JP2017519025A - チオフェン−２−イル−ピリジン−２−イル−１ｈ−ピラゾール−４−カルボン酸誘導体、および可溶性グアニル酸シクラーゼ活性化剤としてのその使用 - Google Patents

Info

Publication number

JP2017519025A

JP2017519025A JP2016574921A JP2016574921A JP2017519025A JP 2017519025 A JP2017519025 A JP 2017519025A JP 2016574921 A JP2016574921 A JP 2016574921A JP 2016574921 A JP2016574921 A JP 2016574921A JP 2017519025 A JP2017519025 A JP 2017519025A

Authority

JP

Japan

Prior art keywords

methyl

alkyl

trifluoromethyl

mmol

pyrazole

Prior art date

2014-07-02

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Withdrawn

Links

• Espacenet
• Global Dossier
• Discuss

• 102000007637 Soluble Guanylyl Cyclase Human genes 0.000 title description 42
• 108010007205 Soluble Guanylyl Cyclase Proteins 0.000 title description 42
• ADKNNQOWOFNISC-UHFFFAOYSA-N 1-pyridin-2-yl-3-thiophen-2-ylpyrazole-4-carboxylic acid Chemical class OC(=O)C1=CN(C=2N=CC=CC=2)N=C1C1=CC=CS1 ADKNNQOWOFNISC-UHFFFAOYSA-N 0.000 title 1
• 229940126514 guanylate cyclase activator Drugs 0.000 title 1
• 239000003119 guanylate cyclase activator Substances 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 339
• 150000003839 salts Chemical class 0.000 claims abstract description 41
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 20
• -1 C 1 -C 4 alkyl Chemical group 0.000 claims description 108
• 238000000034 method Methods 0.000 claims description 68
• 229910052739 hydrogen Inorganic materials 0.000 claims description 61
• 239000001257 hydrogen Substances 0.000 claims description 58
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 38
• 150000002431 hydrogen Chemical group 0.000 claims description 37
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 35
• 230000004410 intraocular pressure Effects 0.000 claims description 32
• 208000010412 Glaucoma Diseases 0.000 claims description 31
• 229920006395 saturated elastomer Polymers 0.000 claims description 27
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 25
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 21
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
• 239000003814 drug Substances 0.000 claims description 19
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 18
• 229910052736 halogen Inorganic materials 0.000 claims description 18
• 150000002367 halogens Chemical class 0.000 claims description 18
• 239000003795 chemical substances by application Substances 0.000 claims description 17
• 229910052760 oxygen Inorganic materials 0.000 claims description 16
• 229910052757 nitrogen Inorganic materials 0.000 claims description 15
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 13
• 229940124597 therapeutic agent Drugs 0.000 claims description 13
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
• 238000002347 injection Methods 0.000 claims description 12
• 239000007924 injection Substances 0.000 claims description 12
• 230000000699 topical effect Effects 0.000 claims description 12
• 125000000623 heterocyclic group Chemical group 0.000 claims description 11
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 10
• 125000005843 halogen group Chemical group 0.000 claims description 10
• 125000005842 heteroatom Chemical group 0.000 claims description 10
• UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 10
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
• 125000001072 heteroaryl group Chemical group 0.000 claims description 7
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 7
• 229910052717 sulfur Inorganic materials 0.000 claims description 7
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
• 125000000217 alkyl group Chemical group 0.000 claims description 5
• 239000002590 phosphodiesterase V inhibitor Substances 0.000 claims description 5
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 4
• 239000000556 agonist Substances 0.000 claims description 4
• 239000003489 carbonate dehydratase inhibitor Substances 0.000 claims description 4
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
• 125000004193 piperazinyl group Chemical group 0.000 claims description 4
• 125000003386 piperidinyl group Chemical group 0.000 claims description 4
• 125000006413 ring segment Chemical group 0.000 claims description 4
• BNRNXUUZRGQAQC-UHFFFAOYSA-N sildenafil Chemical compound CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 BNRNXUUZRGQAQC-UHFFFAOYSA-N 0.000 claims description 4
• 229940122072 Carbonic anhydrase inhibitor Drugs 0.000 claims description 3
• 239000002876 beta blocker Substances 0.000 claims description 3
• 229940097320 beta blocking agent Drugs 0.000 claims description 3
• 239000004090 neuroprotective agent Substances 0.000 claims description 3
• 238000007911 parenteral administration Methods 0.000 claims description 3
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
• 150000003180 prostaglandins Chemical class 0.000 claims description 3
• 210000003786 sclera Anatomy 0.000 claims description 3
• SECKRCOLJRRGGV-UHFFFAOYSA-N Vardenafil Chemical compound CCCC1=NC(C)=C(C(N=2)=O)N1NC=2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(CC)CC1 SECKRCOLJRRGGV-UHFFFAOYSA-N 0.000 claims description 2
• 125000003545 alkoxy group Chemical group 0.000 claims description 2
• 125000005002 aryl methyl group Chemical group 0.000 claims description 2
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 2
• 238000007918 intramuscular administration Methods 0.000 claims description 2
• 238000001990 intravenous administration Methods 0.000 claims description 2
• 229960003310 sildenafil Drugs 0.000 claims description 2
• 238000007920 subcutaneous administration Methods 0.000 claims description 2
• 229960000835 tadalafil Drugs 0.000 claims description 2
• IEHKWSGCTWLXFU-IIBYNOLFSA-N tadalafil Chemical compound C1=C2OCOC2=CC([C@@H]2C3=C([C]4C=CC=CC4=N3)C[C@H]3N2C(=O)CN(C3=O)C)=C1 IEHKWSGCTWLXFU-IIBYNOLFSA-N 0.000 claims description 2
• 229960002381 vardenafil Drugs 0.000 claims description 2
• 230000000394 mitotic effect Effects 0.000 claims 1
• 238000004519 manufacturing process Methods 0.000 abstract description 8
• 230000001225 therapeutic effect Effects 0.000 abstract description 5
• 239000013543 active substance Substances 0.000 abstract 1
• 239000000543 intermediate Substances 0.000 description 296
• 239000000203 mixture Substances 0.000 description 290
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 258
• 235000019439 ethyl acetate Nutrition 0.000 description 128
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 122
• 239000000243 solution Substances 0.000 description 92
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 88
• 239000000460 chlorine Substances 0.000 description 87
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 86
• 239000000741 silica gel Substances 0.000 description 68
• 229910002027 silica gel Inorganic materials 0.000 description 68
• 238000003818 flash chromatography Methods 0.000 description 62
• WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 62
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 58
• ZMXDDKWLCZADIW-UHFFFAOYSA-N Vilsmeier-Haack reagent Natural products CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 56
• 238000006243 chemical reaction Methods 0.000 description 55
• 239000012044 organic layer Substances 0.000 description 54
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
• 239000002904 solvent Substances 0.000 description 48
• 238000011282 treatment Methods 0.000 description 43
• 239000011541 reaction mixture Substances 0.000 description 42
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 41
• 239000011734 sodium Substances 0.000 description 39
• 238000002360 preparation method Methods 0.000 description 38
• 238000005481 NMR spectroscopy Methods 0.000 description 37
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 37
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 34
• 235000002639 sodium chloride Nutrition 0.000 description 34
• MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 32
• 239000012267 brine Substances 0.000 description 32
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 32
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 31
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
• 239000007858 starting material Substances 0.000 description 28
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 26
• 201000010099 disease Diseases 0.000 description 24
• 239000000725 suspension Substances 0.000 description 24
• 229940125526 sGC activator Drugs 0.000 description 23
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
• 239000002253 acid Substances 0.000 description 20
• 239000000706 filtrate Substances 0.000 description 19
• 238000003786 synthesis reaction Methods 0.000 description 19
• 239000002585 base Substances 0.000 description 18
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 17
• 230000015572 biosynthetic process Effects 0.000 description 17
• 229910052805 deuterium Inorganic materials 0.000 description 17
• 239000000047 product Substances 0.000 description 16
• MCLKZJLGDFGFLI-UHFFFAOYSA-N 1-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound OC(=O)C=1C=NN(C(F)(F)F)C=1 MCLKZJLGDFGFLI-UHFFFAOYSA-N 0.000 description 15
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 15
• 238000004007 reversed phase HPLC Methods 0.000 description 15
• 239000012190 activator Substances 0.000 description 14
• 230000000694 effects Effects 0.000 description 14
• 150000001412 amines Chemical class 0.000 description 13
• 208000035475 disorder Diseases 0.000 description 13
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
• 238000005160 1H NMR spectroscopy Methods 0.000 description 12
• ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 12
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 12
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 11
• 239000012298 atmosphere Substances 0.000 description 11
• ZOOGRGPOEVQQDX-KHLHZJAASA-N cyclic guanosine monophosphate Chemical compound C([C@H]1O2)O[P@](O)(=O)O[C@@H]1[C@H](O)[C@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-KHLHZJAASA-N 0.000 description 11
• 238000005984 hydrogenation reaction Methods 0.000 description 11
• DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 11
• 239000003755 preservative agent Substances 0.000 description 11
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Substances BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 10
• 210000004027 cell Anatomy 0.000 description 10
• 238000001914 filtration Methods 0.000 description 10
• 238000010348 incorporation Methods 0.000 description 10
• 239000010410 layer Substances 0.000 description 10
• 239000012071 phase Substances 0.000 description 10
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
• 239000007787 solid Substances 0.000 description 10
• 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 10
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 9
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• 230000004913 activation Effects 0.000 description 9
• 239000007864 aqueous solution Substances 0.000 description 9
• 239000003054 catalyst Substances 0.000 description 9
• 239000002609 medium Substances 0.000 description 9
• 230000002829 reductive effect Effects 0.000 description 9
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 8
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
• 239000004480 active ingredient Substances 0.000 description 8
• 239000013078 crystal Substances 0.000 description 8
• 239000011591 potassium Substances 0.000 description 8
• 229910052700 potassium Inorganic materials 0.000 description 8
• 238000007127 saponification reaction Methods 0.000 description 8
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 7
• PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 7
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 7
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 7
• 230000008901 benefit Effects 0.000 description 7
• IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 7
• 239000000284 extract Substances 0.000 description 7
• 150000003278 haem Chemical class 0.000 description 7
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 7
• 230000003287 optical effect Effects 0.000 description 7
• 239000002244 precipitate Substances 0.000 description 7
• 230000009466 transformation Effects 0.000 description 7
• RTMMSCJWQYWMNK-UHFFFAOYSA-N 2,2,2-trifluoroethyl trifluoromethanesulfonate Chemical compound FC(F)(F)COS(=O)(=O)C(F)(F)F RTMMSCJWQYWMNK-UHFFFAOYSA-N 0.000 description 6
• IWJGMJHAIUBWKT-UHFFFAOYSA-N 4-bromo-2-methylphenol Chemical compound CC1=CC(Br)=CC=C1O IWJGMJHAIUBWKT-UHFFFAOYSA-N 0.000 description 6
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
• 230000005526 G1 to G0 transition Effects 0.000 description 6
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
• 230000008859 change Effects 0.000 description 6
• 239000003153 chemical reaction reagent Substances 0.000 description 6
• 238000002425 crystallisation Methods 0.000 description 6
• 230000008025 crystallization Effects 0.000 description 6
• 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 6
• PSGHZLMVOUCELD-UHFFFAOYSA-N ethyl 1-[6-[3-[(2-methyl-4-piperidin-4-ylphenoxy)methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound CC1=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)OCC)C=CC(=C1)C1CCNCC1 PSGHZLMVOUCELD-UHFFFAOYSA-N 0.000 description 6
• YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 6
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
• 235000011056 potassium acetate Nutrition 0.000 description 6
• 238000003756 stirring Methods 0.000 description 6
• 210000001519 tissue Anatomy 0.000 description 6
• OZMLUMPWPFZWTP-UHFFFAOYSA-N 2-(tributyl-$l^{5}-phosphanylidene)acetonitrile Chemical compound CCCCP(CCCC)(CCCC)=CC#N OZMLUMPWPFZWTP-UHFFFAOYSA-N 0.000 description 5
• 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 5
• DYHSDKLCOJIUFX-UHFFFAOYSA-N Di-tert-butyl dicarbonate Substances CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 5
• 102000004190 Enzymes Human genes 0.000 description 5
• 108090000790 Enzymes Proteins 0.000 description 5
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 5
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
• 239000007821 HATU Substances 0.000 description 5
• 206010030348 Open-Angle Glaucoma Diseases 0.000 description 5
• 101150003085 Pdcl gene Proteins 0.000 description 5
• 150000007513 acids Chemical class 0.000 description 5
• 125000004429 atom Chemical group 0.000 description 5
• YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 5
• 238000004128 high performance liquid chromatography Methods 0.000 description 5
• 238000000338 in vitro Methods 0.000 description 5
• 238000001727 in vivo Methods 0.000 description 5
• 239000000314 lubricant Substances 0.000 description 5
• 229910000027 potassium carbonate Inorganic materials 0.000 description 5
• 201000006366 primary open angle glaucoma Diseases 0.000 description 5
• VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 5
• 229940127296 soluble guanylate cyclase stimulator Drugs 0.000 description 5
• 239000012453 solvate Substances 0.000 description 5
• 239000011877 solvent mixture Substances 0.000 description 5
• 239000003381 stabilizer Substances 0.000 description 5
• 239000000126 substance Substances 0.000 description 5
• 238000004808 supercritical fluid chromatography Methods 0.000 description 5
• CUUQNEXFGPWNPJ-UHFFFAOYSA-N tert-butyl 4-(4-hydroxyphenyl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C1=CC=C(O)C=C1 CUUQNEXFGPWNPJ-UHFFFAOYSA-N 0.000 description 5
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
• LZMHWZHOZLVYDL-UHFFFAOYSA-N 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one Chemical compound C1=CC=C2N3C(=O)ON=C3C=NC2=C1 LZMHWZHOZLVYDL-UHFFFAOYSA-N 0.000 description 4
• ZPWPMAAPQZXPDD-UHFFFAOYSA-N 2-bromo-3-(bromomethyl)thiophene Chemical compound BrCC=1C=CSC=1Br ZPWPMAAPQZXPDD-UHFFFAOYSA-N 0.000 description 4
• KVVDRQDTODKIJD-UHFFFAOYSA-N 2-cyclopropylacetic acid Chemical compound OC(=O)CC1CC1 KVVDRQDTODKIJD-UHFFFAOYSA-N 0.000 description 4
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
• 206010020772 Hypertension Diseases 0.000 description 4
• 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 4
• 241000124008 Mammalia Species 0.000 description 4
• 206010030043 Ocular hypertension Diseases 0.000 description 4
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
• 229920002472 Starch Polymers 0.000 description 4
• 150000008065 acid anhydrides Chemical class 0.000 description 4
• 239000000908 ammonium hydroxide Substances 0.000 description 4
• 210000001742 aqueous humor Anatomy 0.000 description 4
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
• 239000000872 buffer Substances 0.000 description 4
• 229910052799 carbon Inorganic materials 0.000 description 4
• 238000002648 combination therapy Methods 0.000 description 4
• 229940079593 drug Drugs 0.000 description 4
• 239000003937 drug carrier Substances 0.000 description 4
• 239000000839 emulsion Substances 0.000 description 4
• 150000002148 esters Chemical class 0.000 description 4
• 235000019441 ethanol Nutrition 0.000 description 4
• 239000003889 eye drop Substances 0.000 description 4
• 229940012356 eye drops Drugs 0.000 description 4
• 150000004677 hydrates Chemical class 0.000 description 4
• 150000003840 hydrochlorides Chemical class 0.000 description 4
• 230000007062 hydrolysis Effects 0.000 description 4
• 238000006460 hydrolysis reaction Methods 0.000 description 4
• GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 4
• 230000036542 oxidative stress Effects 0.000 description 4
• 229910052763 palladium Inorganic materials 0.000 description 4
• MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 4
• 150000002989 phenols Chemical class 0.000 description 4
• NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 4
• 230000008569 process Effects 0.000 description 4
• RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 4
• WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 4
• 230000009467 reduction Effects 0.000 description 4
• 238000006722 reduction reaction Methods 0.000 description 4
• 238000010992 reflux Methods 0.000 description 4
• 229910052708 sodium Inorganic materials 0.000 description 4
• 239000012279 sodium borohydride Substances 0.000 description 4
• 229910000033 sodium borohydride Inorganic materials 0.000 description 4
• 229910000029 sodium carbonate Inorganic materials 0.000 description 4
• 239000007921 spray Substances 0.000 description 4
• 239000008107 starch Substances 0.000 description 4
• 235000019698 starch Nutrition 0.000 description 4
• 125000001424 substituent group Chemical group 0.000 description 4
• 208000024891 symptom Diseases 0.000 description 4
• VVDCRJGWILREQH-UHFFFAOYSA-N tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC(B2OC(C)(C)C(C)(C)O2)=C1 VVDCRJGWILREQH-UHFFFAOYSA-N 0.000 description 4
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
• ZPHGMBGIFODUMF-UHFFFAOYSA-N thiophen-2-ylmethanol Chemical class OCC1=CC=CS1 ZPHGMBGIFODUMF-UHFFFAOYSA-N 0.000 description 4
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
• 125000005270 trialkylamine group Chemical group 0.000 description 4
• 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 4
• PBIMIGNDTBRRPI-UHFFFAOYSA-N trifluoro borate Chemical compound FOB(OF)OF PBIMIGNDTBRRPI-UHFFFAOYSA-N 0.000 description 4
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
• 230000004382 visual function Effects 0.000 description 4
• PQMFVUNERGGBPG-UHFFFAOYSA-N (6-bromopyridin-2-yl)hydrazine Chemical compound NNC1=CC=CC(Br)=N1 PQMFVUNERGGBPG-UHFFFAOYSA-N 0.000 description 3
• WJUBBZGKAIMZBR-UHFFFAOYSA-N 1-[6-[3-[2-[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylphenyl]ethyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(CCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)C WJUBBZGKAIMZBR-UHFFFAOYSA-N 0.000 description 3
• CIPNFRLWJBKZJA-UHFFFAOYSA-N 1-[6-[3-[[2-methyl-4-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]phenoxy]methyl]-5-propan-2-ylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C(C)(C)C1=CC(=C(S1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)O)COC1=C(C=C(C=C1)C1CCN(CC1)CC(F)(F)F)C CIPNFRLWJBKZJA-UHFFFAOYSA-N 0.000 description 3
• XYEMKCOHHAXZCO-UHFFFAOYSA-N 1-[6-[3-[[2-methyl-4-[1-(pyrrolidine-3-carbonyl)piperidin-4-yl]phenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound CC1=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=CC(=C1)C1CCN(CC1)C(=O)C1CNCC1 XYEMKCOHHAXZCO-UHFFFAOYSA-N 0.000 description 3
• ZDFBKZUDCQQKAC-UHFFFAOYSA-N 1-bromo-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Br)C=C1 ZDFBKZUDCQQKAC-UHFFFAOYSA-N 0.000 description 3
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
• IMBBXSASDSZJSX-UHFFFAOYSA-N 4-Carboxypyrazole Chemical compound OC(=O)C=1C=NNC=1 IMBBXSASDSZJSX-UHFFFAOYSA-N 0.000 description 3
• VHKMTORCXXPIFI-UHFFFAOYSA-N 5-(trifluoromethyl)-1h-pyrazole-4-carboxylic acid Chemical compound OC(=O)C=1C=NNC=1C(F)(F)F VHKMTORCXXPIFI-UHFFFAOYSA-N 0.000 description 3
• MMARFGDTMJBIBK-UHFFFAOYSA-N 5-bromo-2-methoxy-1,3-dimethylbenzene Chemical compound COC1=C(C)C=C(Br)C=C1C MMARFGDTMJBIBK-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-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
• 201000001320 Atherosclerosis Diseases 0.000 description 3
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
• 241000282472 Canis lupus familiaris Species 0.000 description 3
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
• 208000010228 Erectile Dysfunction Diseases 0.000 description 3
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
• 239000012981 Hank's balanced salt solution Substances 0.000 description 3
• 241000282412 Homo Species 0.000 description 3
• 229920002153 Hydroxypropyl cellulose Polymers 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
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
• 241001465754 Metazoa Species 0.000 description 3
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
• 206010067013 Normal tension glaucoma Diseases 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• 229920002125 Sokalan® Polymers 0.000 description 3
• 230000003213 activating effect Effects 0.000 description 3
• 235000010443 alginic acid Nutrition 0.000 description 3
• 229920000615 alginic acid Polymers 0.000 description 3
• 230000029936 alkylation Effects 0.000 description 3
• 238000005804 alkylation reaction Methods 0.000 description 3
• 239000003963 antioxidant agent Substances 0.000 description 3
• 235000006708 antioxidants Nutrition 0.000 description 3
• 238000003556 assay Methods 0.000 description 3
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
• 239000011230 binding agent Substances 0.000 description 3
• 150000001735 carboxylic acids Chemical class 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 239000003086 colorant Substances 0.000 description 3
• 238000010511 deprotection reaction Methods 0.000 description 3
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 3
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
• AXAZMDOAUQTMOW-UHFFFAOYSA-N dimethylzinc Chemical compound C[Zn]C AXAZMDOAUQTMOW-UHFFFAOYSA-N 0.000 description 3
• IXKCRTQEEQPAKY-UHFFFAOYSA-N ethyl 1-[6-[3-(hydroxymethyl)-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound OCC1=C(SC(=C1)C)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)OCC IXKCRTQEEQPAKY-UHFFFAOYSA-N 0.000 description 3
• 238000001704 evaporation Methods 0.000 description 3
• 230000008020 evaporation Effects 0.000 description 3
• 238000002474 experimental method Methods 0.000 description 3
• 239000000796 flavoring agent Substances 0.000 description 3
• 229910052731 fluorine Inorganic materials 0.000 description 3
• 235000003599 food sweetener Nutrition 0.000 description 3
• 238000009472 formulation Methods 0.000 description 3
• 239000000499 gel Substances 0.000 description 3
• 239000007903 gelatin capsule Substances 0.000 description 3
• 239000001863 hydroxypropyl cellulose Substances 0.000 description 3
• 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 201000001881 impotence Diseases 0.000 description 3
• 230000000155 isotopic effect Effects 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• 230000000670 limiting effect Effects 0.000 description 3
• 201000002978 low tension glaucoma Diseases 0.000 description 3
• 235000001055 magnesium Nutrition 0.000 description 3
• 239000011777 magnesium Substances 0.000 description 3
• 229910052749 magnesium Inorganic materials 0.000 description 3
• 230000014759 maintenance of location Effects 0.000 description 3
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
• 239000003921 oil Substances 0.000 description 3
• 230000003647 oxidation Effects 0.000 description 3
• 238000007254 oxidation reaction Methods 0.000 description 3
• 230000001575 pathological effect Effects 0.000 description 3
• 239000008177 pharmaceutical agent Substances 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• 230000002335 preservative effect Effects 0.000 description 3
• 238000000746 purification Methods 0.000 description 3
• 239000003590 rho kinase inhibitor Substances 0.000 description 3
• VNFWTIYUKDMAOP-UHFFFAOYSA-N sphos Chemical group COC1=CC=CC(OC)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 VNFWTIYUKDMAOP-UHFFFAOYSA-N 0.000 description 3
• 239000004094 surface-active agent Substances 0.000 description 3
• 239000003765 sweetening agent Substances 0.000 description 3
• MLMJILGYEYTGNT-UHFFFAOYSA-N tert-butyl 4-(3-methyl-4-nitrophenyl)-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1=C([N+]([O-])=O)C(C)=CC(C=2CCN(CC=2)C(=O)OC(C)(C)C)=C1 MLMJILGYEYTGNT-UHFFFAOYSA-N 0.000 description 3
• ZFZSPLFKSLVQAX-UHFFFAOYSA-N tert-butyl 4-(4-hydroxy-3-methylphenyl)piperidine-1-carboxylate Chemical compound OC1=C(C=C(C=C1)C1CCN(CC1)C(=O)OC(C)(C)C)C ZFZSPLFKSLVQAX-UHFFFAOYSA-N 0.000 description 3
• QCIWZIYBBNEPKB-UHFFFAOYSA-N tert-butyl(dimethyl)silane Chemical compound C[SiH](C)C(C)(C)C QCIWZIYBBNEPKB-UHFFFAOYSA-N 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
• 238000002560 therapeutic procedure Methods 0.000 description 3
• DLQYXUGCCKQSRJ-UHFFFAOYSA-N tris(furan-2-yl)phosphane Chemical compound C1=COC(P(C=2OC=CC=2)C=2OC=CC=2)=C1 DLQYXUGCCKQSRJ-UHFFFAOYSA-N 0.000 description 3
• 239000003981 vehicle Substances 0.000 description 3
• NAVPHGRFAKSAOL-UHFFFAOYSA-N (2-chloro-6-methoxypyridin-3-yl)boronic acid Chemical compound COC1=CC=C(B(O)O)C(Cl)=N1 NAVPHGRFAKSAOL-UHFFFAOYSA-N 0.000 description 2
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 2
• HYXMHAHVUFTVFZ-UHFFFAOYSA-N (3-formylthiophen-2-yl)boronic acid Chemical compound OB(O)C=1SC=CC=1C=O HYXMHAHVUFTVFZ-UHFFFAOYSA-N 0.000 description 2
• QNIVKTTWBMFSBR-UHFFFAOYSA-J 1,2,3,4,5-pentamethylcyclopentane;rhodium(2+);tetrachloride Chemical compound Cl[Rh]Cl.Cl[Rh]Cl.C[C]1[C](C)[C](C)[C](C)[C]1C.C[C]1[C](C)[C](C)[C](C)[C]1C QNIVKTTWBMFSBR-UHFFFAOYSA-J 0.000 description 2
• NCADHSLPNSTDMJ-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxycarbonyl]azetidine-3-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CC(C(O)=O)C1 NCADHSLPNSTDMJ-UHFFFAOYSA-N 0.000 description 2
• HRMRQBJUFWFQLX-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-3-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC(C(O)=O)C1 HRMRQBJUFWFQLX-UHFFFAOYSA-N 0.000 description 2
• WDFNDIYLWSYHKB-UHFFFAOYSA-N 1-[4-(4-hydroxy-3,5-dimethylphenyl)piperidin-1-yl]propan-1-one Chemical compound OC1=C(C=C(C=C1C)C1CCN(CC1)C(CC)=O)C WDFNDIYLWSYHKB-UHFFFAOYSA-N 0.000 description 2
• JIXSYCMWYPBHSP-UHFFFAOYSA-N 1-[6-[3-[2-[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylphenyl]ethyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(CCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)C JIXSYCMWYPBHSP-UHFFFAOYSA-N 0.000 description 2
• FTKYPWRMPVNWFB-UHFFFAOYSA-N 1-[6-[3-[2-[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]phenyl]ethyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC=C(CCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1 FTKYPWRMPVNWFB-UHFFFAOYSA-N 0.000 description 2
• VGSHLDMSRPXBDM-UHFFFAOYSA-N 1-[6-[3-[[2-methyl-4-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]phenoxy]methyl]-5-propylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound CC1=C(OCC2=C(SC(=C2)CCC)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=CC(=C1)C1CCN(CC1)CC(F)(F)F VGSHLDMSRPXBDM-UHFFFAOYSA-N 0.000 description 2
• RFXYOJDMMPINFS-UHFFFAOYSA-N 1-[6-[3-[[2-methyl-4-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]phenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound CC1=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=CC(=C1)C1CCN(CC1)CC(F)(F)F RFXYOJDMMPINFS-UHFFFAOYSA-N 0.000 description 2
• JTOBYTIJKSQNDN-UHFFFAOYSA-N 1-[6-[3-[[4-(1-methoxycarbonylpiperidin-4-yl)-2-methylphenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound COC(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)C JTOBYTIJKSQNDN-UHFFFAOYSA-N 0.000 description 2
• OTTWDFAXZUNFEG-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(2,3-dihydroxypropanoyl)piperidin-4-yl]-3-ethylphenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound OC(C(=O)N1CCC(CC1)C1=C(C=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)CC)CO OTTWDFAXZUNFEG-UHFFFAOYSA-N 0.000 description 2
• YGKMOWMXAIFLOV-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(azetidine-3-carbonyl)piperidin-4-yl]-2-methylphenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound N1CC(C1)C(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)C YGKMOWMXAIFLOV-UHFFFAOYSA-N 0.000 description 2
• KZJMTLAPNGLEFJ-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylanilino]methyl]thiophen-2-yl]pyridin-2-yl]-5-methylpyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(C=C1)NCC1=C(SC=C1)C1=CC=CC(=N1)N1N=CC(=C1C)C(=O)O)C KZJMTLAPNGLEFJ-UHFFFAOYSA-N 0.000 description 2
• AIRIZDWADNYHJQ-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylphenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)C AIRIZDWADNYHJQ-UHFFFAOYSA-N 0.000 description 2
• RDRNSWXCVKPZHA-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-3-ethylanilino]methyl]-4-(trifluoromethyl)thiophen-2-yl]pyridin-2-yl]-5-ethylpyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=C(C=C(C=C1)NCC1=C(SC=C1C(F)(F)F)C1=CC=CC(=N1)N1N=CC(=C1CC)C(=O)O)CC RDRNSWXCVKPZHA-UHFFFAOYSA-N 0.000 description 2
• GHZGBBPCTNNUCH-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-3-ethylanilino]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=C(C=C(C=C1)NCC1=C(SC(=C1)C)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)O)CC GHZGBBPCTNNUCH-UHFFFAOYSA-N 0.000 description 2
• FCZLWWFGTIZQSN-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-3-ethylanilino]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-ethylpyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=C(C=C(C=C1)NCC1=C(SC(=C1)C)C1=CC=CC(=N1)N1N=CC(=C1CC)C(=O)O)CC FCZLWWFGTIZQSN-UHFFFAOYSA-N 0.000 description 2
• HZLAHOYQWOBKGM-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]anilino]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC=C(C=C1)NCC1=C(SC=C1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)O HZLAHOYQWOBKGM-UHFFFAOYSA-N 0.000 description 2
• KYAYGYYFCXFDGS-UHFFFAOYSA-N 1-[6-[5-methyl-3-[2-[2-methyl-4-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]phenyl]ethyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C(C)(C)(C)OC(=O)N1CCC(CC1)C1=CC(=C(CCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)C KYAYGYYFCXFDGS-UHFFFAOYSA-N 0.000 description 2
• SJZKULRDWHPHGG-UHFFFAOYSA-N 1-benzylpiperidin-4-one Chemical compound C1CC(=O)CCN1CC1=CC=CC=C1 SJZKULRDWHPHGG-UHFFFAOYSA-N 0.000 description 2
• KRTVZBZIKULDNU-UHFFFAOYSA-N 1-bromo-2-ethenyl-3-fluoro-4-phenylmethoxybenzene Chemical compound C(C1=CC=CC=C1)OC1=C(C(=C(C=C1)Br)C=C)F KRTVZBZIKULDNU-UHFFFAOYSA-N 0.000 description 2
• WOWNZZYJCUUIFC-UHFFFAOYSA-N 1-bromo-4-methoxy-2,3-dimethylbenzene Chemical compound COC1=CC=C(Br)C(C)=C1C WOWNZZYJCUUIFC-UHFFFAOYSA-N 0.000 description 2
• ITADIVACIVJFJF-UHFFFAOYSA-N 1-bromo-4-methoxy-2-propan-2-ylbenzene Chemical compound COC1=CC=C(Br)C(C(C)C)=C1 ITADIVACIVJFJF-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
• OZPFVBLDYBXHAF-UHFFFAOYSA-N 2,2-dimethyl-1,3-dioxolane-4-carboxylic acid Chemical compound CC1(C)OCC(C(O)=O)O1 OZPFVBLDYBXHAF-UHFFFAOYSA-N 0.000 description 2
• WSNAMSQNHCXVSZ-UHFFFAOYSA-N 2-bromo-3-methoxythiophene Chemical compound COC=1C=CSC=1Br WSNAMSQNHCXVSZ-UHFFFAOYSA-N 0.000 description 2
• SCRQAWQJSSKCFN-UHFFFAOYSA-N 2-bromo-5-hydroxybenzaldehyde Chemical compound OC1=CC=C(Br)C(C=O)=C1 SCRQAWQJSSKCFN-UHFFFAOYSA-N 0.000 description 2
• NRGGMCIBEHEAIL-UHFFFAOYSA-N 2-ethylpyridine Chemical compound CCC1=CC=CC=N1 NRGGMCIBEHEAIL-UHFFFAOYSA-N 0.000 description 2
• CSDSSGBPEUDDEE-UHFFFAOYSA-N 2-formylpyridine Chemical compound O=CC1=CC=CC=N1 CSDSSGBPEUDDEE-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
• FICXHNUJLDDMGP-UHFFFAOYSA-N 2-methyl-4-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]aniline Chemical compound CC1=C(N)C=CC(=C1)C1CCN(CC1)CC(F)(F)F FICXHNUJLDDMGP-UHFFFAOYSA-N 0.000 description 2
• WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
• ONZQYZKCUHFORE-UHFFFAOYSA-N 3-bromo-1,1,1-trifluoropropan-2-one Chemical compound FC(F)(F)C(=O)CBr ONZQYZKCUHFORE-UHFFFAOYSA-N 0.000 description 2
• ROADCYAOHVSOLQ-UHFFFAOYSA-N 3-oxetanone Chemical compound O=C1COC1 ROADCYAOHVSOLQ-UHFFFAOYSA-N 0.000 description 2
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 2
• PAHAIHXVVJMZKU-UHFFFAOYSA-N 4-bromo-2-methyl-1-nitrobenzene Chemical compound CC1=CC(Br)=CC=C1[N+]([O-])=O PAHAIHXVVJMZKU-UHFFFAOYSA-N 0.000 description 2
• FQEYHIPPYOSPLF-UHFFFAOYSA-N 4-bromo-3-chlorophenol Chemical compound OC1=CC=C(Br)C(Cl)=C1 FQEYHIPPYOSPLF-UHFFFAOYSA-N 0.000 description 2
• KWQNNOZROOJVJB-UHFFFAOYSA-N 4-bromo-3-ethylaniline Chemical compound CCC1=CC(N)=CC=C1Br KWQNNOZROOJVJB-UHFFFAOYSA-N 0.000 description 2
• DVKVZPIRWWREJC-UHFFFAOYSA-N 4-chloro-3-ethylphenol Chemical compound CCC1=CC(O)=CC=C1Cl DVKVZPIRWWREJC-UHFFFAOYSA-N 0.000 description 2
• LRFIHWGUGBXFEC-UHFFFAOYSA-N 4-methylthiophene-3-carboxylic acid Chemical compound CC1=CSC=C1C(O)=O LRFIHWGUGBXFEC-UHFFFAOYSA-N 0.000 description 2
• RMWYQKVGQWYCBR-UHFFFAOYSA-N 4-piperidin-4-yl-3-propan-2-ylphenol Chemical compound C(C)(C)C=1C=C(C=CC=1C1CCNCC1)O RMWYQKVGQWYCBR-UHFFFAOYSA-N 0.000 description 2
• GRIVHAIKQQBTIY-UHFFFAOYSA-N 6-bromo-2-fluoro-3-phenylmethoxybenzaldehyde Chemical compound C1=CC(Br)=C(C=O)C(F)=C1OCC1=CC=CC=C1 GRIVHAIKQQBTIY-UHFFFAOYSA-N 0.000 description 2
• 229920001817 Agar Polymers 0.000 description 2
• XYLJNLCSTIOKRM-UHFFFAOYSA-N Alphagan Chemical compound C1=CC2=NC=CN=C2C(Br)=C1NC1=NCCN1 XYLJNLCSTIOKRM-UHFFFAOYSA-N 0.000 description 2
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
• 206010002388 Angina unstable Diseases 0.000 description 2
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• 241000416162 Astragalus gummifer Species 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• 244000303965 Cyamopsis psoralioides Species 0.000 description 2
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
• LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• XKMLYUALXHKNFT-UUOKFMHZSA-N Guanosine-5'-triphosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XKMLYUALXHKNFT-UUOKFMHZSA-N 0.000 description 2
• 206010019280 Heart failures Diseases 0.000 description 2
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
• 240000007472 Leucaena leucocephala Species 0.000 description 2
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
• 229910010082 LiAlH Inorganic materials 0.000 description 2
• 239000004472 Lysine Substances 0.000 description 2
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
• 229930195725 Mannitol Natural products 0.000 description 2
• 241000699670 Mus sp. Species 0.000 description 2
• VHDLBVBQAINTOW-UHFFFAOYSA-N OC1=C(SC=C1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)O Chemical compound OC1=C(SC=C1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)O VHDLBVBQAINTOW-UHFFFAOYSA-N 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• 239000004372 Polyvinyl alcohol Substances 0.000 description 2
• 241000288906 Primates Species 0.000 description 2
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 2
• 241000700159 Rattus Species 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• 208000007718 Stable Angina Diseases 0.000 description 2
• 235000021355 Stearic acid Nutrition 0.000 description 2
• 208000006011 Stroke Diseases 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 238000006069 Suzuki reaction reaction Methods 0.000 description 2
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
• 229920001615 Tragacanth Polymers 0.000 description 2
• 108010018242 Transcription Factor AP-1 Proteins 0.000 description 2
• 102100023118 Transcription factor JunD Human genes 0.000 description 2
• 208000007814 Unstable Angina Diseases 0.000 description 2
• VCCRAEOWYNDZJL-UHFFFAOYSA-M [2-methyl-4-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]phenyl]methyl-triphenylphosphanium bromide Chemical compound [Br-].C(C)(C)(C)OC(=O)N1CCC(CC1)C1=CC(=C(C[P+](C2=CC=CC=C2)(C2=CC=CC=C2)C2=CC=CC=C2)C=C1)C VCCRAEOWYNDZJL-UHFFFAOYSA-M 0.000 description 2
• FQKOKQKXLBWJKK-UHFFFAOYSA-N [4-(4-aminophenyl)piperidin-1-yl]-cyclopropylmethanone Chemical compound C1=CC(N)=CC=C1C1CCN(C(=O)C2CC2)CC1 FQKOKQKXLBWJKK-UHFFFAOYSA-N 0.000 description 2
• QQDRLKRHJOAQDC-FBHGDYMESA-N [4-[(2s)-3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl]phenyl]methyl 2,4-dimethylbenzoate;methanesulfonic acid Chemical compound CS(O)(=O)=O.CS(O)(=O)=O.CC1=CC(C)=CC=C1C(=O)OCC1=CC=C([C@@H](CN)C(=O)NC=2C=C3C=CN=CC3=CC=2)C=C1 QQDRLKRHJOAQDC-FBHGDYMESA-N 0.000 description 2
• IKQCKJSWVAERRG-UHFFFAOYSA-M [Br-].CC(C)[Zn+] Chemical compound [Br-].CC(C)[Zn+] IKQCKJSWVAERRG-UHFFFAOYSA-M 0.000 description 2
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• 239000002671 adjuvant Substances 0.000 description 2
• 239000000443 aerosol Substances 0.000 description 2
• 239000008272 agar Substances 0.000 description 2
• 235000010419 agar Nutrition 0.000 description 2
• 150000001299 aldehydes Chemical class 0.000 description 2
• 239000000783 alginic acid Substances 0.000 description 2
• 229960001126 alginic acid Drugs 0.000 description 2
• 150000004781 alginic acids Chemical class 0.000 description 2
• 150000001408 amides Chemical class 0.000 description 2
• 238000004458 analytical method Methods 0.000 description 2
• 235000010323 ascorbic acid Nutrition 0.000 description 2
• 239000012131 assay buffer Substances 0.000 description 2
• 230000009286 beneficial effect Effects 0.000 description 2
• 230000004071 biological effect Effects 0.000 description 2
• 230000031018 biological processes and functions Effects 0.000 description 2
• 229960003679 brimonidine Drugs 0.000 description 2
• HCRKCZRJWPKOAR-JTQLQIEISA-N brinzolamide Chemical compound CCN[C@H]1CN(CCCOC)S(=O)(=O)C2=C1C=C(S(N)(=O)=O)S2 HCRKCZRJWPKOAR-JTQLQIEISA-N 0.000 description 2
• 229960000722 brinzolamide Drugs 0.000 description 2
• 230000031709 bromination Effects 0.000 description 2
• 238000005893 bromination reaction Methods 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• 239000006172 buffering agent Substances 0.000 description 2
• CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 2
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
• 229910000024 caesium carbonate Inorganic materials 0.000 description 2
• 229910000019 calcium carbonate Inorganic materials 0.000 description 2
• 239000001506 calcium phosphate Substances 0.000 description 2
• 229910000389 calcium phosphate Inorganic materials 0.000 description 2
• 235000011010 calcium phosphates Nutrition 0.000 description 2
• 159000000007 calcium salts Chemical class 0.000 description 2
• 239000001768 carboxy methyl cellulose Substances 0.000 description 2
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
• 229910052801 chlorine Inorganic materials 0.000 description 2
• OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
• 238000004587 chromatography analysis Methods 0.000 description 2
• 238000007796 conventional method Methods 0.000 description 2
• 239000006071 cream Substances 0.000 description 2
• SNRCKKQHDUIRIY-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloromethane;dichloropalladium;iron(2+) Chemical compound [Fe+2].ClCCl.Cl[Pd]Cl.C1=C[CH-]C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.C1=C[CH-]C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 SNRCKKQHDUIRIY-UHFFFAOYSA-L 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• 238000013461 design Methods 0.000 description 2
• 150000001975 deuterium Chemical group 0.000 description 2
• HQWPLXHWEZZGKY-UHFFFAOYSA-N diethylzinc Chemical compound CC[Zn]CC HQWPLXHWEZZGKY-UHFFFAOYSA-N 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 239000003995 emulsifying agent Substances 0.000 description 2
• 210000002889 endothelial cell Anatomy 0.000 description 2
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
• XNGGOXOLHQANRB-WAYWQWQTSA-N ethyl (2z)-2-(ethoxymethylidene)-4,4,4-trifluoro-3-oxobutanoate Chemical compound CCO\C=C(C(=O)C(F)(F)F)/C(=O)OCC XNGGOXOLHQANRB-WAYWQWQTSA-N 0.000 description 2
• QYLMLIKWOSITQG-UHFFFAOYSA-N ethyl 1-(6-bromopyridin-2-yl)-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound FC(F)(F)C1=C(C(=O)OCC)C=NN1C1=CC=CC(Br)=N1 QYLMLIKWOSITQG-UHFFFAOYSA-N 0.000 description 2
• VNZPXEMLXFCTOV-UHFFFAOYSA-N ethyl 1-(6-bromopyridin-2-yl)-5-ethylpyrazole-4-carboxylate Chemical compound BrC1=CC=CC(=N1)N1N=CC(=C1CC)C(=O)OCC VNZPXEMLXFCTOV-UHFFFAOYSA-N 0.000 description 2
• KXMNHMKUWUGBEI-UHFFFAOYSA-N ethyl 1-[6-(3-methoxythiophen-2-yl)pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound COC1=C(SC=C1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)OCC KXMNHMKUWUGBEI-UHFFFAOYSA-N 0.000 description 2
• FMCYJKBGRXBSHT-UHFFFAOYSA-N ethyl 1-[6-[3-(1,2,3,4-tetrahydroisoquinolin-6-yloxymethyl)thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound C1NCCC2=CC(=CC=C12)OCC1=C(SC=C1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)OCC FMCYJKBGRXBSHT-UHFFFAOYSA-N 0.000 description 2
• PCALQEVYUGIAEH-UHFFFAOYSA-N ethyl 1-[6-[3-(hydroxymethyl)-5-methyl-4-propan-2-ylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound OCC1=C(SC(=C1C(C)C)C)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)OCC PCALQEVYUGIAEH-UHFFFAOYSA-N 0.000 description 2
• PVHBKGHDPSUIKW-UHFFFAOYSA-N ethyl 1-[6-[3-[(2-chloro-4-piperidin-4-ylphenoxy)methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound ClC1=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)OCC)C=CC(=C1)C1CCNCC1 PVHBKGHDPSUIKW-UHFFFAOYSA-N 0.000 description 2
• XCXHRWKDSQQENR-UHFFFAOYSA-N ethyl 1-[6-[3-[(4-piperidin-4-ylphenoxy)methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound N1CCC(CC1)C1=CC=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)OCC)C=C1 XCXHRWKDSQQENR-UHFFFAOYSA-N 0.000 description 2
• KIXUDIDVUUMZTD-UHFFFAOYSA-N ethyl 1-[6-[3-[2-(4-bromophenyl)ethenyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound BrC1=CC=C(C=CC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)OCC)C=C1 KIXUDIDVUUMZTD-UHFFFAOYSA-N 0.000 description 2
• XJJPICIFAYFZPY-UHFFFAOYSA-N ethyl 1-[6-[3-[[3-(hydroxymethyl)-4-piperidin-4-ylphenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound OCC=1C=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)OCC)C=CC=1C1CCNCC1 XJJPICIFAYFZPY-UHFFFAOYSA-N 0.000 description 2
• RTISTTFEYWGEMK-UHFFFAOYSA-N ethyl 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-(trifluoromethyl)phenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)OCC)C=C1)C(F)(F)F RTISTTFEYWGEMK-UHFFFAOYSA-N 0.000 description 2
• JZKVITFYVMPLNN-UHFFFAOYSA-N ethyl 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylphenoxy]methyl]-4-cyclopropyl-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC(=C2C2CC2)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)OCC)C=C1)C JZKVITFYVMPLNN-UHFFFAOYSA-N 0.000 description 2
• ZBMWPABPSBRVAF-UHFFFAOYSA-N ethyl 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylphenoxy]methyl]-4-ethyl-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC(=C2CC)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)OCC)C=C1)C ZBMWPABPSBRVAF-UHFFFAOYSA-N 0.000 description 2
• VRCXMNUWXYAMDO-UHFFFAOYSA-N ethyl 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylphenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)OCC)C=C1)C VRCXMNUWXYAMDO-UHFFFAOYSA-N 0.000 description 2
• NLOTXIZVZLUUHH-UHFFFAOYSA-N ethyl 1-[6-[4-bromo-3-(hydroxymethyl)-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound BrC=1C(=C(SC=1C)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)OCC)CO NLOTXIZVZLUUHH-UHFFFAOYSA-N 0.000 description 2
• PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 2
• 230000003176 fibrotic effect Effects 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 235000013355 food flavoring agent Nutrition 0.000 description 2
• 238000001640 fractional crystallisation Methods 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
• 235000011187 glycerol Nutrition 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 238000002513 implantation Methods 0.000 description 2
• 238000011065 in-situ storage Methods 0.000 description 2
• 239000003701 inert diluent Substances 0.000 description 2
• 230000002401 inhibitory effect Effects 0.000 description 2
• 150000007529 inorganic bases Chemical class 0.000 description 2
• 201000004332 intermediate coronary syndrome Diseases 0.000 description 2
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
• 150000002500 ions Chemical class 0.000 description 2
• 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 208000017169 kidney disease Diseases 0.000 description 2
• 239000007788 liquid Substances 0.000 description 2
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
• 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 2
• 210000004072 lung Anatomy 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
• BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
• 229960002510 mandelic acid Drugs 0.000 description 2
• 235000010355 mannitol Nutrition 0.000 description 2
• 239000000594 mannitol Substances 0.000 description 2
• 239000000463 material Substances 0.000 description 2
• BCVXHSPFUWZLGQ-UHFFFAOYSA-N mecn acetonitrile Chemical compound CC#N.CC#N BCVXHSPFUWZLGQ-UHFFFAOYSA-N 0.000 description 2
• 230000002503 metabolic effect Effects 0.000 description 2
• JOAQPMUQGGFQDE-UHFFFAOYSA-N methyl 1-[6-(3-hydroxythiophen-2-yl)pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound OC1=C(SC=C1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)OC JOAQPMUQGGFQDE-UHFFFAOYSA-N 0.000 description 2
• DSVLFSAWVFGCEJ-UHFFFAOYSA-N methyl 5-methylthiophene-3-carboxylate Chemical compound COC(=O)C1=CSC(C)=C1 DSVLFSAWVFGCEJ-UHFFFAOYSA-N 0.000 description 2
• 229920000609 methyl cellulose Polymers 0.000 description 2
• QRPRIOOKPZSVFN-UHFFFAOYSA-M methyl(triphenyl)phosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 QRPRIOOKPZSVFN-UHFFFAOYSA-M 0.000 description 2
• 239000001923 methylcellulose Substances 0.000 description 2
• 235000010981 methylcellulose Nutrition 0.000 description 2
• 238000004452 microanalysis Methods 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 2
• WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 2
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 239000002736 nonionic surfactant Substances 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
• 235000019198 oils Nutrition 0.000 description 2
• 239000002674 ointment Substances 0.000 description 2
• 210000001328 optic nerve Anatomy 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• 150000007530 organic bases Chemical class 0.000 description 2
• MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 2
• 230000037361 pathway Effects 0.000 description 2
• 238000005897 peptide coupling reaction Methods 0.000 description 2
• 235000021317 phosphate Nutrition 0.000 description 2
• 239000002953 phosphate buffered saline Substances 0.000 description 2
• 229910052698 phosphorus Inorganic materials 0.000 description 2
• 239000011574 phosphorus Substances 0.000 description 2
• 229910003446 platinum oxide Inorganic materials 0.000 description 2
• 229920005862 polyol Polymers 0.000 description 2
• 150000003077 polyols Chemical class 0.000 description 2
• 229920002451 polyvinyl alcohol Polymers 0.000 description 2
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
• 238000002600 positron emission tomography Methods 0.000 description 2
• 239000011698 potassium fluoride Substances 0.000 description 2
• 235000003270 potassium fluoride Nutrition 0.000 description 2
• 229910000160 potassium phosphate Inorganic materials 0.000 description 2
• 235000011009 potassium phosphates Nutrition 0.000 description 2
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
• XKMLYUALXHKNFT-UHFFFAOYSA-N rGTP Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O XKMLYUALXHKNFT-UHFFFAOYSA-N 0.000 description 2
• 230000002285 radioactive effect Effects 0.000 description 2
• 239000003642 reactive oxygen metabolite Substances 0.000 description 2
• 238000006268 reductive amination reaction Methods 0.000 description 2
• 230000011664 signaling Effects 0.000 description 2
• 238000002603 single-photon emission computed tomography Methods 0.000 description 2
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
• 239000000600 sorbitol Substances 0.000 description 2
• 235000010356 sorbitol Nutrition 0.000 description 2
• 239000008117 stearic acid Substances 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 230000002459 sustained effect Effects 0.000 description 2
• 239000000454 talc Substances 0.000 description 2
• 235000012222 talc Nutrition 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• 239000011975 tartaric acid Substances 0.000 description 2
• 235000002906 tartaric acid Nutrition 0.000 description 2
• ANAVEQYVVUEPAF-UHFFFAOYSA-N tert-butyl 4-(2-chloro-4-hydroxyphenyl)-3,6-dihydro-2H-pyridine-1-carboxylate Chemical compound ClC1=C(C=CC(=C1)O)C1=CCN(CC1)C(=O)OC(C)(C)C ANAVEQYVVUEPAF-UHFFFAOYSA-N 0.000 description 2
• GXSBBRJGBDDOGG-UHFFFAOYSA-N tert-butyl 4-(2-ethenyl-3-fluoro-4-phenylmethoxyphenyl)-3,6-dihydro-2H-pyridine-1-carboxylate Chemical compound C(C1=CC=CC=C1)OC1=C(C(=C(C=C1)C1=CCN(CC1)C(=O)OC(C)(C)C)C=C)F GXSBBRJGBDDOGG-UHFFFAOYSA-N 0.000 description 2
• LOVKILUSQSZJSJ-UHFFFAOYSA-N tert-butyl 4-(2-ethyl-4-hydroxyphenyl)piperidine-1-carboxylate Chemical compound C(C)C1=C(C=CC(=C1)O)C1CCN(CC1)C(=O)OC(C)(C)C LOVKILUSQSZJSJ-UHFFFAOYSA-N 0.000 description 2
• HKCXJSVPYCSVOR-UHFFFAOYSA-N tert-butyl 4-(3-chloro-5-hydroxypyridin-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylate Chemical compound ClC=1C(=NC=C(C=1)O)C1=CCN(CC1)C(=O)OC(C)(C)C HKCXJSVPYCSVOR-UHFFFAOYSA-N 0.000 description 2
• VSRPOQDOXMYYNF-UHFFFAOYSA-N tert-butyl 4-(4-amino-2-ethylphenyl)-3,6-dihydro-2H-pyridine-1-carboxylate Chemical compound NC1=CC(=C(C=C1)C1=CCN(CC1)C(=O)OC(C)(C)C)CC VSRPOQDOXMYYNF-UHFFFAOYSA-N 0.000 description 2
• YRLQFRXDWBFGMK-UHFFFAOYSA-N tert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C1=CC=C(N)C=C1 YRLQFRXDWBFGMK-UHFFFAOYSA-N 0.000 description 2
• PNWXNBIUASCWBN-UHFFFAOYSA-N tert-butyl 4-[4-(bromomethyl)-3-methylphenyl]piperidine-1-carboxylate Chemical compound BrCC1=C(C=C(C=C1)C1CCN(CC1)C(=O)OC(C)(C)C)C PNWXNBIUASCWBN-UHFFFAOYSA-N 0.000 description 2
• KOUUZSVQZUIQNU-UHFFFAOYSA-N tert-butyl 4-[4-(hydroxymethyl)-3-methylphenyl]piperidine-1-carboxylate Chemical compound OCC1=C(C=C(C=C1)C1CCN(CC1)C(=O)OC(C)(C)C)C KOUUZSVQZUIQNU-UHFFFAOYSA-N 0.000 description 2
• YPAVHCJZNOTJLF-UHFFFAOYSA-N tert-butyl 4-[4-(hydroxymethyl)phenyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C1=CC=C(CO)C=C1 YPAVHCJZNOTJLF-UHFFFAOYSA-N 0.000 description 2
• IVHHZZKGSYGTKZ-UHFFFAOYSA-N tert-butyl 6-hydroxy-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound OC1=CC=C2CN(C(=O)OC(C)(C)C)CCC2=C1 IVHHZZKGSYGTKZ-UHFFFAOYSA-N 0.000 description 2
• IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 2
• 238000004809 thin layer chromatography Methods 0.000 description 2
• YNVOMSDITJMNET-UHFFFAOYSA-N thiophene-3-carboxylic acid Chemical compound OC(=O)C=1C=CSC=1 YNVOMSDITJMNET-UHFFFAOYSA-N 0.000 description 2
• 230000009424 thromboembolic effect Effects 0.000 description 2
• 238000011200 topical administration Methods 0.000 description 2
• 210000001585 trabecular meshwork Anatomy 0.000 description 2
• 235000010487 tragacanth Nutrition 0.000 description 2
• 239000000196 tragacanth Substances 0.000 description 2
• 229940116362 tragacanth Drugs 0.000 description 2
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
• 208000014001 urinary system disease Diseases 0.000 description 2
• 229920002554 vinyl polymer Polymers 0.000 description 2
• 239000000080 wetting agent Substances 0.000 description 2
• DYWNLSQWJMTVGJ-UHFFFAOYSA-N (1-hydroxy-1-phenylpropan-2-yl)azanium;chloride Chemical compound Cl.CC(N)C(O)C1=CC=CC=C1 DYWNLSQWJMTVGJ-UHFFFAOYSA-N 0.000 description 1
• RRZBXOSETANGLP-UHFFFAOYSA-N (2-bromo-4-methylthiophen-3-yl)methanol Chemical compound BrC=1SC=C(C=1CO)C RRZBXOSETANGLP-UHFFFAOYSA-N 0.000 description 1
• ZIRDZICIIVGANO-UHFFFAOYSA-N (2-bromo-5-methylthiophen-3-yl)methanol Chemical compound BrC=1SC(=CC=1CO)C ZIRDZICIIVGANO-UHFFFAOYSA-N 0.000 description 1
• DNISEZBAYYIQFB-PHDIDXHHSA-N (2r,3r)-2,3-diacetyloxybutanedioic acid Chemical compound CC(=O)O[C@@H](C(O)=O)[C@H](C(O)=O)OC(C)=O DNISEZBAYYIQFB-PHDIDXHHSA-N 0.000 description 1
• FQJYKXVQABPCRA-UHFFFAOYSA-M (4-bromophenyl)methyl-triphenylphosphanium;bromide Chemical compound [Br-].C1=CC(Br)=CC=C1C[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 FQJYKXVQABPCRA-UHFFFAOYSA-M 0.000 description 1
• NRQHBNNTBIDSRK-YRNVUSSQSA-N (4e)-4-[(4-methoxyphenyl)methylidene]-2-methyl-1,3-oxazol-5-one Chemical compound C1=CC(OC)=CC=C1\C=C\1C(=O)OC(C)=N/1 NRQHBNNTBIDSRK-YRNVUSSQSA-N 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• FMRFUKZPHGBWHF-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinolin-1-ol Chemical class C1=CC=C2C(O)NCCC2=C1 FMRFUKZPHGBWHF-UHFFFAOYSA-N 0.000 description 1
• ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 description 1
• GGUSQTSTQSHJAH-UHFFFAOYSA-N 1-(4-chlorophenyl)-2-[4-(4-fluorobenzyl)piperidin-1-yl]ethanol Chemical compound C=1C=C(Cl)C=CC=1C(O)CN(CC1)CCC1CC1=CC=C(F)C=C1 GGUSQTSTQSHJAH-UHFFFAOYSA-N 0.000 description 1
• VAZJLPXFVQHDFB-UHFFFAOYSA-N 1-(diaminomethylidene)-2-hexylguanidine Polymers CCCCCCN=C(N)N=C(N)N VAZJLPXFVQHDFB-UHFFFAOYSA-N 0.000 description 1
• VPKYLEJROXEZNN-UHFFFAOYSA-N 1-[3-[3-[1-[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylanilino]ethyl]thiophen-2-yl]phenyl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(C=C1)NC(C)C1=C(SC=C1)C=1C=C(C=CC=1)N1N=CC(=C1C(F)(F)F)C(=O)O)C VPKYLEJROXEZNN-UHFFFAOYSA-N 0.000 description 1
• LNSNOCOJSAPLPF-UHFFFAOYSA-N 1-[3-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylphenoxy]methyl]thiophen-2-yl]phenyl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC=C2)C=2C=C(C=CC=2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)C LNSNOCOJSAPLPF-UHFFFAOYSA-N 0.000 description 1
• HNEFHOAFNZETAQ-UHFFFAOYSA-N 1-[4-(4-hydroxy-3-methylphenyl)piperidin-1-yl]propan-1-one Chemical compound OC1=C(C=C(C=C1)C1CCN(CC1)C(CC)=O)C HNEFHOAFNZETAQ-UHFFFAOYSA-N 0.000 description 1
• VAWNNVUDSTYGEJ-UHFFFAOYSA-N 1-[4-(4-methoxy-3-methylphenyl)piperidin-1-yl]propan-1-one Chemical compound COC1=C(C=C(C=C1)C1CCN(CC1)C(CC)=O)C VAWNNVUDSTYGEJ-UHFFFAOYSA-N 0.000 description 1
• NVYJSCWBZJICKM-UHFFFAOYSA-N 1-[4-[4-[(2-bromo-5-methylthiophen-3-yl)methoxy]phenyl]piperidin-1-yl]propan-1-one Chemical compound BrC=1SC(=CC=1COC1=CC=C(C=C1)C1CCN(CC1)C(CC)=O)C NVYJSCWBZJICKM-UHFFFAOYSA-N 0.000 description 1
• SMHXMHQNTZGWPG-UHFFFAOYSA-N 1-[6-[3-[2-[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylphenyl]ethyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-ethylpyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(C=C1)CCC1=C(SC(=C1)C)C1=CC=CC(=N1)N1N=CC(=C1CC)C(=O)O)C SMHXMHQNTZGWPG-UHFFFAOYSA-N 0.000 description 1
• QVEHPIVXTFUJHH-UHFFFAOYSA-N 1-[6-[3-[[2,6-dimethyl-4-(1-propanoylpiperidin-4-yl)phenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound CC1=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C(=CC(=C1)C1CCN(CC1)C(CC)=O)C QVEHPIVXTFUJHH-UHFFFAOYSA-N 0.000 description 1
• LOSDGAZQOXNIBL-UHFFFAOYSA-N 1-[6-[3-[[2-(pyridin-2-ylmethyl)-3,4-dihydro-1H-isoquinolin-6-yl]oxymethyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound N1=C(C=CC=C1)CN1CC2=CC=C(C=C2CC1)OCC1=C(SC=C1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)O LOSDGAZQOXNIBL-UHFFFAOYSA-N 0.000 description 1
• WGZHISGEOJYPCV-UHFFFAOYSA-N 1-[6-[3-[[2-chloro-4-(1-propanoylpiperidin-4-yl)phenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound ClC1=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=CC(=C1)C1CCN(CC1)C(CC)=O WGZHISGEOJYPCV-UHFFFAOYSA-N 0.000 description 1
• YGRXLFVDEJQOEP-UHFFFAOYSA-N 1-[6-[3-[[2-chloro-4-[1-(cyclopropanecarbonyl)piperidin-4-yl]phenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound ClC1=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=CC(=C1)C1CCN(CC1)C(=O)C1CC1 YGRXLFVDEJQOEP-UHFFFAOYSA-N 0.000 description 1
• AJONNHOEYKNDDH-UHFFFAOYSA-N 1-[6-[3-[[2-methyl-4-(1-propanoylpiperidin-4-yl)phenoxy]methyl]-4-(trifluoromethyl)thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound CC1=C(OCC2=C(SC=C2C(F)(F)F)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=CC(=C1)C1CCN(CC1)C(CC)=O AJONNHOEYKNDDH-UHFFFAOYSA-N 0.000 description 1
• FQTGLXVGVNWFCD-UHFFFAOYSA-N 1-[6-[3-[[2-methyl-4-(1-propanoylpiperidin-4-yl)phenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound CC1=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=CC(=C1)C1CCN(CC1)C(CC)=O FQTGLXVGVNWFCD-UHFFFAOYSA-N 0.000 description 1
• HCZKGPXSTMAQKA-UHFFFAOYSA-N 1-[6-[3-[[2-methyl-4-[1-(oxetan-3-yl)piperidin-4-yl]phenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound CC1=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=CC(=C1)C1CCN(CC1)C1COC1 HCZKGPXSTMAQKA-UHFFFAOYSA-N 0.000 description 1
• ZNSXMHSURUICCW-UHFFFAOYSA-N 1-[6-[3-[[2-methyl-4-[1-(oxetane-3-carbonyl)piperidin-4-yl]phenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound CC1=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=CC(=C1)C1CCN(CC1)C(=O)C1COC1 ZNSXMHSURUICCW-UHFFFAOYSA-N 0.000 description 1
• FLRMETBQJGWWGF-UHFFFAOYSA-N 1-[6-[3-[[2-methyl-4-[1-(oxolane-3-carbonyl)piperidin-4-yl]phenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound CC1=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=CC(=C1)C1CCN(CC1)C(=O)C1COCC1 FLRMETBQJGWWGF-UHFFFAOYSA-N 0.000 description 1
• BQUXOJLKBUYAFH-UHFFFAOYSA-N 1-[6-[3-[[3-ethyl-4-[1-(2-hydroxyacetyl)piperidin-4-yl]phenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C(C)C=1C=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=CC=1C1CCN(CC1)C(CO)=O BQUXOJLKBUYAFH-UHFFFAOYSA-N 0.000 description 1
• CBPWWNDKIQBBFY-UHFFFAOYSA-N 1-[6-[3-[[3-ethyl-4-[1-(3-hydroxy-2,2-dimethylpropanoyl)piperidin-4-yl]phenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C(C)C=1C=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=CC=1C1CCN(CC1)C(C(CO)(C)C)=O CBPWWNDKIQBBFY-UHFFFAOYSA-N 0.000 description 1
• JYVJPDONBQBCKM-IBGZPJMESA-N 1-[6-[3-[[3-ethyl-4-[1-[(2S)-2-hydroxypropanoyl]piperidin-4-yl]phenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound CCC1=CC(OCC2=C(SC(C)=C2)C2=CC=CC(=N2)N2N=CC(C(O)=O)=C2C(F)(F)F)=CC=C1C1CCN(CC1)C(=O)[C@H](C)O JYVJPDONBQBCKM-IBGZPJMESA-N 0.000 description 1
• SGGQRGDBYCYMMV-UHFFFAOYSA-N 1-[6-[3-[[4-(1-methoxycarbonylpiperidin-4-yl)phenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound COC(=O)N1CCC(CC1)C1=CC=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1 SGGQRGDBYCYMMV-UHFFFAOYSA-N 0.000 description 1
• ZMNWTMSBKKTLHF-UHFFFAOYSA-N 1-[6-[3-[[4-(1-propanoylpiperidin-4-yl)phenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C(CC)(=O)N1CCC(CC1)C1=CC=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1 ZMNWTMSBKKTLHF-UHFFFAOYSA-N 0.000 description 1
• MBPDVYSOFWADAX-UHFFFAOYSA-N 1-[6-[3-[[4-(1-propanoylpiperidin-4-yl)phenyl]methoxy]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C(CC)(=O)N1CCC(CC1)C1=CC=C(COC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1 MBPDVYSOFWADAX-UHFFFAOYSA-N 0.000 description 1
• LPPBEDBWNCEYRD-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]phenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound FC(CN1CCC(CC1)C1=CC=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)(F)F LPPBEDBWNCEYRD-UHFFFAOYSA-N 0.000 description 1
• LROYNOKIZQFBHU-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(2,2-dimethyl-1,3-dioxolane-4-carbonyl)piperidin-4-yl]-2-methylphenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound CC1(OCC(O1)C(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)C)C LROYNOKIZQFBHU-UHFFFAOYSA-N 0.000 description 1
• HCBWKHZPDCOFOU-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(2-cyclopropylacetyl)piperidin-4-yl]-2-methylphenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)CC(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)C HCBWKHZPDCOFOU-UHFFFAOYSA-N 0.000 description 1
• XOBDRVIZCBYZLM-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(2-cyclopropylacetyl)piperidin-4-yl]-3-ethylphenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)CC(=O)N1CCC(CC1)C1=C(C=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)CC XOBDRVIZCBYZLM-UHFFFAOYSA-N 0.000 description 1
• AKVHZTACUXZLDE-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(2-cyclopropylacetyl)piperidin-4-yl]-3-ethylphenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-methylpyrazole-4-carboxylic acid Chemical compound C1(CC1)CC(=O)N1CCC(CC1)C1=C(C=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C)C(=O)O)C=C1)CC AKVHZTACUXZLDE-UHFFFAOYSA-N 0.000 description 1
• JISHTCNZCYCKSE-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(3-hydroxycyclobutanecarbonyl)piperidin-4-yl]-2-methylphenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound OC1CC(C1)C(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)C JISHTCNZCYCKSE-UHFFFAOYSA-N 0.000 description 1
• UTWGLVXHFVUDSQ-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclobutanecarbonyl)piperidin-4-yl]-2-methylphenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CCC1)C(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)C UTWGLVXHFVUDSQ-UHFFFAOYSA-N 0.000 description 1
• UOONXMUKMUDUKL-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)-2,2,6,6-tetramethylpiperidin-4-yl]-2-methylphenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1C(CC(CC1(C)C)C1=CC(=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)C)(C)C UOONXMUKMUDUKL-UHFFFAOYSA-N 0.000 description 1
• PYNGOYLLPJXMGO-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2,3-dimethylphenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=C(C(=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)C)C PYNGOYLLPJXMGO-UHFFFAOYSA-N 0.000 description 1
• YBAREVRZCUECPT-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-(trifluoromethyl)phenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)C(F)(F)F YBAREVRZCUECPT-UHFFFAOYSA-N 0.000 description 1
• QCSZYEDUCDOCRO-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-(trifluoromethyl)phenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)C(F)(F)F QCSZYEDUCDOCRO-UHFFFAOYSA-N 0.000 description 1
• YXVRJFDQWBMYQX-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-ethylphenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)CC YXVRJFDQWBMYQX-UHFFFAOYSA-N 0.000 description 1
• KGYVDAZBIJZIRC-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-fluorophenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)F KGYVDAZBIJZIRC-UHFFFAOYSA-N 0.000 description 1
• PYZCPDVEFFDVEX-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylanilino]methyl]-4,5-dimethylthiophen-2-yl]pyridin-2-yl]-5-ethylpyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(C=C1)NCC1=C(SC(=C1C)C)C1=CC=CC(=N1)N1N=CC(=C1CC)C(=O)O)C PYZCPDVEFFDVEX-UHFFFAOYSA-N 0.000 description 1
• PGNUHILZKGHBHG-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylanilino]methyl]-4-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(C=C1)NCC1=C(SC=C1C)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)O)C PGNUHILZKGHBHG-UHFFFAOYSA-N 0.000 description 1
• BQLRXXHXIIUTJY-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylanilino]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-methylpyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(C=C1)NCC1=C(SC(=C1)C)C1=CC=CC(=N1)N1N=CC(=C1C)C(=O)O)C BQLRXXHXIIUTJY-UHFFFAOYSA-N 0.000 description 1
• YBPCKIJBCIKYCO-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylanilino]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(C=C1)NCC1=C(SC=C1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)O)C YBPCKIJBCIKYCO-UHFFFAOYSA-N 0.000 description 1
• OUHMTWFSKWBCIU-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylphenoxy]methyl]-4,5-dimethylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC(=C2C)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)C OUHMTWFSKWBCIU-UHFFFAOYSA-N 0.000 description 1
• UWHRLMNVFALIQM-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylphenoxy]methyl]-4,5-dimethylthiophen-2-yl]pyridin-2-yl]-5-ethylpyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC(=C2C)C)C2=CC=CC(=N2)N2N=CC(=C2CC)C(=O)O)C=C1)C UWHRLMNVFALIQM-UHFFFAOYSA-N 0.000 description 1
• VAMXMPCGSNCSQP-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylphenoxy]methyl]-4-ethyl-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC(=C2CC)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)C VAMXMPCGSNCSQP-UHFFFAOYSA-N 0.000 description 1
• XVAYAHBVMXBETC-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylphenoxy]methyl]-4-ethylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC=C2CC)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)C XVAYAHBVMXBETC-UHFFFAOYSA-N 0.000 description 1
• AKIOCJUOEKYWLH-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylphenoxy]methyl]-4-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC=C2C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)C AKIOCJUOEKYWLH-UHFFFAOYSA-N 0.000 description 1
• TWCNQWJJXQBNNI-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylphenoxy]methyl]-5-cyclopropylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC(=C2)C2CC2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)C TWCNQWJJXQBNNI-UHFFFAOYSA-N 0.000 description 1
• NZXVVTFUXCIIOH-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylphenoxy]methyl]-5-ethylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC(=C2)CC)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)C NZXVVTFUXCIIOH-UHFFFAOYSA-N 0.000 description 1
• LEWYYHUMXLPRNX-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylphenoxy]methyl]-5-methyl-4-propan-2-ylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC(=C2C(C)C)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)C LEWYYHUMXLPRNX-UHFFFAOYSA-N 0.000 description 1
• DQHUKHSBISNXAA-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylphenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-ethylpyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2CC)C(=O)O)C=C1)C DQHUKHSBISNXAA-UHFFFAOYSA-N 0.000 description 1
• IRJHSLTWVSXFKH-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylphenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-methylpyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C)C(=O)O)C=C1)C IRJHSLTWVSXFKH-UHFFFAOYSA-N 0.000 description 1
• YLQBWVYWMSJOBK-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylphenoxy]methyl]-5-propan-2-ylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC(=C2)C(C)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)C YLQBWVYWMSJOBK-UHFFFAOYSA-N 0.000 description 1
• WXYIZQKSZUJVIC-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylphenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-methylpyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C)C(=O)O)C=C1)C WXYIZQKSZUJVIC-UHFFFAOYSA-N 0.000 description 1
• FAAZWMQTZVQNAN-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-3-(hydroxymethyl)phenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=C(C=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)CO FAAZWMQTZVQNAN-UHFFFAOYSA-N 0.000 description 1
• SJEKQLLVAFHUAY-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-3-ethyl-2-fluorophenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=C(C(=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)F)CC SJEKQLLVAFHUAY-UHFFFAOYSA-N 0.000 description 1
• DREQKOUZDXWKFZ-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-3-ethylphenoxy]methyl]-4-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=C(C=C(OCC2=C(SC=C2C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)CC DREQKOUZDXWKFZ-UHFFFAOYSA-N 0.000 description 1
• CNIRUZPSWFWFSU-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-3-ethylphenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=C(C=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)CC CNIRUZPSWFWFSU-UHFFFAOYSA-N 0.000 description 1
• UCNSVPVNYRTKFQ-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-3-ethylphenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-ethylpyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=C(C=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2CC)C(=O)O)C=C1)CC UCNSVPVNYRTKFQ-UHFFFAOYSA-N 0.000 description 1
• VTYMYTWRESPCNP-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-3-ethylphenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-methylpyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=C(C=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C)C(=O)O)C=C1)CC VTYMYTWRESPCNP-UHFFFAOYSA-N 0.000 description 1
• VNKHAUHCXHUWCC-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-3-ethylphenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-ethylpyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=C(C=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2CC)C(=O)O)C=C1)CC VNKHAUHCXHUWCC-UHFFFAOYSA-N 0.000 description 1
• NBQWVDXNJBVDFI-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-3-ethylphenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-methylpyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=C(C=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C)C(=O)O)C=C1)CC NBQWVDXNJBVDFI-UHFFFAOYSA-N 0.000 description 1
• ZGMSGQUPBOUNGK-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-3-fluorophenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=C(C=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)F ZGMSGQUPBOUNGK-UHFFFAOYSA-N 0.000 description 1
• GDYKTZMATSMXGO-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-3-methylphenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=C(C=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)C GDYKTZMATSMXGO-UHFFFAOYSA-N 0.000 description 1
• NMBMIAGSWFAISW-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-3-propan-2-ylphenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=C(C=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)C(C)C NMBMIAGSWFAISW-UHFFFAOYSA-N 0.000 description 1
• ZPVSTABQLJVPOY-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-3-propylphenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=C(C=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)CCC ZPVSTABQLJVPOY-UHFFFAOYSA-N 0.000 description 1
• JRMDMCKYPAVPKZ-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]anilino]methyl]-4-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC=C(C=C1)NCC1=C(SC=C1C)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)O JRMDMCKYPAVPKZ-UHFFFAOYSA-N 0.000 description 1
• JXPDJWJXOFOQTK-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]anilino]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-methylpyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC=C(C=C1)NCC1=C(SC(=C1)C)C1=CC=CC(=N1)N1N=CC(=C1C)C(=O)O JXPDJWJXOFOQTK-UHFFFAOYSA-N 0.000 description 1
• WKNNSQGFMSYJPF-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]phenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1 WKNNSQGFMSYJPF-UHFFFAOYSA-N 0.000 description 1
• JQOWBFLNGKVRQT-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(dimethylcarbamoyl)piperidin-4-yl]-3-ethylphenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound CN(C(=O)N1CCC(CC1)C1=C(C=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)CC)C JQOWBFLNGKVRQT-UHFFFAOYSA-N 0.000 description 1
• FLZOCUNCYOLZLM-UHFFFAOYSA-N 1-[6-[3-[[4-[1-(dimethylcarbamoyl)piperidin-4-yl]-3-ethylphenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-methylpyrazole-4-carboxylic acid Chemical compound CN(C(=O)N1CCC(CC1)C1=C(C=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C)C(=O)O)C=C1)CC)C FLZOCUNCYOLZLM-UHFFFAOYSA-N 0.000 description 1
• RFNKHHIPFYRKDR-UHFFFAOYSA-N 1-[6-[3-[[5-[1-(cyclopropanecarbonyl)piperidin-4-yl]pyridin-2-yl]oxymethyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C=1C=CC(=NC=1)OCC1=C(SC=C1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)O RFNKHHIPFYRKDR-UHFFFAOYSA-N 0.000 description 1
• ATOYAEMJQZICIS-UHFFFAOYSA-N 1-[6-[3-[[5-methyl-2-(pyridin-2-ylmethyl)-3,4-dihydro-1H-isoquinolin-6-yl]oxymethyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound CC1=C2CCN(CC2=CC=C1OCC1=C(SC=C1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)O)CC1=NC=CC=C1 ATOYAEMJQZICIS-UHFFFAOYSA-N 0.000 description 1
• WDDKHWNMFXPGPS-UHFFFAOYSA-N 1-[6-[3-[[6-[1-(cyclopropanecarbonyl)piperidin-4-yl]-5-ethylpyridin-3-yl]oxymethyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=C(C=C(C=N1)OCC1=C(SC(=C1)C)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)O)CC WDDKHWNMFXPGPS-UHFFFAOYSA-N 0.000 description 1
• JXUDHTVIDDQRDC-UHFFFAOYSA-N 1-[6-[4,5-dimethyl-3-[[2-methyl-4-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]phenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound CC=1C(=C(SC=1C)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)O)COC1=C(C=C(C=C1)C1CCN(CC1)CC(F)(F)F)C JXUDHTVIDDQRDC-UHFFFAOYSA-N 0.000 description 1
• HXENOXNYSIVNRZ-UHFFFAOYSA-N 1-[6-[4,5-dimethyl-3-[[2-methyl-4-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]phenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-ethylpyrazole-4-carboxylic acid Chemical compound CC=1C(=C(SC=1C)C1=CC=CC(=N1)N1N=CC(=C1CC)C(=O)O)COC1=C(C=C(C=C1)C1CCN(CC1)CC(F)(F)F)C HXENOXNYSIVNRZ-UHFFFAOYSA-N 0.000 description 1
• GVHNMOAAPLPMMT-UHFFFAOYSA-N 1-[6-[4-cyclopropyl-5-methyl-3-[[2-methyl-4-(1-propanoylpiperidin-4-yl)phenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C1(CC1)C=1C(=C(SC=1C)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)O)COC1=C(C=C(C=C1)C1CCN(CC1)C(CC)=O)C GVHNMOAAPLPMMT-UHFFFAOYSA-N 0.000 description 1
• CUCIGZUIGDJJCM-UHFFFAOYSA-N 1-[6-[4-ethyl-3-[[2-methyl-4-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]phenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C(C)C=1C(=C(SC=1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)O)COC1=C(C=C(C=C1)C1CCN(CC1)CC(F)(F)F)C CUCIGZUIGDJJCM-UHFFFAOYSA-N 0.000 description 1
• OFQWNMLSAWPKQY-UHFFFAOYSA-N 1-[6-[4-ethyl-5-methyl-3-[[2-methyl-4-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]phenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C(C)C=1C(=C(SC=1C)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)O)COC1=C(C=C(C=C1)C1CCN(CC1)CC(F)(F)F)C OFQWNMLSAWPKQY-UHFFFAOYSA-N 0.000 description 1
• DNKASVYKQIWJIB-UHFFFAOYSA-N 1-[6-[4-methyl-3-[[2-methyl-4-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]anilino]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound CC=1C(=C(SC=1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)O)CNC1=C(C=C(C=C1)C1CCN(CC1)CC(F)(F)F)C DNKASVYKQIWJIB-UHFFFAOYSA-N 0.000 description 1
• RFBAYQVPIKOLJD-UHFFFAOYSA-N 1-[6-[4-methyl-3-[[2-methyl-4-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]phenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound CC=1C(=C(SC=1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)O)COC1=C(C=C(C=C1)C1CCN(CC1)CC(F)(F)F)C RFBAYQVPIKOLJD-UHFFFAOYSA-N 0.000 description 1
• MCBUIULZXZTHMY-UHFFFAOYSA-N 1-[6-[5-chloro-3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylphenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound ClC1=CC(=C(S1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)O)COC1=C(C=C(C=C1)C1CCN(CC1)C(=O)C1CC1)C MCBUIULZXZTHMY-UHFFFAOYSA-N 0.000 description 1
• UVIREOQNBARRRN-UHFFFAOYSA-N 1-[6-[5-ethyl-3-[[2-methyl-4-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]phenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C(C)C1=CC(=C(S1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)O)COC1=C(C=C(C=C1)C1CCN(CC1)CC(F)(F)F)C UVIREOQNBARRRN-UHFFFAOYSA-N 0.000 description 1
• OSMRSLHPFVQPIY-UHFFFAOYSA-N 1-[6-[5-ethyl-3-[[4-(1-methoxycarbonylpiperidin-4-yl)-2-methylphenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound C(C)C1=CC(=C(S1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)O)COC1=C(C=C(C=C1)C1CCN(CC1)C(=O)OC)C OSMRSLHPFVQPIY-UHFFFAOYSA-N 0.000 description 1
• YCWORTUVPSSRPT-UHFFFAOYSA-N 1-[6-[5-methyl-3-[[2-methyl-4-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]phenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound CC1=CC(=C(S1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)O)COC1=C(C=C(C=C1)C1CCN(CC1)CC(F)(F)F)C YCWORTUVPSSRPT-UHFFFAOYSA-N 0.000 description 1
• DVLXBEHCUYYYCD-UHFFFAOYSA-N 1-[6-[5-methyl-3-[[4-(1-propanoylpiperidin-4-yl)phenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylic acid Chemical compound CC1=CC(=C(S1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)O)COC1=CC=C(C=C1)C1CCN(CC1)C(CC)=O DVLXBEHCUYYYCD-UHFFFAOYSA-N 0.000 description 1
• FQLLUPPDTXCICZ-UHFFFAOYSA-N 1-benzyl-4-(4-methoxy-3-methylphenyl)-3,6-dihydro-2H-pyridine Chemical compound C(C1=CC=CC=C1)N1CCC(=CC1)C1=CC(=C(C=C1)OC)C FQLLUPPDTXCICZ-UHFFFAOYSA-N 0.000 description 1
• IZMHBVDXCBPHTH-UHFFFAOYSA-N 1-benzyl-4-(4-methoxy-3-methylphenyl)piperidin-4-ol Chemical compound C(C1=CC=CC=C1)N1CCC(CC1)(O)C1=CC(=C(C=C1)OC)C IZMHBVDXCBPHTH-UHFFFAOYSA-N 0.000 description 1
• MICMHFIQSAMEJG-UHFFFAOYSA-N 1-bromopyrrolidine-2,5-dione Chemical compound BrN1C(=O)CCC1=O.BrN1C(=O)CCC1=O MICMHFIQSAMEJG-UHFFFAOYSA-N 0.000 description 1
• OUUCZGCOAXRCHN-UHFFFAOYSA-N 1-hexadecoxyoctadecane Chemical class CCCCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCC OUUCZGCOAXRCHN-UHFFFAOYSA-N 0.000 description 1
• LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 description 1
• YYKBFGMYHQMXIL-UHFFFAOYSA-N 1-phenyl-2,3,4-tri(propan-2-yl)benzene Chemical group CC(C)C1=C(C(C)C)C(C(C)C)=CC=C1C1=CC=CC=C1 YYKBFGMYHQMXIL-UHFFFAOYSA-N 0.000 description 1
• YYVIRFZZNQUTKP-UHFFFAOYSA-N 2,2,6,6-tetramethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydropyridine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC(C)(C)NC(C)(C)C1 YYVIRFZZNQUTKP-UHFFFAOYSA-N 0.000 description 1
• FZWBNHMXJMCXLU-UHFFFAOYSA-N 2,3,4,5-tetrahydroxy-6-[3,4,5-trihydroxy-6-[[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]oxan-2-yl]oxyhexanal Chemical compound OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OCC(O)C(O)C(O)C(O)C=O)O1 FZWBNHMXJMCXLU-UHFFFAOYSA-N 0.000 description 1
• IWWLVWWEZSOTJH-UHFFFAOYSA-N 2,3-dihydroxy-4-(4-methylbenzoyl)oxy-4-oxobutanoic acid Chemical compound CC1=CC=C(C(=O)OC(=O)C(O)C(O)C(O)=O)C=C1 IWWLVWWEZSOTJH-UHFFFAOYSA-N 0.000 description 1
• ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 description 1
• DOSGEBYQRMBTGS-UHFFFAOYSA-N 2-(3,6-dihydro-2h-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound O1C(C)(C)C(C)(C)OB1C1=CCOCC1 DOSGEBYQRMBTGS-UHFFFAOYSA-N 0.000 description 1
• JQDNCGRNPYKRAO-UHFFFAOYSA-N 2-(bromomethyl)pyridine;hydron;bromide Chemical compound Br.BrCC1=CC=CC=N1 JQDNCGRNPYKRAO-UHFFFAOYSA-N 0.000 description 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
• UHTQHHLSGVOGQR-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-4-ium-1-yl]ethanesulfonate Chemical compound OCCN1CCN(CCS(O)(=O)=O)CC1.OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 UHTQHHLSGVOGQR-UHFFFAOYSA-N 0.000 description 1
• WXHLLJAMBQLULT-UHFFFAOYSA-N 2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-n-(2-methyl-6-sulfanylphenyl)-1,3-thiazole-5-carboxamide;hydrate Chemical compound O.C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1S WXHLLJAMBQLULT-UHFFFAOYSA-N 0.000 description 1
• KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 description 1
• UZGAFXRKFGZBRQ-UHFFFAOYSA-N 2-bromo-4-methylthiophene-3-carboxylic acid Chemical compound CC1=CSC(Br)=C1C(O)=O UZGAFXRKFGZBRQ-UHFFFAOYSA-N 0.000 description 1
• JVTIXNMXDLQEJE-UHFFFAOYSA-N 2-decanoyloxypropyl decanoate 2-octanoyloxypropyl octanoate Chemical compound C(CCCCCCC)(=O)OCC(C)OC(CCCCCCC)=O.C(=O)(CCCCCCCCC)OCC(C)OC(=O)CCCCCCCCC JVTIXNMXDLQEJE-UHFFFAOYSA-N 0.000 description 1
• MHDFOXVWKGLZJX-UHFFFAOYSA-N 2-methyl-4-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]phenol Chemical compound CC1=C(C=CC(=C1)C1CCN(CC1)CC(F)(F)F)O MHDFOXVWKGLZJX-UHFFFAOYSA-N 0.000 description 1
• PQARDSOLYLHRQD-UHFFFAOYSA-N 2-methyl-4-piperidin-4-ylphenol Chemical compound C1=C(O)C(C)=CC(C2CCNCC2)=C1 PQARDSOLYLHRQD-UHFFFAOYSA-N 0.000 description 1
• TWBPWBPGNQWFSJ-UHFFFAOYSA-N 2-phenylaniline Chemical group NC1=CC=CC=C1C1=CC=CC=C1 TWBPWBPGNQWFSJ-UHFFFAOYSA-N 0.000 description 1
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• APIXJSLKIYYUKG-UHFFFAOYSA-N 3 Isobutyl 1 methylxanthine Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N=CN2 APIXJSLKIYYUKG-UHFFFAOYSA-N 0.000 description 1
• YIRNNHURQFNQDX-UHFFFAOYSA-N 3,6-dihydro-2h-pyridine-1-carboxylic acid Chemical compound OC(=O)N1CCC=CC1 YIRNNHURQFNQDX-UHFFFAOYSA-N 0.000 description 1
• UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• UCFSYHMCKWNKAH-UHFFFAOYSA-N 4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound CC1(C)OBOC1(C)C UCFSYHMCKWNKAH-UHFFFAOYSA-N 0.000 description 1
• COPMASWDWLENMV-VOTSOKGWSA-N 4,4,5,5-tetramethyl-2-[(e)-prop-1-enyl]-1,3,2-dioxaborolane Chemical compound C\C=C\B1OC(C)(C)C(C)(C)O1 COPMASWDWLENMV-VOTSOKGWSA-N 0.000 description 1
• KAMGNFJZBIIAQE-UHFFFAOYSA-N 4-(3-methyl-4-phenylmethoxyphenyl)-1-(2,2,2-trifluoroethyl)piperidine Chemical compound C(C1=CC=CC=C1)OC1=C(C=C(C=C1)C1CCN(CC1)CC(F)(F)F)C KAMGNFJZBIIAQE-UHFFFAOYSA-N 0.000 description 1
• LFSVHCZJBFRGKH-UHFFFAOYSA-N 4-(4-methoxy-3-methylphenyl)piperidine Chemical compound C1=C(C)C(OC)=CC=C1C1CCNCC1 LFSVHCZJBFRGKH-UHFFFAOYSA-N 0.000 description 1
• UDLRGQOHGYWLCS-UHFFFAOYSA-N 4-bromo-1-methoxy-2-methylbenzene Chemical compound COC1=CC=C(Br)C=C1C UDLRGQOHGYWLCS-UHFFFAOYSA-N 0.000 description 1
• CWOUYJWXWZFCMM-UHFFFAOYSA-N 4-bromo-2-[6-[4-ethoxycarbonyl-5-(trifluoromethyl)pyrazol-1-yl]pyridin-2-yl]thiophene-3-carboxylic acid Chemical compound BrC=1C(=C(SC=1)C1=NC(=CC=C1)N1N=CC(=C1C(F)(F)F)C(=O)OCC)C(=O)O CWOUYJWXWZFCMM-UHFFFAOYSA-N 0.000 description 1
• JVVRCYWZTJLJSG-UHFFFAOYSA-N 4-dimethylaminophenol Chemical compound CN(C)C1=CC=C(O)C=C1 JVVRCYWZTJLJSG-UHFFFAOYSA-N 0.000 description 1
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical class OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• QJNLUNBGDFUULX-UHFFFAOYSA-N 4-n,4-n'-dimethyl-3h-pyridine-4,4-diamine Chemical compound CNC1(NC)CC=NC=C1 QJNLUNBGDFUULX-UHFFFAOYSA-N 0.000 description 1
• KAKYNGJFPXFCDD-PPHPATTJSA-N 5-bromo-n-(4,5-dihydro-1h-imidazol-2-yl)quinoxalin-6-amine;(4r)-4-(ethylamino)-2-(3-methoxypropyl)-1,1-dioxo-3,4-dihydrothieno[3,2-e]thiazine-6-sulfonamide Chemical compound C1=CC2=NC=CN=C2C(Br)=C1NC1=NCCN1.CCN[C@H]1CN(CCCOC)S(=O)(=O)C2=C1C=C(S(N)(=O)=O)S2 KAKYNGJFPXFCDD-PPHPATTJSA-N 0.000 description 1
• SCZFBZIEMXKKDS-UHFFFAOYSA-N 5-methyl-1,2,3,4-tetrahydroisoquinolin-6-ol Chemical compound C1NCCC2=C1C=CC(O)=C2C SCZFBZIEMXKKDS-UHFFFAOYSA-N 0.000 description 1
• DHKTYYVUEJTFHF-UHFFFAOYSA-N 6-bromo-5-chloropyridin-3-ol Chemical compound OC1=CN=C(Br)C(Cl)=C1 DHKTYYVUEJTFHF-UHFFFAOYSA-N 0.000 description 1
• FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• 208000024827 Alzheimer disease Diseases 0.000 description 1
• 206010003225 Arteriospasm coronary Diseases 0.000 description 1
• 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 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
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
• KXYKSKAFMRRNMS-UHFFFAOYSA-N C(C1=CC=CC=C1)OC1=C(C=C(C=C1)C1CCNCC1)C Chemical compound C(C1=CC=CC=C1)OC1=C(C=C(C=C1)C1CCNCC1)C KXYKSKAFMRRNMS-UHFFFAOYSA-N 0.000 description 1
• JEBRKULJHOQDCN-WIOPSUGQSA-N C1(CC1)C(=O)N1C[C@H]([C@@H](CC1)C1=CC=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)O Chemical compound C1(CC1)C(=O)N1C[C@H]([C@@H](CC1)C1=CC=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)O)C=C1)O JEBRKULJHOQDCN-WIOPSUGQSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• CKDWPUIZGOQOOM-UHFFFAOYSA-N Carbamyl chloride Chemical compound NC(Cl)=O CKDWPUIZGOQOOM-UHFFFAOYSA-N 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 241000282693 Cercopithecidae Species 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• 108020004635 Complementary DNA Proteins 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 241000699802 Cricetulus griseus Species 0.000 description 1
• 102000004654 Cyclic GMP-Dependent Protein Kinases Human genes 0.000 description 1
• 108010003591 Cyclic GMP-Dependent Protein Kinases Proteins 0.000 description 1
• LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 1
• RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
• UYUXSRADSPPKRZ-SKNVOMKLSA-N D-glucurono-6,3-lactone Chemical compound O=C[C@H](O)[C@H]1OC(=O)[C@@H](O)[C@H]1O UYUXSRADSPPKRZ-SKNVOMKLSA-N 0.000 description 1
• 229920002307 Dextran Polymers 0.000 description 1
• YIIMEMSDCNDGTB-UHFFFAOYSA-N Dimethylcarbamoyl chloride Chemical compound CN(C)C(Cl)=O YIIMEMSDCNDGTB-UHFFFAOYSA-N 0.000 description 1
• 206010061818 Disease progression Diseases 0.000 description 1
• 206010048554 Endothelial dysfunction Diseases 0.000 description 1
• 241000283086 Equidae Species 0.000 description 1
• CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 206010016654 Fibrosis Diseases 0.000 description 1
• 206010018307 Glaucoma and ocular hypertension Diseases 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
• AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
• 229920000569 Gum karaya Polymers 0.000 description 1
• 206010020853 Hypertonic bladder Diseases 0.000 description 1
• 238000004566 IR spectroscopy Methods 0.000 description 1
• 102000004310 Ion Channels Human genes 0.000 description 1
• 150000000994 L-ascorbates Chemical class 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• 239000012097 Lipofectamine 2000 Substances 0.000 description 1
• 239000012448 Lithium borohydride Substances 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
• 102000005741 Metalloproteases Human genes 0.000 description 1
• 108010006035 Metalloproteases Proteins 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
• 229920000881 Modified starch Polymers 0.000 description 1
• 102000005640 Myosin Type II Human genes 0.000 description 1
• 108010045128 Myosin Type II Proteins 0.000 description 1
• XPOPNAOUHJCNQU-UHFFFAOYSA-N N-[2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenyl]thiophene-3-carboxamide Chemical compound FC1=C(C(=C(C(=C1F)C(F)(F)F)F)F)NC(=O)C1=CSC=C1 XPOPNAOUHJCNQU-UHFFFAOYSA-N 0.000 description 1
• QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• 102000002451 NPR2 Human genes 0.000 description 1
• 208000028389 Nerve injury Diseases 0.000 description 1
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 1
• 239000000006 Nitroglycerin Substances 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 208000009722 Overactive Urinary Bladder Diseases 0.000 description 1
• 208000018737 Parkinson disease Diseases 0.000 description 1
• 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 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 208000005764 Peripheral Arterial Disease Diseases 0.000 description 1
• 208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
• 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 1
• 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 229920002413 Polyhexanide Polymers 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
• 102000001708 Protein Isoforms Human genes 0.000 description 1
• 108010029485 Protein Isoforms Proteins 0.000 description 1
• 201000004681 Psoriasis Diseases 0.000 description 1
• 206010064911 Pulmonary arterial hypertension Diseases 0.000 description 1
• 206010063837 Reperfusion injury Diseases 0.000 description 1
• 208000017442 Retinal disease Diseases 0.000 description 1
• 206010038923 Retinopathy Diseases 0.000 description 1
• BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
• 208000000453 Skin Neoplasms Diseases 0.000 description 1
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
• MKRNVBXERAPZOP-UHFFFAOYSA-N Starch acetate Chemical compound O1C(CO)C(OC)C(O)C(O)C1OCC1C(OC2C(C(O)C(OC)C(CO)O2)OC(C)=O)C(O)C(O)C(OC2C(OC(C)C(O)C2O)CO)O1 MKRNVBXERAPZOP-UHFFFAOYSA-N 0.000 description 1
• 241000934878 Sterculia Species 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 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
• 208000007536 Thrombosis Diseases 0.000 description 1
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
• 206010047555 Visual field defect Diseases 0.000 description 1
• 238000002441 X-ray diffraction Methods 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• CHPDCDRDTOQRAG-UHFFFAOYSA-N [2-(2,6-dimethoxyphenyl)phenyl]phosphane Chemical group COC1=CC=CC(OC)=C1C1=CC=CC=C1P CHPDCDRDTOQRAG-UHFFFAOYSA-N 0.000 description 1
• KTYNIRXEEFFLOJ-UHFFFAOYSA-N [2-bromo-4-(trifluoromethyl)thiophen-3-yl]methanol Chemical compound BrC=1SC=C(C=1CO)C(F)(F)F KTYNIRXEEFFLOJ-UHFFFAOYSA-N 0.000 description 1
• ZJFOCFOLJFKHIL-UHFFFAOYSA-N [2-chloro-6-(2,6-dimethoxyphenyl)phenyl]-dicyclohexylphosphane Chemical group ClC=1C(=C(C=CC=1)C1=C(C=CC=C1OC)OC)P(C1CCCCC1)C1CCCCC1 ZJFOCFOLJFKHIL-UHFFFAOYSA-N 0.000 description 1
• IMTLECOSKPMJEX-UHFFFAOYSA-N [4-(4-amino-3-methylphenyl)piperidin-1-yl]-cyclopropylmethanone Chemical compound NC1=C(C=C(C=C1)C1CCN(CC1)C(=O)C1CC1)C IMTLECOSKPMJEX-UHFFFAOYSA-N 0.000 description 1
• BRGZNWYADAFVAK-UHFFFAOYSA-N [4-[4-[(2-bromo-4-methylthiophen-3-yl)methoxy]-3-methylphenyl]piperidin-1-yl]-cyclopropylmethanone Chemical compound BrC=1SC=C(C=1COC1=C(C=C(C=C1)C1CCN(CC1)C(=O)C1CC1)C)C BRGZNWYADAFVAK-UHFFFAOYSA-N 0.000 description 1
• LKBREHQHCVRNFR-UHFFFAOYSA-K [B+3].[Br-].[Br-].[Br-] Chemical compound [B+3].[Br-].[Br-].[Br-] LKBREHQHCVRNFR-UHFFFAOYSA-K 0.000 description 1
• XJQXCHHPKLIOBW-UHFFFAOYSA-N [Si](C)(C)(C(C)(C)C)OCC1=C(SC=C1C)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)OCC Chemical compound [Si](C)(C)(C(C)(C)C)OCC1=C(SC=C1C)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)OCC XJQXCHHPKLIOBW-UHFFFAOYSA-N 0.000 description 1
• 230000002159 abnormal effect Effects 0.000 description 1
• 239000002250 absorbent Substances 0.000 description 1
• 230000002745 absorbent Effects 0.000 description 1
• 239000003070 absorption delaying agent Substances 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 239000000370 acceptor Substances 0.000 description 1
• 150000001242 acetic acid derivatives Chemical class 0.000 description 1
• JXYRIQRQKAUQIY-UHFFFAOYSA-N acetic acid;oxolane Chemical compound CC(O)=O.C1CCOC1 JXYRIQRQKAUQIY-UHFFFAOYSA-N 0.000 description 1
• CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 1
• 150000008043 acidic salts Chemical class 0.000 description 1
• 239000000362 adenosine triphosphatase inhibitor Substances 0.000 description 1
• WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
• 239000000951 adrenergic alpha-1 receptor antagonist Substances 0.000 description 1
• 239000000384 adrenergic alpha-2 receptor agonist Substances 0.000 description 1
• 239000003463 adsorbent Substances 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• 229940072056 alginate Drugs 0.000 description 1
• 150000001447 alkali salts Chemical class 0.000 description 1
• 150000001336 alkenes Chemical class 0.000 description 1
• 239000012036 alkyl zinc reagent Substances 0.000 description 1
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 235000012211 aluminium silicate Nutrition 0.000 description 1
• SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
• 235000019270 ammonium chloride Nutrition 0.000 description 1
• VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 239000003708 ampul Substances 0.000 description 1
• 150000008064 anhydrides Chemical class 0.000 description 1
• 210000002159 anterior chamber Anatomy 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 239000003429 antifungal agent Substances 0.000 description 1
• 229940121375 antifungal agent Drugs 0.000 description 1
• 229940006133 antiglaucoma drug and miotics carbonic anhydrase inhibitors Drugs 0.000 description 1
• 230000003078 antioxidant effect Effects 0.000 description 1
• 229940027983 antiseptic and disinfectant quaternary ammonium compound Drugs 0.000 description 1
• 230000004509 aqueous humor production Effects 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• 238000010936 aqueous wash Methods 0.000 description 1
• 229910052786 argon Inorganic materials 0.000 description 1
• 210000001367 artery Anatomy 0.000 description 1
• 206010003246 arthritis Diseases 0.000 description 1
• 229940072107 ascorbate Drugs 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 229940009098 aspartate Drugs 0.000 description 1
• 208000006673 asthma Diseases 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 108010038664 atrial natriuretic factor receptor B Proteins 0.000 description 1
• WEAJZXNPAWBCOA-INIZCTEOSA-N avanafil Chemical compound C1=C(Cl)C(OC)=CC=C1CNC1=NC(N2[C@@H](CCC2)CO)=NC=C1C(=O)NCC1=NC=CC=N1 WEAJZXNPAWBCOA-INIZCTEOSA-N 0.000 description 1
• 229960000307 avanafil Drugs 0.000 description 1
• 125000005604 azodicarboxylate group Chemical group 0.000 description 1
• 230000003385 bacteriostatic effect Effects 0.000 description 1
• 230000004888 barrier function Effects 0.000 description 1
• 150000007514 bases Chemical class 0.000 description 1
• 229960000686 benzalkonium chloride Drugs 0.000 description 1
• JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
• CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• 229960004324 betaxolol Drugs 0.000 description 1
• CHDPSNLJFOQTRK-UHFFFAOYSA-N betaxolol hydrochloride Chemical compound [Cl-].C1=CC(OCC(O)C[NH2+]C(C)C)=CC=C1CCOCC1CC1 CHDPSNLJFOQTRK-UHFFFAOYSA-N 0.000 description 1
• 230000003115 biocidal effect Effects 0.000 description 1
• 239000012620 biological material Substances 0.000 description 1
• 239000004305 biphenyl Substances 0.000 description 1
• HTJWUNNIRKDDIV-UHFFFAOYSA-N bis(1-adamantyl)-butylphosphane Chemical compound C1C(C2)CC(C3)CC2CC13P(CCCC)C1(C2)CC(C3)CC2CC3C1 HTJWUNNIRKDDIV-UHFFFAOYSA-N 0.000 description 1
• QJKJIULTPCUPFN-UHFFFAOYSA-M bis(1-adamantyl)-butylphosphane chloropalladium(1+) 2-phenylaniline Chemical compound [Pd+]Cl.NC1=CC=CC=C1C1=CC=CC=[C-]1.C1C(C2)CC(C3)CC2CC13P(CCCC)C1(C2)CC(C3)CC2CC3C1 QJKJIULTPCUPFN-UHFFFAOYSA-M 0.000 description 1
• SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
• 150000001642 boronic acid derivatives Chemical class 0.000 description 1
• 229940098773 bovine serum albumin Drugs 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 1
• 239000007853 buffer solution Substances 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• ZRFFGWCOKPCRGR-UHFFFAOYSA-N butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1N(C(=O)OCCCC)CCC(B2OC(C)(C)C(C)(C)O2)=C1 ZRFFGWCOKPCRGR-UHFFFAOYSA-N 0.000 description 1
• DVECBJCOGJRVPX-UHFFFAOYSA-N butyryl chloride Chemical compound CCCC(Cl)=O DVECBJCOGJRVPX-UHFFFAOYSA-N 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 235000001465 calcium Nutrition 0.000 description 1
• 235000010216 calcium carbonate Nutrition 0.000 description 1
• 229940003871 calcium ion Drugs 0.000 description 1
• MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• XNRHTMDHGDWBGP-UHFFFAOYSA-N carbamic acid;hydrochloride Chemical compound Cl.NC(O)=O XNRHTMDHGDWBGP-UHFFFAOYSA-N 0.000 description 1
• 229960001631 carbomer Drugs 0.000 description 1
• 229940049638 carbomer homopolymer type c Drugs 0.000 description 1
• 229940043234 carbomer-940 Drugs 0.000 description 1
• 229940031663 carbomer-974p Drugs 0.000 description 1
• 125000004432 carbon atom Chemical group C* 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 1
• 235000010418 carrageenan Nutrition 0.000 description 1
• 229920001525 carrageenan Polymers 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 239000002738 chelating agent Substances 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
• 238000004296 chiral HPLC Methods 0.000 description 1
• 239000012069 chiral reagent Substances 0.000 description 1
• 150000003841 chloride salts Chemical class 0.000 description 1
• 150000001805 chlorine compounds Chemical class 0.000 description 1
• FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
• 229960004926 chlorobutanol Drugs 0.000 description 1
• 230000007882 cirrhosis Effects 0.000 description 1
• 208000019425 cirrhosis of liver Diseases 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 238000011260 co-administration Methods 0.000 description 1
• 238000003181 co-melting Methods 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 239000002299 complementary DNA Substances 0.000 description 1
• 238000009833 condensation Methods 0.000 description 1
• 230000005494 condensation Effects 0.000 description 1
• 239000000470 constituent Substances 0.000 description 1
• 239000012050 conventional carrier Substances 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 239000002537 cosmetic Substances 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 238000011461 current therapy Methods 0.000 description 1
• ZKWSXJLPBZLNMC-UHFFFAOYSA-N cyclohexyl-[1-cyclohexylphosphanyl-2-[2,4,6-tri(propan-2-yl)phenyl]cyclohexa-2,4-dien-1-yl]phosphane Chemical group C1(CCCCC1)PC1(C(=CC=CC1)C1=C(C=C(C=C1C(C)C)C(C)C)C(C)C)PC1CCCCC1 ZKWSXJLPBZLNMC-UHFFFAOYSA-N 0.000 description 1
• NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 1
• JCWIWBWXCVGEAN-UHFFFAOYSA-L cyclopentyl(diphenyl)phosphane;dichloropalladium;iron Chemical compound [Fe].Cl[Pd]Cl.[CH]1[CH][CH][CH][C]1P(C=1C=CC=CC=1)C1=CC=CC=C1.[CH]1[CH][CH][CH][C]1P(C=1C=CC=CC=1)C1=CC=CC=C1 JCWIWBWXCVGEAN-UHFFFAOYSA-L 0.000 description 1
• VXACHMDJVCSSCT-UHFFFAOYSA-N cyclopropyl-[4-(3-methyl-4-nitrophenyl)-3,6-dihydro-2H-pyridin-1-yl]methanone Chemical compound C1(CC1)C(=O)N1CC=C(CC1)C1=CC(=C(C=C1)[N+](=O)[O-])C VXACHMDJVCSSCT-UHFFFAOYSA-N 0.000 description 1
• SUPXSLOYVLXQQP-UHFFFAOYSA-N cyclopropyl-[4-(4-hydroxy-2,3-dimethylphenyl)piperidin-1-yl]methanone Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=C(C(=C(C=C1)O)C)C SUPXSLOYVLXQQP-UHFFFAOYSA-N 0.000 description 1
• SIPHCJREFROUKT-UHFFFAOYSA-N cyclopropyl-[4-(4-hydroxy-2-propan-2-ylphenyl)piperidin-1-yl]methanone Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=C(C=C(C=C1)O)C(C)C SIPHCJREFROUKT-UHFFFAOYSA-N 0.000 description 1
• JQIZNMHBQPDBGC-UHFFFAOYSA-N cyclopropyl-[4-(4-hydroxy-3-methylphenyl)-2,2,6,6-tetramethylpiperidin-1-yl]methanone Chemical compound C1(CC1)C(=O)N1C(CC(CC1(C)C)C1=CC(=C(C=C1)O)C)(C)C JQIZNMHBQPDBGC-UHFFFAOYSA-N 0.000 description 1
• XOCQYWKXKXKXSU-UHFFFAOYSA-N cyclopropyl-[4-(4-hydroxy-3-methylphenyl)piperidin-1-yl]methanone Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(C=C1)O)C XOCQYWKXKXKXSU-UHFFFAOYSA-N 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
• GHVNFZFCNZKVNT-UHFFFAOYSA-M decanoate Chemical compound CCCCCCCCCC([O-])=O GHVNFZFCNZKVNT-UHFFFAOYSA-M 0.000 description 1
• 230000007547 defect Effects 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 230000036576 dermal application Effects 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 229940119743 dextran 70 Drugs 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 206010012601 diabetes mellitus Diseases 0.000 description 1
• UOPIRNHVGHLLDZ-UHFFFAOYSA-L dichlororhodium Chemical compound Cl[Rh]Cl UOPIRNHVGHLLDZ-UHFFFAOYSA-L 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
• 229940043279 diisopropylamine Drugs 0.000 description 1
• JMRYOSQOYJBDOI-UHFFFAOYSA-N dilithium;di(propan-2-yl)azanide Chemical compound [Li+].CC(C)[N-]C(C)C.CC(C)N([Li])C(C)C JMRYOSQOYJBDOI-UHFFFAOYSA-N 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• UMCMPZBLKLEWAF-UHFFFAOYSA-O dimethyl-(3-sulfopropyl)-[3-[4-(3,7,12-trihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl)pentanoylamino]propyl]azanium Chemical compound OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCCC[N+](C)(C)CCCS(O)(=O)=O)C)C1(C)C(O)C2 UMCMPZBLKLEWAF-UHFFFAOYSA-O 0.000 description 1
• UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
• WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 description 1
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
• 230000005750 disease progression Effects 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 239000002612 dispersion medium Substances 0.000 description 1
• CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
• MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
• 229940043264 dodecyl sulfate Drugs 0.000 description 1
• 239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 229940112141 dry powder inhaler Drugs 0.000 description 1
• 239000012039 electrophile Substances 0.000 description 1
• 229950005455 eliprodil Drugs 0.000 description 1
• 239000003974 emollient agent Substances 0.000 description 1
• 238000003821 enantio-separation Methods 0.000 description 1
• 230000008694 endothelial dysfunction Effects 0.000 description 1
• 230000002708 enhancing effect Effects 0.000 description 1
• 210000002919 epithelial cell Anatomy 0.000 description 1
• LHWWETDBWVTKJO-UHFFFAOYSA-N et3n triethylamine Chemical compound CCN(CC)CC.CCN(CC)CC LHWWETDBWVTKJO-UHFFFAOYSA-N 0.000 description 1
• AFAXGSQYZLGZPG-UHFFFAOYSA-L ethane-1,2-disulfonate Chemical compound [O-]S(=O)(=O)CCS([O-])(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-L 0.000 description 1
• NUIWRMGOBPOIOY-UHFFFAOYSA-N ethanesulfonic acid;methanesulfonic acid Chemical compound CS(O)(=O)=O.CCS(O)(=O)=O NUIWRMGOBPOIOY-UHFFFAOYSA-N 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• AFECQUUSJNXMNL-BQYQJAHWSA-N ethyl (2e)-2-(dimethylaminomethylidene)-3-oxopentanoate Chemical compound CCOC(=O)C(=C\N(C)C)\C(=O)CC AFECQUUSJNXMNL-BQYQJAHWSA-N 0.000 description 1
• HKUSNFDWRQCFFK-UHFFFAOYSA-N ethyl 1-(6-chloropyridin-2-yl)-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound FC(F)(F)C1=C(C(=O)OCC)C=NN1C1=CC=CC(Cl)=N1 HKUSNFDWRQCFFK-UHFFFAOYSA-N 0.000 description 1
• BLMAMPYPUAWKJI-UHFFFAOYSA-N ethyl 1-[3-(3-acetylthiophen-2-yl)phenyl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound C(C)(=O)C1=C(SC=C1)C=1C=C(C=CC=1)N1N=CC(=C1C(F)(F)F)C(=O)OCC BLMAMPYPUAWKJI-UHFFFAOYSA-N 0.000 description 1
• SXGGKSWWPGBLFV-UHFFFAOYSA-N ethyl 1-[3-[3-(1-hydroxyethyl)thiophen-2-yl]phenyl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound OC(C)C1=C(SC=C1)C=1C=C(C=CC=1)N1N=CC(=C1C(F)(F)F)C(=O)OCC SXGGKSWWPGBLFV-UHFFFAOYSA-N 0.000 description 1
• ZRQZFLTZMYAOBY-UHFFFAOYSA-N ethyl 1-[3-[3-[1-[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylanilino]ethyl]thiophen-2-yl]phenyl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(C=C1)NC(C)C1=C(SC=C1)C=1C=C(C=CC=1)N1N=CC(=C1C(F)(F)F)C(=O)OCC)C ZRQZFLTZMYAOBY-UHFFFAOYSA-N 0.000 description 1
• GIRAKACFDUXQRI-UHFFFAOYSA-N ethyl 1-[6-(3-ethenyl-5-methylthiophen-2-yl)pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound CC1=CC(=C(S1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)OCC)C=C GIRAKACFDUXQRI-UHFFFAOYSA-N 0.000 description 1
• IPIVDLMLUATSOV-UHFFFAOYSA-N ethyl 1-[6-(3-ethenylthiophen-2-yl)pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound FC(C1=C(C=NN1C1=NC(=CC=C1)C=1SC=CC=1C=C)C(=O)OCC)(F)F IPIVDLMLUATSOV-UHFFFAOYSA-N 0.000 description 1
• ZMDYCKXINDYKNV-UHFFFAOYSA-N ethyl 1-[6-(3-formyl-5-methylthiophen-2-yl)pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound C(=O)C1=C(SC(=C1)C)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)OCC ZMDYCKXINDYKNV-UHFFFAOYSA-N 0.000 description 1
• QGXGIOCJXBSCFM-UHFFFAOYSA-N ethyl 1-[6-(3-formyl-5-methylthiophen-2-yl)pyridin-2-yl]-5-methylpyrazole-4-carboxylate Chemical compound C(=O)C1=C(SC(=C1)C)C1=CC=CC(=N1)N1N=CC(=C1C)C(=O)OCC QGXGIOCJXBSCFM-UHFFFAOYSA-N 0.000 description 1
• OUWHIUJOIKIBKU-UHFFFAOYSA-N ethyl 1-[6-(3-formylthiophen-2-yl)pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound C(=O)C1=C(SC=C1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)OCC OUWHIUJOIKIBKU-UHFFFAOYSA-N 0.000 description 1
• MQDLVKGCXLQUIY-UHFFFAOYSA-N ethyl 1-[6-[3-(hydroxymethyl)-4,5-dimethylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound OCC1=C(SC(=C1C)C)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)OCC MQDLVKGCXLQUIY-UHFFFAOYSA-N 0.000 description 1
• NVVDKUSPAMTMRO-UHFFFAOYSA-N ethyl 1-[6-[3-(hydroxymethyl)-4-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound OCC1=C(SC=C1C)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)OCC NVVDKUSPAMTMRO-UHFFFAOYSA-N 0.000 description 1
• DFDWWQPREFKGAT-UHFFFAOYSA-N ethyl 1-[6-[3-(hydroxymethyl)-5-prop-1-en-2-ylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound OCC1=C(SC(=C1)C(=C)C)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)OCC DFDWWQPREFKGAT-UHFFFAOYSA-N 0.000 description 1
• OURHOXCYRSUCLW-UHFFFAOYSA-N ethyl 1-[6-[3-(hydroxymethyl)-5-propan-2-ylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound OCC1=C(SC(=C1)C(C)C)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)OCC OURHOXCYRSUCLW-UHFFFAOYSA-N 0.000 description 1
• BXLPUVDMKGQHJD-UHFFFAOYSA-N ethyl 1-[6-[3-(hydroxymethyl)-5-propylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound OCC1=C(SC(=C1)CCC)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)OCC BXLPUVDMKGQHJD-UHFFFAOYSA-N 0.000 description 1
• BVYPYWIYAOLALG-UHFFFAOYSA-N ethyl 1-[6-[3-(hydroxymethyl)thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound OCC1=C(SC=C1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)OCC BVYPYWIYAOLALG-UHFFFAOYSA-N 0.000 description 1
• MSSLISPOGAWSAD-UHFFFAOYSA-N ethyl 1-[6-[3-[(4-bromo-3-formylphenoxy)methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound BrC1=C(C=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)OCC)C=C1)C=O MSSLISPOGAWSAD-UHFFFAOYSA-N 0.000 description 1
• GIXZDGKXFZOVAY-UHFFFAOYSA-N ethyl 1-[6-[3-[[2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenyl]carbamoyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound FC1=C(C(=C(C(=C1F)C(F)(F)F)F)F)NC(=O)C1=C(SC=C1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)OCC GIXZDGKXFZOVAY-UHFFFAOYSA-N 0.000 description 1
• YXOKJUKMTIFXRU-UHFFFAOYSA-N ethyl 1-[6-[3-[[2-(pyridin-2-ylmethyl)-3,4-dihydro-1H-isoquinolin-6-yl]oxymethyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound N1=C(C=CC=C1)CN1CC2=CC=C(C=C2CC1)OCC1=C(SC=C1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)OCC YXOKJUKMTIFXRU-UHFFFAOYSA-N 0.000 description 1
• DLFRXZALXRAFGB-UHFFFAOYSA-N ethyl 1-[6-[3-[[2-chloro-4-(1-propanoylpiperidin-4-yl)phenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound ClC1=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)OCC)C=CC(=C1)C1CCN(CC1)C(CC)=O DLFRXZALXRAFGB-UHFFFAOYSA-N 0.000 description 1
• PDBVUEYIVYOHEI-UHFFFAOYSA-N ethyl 1-[6-[3-[[2-methyl-4-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]phenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound CC1=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)OCC)C=CC(=C1)C1CCN(CC1)CC(F)(F)F PDBVUEYIVYOHEI-UHFFFAOYSA-N 0.000 description 1
• UVIVDAKLZBCFCV-UHFFFAOYSA-N ethyl 1-[6-[3-[[2-methyl-4-[1-(oxetan-3-yl)piperidin-4-yl]phenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound CC1=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)OCC)C=CC(=C1)C1CCN(CC1)C1COC1 UVIVDAKLZBCFCV-UHFFFAOYSA-N 0.000 description 1
• VVUSPYARRPSYOG-UHFFFAOYSA-N ethyl 1-[6-[3-[[4-(1-propanoylpiperidin-4-yl)phenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound C(CC)(=O)N1CCC(CC1)C1=CC=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)OCC)C=C1 VVUSPYARRPSYOG-UHFFFAOYSA-N 0.000 description 1
• WLWZDAZYOXETQM-UHFFFAOYSA-N ethyl 1-[6-[3-[[4-[1-(2,3-dihydroxypropanoyl)piperidin-4-yl]-3-ethylphenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound OC(C(=O)N1CCC(CC1)C1=C(C=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)OCC)C=C1)CC)CO WLWZDAZYOXETQM-UHFFFAOYSA-N 0.000 description 1
• WYYCFURSQJWGOL-UHFFFAOYSA-N ethyl 1-[6-[3-[[4-[1-(2-cyclopropylacetyl)piperidin-4-yl]-2-methylphenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound C1(CC1)CC(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)OCC)C=C1)C WYYCFURSQJWGOL-UHFFFAOYSA-N 0.000 description 1
• BFYILRPOLUSHTI-UHFFFAOYSA-N ethyl 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylanilino]methyl]-4-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(C=C1)NCC1=C(SC=C1C)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)OCC)C BFYILRPOLUSHTI-UHFFFAOYSA-N 0.000 description 1
• IXHITDUJCORAGP-UHFFFAOYSA-N ethyl 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylanilino]methyl]thiophen-2-yl]pyridin-2-yl]-5-methylpyrazole-4-carboxylate Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(C=C1)NCC1=C(SC=C1)C1=CC=CC(=N1)N1N=CC(=C1C)C(=O)OCC)C IXHITDUJCORAGP-UHFFFAOYSA-N 0.000 description 1
• QAHJGTYAYAKLPT-UHFFFAOYSA-N ethyl 1-[6-[3-[[4-[1-(cyclopropanecarbonyl)piperidin-4-yl]-2-methylphenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-methylpyrazole-4-carboxylate Chemical compound C1(CC1)C(=O)N1CCC(CC1)C1=CC(=C(OCC2=C(SC=C2)C2=CC=CC(=N2)N2N=CC(=C2C)C(=O)OCC)C=C1)C QAHJGTYAYAKLPT-UHFFFAOYSA-N 0.000 description 1
• ZUWIPAITRPREJH-UHFFFAOYSA-N ethyl 1-[6-[3-[[4-bromo-3-(hydroxymethyl)phenoxy]methyl]-5-methylthiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound BrC1=C(C=C(OCC2=C(SC(=C2)C)C2=CC=CC(=N2)N2N=CC(=C2C(F)(F)F)C(=O)OCC)C=C1)CO ZUWIPAITRPREJH-UHFFFAOYSA-N 0.000 description 1
• CKFKKTUCENQBCO-UHFFFAOYSA-N ethyl 1-[6-[4-bromo-3-(hydroxymethyl)thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound BrC=1C(=C(SC=1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)OCC)CO CKFKKTUCENQBCO-UHFFFAOYSA-N 0.000 description 1
• DPOHYGZDWVIMFB-UHFFFAOYSA-N ethyl 1-[6-[4-bromo-3-[[2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenyl]carbamoyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound BrC=1C(=C(SC=1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)OCC)C(NC1=C(C(=C(C(=C1F)F)C(F)(F)F)F)F)=O DPOHYGZDWVIMFB-UHFFFAOYSA-N 0.000 description 1
• JLSZQTSCVGIGKF-UHFFFAOYSA-N ethyl 1-[6-[4-cyclopropyl-5-methyl-3-[(2-methyl-4-piperidin-4-ylphenoxy)methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound C1(CC1)C=1C(=C(SC=1C)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)OCC)COC1=C(C=C(C=C1)C1CCNCC1)C JLSZQTSCVGIGKF-UHFFFAOYSA-N 0.000 description 1
• LXXSRZICFKSNDH-UHFFFAOYSA-N ethyl 1-[6-[4-ethyl-3-(hydroxymethyl)thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound C(C)C=1C(=C(SC=1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)OCC)CO LXXSRZICFKSNDH-UHFFFAOYSA-N 0.000 description 1
• JDSREQZHJDCHJN-UHFFFAOYSA-N ethyl 1-[6-[5-bromo-3-(hydroxymethyl)thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound BrC1=CC(=C(S1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)OCC)CO JDSREQZHJDCHJN-UHFFFAOYSA-N 0.000 description 1
• HMKAOWUGFFMHAI-UHFFFAOYSA-N ethyl 1-[6-[5-chloro-3-(hydroxymethyl)thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound ClC1=CC(=C(S1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)OCC)CO HMKAOWUGFFMHAI-UHFFFAOYSA-N 0.000 description 1
• WMGXGPWORPDOTD-UHFFFAOYSA-N ethyl 1-[6-[5-cyclopropyl-3-(hydroxymethyl)thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound C1(CC1)C1=CC(=C(S1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)OCC)CO WMGXGPWORPDOTD-UHFFFAOYSA-N 0.000 description 1
• XCWITETYZSBJPQ-UHFFFAOYSA-N ethyl 1-[6-[5-methyl-3-[[2-methyl-4-(1-propanoylpiperidin-4-yl)phenoxy]methyl]thiophen-2-yl]pyridin-2-yl]-5-(trifluoromethyl)pyrazole-4-carboxylate Chemical compound CC1=CC(=C(S1)C1=CC=CC(=N1)N1N=CC(=C1C(F)(F)F)C(=O)OCC)COC1=C(C=C(C=C1)C1CCN(CC1)C(CC)=O)C XCWITETYZSBJPQ-UHFFFAOYSA-N 0.000 description 1
• AFECQUUSJNXMNL-UHFFFAOYSA-N ethyl 2-(dimethylaminomethylidene)-3-oxopentanoate Chemical compound CCOC(=O)C(=CN(C)C)C(=O)CC AFECQUUSJNXMNL-UHFFFAOYSA-N 0.000 description 1
• RGKAODVRJJBFKW-UHFFFAOYSA-N ethyl 5-ethyl-1-[6-(3-formyl-5-methylthiophen-2-yl)pyridin-2-yl]pyrazole-4-carboxylate Chemical compound C(C)C1=C(C=NN1C1=NC(=CC=C1)C=1SC(=CC=1C=O)C)C(=O)OCC RGKAODVRJJBFKW-UHFFFAOYSA-N 0.000 description 1
• KNKLMFDEULYLFH-UHFFFAOYSA-N ethyl 5-ethyl-1-[6-[3-(hydroxymethyl)-4-(trifluoromethyl)thiophen-2-yl]pyridin-2-yl]pyrazole-4-carboxylate Chemical compound C(C)C1=C(C=NN1C1=NC(=CC=C1)C=1SC=C(C=1CO)C(F)(F)F)C(=O)OCC KNKLMFDEULYLFH-UHFFFAOYSA-N 0.000 description 1
• NODHPPXKIFIWAI-UHFFFAOYSA-N ethyl 5-ethyl-1-[6-[3-(hydroxymethyl)-5-methylthiophen-2-yl]pyridin-2-yl]pyrazole-4-carboxylate Chemical compound C(C)C1=C(C=NN1C1=NC(=CC=C1)C=1SC(=CC=1CO)C)C(=O)OCC NODHPPXKIFIWAI-UHFFFAOYSA-N 0.000 description 1
• 239000013604 expression vector Substances 0.000 description 1
• 208000030533 eye disease Diseases 0.000 description 1
• 210000000744 eyelid Anatomy 0.000 description 1
• 238000011049 filling Methods 0.000 description 1
• 239000012467 final product Substances 0.000 description 1
• 235000019634 flavors Nutrition 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 229940050410 gluconate Drugs 0.000 description 1
• 229930195712 glutamate Natural products 0.000 description 1
• JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical compound OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
• 229940074045 glyceryl distearate Drugs 0.000 description 1
• 229940075507 glyceryl monostearate Drugs 0.000 description 1
• 229960003711 glyceryl trinitrate Drugs 0.000 description 1
• 150000002357 guanidines Chemical class 0.000 description 1
• 229940083094 guanine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
• 239000007902 hard capsule Substances 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 239000000833 heterodimer Substances 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
• 238000002868 homogeneous time resolved fluorescence Methods 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical class OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
• 239000005457 ice water Substances 0.000 description 1
• 238000003384 imaging method Methods 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 208000027866 inflammatory disease Diseases 0.000 description 1
• 230000005764 inhibitory process Effects 0.000 description 1
• 239000007972 injectable composition Substances 0.000 description 1
• 239000013067 intermediate product Substances 0.000 description 1
• 208000001286 intracranial vasospasm Diseases 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 239000003456 ion exchange resin Substances 0.000 description 1
• 229920003303 ion-exchange polymer Polymers 0.000 description 1
• 239000002563 ionic surfactant Substances 0.000 description 1
• 229910052742 iron Inorganic materials 0.000 description 1
• 230000002427 irreversible effect Effects 0.000 description 1
• 208000012947 ischemia reperfusion injury Diseases 0.000 description 1
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
• 238000006317 isomerization reaction Methods 0.000 description 1
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
• 239000000644 isotonic solution Substances 0.000 description 1
• 239000007951 isotonicity adjuster Substances 0.000 description 1
• NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
• 235000010494 karaya gum Nutrition 0.000 description 1
• 239000000231 karaya gum Substances 0.000 description 1
• 229940039371 karaya gum Drugs 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 229940001447 lactate Drugs 0.000 description 1
• 229940099584 lactobionate Drugs 0.000 description 1
• JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
• 238000004811 liquid chromatography Methods 0.000 description 1
• 229940057995 liquid paraffin Drugs 0.000 description 1
• 229910003002 lithium salt Inorganic materials 0.000 description 1
• 159000000002 lithium salts Chemical class 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 229960003646 lysine Drugs 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• CCERQOYLJJULMD-UHFFFAOYSA-M magnesium;carbanide;chloride Chemical compound [CH3-].[Mg+2].[Cl-] CCERQOYLJJULMD-UHFFFAOYSA-M 0.000 description 1
• 238000011418 maintenance treatment Methods 0.000 description 1
• 229940049920 malate Drugs 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 229960003194 meglumine Drugs 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 229960004640 memantine Drugs 0.000 description 1
• LDDHMLJTFXJGPI-UHFFFAOYSA-N memantine hydrochloride Chemical compound Cl.C1C(C2)CC3(C)CC1(C)CC2(N)C3 LDDHMLJTFXJGPI-UHFFFAOYSA-N 0.000 description 1
• COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 150000002739 metals Chemical class 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 1
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
• VFTZKSMAJVLWOV-UHFFFAOYSA-N methyl 1h-pyrazole-4-carboxylate Chemical compound COC(=O)C=1C=NNC=1 VFTZKSMAJVLWOV-UHFFFAOYSA-N 0.000 description 1
• DSXCCQZUWIGHJW-UHFFFAOYSA-N methyl 2-bromo-4-(trifluoromethyl)thiophene-3-carboxylate Chemical compound BrC=1SC=C(C=1C(=O)OC)C(F)(F)F DSXCCQZUWIGHJW-UHFFFAOYSA-N 0.000 description 1
• ROKSORSRSUAPHR-UHFFFAOYSA-N methyl 2-bromo-5-methylthiophene-3-carboxylate Chemical compound COC(=O)C=1C=C(C)SC=1Br ROKSORSRSUAPHR-UHFFFAOYSA-N 0.000 description 1
• ISMJVGFYZAMASD-UHFFFAOYSA-N methyl 4-[4-[(2-bromo-5-methylthiophen-3-yl)methoxy]-3-methylphenyl]piperidine-1-carboxylate Chemical compound BrC=1SC(=CC=1COC1=C(C=C(C=C1)C1CCN(CC1)C(=O)OC)C)C ISMJVGFYZAMASD-UHFFFAOYSA-N 0.000 description 1
• CYEXEOXALMJXDI-UHFFFAOYSA-N methyl 4-bromo-2-methylbenzoate Chemical compound COC(=O)C1=CC=C(Br)C=C1C CYEXEOXALMJXDI-UHFFFAOYSA-N 0.000 description 1
• GCHTVSJQOZUHSH-UHFFFAOYSA-N methyl 5-amino-3-hydroxy-3-(trifluoromethyl)-2h-thiophene-4-carboxylate Chemical compound COC(=O)C1=C(N)SCC1(O)C(F)(F)F GCHTVSJQOZUHSH-UHFFFAOYSA-N 0.000 description 1
• XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
• ANGDWNBGPBMQHW-UHFFFAOYSA-N methyl cyanoacetate Chemical compound COC(=O)CC#N ANGDWNBGPBMQHW-UHFFFAOYSA-N 0.000 description 1
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
• JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
• AZFQCTBZOPUVOW-UHFFFAOYSA-N methyl(triphenyl)phosphanium Chemical class C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 AZFQCTBZOPUVOW-UHFFFAOYSA-N 0.000 description 1
• JNMIXMFEVJHFNY-UHFFFAOYSA-M methyl(triphenyl)phosphanium;iodide Chemical compound [I-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 JNMIXMFEVJHFNY-UHFFFAOYSA-M 0.000 description 1
• RQNMYNYHBQQZSP-UHFFFAOYSA-M methylmagnesium chloride Chemical compound C[Mg]Cl RQNMYNYHBQQZSP-UHFFFAOYSA-M 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 230000003547 miosis Effects 0.000 description 1
• 239000003604 miotic agent Substances 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 235000019426 modified starch Nutrition 0.000 description 1
• 201000006417 multiple sclerosis Diseases 0.000 description 1
• 210000000663 muscle cell Anatomy 0.000 description 1
• 208000010125 myocardial infarction Diseases 0.000 description 1
• SQMJDLXORYKZGJ-UHFFFAOYSA-N n',n'-bis(methylamino)ethane-1,2-diamine Chemical compound CNN(NC)CCN SQMJDLXORYKZGJ-UHFFFAOYSA-N 0.000 description 1
• DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 1
• 229930014626 natural product Natural products 0.000 description 1
• 210000005036 nerve Anatomy 0.000 description 1
• 230000008764 nerve damage Effects 0.000 description 1
• 210000003061 neural cell Anatomy 0.000 description 1
• 208000004296 neuralgia Diseases 0.000 description 1
• 208000021722 neuropathic pain Diseases 0.000 description 1
• 201000001119 neuropathy Diseases 0.000 description 1
• 230000007823 neuropathy Effects 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 239000012299 nitrogen atmosphere Substances 0.000 description 1
• 230000004493 normal intraocular pressure Effects 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-M octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC([O-])=O QIQXTHQIDYTFRH-UHFFFAOYSA-M 0.000 description 1
• 229940049964 oleate Drugs 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 239000004006 olive oil Substances 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 208000020629 overactive bladder Diseases 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 239000007800 oxidant agent Substances 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 239000006072 paste Substances 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 235000010987 pectin Nutrition 0.000 description 1
• 229920001277 pectin Polymers 0.000 description 1
• 239000001814 pectin Substances 0.000 description 1
• 229960000292 pectin Drugs 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• 235000019371 penicillin G benzathine Nutrition 0.000 description 1
• 125000002097 pentamethylcyclopentadienyl group Chemical group 0.000 description 1
• 230000000737 periodic effect Effects 0.000 description 1
• 208000033808 peripheral neuropathy Diseases 0.000 description 1
• 229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
• WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
• 150000003904 phospholipids Chemical class 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 229960005141 piperazine Drugs 0.000 description 1
• LWMPFIOTEAXAGV-UHFFFAOYSA-N piperidin-1-amine Chemical compound NN1CCCCC1 LWMPFIOTEAXAGV-UHFFFAOYSA-N 0.000 description 1
• 230000010287 polarization Effects 0.000 description 1
• 229920001983 poloxamer Polymers 0.000 description 1
• 229920001993 poloxamer 188 Polymers 0.000 description 1
• 229920002432 poly(vinyl methyl ether) polymer Polymers 0.000 description 1
• 239000004584 polyacrylic acid Substances 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• 230000002250 progressing effect Effects 0.000 description 1
• 230000000750 progressive effect Effects 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
• 150000003169 prostaglandin F2α derivatives Chemical class 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• 238000010298 pulverizing process Methods 0.000 description 1
• 150000003217 pyrazoles Chemical class 0.000 description 1
• 238000011002 quantification Methods 0.000 description 1
• 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• 102000005962 receptors Human genes 0.000 description 1
• 108020003175 receptors Proteins 0.000 description 1
• 201000002793 renal fibrosis Diseases 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 208000037803 restenosis Diseases 0.000 description 1
• 210000003994 retinal ganglion cell Anatomy 0.000 description 1
• WXXSNCNJFUAIDG-UHFFFAOYSA-N riociguat Chemical compound N1=C(N)C(N(C)C(=O)OC)=C(N)N=C1C(C1=CC=CN=C11)=NN1CC1=CC=CC=C1F WXXSNCNJFUAIDG-UHFFFAOYSA-N 0.000 description 1
• 229960000529 riociguat Drugs 0.000 description 1
• 230000000630 rising effect Effects 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
• 229940116351 sebacate Drugs 0.000 description 1
• CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 239000003478 serotonin 5-HT2 receptor agonist Substances 0.000 description 1
• 239000000377 silicon dioxide Substances 0.000 description 1
• 229910052709 silver Inorganic materials 0.000 description 1
• 239000004332 silver Substances 0.000 description 1
• LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 1
• 229910001958 silver carbonate Inorganic materials 0.000 description 1
• 229940015676 simbrinza Drugs 0.000 description 1
• 238000009097 single-agent therapy Methods 0.000 description 1
• 201000000849 skin cancer Diseases 0.000 description 1
• 239000002002 slurry Substances 0.000 description 1
• 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 1
• 229960002218 sodium chlorite Drugs 0.000 description 1
• 229960001922 sodium perborate Drugs 0.000 description 1
• 239000001488 sodium phosphate Substances 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• 229910052938 sodium sulfate Inorganic materials 0.000 description 1
• 235000011152 sodium sulphate Nutrition 0.000 description 1
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
• YKLJGMBLPUQQOI-UHFFFAOYSA-M sodium;oxidooxy(oxo)borane Chemical compound [Na+].[O-]OB=O YKLJGMBLPUQQOI-UHFFFAOYSA-M 0.000 description 1
• ZNKXTIAQRUWLRL-UHFFFAOYSA-M sodium;sulfane;hydroxide Chemical compound O.[Na+].[SH-] ZNKXTIAQRUWLRL-UHFFFAOYSA-M 0.000 description 1
• 239000007901 soft capsule Substances 0.000 description 1
• 239000008137 solubility enhancer Substances 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 238000004611 spectroscopical analysis Methods 0.000 description 1
• 230000006641 stabilisation Effects 0.000 description 1
• 238000011105 stabilization Methods 0.000 description 1
• 230000001954 sterilising effect Effects 0.000 description 1
• 238000004659 sterilization and disinfection Methods 0.000 description 1
• 230000004936 stimulating effect Effects 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
• 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 238000007910 systemic administration Methods 0.000 description 1
• 239000003826 tablet Substances 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• MSIRZXLJORDERI-UHFFFAOYSA-N tert-butyl 4-(2-chloro-4-hydroxyphenyl)piperidine-1-carboxylate Chemical compound ClC1=C(C=CC(=C1)O)C1CCN(CC1)C(=O)OC(C)(C)C MSIRZXLJORDERI-UHFFFAOYSA-N 0.000 description 1
• IYNLFTHNQLCXAS-UHFFFAOYSA-N tert-butyl 4-(2-chloro-6-methoxypyridin-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylate Chemical compound ClC1=NC(=CC=C1C1=CCN(CC1)C(=O)OC(C)(C)C)OC IYNLFTHNQLCXAS-UHFFFAOYSA-N 0.000 description 1
• JDFDFVCIRJHZAW-UHFFFAOYSA-N tert-butyl 4-(2-cyclopropyl-4-hydroxyphenyl)piperidine-1-carboxylate Chemical compound C1(CC1)C1=C(C=CC(=C1)O)C1CCN(CC1)C(=O)OC(C)(C)C JDFDFVCIRJHZAW-UHFFFAOYSA-N 0.000 description 1
• ZNOFGLQGCIKRNL-UHFFFAOYSA-N tert-butyl 4-(2-ethyl-3-fluoro-4-hydroxyphenyl)piperidine-1-carboxylate Chemical compound C(C)C1=C(C=CC(=C1F)O)C1CCN(CC1)C(=O)OC(C)(C)C ZNOFGLQGCIKRNL-UHFFFAOYSA-N 0.000 description 1
• GASMIAYYKCUENM-UHFFFAOYSA-N tert-butyl 4-(2-ethyl-4-hydroxyphenyl)-3,6-dihydro-2H-pyridine-1-carboxylate Chemical compound C(C)C1=C(C=CC(=C1)O)C1=CCN(CC1)C(=O)OC(C)(C)C GASMIAYYKCUENM-UHFFFAOYSA-N 0.000 description 1
• USBGQDLNSJEGEN-UHFFFAOYSA-N tert-butyl 4-(2-ethyl-6-methoxypyridin-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylate Chemical compound C(C)C1=NC(=CC=C1C1=CCN(CC1)C(=O)OC(C)(C)C)OC USBGQDLNSJEGEN-UHFFFAOYSA-N 0.000 description 1
• MODOGKRTFTXVLG-UHFFFAOYSA-N tert-butyl 4-(2-ethyl-6-methoxypyridin-3-yl)piperidine-1-carboxylate Chemical compound C(C)C1=NC(=CC=C1C1CCN(CC1)C(=O)OC(C)(C)C)OC MODOGKRTFTXVLG-UHFFFAOYSA-N 0.000 description 1
• NOLPZKMKZPRBEZ-UHFFFAOYSA-N tert-butyl 4-(3-chloro-4-hydroxyphenyl)piperidine-1-carboxylate Chemical compound ClC=1C=C(C=CC=1O)C1CCN(CC1)C(=O)OC(C)(C)C NOLPZKMKZPRBEZ-UHFFFAOYSA-N 0.000 description 1
• DYIXRLOWAQEDDL-UHFFFAOYSA-N tert-butyl 4-(3-ethyl-5-hydroxypyridin-2-yl)piperidine-1-carboxylate Chemical compound C(C)C=1C(=NC=C(C=1)O)C1CCN(CC1)C(=O)OC(C)(C)C DYIXRLOWAQEDDL-UHFFFAOYSA-N 0.000 description 1
• GNLMUOBRTDOQID-UHFFFAOYSA-N tert-butyl 4-(4-amino-2-ethylphenyl)piperidine-1-carboxylate Chemical compound NC1=CC(=C(C=C1)C1CCN(CC1)C(=O)OC(C)(C)C)CC GNLMUOBRTDOQID-UHFFFAOYSA-N 0.000 description 1
• CZGMDLYFBULKGX-UHFFFAOYSA-N tert-butyl 4-(4-hydroxy-2-propylphenyl)piperidine-1-carboxylate Chemical compound OC1=CC(=C(C=C1)C1CCN(CC1)C(=O)OC(C)(C)C)CCC CZGMDLYFBULKGX-UHFFFAOYSA-N 0.000 description 1
• GKBNVJLJNRKSAF-UHFFFAOYSA-N tert-butyl 4-(4-hydroxy-3-methylphenyl)-3,6-dihydro-2H-pyridine-1-carboxylate Chemical compound OC1=C(C=C(C=C1)C1=CCN(CC1)C(=O)OC(C)(C)C)C GKBNVJLJNRKSAF-UHFFFAOYSA-N 0.000 description 1
• XKQQXMJVWLOPDH-UHFFFAOYSA-N tert-butyl 4-[4-[(2-bromothiophen-3-yl)methoxy]phenyl]piperidine-1-carboxylate Chemical compound BrC=1SC=CC=1COC1=CC=C(C=C1)C1CCN(CC1)C(=O)OC(C)(C)C XKQQXMJVWLOPDH-UHFFFAOYSA-N 0.000 description 1
• POCDUGZQMXWOAO-UHFFFAOYSA-N tert-butyl 4-[4-[2-[2-[6-[4-ethoxycarbonyl-5-(trifluoromethyl)pyrazol-1-yl]pyridin-2-yl]thiophen-3-yl]ethenyl]phenyl]-3,6-dihydro-2H-pyridine-1-carboxylate Chemical compound C(C)OC(=O)C=1C=NN(C=1C(F)(F)F)C1=CC=CC(=N1)C=1SC=CC=1C=CC1=CC=C(C=C1)C1=CCN(CC1)C(=O)OC(C)(C)C POCDUGZQMXWOAO-UHFFFAOYSA-N 0.000 description 1
• GFJXOPGTBDCOCW-UHFFFAOYSA-N tert-butyl 4-[4-[[2-bromo-4-(trifluoromethyl)thiophen-3-yl]methoxy]-3-methylphenyl]piperidine-1-carboxylate Chemical compound BrC=1SC=C(C=1COC1=C(C=C(C=C1)C1CCN(CC1)C(=O)OC(C)(C)C)C)C(F)(F)F GFJXOPGTBDCOCW-UHFFFAOYSA-N 0.000 description 1
• QELOANLIBNLHHH-UHFFFAOYSA-N tert-butyl 4-[4-[[2-bromo-4-(trifluoromethyl)thiophen-3-yl]methoxy]phenyl]piperidine-1-carboxylate Chemical compound BrC=1SC=C(C=1COC1=CC=C(C=C1)C1CCN(CC1)C(=O)OC(C)(C)C)C(F)(F)F QELOANLIBNLHHH-UHFFFAOYSA-N 0.000 description 1
• PQILACDFDBWRNK-UHFFFAOYSA-N tert-butyl 4-bromo-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(Br)=CC1 PQILACDFDBWRNK-UHFFFAOYSA-N 0.000 description 1
• VBGLHBOXTRXGBZ-UHFFFAOYSA-N tert-butyl 6-[(2-bromothiophen-3-yl)methoxy]-3,4-dihydro-1H-isoquinoline-2-carboxylate Chemical compound BrC=1SC=CC=1COC=1C=C2CCN(CC2=CC=1)C(=O)OC(C)(C)C VBGLHBOXTRXGBZ-UHFFFAOYSA-N 0.000 description 1
• 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 238000012360 testing method Methods 0.000 description 1
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
• NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
• 231100001274 therapeutic index Toxicity 0.000 description 1
• ARYHTUPFQTUBBG-UHFFFAOYSA-N thiophen-2-ylboronic acid Chemical compound OB(O)C1=CC=CS1 ARYHTUPFQTUBBG-UHFFFAOYSA-N 0.000 description 1
• VNVAUIHQJKDHBN-UHFFFAOYSA-N thiophene;hydrobromide Chemical compound Br.C=1C=CSC=1 VNVAUIHQJKDHBN-UHFFFAOYSA-N 0.000 description 1
• 238000003354 tissue distribution assay Methods 0.000 description 1
• 239000012929 tonicity agent Substances 0.000 description 1
• 239000012443 tonicity enhancing agent Substances 0.000 description 1
• 239000008181 tonicity modifier Substances 0.000 description 1
• 239000012049 topical pharmaceutical composition Substances 0.000 description 1
• 230000037317 transdermal delivery Effects 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• MKPLKVHSHYCHOC-AHTXBMBWSA-N travoprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\[C@@H](O)COC1=CC=CC(C(F)(F)F)=C1 MKPLKVHSHYCHOC-AHTXBMBWSA-N 0.000 description 1
• 229960002368 travoprost Drugs 0.000 description 1
• 238000011269 treatment regimen Methods 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
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
• 229960000281 trometamol Drugs 0.000 description 1
• 229960000438 udenafil Drugs 0.000 description 1
• IYFNEFQTYQPVOC-UHFFFAOYSA-N udenafil Chemical compound C1=C(C=2NC=3C(CCC)=NN(C)C=3C(=O)N=2)C(OCCC)=CC=C1S(=O)(=O)NCCC1CCCN1C IYFNEFQTYQPVOC-UHFFFAOYSA-N 0.000 description 1
• 238000001195 ultra high performance liquid chromatography Methods 0.000 description 1
• 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
• 210000003606 umbilical vein Anatomy 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 235000013311 vegetables Nutrition 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 230000004393 visual impairment Effects 0.000 description 1
• 239000003643 water by type Substances 0.000 description 1
• 229920003169 water-soluble polymer Polymers 0.000 description 1
• 238000009736 wetting Methods 0.000 description 1
• 235000010493 xanthan gum Nutrition 0.000 description 1
• 239000000230 xanthan gum Substances 0.000 description 1
• 229920001285 xanthan gum Polymers 0.000 description 1
• 229940082509 xanthan gum Drugs 0.000 description 1
• 229950000339 xinafoate Drugs 0.000 description 1
• UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical group CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1