 description 4
FATBGEAMYMYZAF-KTKRTIGZSA-N oleamide Chemical compound CCCCCCCC\C=C/CCCCCCCC(N)=O FATBGEAMYMYZAF-KTKRTIGZSA-N 0.000 description 4
FATBGEAMYMYZAF-UHFFFAOYSA-N oleicacidamide-heptaglycolether Natural products CCCCCCCCC=CCCCCCCCC(N)=O FATBGEAMYMYZAF-UHFFFAOYSA-N 0.000 description 4
150000007524 organic acids Chemical class 0.000 description 4
HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 4
SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 4
239000000843 powder Substances 0.000 description 4
230000008707 rearrangement Effects 0.000 description 4
230000004044 response Effects 0.000 description 4
230000002441 reversible effect Effects 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
239000012453 solvate Substances 0.000 description 4
125000004434 sulfur atom Chemical group 0.000 description 4
230000002459 sustained effect Effects 0.000 description 4
239000003826 tablet Substances 0.000 description 4
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
230000001225 therapeutic effect Effects 0.000 description 4
125000001544 thienyl group Chemical group 0.000 description 4
VMFXIELMHBXUBH-UHFFFAOYSA-N (5-phenoxy-2,3-dihydro-1h-inden-2-yl)methanol Chemical compound C1=C2CC(CO)CC2=CC=C1OC1=CC=CC=C1 VMFXIELMHBXUBH-UHFFFAOYSA-N 0.000 description 3
150000005072 1,3,4-oxadiazoles Chemical class 0.000 description 3
VAXHEKQAFXJZOQ-UHFFFAOYSA-N 1,3-oxazol-2-yl-(5-phenyl-2,3-dihydro-1h-inden-2-yl)methanol Chemical compound N=1C=COC=1C(O)C(CC1=C2)CC1=CC=C2C1=CC=CC=C1 VAXHEKQAFXJZOQ-UHFFFAOYSA-N 0.000 description 3
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
XUDCMQBOWOLYCF-UHFFFAOYSA-N 2,3-dihydro-1h-indene-2-carboxylic acid Chemical compound C1=CC=C2CC(C(=O)O)CC2=C1 XUDCMQBOWOLYCF-UHFFFAOYSA-N 0.000 description 3
VEUMBMHMMCOFAG-UHFFFAOYSA-N 2,3-dihydrooxadiazole Chemical compound N1NC=CO1 VEUMBMHMMCOFAG-UHFFFAOYSA-N 0.000 description 3
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
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 3
BADRNRBHCSFVPO-UHFFFAOYSA-N 5-phenyl-2,3-dihydro-1h-indene-2-carbaldehyde Chemical compound C1=C2CC(C=O)CC2=CC=C1C1=CC=CC=C1 BADRNRBHCSFVPO-UHFFFAOYSA-N 0.000 description 3
NXAYYSHEARRBLR-UHFFFAOYSA-N 7-(3,5-diethyl-1-methylpyrazol-4-yl)-1-(2-morpholin-4-ylethyl)-3-(3-naphthalen-1-yloxypropyl)indole-2-carboxylic acid Chemical compound CCc1nn(C)c(CC)c1-c1cccc2c(CCCOc3cccc4ccccc34)c(C(O)=O)n(CCN3CCOCC3)c12 NXAYYSHEARRBLR-UHFFFAOYSA-N 0.000 description 3
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 3
238000011740 C57BL/6 mouse Methods 0.000 description 3
241000588724 Escherichia coli Species 0.000 description 3
JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 3
241000282412 Homo Species 0.000 description 3
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 3
229910002651 NO3 Inorganic materials 0.000 description 3
NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
229940035676 analgesics Drugs 0.000 description 3
238000004873 anchoring Methods 0.000 description 3
238000010171 animal model Methods 0.000 description 3
239000000730 antalgic agent Substances 0.000 description 3
238000013459 approach Methods 0.000 description 3
XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 3
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 3
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 3
235000019445 benzyl alcohol Nutrition 0.000 description 3
239000000872 buffer Substances 0.000 description 3
125000002837 carbocyclic group Chemical group 0.000 description 3
125000004452 carbocyclyl group Chemical group 0.000 description 3
150000007942 carboxylates Chemical class 0.000 description 3
210000003169 central nervous system Anatomy 0.000 description 3
230000002860 competitive effect Effects 0.000 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 description 3
230000001086 cytosolic effect Effects 0.000 description 3
238000011161 development Methods 0.000 description 3
VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical group [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 3
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 3
208000035475 disorder Diseases 0.000 description 3
229940079593 drug Drugs 0.000 description 3
238000000132 electrospray ionisation Methods 0.000 description 3
239000000839 emulsion Substances 0.000 description 3
238000001952 enzyme assay Methods 0.000 description 3
238000011156 evaluation Methods 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
235000019253 formic acid Nutrition 0.000 description 3
239000007903 gelatin capsule Substances 0.000 description 3
230000002427 irreversible effect Effects 0.000 description 3
125000000842 isoxazolyl group Chemical group 0.000 description 3
239000008101 lactose Substances 0.000 description 3
125000005647 linker group Chemical group 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
150000007522 mineralic acids Chemical class 0.000 description 3
230000004048 modification Effects 0.000 description 3
238000012986 modification Methods 0.000 description 3
125000001624 naphthyl group Chemical group 0.000 description 3
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 3
230000002093 peripheral effect Effects 0.000 description 3
238000012545 processing Methods 0.000 description 3
102000004169 proteins and genes Human genes 0.000 description 3
108090000623 proteins and genes Proteins 0.000 description 3
BAQLNPIEFOYKNB-UHFFFAOYSA-N pyridine-2-carbohydrazide Chemical compound NNC(=O)C1=CC=CC=N1 BAQLNPIEFOYKNB-UHFFFAOYSA-N 0.000 description 3
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 3
239000012047 saturated solution Substances 0.000 description 3
KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical compound [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 3
229910000080 stannane Inorganic materials 0.000 description 3
238000006467 substitution reaction Methods 0.000 description 3
239000000375 suspending agent Substances 0.000 description 3
239000000725 suspension Substances 0.000 description 3
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 3
210000001519 tissue Anatomy 0.000 description 3
LHVSFPGUDMWCAO-UHFFFAOYSA-N (5-phenylmethoxy-2,3-dihydro-1h-inden-2-yl)-(5-pyridin-2-yl-1,3-oxazol-2-yl)methanone Chemical compound N=1C=C(C=2N=CC=CC=2)OC=1C(=O)C(CC1=C2)CC1=CC=C2OCC1=CC=CC=C1 LHVSFPGUDMWCAO-UHFFFAOYSA-N 0.000 description 2
ZUXSLBHXHKZMBY-UHFFFAOYSA-N (5-pyridin-2-yl-1,3-oxazol-2-yl)-(1,2,3,4-tetrahydronaphthalen-2-yl)methanone Chemical compound C1CC2=CC=CC=C2CC1C(=O)C(O1)=NC=C1C1=CC=CC=N1 ZUXSLBHXHKZMBY-UHFFFAOYSA-N 0.000 description 2
WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
SNCKCAOSQQVTES-UHFFFAOYSA-N 1,3-oxazol-2-yl-(5-phenoxy-2,3-dihydro-1h-inden-2-yl)methanone Chemical compound N=1C=COC=1C(=O)C(CC1=C2)CC1=CC=C2OC1=CC=CC=C1 SNCKCAOSQQVTES-UHFFFAOYSA-N 0.000 description 2
SJJCQDRGABAVBB-UHFFFAOYSA-N 1-hydroxy-2-naphthoic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=CC=C21 SJJCQDRGABAVBB-UHFFFAOYSA-N 0.000 description 2
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
XTTOATOQGMLZCL-UHFFFAOYSA-N 2,3-dihydro-1h-inden-2-yl-(5-pyridin-2-yl-1,3-oxazol-2-yl)methanone Chemical compound C1C2=CC=CC=C2CC1C(=O)C(O1)=NC=C1C1=CC=CC=N1 XTTOATOQGMLZCL-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
KWVPFECTOKLOBL-KTKRTIGZSA-N 2-[(z)-octadec-9-enoxy]ethanol Chemical compound CCCCCCCC\C=C/CCCCCCCCOCCO KWVPFECTOKLOBL-KTKRTIGZSA-N 0.000 description 2
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
BNBQQYFXBLBYJK-UHFFFAOYSA-N 2-pyridin-2-yl-1,3-oxazole Chemical compound C1=COC(C=2N=CC=CC=2)=N1 BNBQQYFXBLBYJK-UHFFFAOYSA-N 0.000 description 2
LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
UJGDLLGKMWVCPT-UHFFFAOYSA-N 6-methoxy-2,3-dihydroinden-1-one Chemical compound COC1=CC=C2CCC(=O)C2=C1 UJGDLLGKMWVCPT-UHFFFAOYSA-N 0.000 description 2
MNALUTYMBUBKNX-UHFFFAOYSA-N 6-methoxy-3,4-dihydro-2h-naphthalen-1-one Chemical compound O=C1CCCC2=CC(OC)=CC=C21 MNALUTYMBUBKNX-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 2
108700023418 Amidases Proteins 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
108010010803 Gelatin Proteins 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
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 2
241000699666 Mus <mouse, genus> Species 0.000 description 2
OKIZCWYLBDKLSU-UHFFFAOYSA-M N,N,N-Trimethylmethanaminium chloride Chemical compound [Cl-].C[N+](C)(C)C OKIZCWYLBDKLSU-UHFFFAOYSA-M 0.000 description 2
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 description 2
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 2
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
239000005642 Oleic acid Substances 0.000 description 2
ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
238000006619 Stille reaction Methods 0.000 description 2
239000007983 Tris buffer Substances 0.000 description 2
238000007301 Vedej hydroxylation reaction Methods 0.000 description 2
TUEIURIZJQRMQE-UHFFFAOYSA-N [2-(tert-butylsulfamoyl)phenyl]boronic acid Chemical compound CC(C)(C)NS(=O)(=O)C1=CC=CC=C1B(O)O TUEIURIZJQRMQE-UHFFFAOYSA-N 0.000 description 2
230000035508 accumulation Effects 0.000 description 2
238000009825 accumulation Methods 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
125000003647 acryloyl group Chemical group O=C([*])C([H])=C([H])[H] 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 2
239000000654 additive Substances 0.000 description 2
239000000443 aerosol Substances 0.000 description 2
102000005922 amidase Human genes 0.000 description 2
125000003368 amide group Chemical group 0.000 description 2
150000001409 amidines Chemical class 0.000 description 2
230000036592 analgesia Effects 0.000 description 2
238000000540 analysis of variance Methods 0.000 description 2
125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 2
125000002102 aryl alkyloxo group Chemical group 0.000 description 2
239000012298 atmosphere Substances 0.000 description 2
125000005602 azabenzimidazolyl group Chemical group 0.000 description 2
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 2
230000003542 behavioural effect Effects 0.000 description 2
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 2
238000004166 bioassay Methods 0.000 description 2
229920002988 biodegradable polymer Polymers 0.000 description 2
239000004621 biodegradable polymer Substances 0.000 description 2
230000037396 body weight Effects 0.000 description 2
235000013877 carbamide Nutrition 0.000 description 2
125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 2
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
239000000969 carrier Substances 0.000 description 2
239000004359 castor oil Substances 0.000 description 2
235000019438 castor oil Nutrition 0.000 description 2
230000001925 catabolic effect Effects 0.000 description 2
239000001913 cellulose Substances 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
235000010980 cellulose Nutrition 0.000 description 2
238000009833 condensation Methods 0.000 description 2
230000005494 condensation Effects 0.000 description 2
OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 2
230000008878 coupling Effects 0.000 description 2
238000010168 coupling process Methods 0.000 description 2
238000005859 coupling reaction Methods 0.000 description 2
238000005564 crystal structure determination Methods 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
125000006165 cyclic alkyl group Chemical group 0.000 description 2
125000000392 cycloalkenyl group Chemical group 0.000 description 2
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 2
125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 2
125000004855 decalinyl group Chemical group C1(CCCC2CCCCC12)* 0.000 description 2
IEJIGPNLZYLLBP-UHFFFAOYSA-N dimethyl carbonate Chemical compound COC(=O)OC IEJIGPNLZYLLBP-UHFFFAOYSA-N 0.000 description 2
238000009826 distribution Methods 0.000 description 2
231100000673 dose–response relationship Toxicity 0.000 description 2
239000008298 dragée Substances 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
238000006911 enzymatic reaction Methods 0.000 description 2
239000000284 extract Substances 0.000 description 2
239000011737 fluorine Substances 0.000 description 2
239000008273 gelatin Substances 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
235000011852 gelatine desserts Nutrition 0.000 description 2
ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 2
125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 2
230000036541 health Effects 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
210000000548 hind-foot Anatomy 0.000 description 2
229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 description 2
125000001041 indolyl group Chemical group 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 2
230000003447 ipsilateral effect Effects 0.000 description 2
QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 2
239000010410 layer Substances 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
239000000463 material Substances 0.000 description 2
239000012528 membrane Substances 0.000 description 2
230000002503 metabolic effect Effects 0.000 description 2
TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
238000000302 molecular modelling Methods 0.000 description 2
239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
210000003205 muscle Anatomy 0.000 description 2
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 2
235000005985 organic acids Nutrition 0.000 description 2
150000002916 oxazoles Chemical class 0.000 description 2
HXYVTAGFYLMHSO-UHFFFAOYSA-N palmitoyl ethanolamide Chemical compound CCCCCCCCCCCCCCCC(=O)NCCO HXYVTAGFYLMHSO-UHFFFAOYSA-N 0.000 description 2
230000036961 partial effect Effects 0.000 description 2
238000005192 partition Methods 0.000 description 2
239000008188 pellet Substances 0.000 description 2
125000005010 perfluoroalkyl group Chemical group 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
RGCLLPNLLBQHPF-HJWRWDBZSA-N phosphamidon Chemical compound CCN(CC)C(=O)C(\Cl)=C(/C)OP(=O)(OC)OC RGCLLPNLLBQHPF-HJWRWDBZSA-N 0.000 description 2
230000000704 physical effect Effects 0.000 description 2
229940081066 picolinic acid Drugs 0.000 description 2
125000003386 piperidinyl group Chemical group 0.000 description 2
229920001223 polyethylene glycol Polymers 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
239000011591 potassium Substances 0.000 description 2
229910000343 potassium bisulfate Inorganic materials 0.000 description 2
239000002243 precursor Substances 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
230000002035 prolonged effect Effects 0.000 description 2
125000003226 pyrazolyl group Chemical group 0.000 description 2
125000000168 pyrrolyl group Chemical group 0.000 description 2
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 2
230000006340 racemization Effects 0.000 description 2
230000001105 regulatory effect Effects 0.000 description 2
125000006413 ring segment Chemical group 0.000 description 2
210000003497 sciatic nerve Anatomy 0.000 description 2
125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 2
230000011664 signaling Effects 0.000 description 2
238000004088 simulation Methods 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
229910000029 sodium carbonate Inorganic materials 0.000 description 2
241000894007 species Species 0.000 description 2
125000005346 substituted cycloalkyl group Chemical group 0.000 description 2
229940124530 sulfonamide Drugs 0.000 description 2
125000000565 sulfonamide group Chemical group 0.000 description 2
150000003456 sulfonamides Chemical class 0.000 description 2
230000008093 supporting effect Effects 0.000 description 2
239000004094 surface-active agent Substances 0.000 description 2
208000024891 symptom Diseases 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
230000009897 systematic effect Effects 0.000 description 2
239000000454 talc Substances 0.000 description 2
229910052623 talc Inorganic materials 0.000 description 2
125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 2
125000003831 tetrazolyl group Chemical group 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
125000004927 thianaphthalenyl group Chemical group S1C(C=CC2=CC=CC=C12)* 0.000 description 2
YOWGRWHKDCHINP-UHFFFAOYSA-N tributyl(1,3-oxazol-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=NC=CO1 YOWGRWHKDCHINP-UHFFFAOYSA-N 0.000 description 2
WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
238000003260 vortexing Methods 0.000 description 2
239000000080 wetting agent Substances 0.000 description 2
DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical group C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 description 1
SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
QEHZZWCTYXYHOV-UHFFFAOYSA-N (5-phenylmethoxy-2,3-dihydro-1h-inden-2-yl)methanol Chemical compound C1=C2CC(CO)CC2=CC=C1OCC1=CC=CC=C1 QEHZZWCTYXYHOV-UHFFFAOYSA-N 0.000 description 1
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
125000003161 (C1-C6) alkylene group Chemical group 0.000 description 1
ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 description 1
LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical class OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 1
MJIQOLXBEVWIQH-UHFFFAOYSA-N 1,3-oxazol-2-yl-(5-phenoxy-2,3-dihydro-1h-inden-2-yl)methanol Chemical compound N=1C=COC=1C(O)C(CC1=C2)CC1=CC=C2OC1=CC=CC=C1 MJIQOLXBEVWIQH-UHFFFAOYSA-N 0.000 description 1
LKMZZABCGFMJAA-UHFFFAOYSA-N 1,3-oxazol-2-yl-(5-phenylmethoxy-2,3-dihydro-1h-inden-2-yl)methanol Chemical compound N=1C=COC=1C(O)C(CC1=C2)CC1=CC=C2OCC1=CC=CC=C1 LKMZZABCGFMJAA-UHFFFAOYSA-N 0.000 description 1
OBQVZZWUONMEKP-UHFFFAOYSA-N 1,3-oxazol-2-yl-(5-phenylmethoxy-2,3-dihydro-1h-inden-2-yl)methanone Chemical compound N=1C=COC=1C(=O)C(CC1=C2)CC1=CC=C2OCC1=CC=CC=C1 OBQVZZWUONMEKP-UHFFFAOYSA-N 0.000 description 1
TXDQYFVLOCGCBV-UHFFFAOYSA-N 1,3-oxazol-2-yl-(6-phenoxy-1,2,3,4-tetrahydronaphthalen-2-yl)methanol Chemical compound N=1C=COC=1C(O)C(CC1=CC=2)CCC1=CC=2OC1=CC=CC=C1 TXDQYFVLOCGCBV-UHFFFAOYSA-N 0.000 description 1
NBRXQTNPBIEMFJ-UHFFFAOYSA-N 1,3-oxazole;1,2,3,4-tetrahydronaphthalene Chemical class C1=COC=N1.C1=CC=C2CCCCC2=C1 NBRXQTNPBIEMFJ-UHFFFAOYSA-N 0.000 description 1
CPKVUHPKYQGHMW-UHFFFAOYSA-N 1-ethenylpyrrolidin-2-one;molecular iodine Chemical compound II.C=CN1CCCC1=O CPKVUHPKYQGHMW-UHFFFAOYSA-N 0.000 description 1
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-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
ZOAGIUDRIIZXKH-UHFFFAOYSA-N 2,3-dihydro-1h-inden-2-yl(1,3-oxazol-2-yl)methanol Chemical compound C1C2=CC=CC=C2CC1C(O)C1=NC=CO1 ZOAGIUDRIIZXKH-UHFFFAOYSA-N 0.000 description 1
ULVJTHHSGWAIOA-UHFFFAOYSA-N 2,3-dihydro-1h-inden-2-ylmethanol Chemical compound C1=CC=C2CC(CO)CC2=C1 ULVJTHHSGWAIOA-UHFFFAOYSA-N 0.000 description 1
KPTYDOSQASSERS-UHFFFAOYSA-N 2,3-dihydro-1h-indene-2-carbaldehyde Chemical compound C1=CC=C2CC(C=O)CC2=C1 KPTYDOSQASSERS-UHFFFAOYSA-N 0.000 description 1
IKEBOBAZMXJSFB-UHFFFAOYSA-N 2-[tert-butyl(dimethyl)silyl]oxy-2-(6-phenoxy-1,2,3,4-tetrahydronaphthalen-2-yl)acetic acid Chemical compound C=1C=C2CC(C(O[Si](C)(C)C(C)(C)C)C(O)=O)CCC2=CC=1OC1=CC=CC=C1 IKEBOBAZMXJSFB-UHFFFAOYSA-N 0.000 description 1
ZBMRKNMTMPPMMK-UHFFFAOYSA-N 2-amino-4-[hydroxy(methyl)phosphoryl]butanoic acid;azane Chemical compound [NH4+].CP(O)(=O)CCC(N)C([O-])=O ZBMRKNMTMPPMMK-UHFFFAOYSA-N 0.000 description 1
ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 1
RCRCTBLIHCHWDZ-DOFZRALJSA-N 2-arachidonoylglycerol Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)OC(CO)CO RCRCTBLIHCHWDZ-DOFZRALJSA-N 0.000 description 1
125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
IGRCWJPBLWGNPX-UHFFFAOYSA-N 3-(2-chlorophenyl)-n-(4-chlorophenyl)-n,5-dimethyl-1,2-oxazole-4-carboxamide Chemical compound C=1C=C(Cl)C=CC=1N(C)C(=O)C1=C(C)ON=C1C1=CC=CC=C1Cl IGRCWJPBLWGNPX-UHFFFAOYSA-N 0.000 description 1
YGYGASJNJTYNOL-CQSZACIVSA-N 3-[(4r)-2,2-dimethyl-1,1-dioxothian-4-yl]-5-(4-fluorophenyl)-1h-indole-7-carboxamide Chemical compound C1CS(=O)(=O)C(C)(C)C[C@@H]1C1=CNC2=C(C(N)=O)C=C(C=3C=CC(F)=CC=3)C=C12 YGYGASJNJTYNOL-CQSZACIVSA-N 0.000 description 1
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
125000005274 4-hydroxybenzoic acid group Chemical group 0.000 description 1
CFFDJOAAJJTVCY-UHFFFAOYSA-N 5-hydroxy-2,3-dihydro-1h-indene-2-carboxylic acid Chemical compound C1=C(O)C=C2CC(C(=O)O)CC2=C1 CFFDJOAAJJTVCY-UHFFFAOYSA-N 0.000 description 1
JOJYSTFJWOBDFF-UHFFFAOYSA-N 5-phenoxy-2,3-dihydro-1h-indene-2-carbaldehyde Chemical compound C1=C2CC(C=O)CC2=CC=C1OC1=CC=CC=C1 JOJYSTFJWOBDFF-UHFFFAOYSA-N 0.000 description 1
FSZSCNARRHWFHT-UHFFFAOYSA-N 5-phenylmethoxy-2,3-dihydro-1h-indene-2-carbaldehyde Chemical compound C1=C2CC(C=O)CC2=CC=C1OCC1=CC=CC=C1 FSZSCNARRHWFHT-UHFFFAOYSA-N 0.000 description 1
CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
ROVLSQFHWZHYHB-UHFFFAOYSA-N 6-phenoxy-1,2,3,4-tetrahydronaphthalene Chemical group C=1C=C2CCCCC2=CC=1OC1=CC=CC=C1 ROVLSQFHWZHYHB-UHFFFAOYSA-N 0.000 description 1
LNXQSPLERBMJGY-UHFFFAOYSA-N 6-phenoxy-1,2,3,4-tetrahydronaphthalene-2-carbaldehyde Chemical compound C=1C=C2CC(C=O)CCC2=CC=1OC1=CC=CC=C1 LNXQSPLERBMJGY-UHFFFAOYSA-N 0.000 description 1
ZGGJEKJBKMRUCY-UHFFFAOYSA-N 6-phenylmethoxy-1,2,3,4-tetrahydronaphthalene-2-carbaldehyde Chemical compound C=1C=C2CC(C=O)CCC2=CC=1OCC1=CC=CC=C1 ZGGJEKJBKMRUCY-UHFFFAOYSA-N 0.000 description 1
ILOIOIGZFHGSMS-UHFFFAOYSA-N 7-phenyl-1-(5-pyridin-2-yl-1,3-oxazol-2-yl)heptan-1-one Chemical compound N=1C=C(C=2N=CC=CC=2)OC=1C(=O)CCCCCCC1=CC=CC=C1 ILOIOIGZFHGSMS-UHFFFAOYSA-N 0.000 description 1
LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 1
241000251468 Actinopterygii Species 0.000 description 1
229910002012 Aerosil® Inorganic materials 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
241000270730 Alligator mississippiensis Species 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
206010002091 Anaesthesia Diseases 0.000 description 1
208000019901 Anxiety disease Diseases 0.000 description 1
241001076939 Artines Species 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
GTNKAJJMCCFDIU-QGZVFWFLSA-N CCCCCC[C@H](C(=O)O)SC1=NC2=C(S1)C=C(C=C2)NS(=O)(=O)C3=C(C=C(C=C3)Cl)Cl Chemical compound CCCCCC[C@H](C(=O)O)SC1=NC2=C(S1)C=C(C=C2)NS(=O)(=O)C3=C(C=C(C=C3)Cl)Cl GTNKAJJMCCFDIU-QGZVFWFLSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
102000018208 Cannabinoid Receptor Human genes 0.000 description 1
108050007331 Cannabinoid receptor Proteins 0.000 description 1
241000283707 Capra Species 0.000 description 1
UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical class [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
208000009132 Catalepsy Diseases 0.000 description 1
241000282693 Cercopithecidae Species 0.000 description 1
241001000171 Chira Species 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
241000241985 Cnides Species 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
229920000858 Cyclodextrin Polymers 0.000 description 1
102100025698 Cytosolic carboxypeptidase 4 Human genes 0.000 description 1
206010012335 Dependence Diseases 0.000 description 1
238000006646 Dess-Martin oxidation reaction Methods 0.000 description 1
239000004375 Dextrin Substances 0.000 description 1
229920001353 Dextrin Polymers 0.000 description 1
102100025027 E3 ubiquitin-protein ligase TRIM69 Human genes 0.000 description 1
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
241000283086 Equidae Species 0.000 description 1
108090000371 Esterases Proteins 0.000 description 1
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
208000026097 Factitious disease Diseases 0.000 description 1
102100029114 Fatty-acid amide hydrolase 2 Human genes 0.000 description 1
241000282326 Felis catus Species 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical group NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Polymers OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
241001272567 Hominoidea Species 0.000 description 1
101000932590 Homo sapiens Cytosolic carboxypeptidase 4 Proteins 0.000 description 1
101000830203 Homo sapiens E3 ubiquitin-protein ligase TRIM69 Proteins 0.000 description 1
101000918490 Homo sapiens Fatty-acid amide hydrolase 2 Proteins 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 1
HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
206010061218 Inflammation Diseases 0.000 description 1
PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
241000581650 Ivesia Species 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
229910010084 LiAlH4 Inorganic materials 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
238000000342 Monte Carlo simulation Methods 0.000 description 1
101001033003 Mus musculus Granzyme F Proteins 0.000 description 1
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
150000001204 N-oxides Chemical group 0.000 description 1
208000012902 Nervous system disease Diseases 0.000 description 1
208000001294 Nociceptive Pain Diseases 0.000 description 1
239000004677 Nylon Substances 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
241001494479 Pecora Species 0.000 description 1
229920005372 Plexiglas® Polymers 0.000 description 1
229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
229920002732 Polyanhydride Polymers 0.000 description 1
229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
229920000954 Polyglycolide Polymers 0.000 description 1
229920001710 Polyorthoester Polymers 0.000 description 1
239000004743 Polypropylene Substances 0.000 description 1
208000004550 Postoperative Pain Diseases 0.000 description 1
241000288906 Primates Species 0.000 description 1
208000003251 Pruritus Diseases 0.000 description 1
229940124639 Selective inhibitor Drugs 0.000 description 1
OZPDGESCTGGNAD-CIUDSAMLSA-N Ser-Ser-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CO OZPDGESCTGGNAD-CIUDSAMLSA-N 0.000 description 1
108010022999 Serine Proteases Proteins 0.000 description 1
102000012479 Serine Proteases Human genes 0.000 description 1
208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
235000021355 Stearic acid Nutrition 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
238000006069 Suzuki reaction reaction Methods 0.000 description 1
229920004890 Triton X-100 Polymers 0.000 description 1
239000013504 Triton X-100 Substances 0.000 description 1
ROFVXGGUISEHAM-UHFFFAOYSA-N URB597 Chemical compound NC(=O)C1=CC=CC(C=2C=C(OC(=O)NC3CCCCC3)C=CC=2)=C1 ROFVXGGUISEHAM-UHFFFAOYSA-N 0.000 description 1
206010047853 Waxy flexibility Diseases 0.000 description 1
238000002441 X-ray diffraction Methods 0.000 description 1
TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
CAMMWOIMMVZFIC-UHFFFAOYSA-N [N].C1=COC=N1 Chemical compound [N].C1=COC=N1 CAMMWOIMMVZFIC-UHFFFAOYSA-N 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
239000008186 active pharmaceutical agent Substances 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
125000005426 adeninyl group Chemical group N1=C(N=C2N=CNC2=C1N)* 0.000 description 1
239000008272 agar Substances 0.000 description 1
235000010419 agar Nutrition 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
150000001342 alkaline earth metals Chemical class 0.000 description 1
150000003973 alkyl amines Chemical class 0.000 description 1
125000003282 alkyl amino group Chemical group 0.000 description 1
150000005215 alkyl ethers Chemical class 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
125000005529 alkyleneoxy group Chemical group 0.000 description 1
125000005336 allyloxy group Chemical group 0.000 description 1
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
239000003708 ampul Substances 0.000 description 1
230000037005 anaesthesia Effects 0.000 description 1
125000000129 anionic group Chemical group 0.000 description 1
230000036506 anxiety Effects 0.000 description 1
230000000949 anxiolytic effect Effects 0.000 description 1
239000008365 aqueous carrier Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
125000004097 arachidonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])/C([H])=C([H])\C([H])([H])/C([H])=C([H])\C([H])([H])/C([H])=C([H])\C([H])([H])/C([H])=C([H])\C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
150000003974 aralkylamines Chemical class 0.000 description 1
150000004982 aromatic amines Chemical class 0.000 description 1
150000001502 aryl halides Chemical class 0.000 description 1
125000005002 aryl methyl group Chemical group 0.000 description 1
125000004104 aryloxy group Chemical group 0.000 description 1
239000012752 auxiliary agent Substances 0.000 description 1
125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 description 1
125000003828 azulenyl group Chemical group 0.000 description 1
230000008901 benefit Effects 0.000 description 1
125000005605 benzo group Chemical group 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
QNUVWKPHHOWGAW-UHFFFAOYSA-M benzyl-(2-dodecoxyethyl)-dimethylazanium;chloride Chemical compound [Cl-].CCCCCCCCCCCCOCC[N+](C)(C)CC1=CC=CC=C1 QNUVWKPHHOWGAW-UHFFFAOYSA-M 0.000 description 1
229940064804 betadine Drugs 0.000 description 1
150000005347 biaryls Chemical group 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
239000004305 biphenyl Substances 0.000 description 1
235000010290 biphenyl Nutrition 0.000 description 1
125000002529 biphenylenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C12)* 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 1
238000004422 calculation algorithm Methods 0.000 description 1
238000004364 calculation method Methods 0.000 description 1
230000003375 cannabimimetic effect Effects 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
235000014633 carbohydrates Nutrition 0.000 description 1
150000001720 carbohydrates Chemical class 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
125000002843 carboxylic acid group Chemical group 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
208000015114 central nervous system disease Diseases 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
150000003841 chloride salts Chemical class 0.000 description 1
VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
229960002023 chloroprocaine Drugs 0.000 description 1
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
229960001231 choline Drugs 0.000 description 1
125000002676 chrysenyl group Chemical group C1(=CC=CC=2C3=CC=C4C=CC=CC4=C3C=CC12)* 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
238000000576 coating method Methods 0.000 description 1
229940075614 colloidal silicon dioxide Drugs 0.000 description 1
238000004040 coloring Methods 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
230000006957 competitive inhibition Effects 0.000 description 1
239000002299 complementary DNA Substances 0.000 description 1
229940126086 compound 21 Drugs 0.000 description 1
239000000356 contaminant Substances 0.000 description 1
238000013270 controlled release Methods 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
150000001913 cyanates Chemical class 0.000 description 1
WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
150000003997 cyclic ketones Chemical class 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001352 cyclobutyloxy group Chemical group C1(CCC1)O* 0.000 description 1
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
238000007405 data analysis Methods 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000013461 design Methods 0.000 description 1
230000000368 destabilizing effect Effects 0.000 description 1
238000001514 detection method Methods 0.000 description 1
235000019425 dextrin Nutrition 0.000 description 1
125000004663 dialkyl amino group Chemical group 0.000 description 1
125000005265 dialkylamine group Chemical group 0.000 description 1
150000004985 diamines Chemical class 0.000 description 1
125000005266 diarylamine group Chemical group 0.000 description 1
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
229940043237 diethanolamine Drugs 0.000 description 1
238000009792 diffusion process Methods 0.000 description 1
150000004683 dihydrates Chemical class 0.000 description 1
125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 description 1
125000001070 dihydroindolyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
VDQVEACBQKUUSU-UHFFFAOYSA-M disodium;sulfanide Chemical compound [Na+].[Na+].[SH-] VDQVEACBQKUUSU-UHFFFAOYSA-M 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000003651 drinking water Substances 0.000 description 1
235000020188 drinking water Nutrition 0.000 description 1
238000001647 drug administration Methods 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
RDYMFSUJUZBWLH-UHFFFAOYSA-N endosulfan Chemical compound C12COS(=O)OCC2C2(Cl)C(Cl)=C(Cl)C1(Cl)C2(Cl)Cl RDYMFSUJUZBWLH-UHFFFAOYSA-N 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
239000003623 enhancer Substances 0.000 description 1
238000007824 enzymatic assay Methods 0.000 description 1
239000002532 enzyme inhibitor Substances 0.000 description 1
150000002118 epoxides Chemical group 0.000 description 1
238000011067 equilibration Methods 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
125000001033 ether group Chemical group 0.000 description 1
UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
CGAJYBUEWWHRDO-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate;triphenylphosphane Chemical compound CCOC(=O)N=NC(=O)OCC.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 CGAJYBUEWWHRDO-UHFFFAOYSA-N 0.000 description 1
229940012017 ethylenediamine Drugs 0.000 description 1
OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
230000001747 exhibiting effect Effects 0.000 description 1
238000013265 extended release Methods 0.000 description 1
239000007888 film coating Substances 0.000 description 1
238000009501 film coating Methods 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
239000011888 foil Substances 0.000 description 1
235000013305 food Nutrition 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
239000012634 fragment Substances 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
230000006870 function Effects 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
239000007789 gas Substances 0.000 description 1
238000007429 general method Methods 0.000 description 1
229940074045 glyceryl distearate Drugs 0.000 description 1
229940075507 glyceryl monostearate Drugs 0.000 description 1
239000008187 granular material Substances 0.000 description 1
150000002357 guanidines Chemical class 0.000 description 1
150000003278 haem Chemical class 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
125000005252 haloacyl group Chemical group 0.000 description 1
125000002192 heptalenyl group Chemical group 0.000 description 1
150000002391 heterocyclic compounds Chemical group 0.000 description 1
125000004415 heterocyclylalkyl group Chemical group 0.000 description 1
238000004896 high resolution mass spectrometry Methods 0.000 description 1
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 1
150000007857 hydrazones Chemical class 0.000 description 1
150000002430 hydrocarbons Chemical group 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
125000004356 hydroxy functional group Chemical group O* 0.000 description 1
150000002443 hydroxylamines Chemical group 0.000 description 1
229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
230000002631 hypothermal effect Effects 0.000 description 1
229960001680 ibuprofen Drugs 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
150000003949 imides Chemical class 0.000 description 1
150000002466 imines Chemical class 0.000 description 1
125000001841 imino group Chemical group [H]N=* 0.000 description 1
230000003116 impacting effect Effects 0.000 description 1
239000007943 implant Substances 0.000 description 1
230000006872 improvement Effects 0.000 description 1
239000012535 impurity Substances 0.000 description 1
238000000126 in silico method Methods 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
125000003427 indacenyl group Chemical group 0.000 description 1
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical group CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
238000001802 infusion Methods 0.000 description 1
206010022437 insomnia Diseases 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
239000011630 iodine Substances 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
238000004255 ion exchange chromatography Methods 0.000 description 1
YAQXGBBDJYBXKL-UHFFFAOYSA-N iron(2+);1,10-phenanthroline;dicyanide Chemical compound [Fe+2].N#[C-].N#[C-].C1=CN=C2C3=NC=CC=C3C=CC2=C1.C1=CN=C2C3=NC=CC=C3C=CC2=C1 YAQXGBBDJYBXKL-UHFFFAOYSA-N 0.000 description 1
239000013038 irreversible inhibitor Substances 0.000 description 1
229960002725 isoflurane Drugs 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
230000002045 lasting effect Effects 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
229940067606 lecithin Drugs 0.000 description 1
239000002502 liposome Substances 0.000 description 1
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
239000011344 liquid material Substances 0.000 description 1
239000006193 liquid solution Substances 0.000 description 1
239000006194 liquid suspension Substances 0.000 description 1
238000000622 liquid--liquid extraction Methods 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
229910003002 lithium salt Inorganic materials 0.000 description 1
159000000002 lithium salts Chemical class 0.000 description 1
CCZVEWRRAVASGL-UHFFFAOYSA-N lithium;2-methanidylpropane Chemical compound [Li+].CC(C)[CH2-] CCZVEWRRAVASGL-UHFFFAOYSA-N 0.000 description 1
UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
210000001853 liver microsome Anatomy 0.000 description 1
210000003141 lower extremity Anatomy 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
239000006166 lysate Substances 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
239000001095 magnesium carbonate Substances 0.000 description 1
229910000021 magnesium carbonate Inorganic materials 0.000 description 1
235000014380 magnesium carbonate Nutrition 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
238000005259 measurement Methods 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
230000007721 medicinal effect Effects 0.000 description 1
239000002609 medium Substances 0.000 description 1
229960003194 meglumine Drugs 0.000 description 1
COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
239000002207 metabolite Substances 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
238000006263 metalation reaction Methods 0.000 description 1
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
RQGGBXUVWKHZCD-UHFFFAOYSA-N methyl 2-[hydroxy-(6-phenoxy-1,2,3,4-tetrahydronaphthalen-2-yl)methyl]-1,3-oxazole-5-carboxylate Chemical compound O1C(C(=O)OC)=CN=C1C(O)C1CC2=CC=C(OC=3C=CC=CC=3)C=C2CC1 RQGGBXUVWKHZCD-UHFFFAOYSA-N 0.000 description 1
WYDBDSDBIDKXAR-UHFFFAOYSA-N methyl 5-phenoxy-2,3-dihydro-1h-indene-2-carboxylate Chemical compound C1=C2CC(C(=O)OC)CC2=CC=C1OC1=CC=CC=C1 WYDBDSDBIDKXAR-UHFFFAOYSA-N 0.000 description 1
RUVQYUFOVXWESA-UHFFFAOYSA-N methyl 5-phenyl-2,3-dihydro-1h-indene-2-carboxylate Chemical compound C1=C2CC(C(=O)OC)CC2=CC=C1C1=CC=CC=C1 RUVQYUFOVXWESA-UHFFFAOYSA-N 0.000 description 1
FKSZWRASDUCCOB-UHFFFAOYSA-N methyl 5-phenylmethoxy-2,3-dihydro-1h-indene-2-carboxylate Chemical compound C1=C2CC(C(=O)OC)CC2=CC=C1OCC1=CC=CC=C1 FKSZWRASDUCCOB-UHFFFAOYSA-N 0.000 description 1
OFAIECRUWLFIBB-UHFFFAOYSA-N methyl 6-(trifluoromethylsulfonyloxy)-1,2,3,4-tetrahydronaphthalene-2-carboxylate Chemical compound FC(F)(F)S(=O)(=O)OC1=CC=C2CC(C(=O)OC)CCC2=C1 OFAIECRUWLFIBB-UHFFFAOYSA-N 0.000 description 1
ILQDKYQIZXNRCZ-UHFFFAOYSA-N methyl 6-[2-[[tert-butyl(dimethyl)silyl]oxy-(6-phenoxy-1,2,3,4-tetrahydronaphthalen-2-yl)methyl]-1,3-oxazol-5-yl]pyridine-2-carboxylate Chemical compound COC(=O)C1=CC=CC(C=2OC(=NC=2)C(O[Si](C)(C)C(C)(C)C)C2CC3=CC=C(OC=4C=CC=CC=4)C=C3CC2)=N1 ILQDKYQIZXNRCZ-UHFFFAOYSA-N 0.000 description 1
TWUXBVMXSBEKHA-UHFFFAOYSA-N methyl 6-chloropyridine-2-carboxylate Chemical compound COC(=O)C1=CC=CC(Cl)=N1 TWUXBVMXSBEKHA-UHFFFAOYSA-N 0.000 description 1
UYYYXEXMVFBJDR-UHFFFAOYSA-N methyl 6-phenylmethoxy-1,2,3,4-tetrahydronaphthalene-2-carboxylate Chemical compound C=1C=C2CC(C(=O)OC)CCC2=CC=1OCC1=CC=CC=C1 UYYYXEXMVFBJDR-UHFFFAOYSA-N 0.000 description 1
YMWUJEATGCHHMB-UHFFFAOYSA-N methylene chloride Substances ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 1
239000000693 micelle Substances 0.000 description 1
238000002156 mixing Methods 0.000 description 1
238000010513 modified Ullmann reaction Methods 0.000 description 1
239000003607 modifier Substances 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
125000002950 monocyclic group Chemical group 0.000 description 1
125000006682 monohaloalkyl group Chemical group 0.000 description 1
150000004682 monohydrates Chemical class 0.000 description 1
239000000178 monomer Substances 0.000 description 1
125000002757 morpholinyl group Chemical group 0.000 description 1
238000010172 mouse model Methods 0.000 description 1
WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
210000005036 nerve Anatomy 0.000 description 1
230000000926 neurological effect Effects 0.000 description 1
229960002715 nicotine Drugs 0.000 description 1
SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
150000002826 nitrites Chemical group 0.000 description 1
125000000018 nitroso group Chemical group N(=O)* 0.000 description 1
230000003040 nociceptive effect Effects 0.000 description 1
125000006574 non-aromatic ring group Chemical group 0.000 description 1
238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
230000001473 noxious effect Effects 0.000 description 1
229920001778 nylon Polymers 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
239000012053 oil suspension Substances 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
239000002997 ophthalmic solution Substances 0.000 description 1
229940054534 ophthalmic solution Drugs 0.000 description 1
238000005457 optimization Methods 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
125000000962 organic group Chemical group 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical group C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
150000002923 oximes Chemical class 0.000 description 1
125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 1
239000003002 pH adjusting agent Substances 0.000 description 1
239000005022 packaging material Substances 0.000 description 1
230000003119 painkilling effect Effects 0.000 description 1
229960005489 paracetamol Drugs 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
230000007170 pathology Effects 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
239000001814 pectin Substances 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 1
230000003285 pharmacodynamic effect Effects 0.000 description 1
125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
235000011007 phosphoric acid Nutrition 0.000 description 1
150000003016 phosphoric acids Chemical class 0.000 description 1
239000002504 physiological saline solution Substances 0.000 description 1
PJPOCNJHYFUPCE-UHFFFAOYSA-N picen-1-ol Chemical compound C1=CC=CC2=C(C=CC=3C4=CC=C5C=CC=C(C=35)O)C4=CC=C21 PJPOCNJHYFUPCE-UHFFFAOYSA-N 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
239000004014 plasticizer Substances 0.000 description 1
239000004417 polycarbonate Substances 0.000 description 1
229920000515 polycarbonate Polymers 0.000 description 1
125000006684 polyhaloalkyl group Polymers 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
239000004926 polymethyl methacrylate Substances 0.000 description 1
229920001155 polypropylene Polymers 0.000 description 1
229920001296 polysiloxane Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
208000028173 post-traumatic stress disease Diseases 0.000 description 1
CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
150000003138 primary alcohols Chemical class 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
150000003858 primary carboxamides Chemical group 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
230000008569 process Effects 0.000 description 1
230000000770 proinflammatory effect Effects 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
150000003217 pyrazoles Chemical class 0.000 description 1
125000001725 pyrenyl group Chemical group 0.000 description 1
125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
125000004941 pyridazin-5-yl group Chemical group N1=NC=CC(=C1)* 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000005493 quinolyl group Chemical group 0.000 description 1
239000011535 reaction buffer Substances 0.000 description 1
239000000018 receptor agonist Substances 0.000 description 1
229940044601 receptor agonist Drugs 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
230000008521 reorganization Effects 0.000 description 1
238000010405 reoxidation reaction Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
238000004366 reverse phase liquid chromatography Methods 0.000 description 1
230000006965 reversible inhibition Effects 0.000 description 1
239000013037 reversible inhibitor Substances 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
229960001860 salicylate Drugs 0.000 description 1
239000012266 salt solution Substances 0.000 description 1
238000005070 sampling Methods 0.000 description 1
238000007127 saponification reaction Methods 0.000 description 1
HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
238000007789 sealing Methods 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
230000001624 sedative effect Effects 0.000 description 1
239000012056 semi-solid material Substances 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
235000012239 silicon dioxide Nutrition 0.000 description 1
238000001542 size-exclusion chromatography Methods 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
229910052979 sodium sulfide Inorganic materials 0.000 description 1
239000011343 solid material Substances 0.000 description 1
238000000638 solvent extraction Methods 0.000 description 1
210000001032 spinal nerve Anatomy 0.000 description 1
239000007921 spray Substances 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
238000003860 storage Methods 0.000 description 1
238000000547 structure data Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 1
125000001174 sulfone group Chemical group 0.000 description 1
125000003375 sulfoxide group Chemical group 0.000 description 1
125000005555 sulfoximide group Chemical group 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
230000005469 synchrotron radiation Effects 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
QYTRLCUGXDHBKF-UHFFFAOYSA-N tert-butyl-[(5-iodo-1,3-oxazol-2-yl)-(6-phenylmethoxy-1,2,3,4-tetrahydronaphthalen-2-yl)methoxy]-dimethylsilane Chemical compound N=1C=C(I)OC=1C(O[Si](C)(C)C(C)(C)C)C(CC1=CC=2)CCC1=CC=2OCC1=CC=CC=C1 QYTRLCUGXDHBKF-UHFFFAOYSA-N 0.000 description 1
DJXJZROPUJQTMP-UHFFFAOYSA-N tert-butyl-[2,3-dihydro-1h-inden-2-yl(1,3-oxazol-2-yl)methoxy]-dimethylsilane Chemical compound C1C2=CC=CC=C2CC1C(O[Si](C)(C)C(C)(C)C)C1=NC=CO1 DJXJZROPUJQTMP-UHFFFAOYSA-N 0.000 description 1
GKXCNMFAHRYOIB-UHFFFAOYSA-N tert-butyl-[2,3-dihydro-1h-inden-2-yl-(5-pyridin-2-yl-1,3-oxazol-2-yl)methoxy]-dimethylsilane Chemical compound C1C2=CC=CC=C2CC1C(O[Si](C)(C)C(C)(C)C)C(O1)=NC=C1C1=CC=CC=N1 GKXCNMFAHRYOIB-UHFFFAOYSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
125000001302 tertiary amino group Chemical group 0.000 description 1
150000005621 tetraalkylammonium salts Chemical class 0.000 description 1
125000001935 tetracenyl group Chemical group C1(=CC=CC2=CC3=CC4=CC=CC=C4C=C3C=C12)* 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
125000004149 thio group Chemical group *S* 0.000 description 1
125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
125000000101 thioether group Chemical group 0.000 description 1
125000003396 thiol group Chemical group [H]S* 0.000 description 1
230000036962 time dependent Effects 0.000 description 1
230000000451 tissue damage Effects 0.000 description 1
231100000827 tissue damage Toxicity 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
231100000440 toxicity profile Toxicity 0.000 description 1
229910052723 transition metal Inorganic materials 0.000 description 1
230000032258 transport Effects 0.000 description 1
238000011269 treatment regimen Methods 0.000 description 1
150000003626 triacylglycerols Chemical class 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
125000004954 trialkylamino group Chemical group 0.000 description 1
125000005259 triarylamine group Chemical group 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical class CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
SZYJELPVAFJOGJ-UHFFFAOYSA-N trimethylamine hydrochloride Chemical compound Cl.CN(C)C SZYJELPVAFJOGJ-UHFFFAOYSA-N 0.000 description 1
125000003960 triphenylenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C3=CC=CC=C3C12)* 0.000 description 1
GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
210000000689 upper leg Anatomy 0.000 description 1
150000003672 ureas Chemical class 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
230000003442 weekly effect Effects 0.000 description 1
239000000811 xylitol Substances 0.000 description 1
HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
235000010447 xylitol Nutrition 0.000 description 1
229960002675 xylitol Drugs 0.000 description 1
150000003751 zinc Chemical class 0.000 description 1