NO324843B1 - Substituerte pyrrolpyridinonderivater nyttige som fosfordiesterase-inhibitorer, og farmasoytiske preparater som innbefatter slike - Google Patents

Info

Publication number

NO324843B1

NO324843B1 NO20025525A NO20025525A NO324843B1 NO 324843 B1 NO324843 B1 NO 324843B1 NO 20025525 A NO20025525 A NO 20025525A NO 20025525 A NO20025525 A NO 20025525A NO 324843 B1 NO324843 B1 NO 324843B1

Authority

NO

Norway

Prior art keywords

pyridinyl

tetrahydro

mmol

pyrrolo

group

Prior art date

2000-05-17

Links

• Espacenet
• Global Dossier
• Discuss

• 239000003112 inhibitor Substances 0.000 title description 11
• 239000008194 pharmaceutical composition Substances 0.000 title description 2
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 title 1
• 229910052698 phosphorus Inorganic materials 0.000 title 1
• 239000011574 phosphorus Substances 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims description 214
• -1 hydroxy, carboxy Chemical group 0.000 claims description 120
• 150000003839 salts Chemical class 0.000 claims description 25
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
• 229910052739 hydrogen Inorganic materials 0.000 claims description 16
• 229910052736 halogen Inorganic materials 0.000 claims description 15
• 150000002367 halogens Chemical class 0.000 claims description 15
• 239000001257 hydrogen Substances 0.000 claims description 15
• 125000001424 substituent group Chemical group 0.000 claims description 14
• 125000000217 alkyl group Chemical group 0.000 claims description 12
• 239000000825 pharmaceutical preparation Substances 0.000 claims description 12
• 239000003937 drug carrier Substances 0.000 claims description 11
• 125000001072 heteroaryl group Chemical group 0.000 claims description 9
• 125000004076 pyridyl group Chemical group 0.000 claims description 8
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 7
• 125000003545 alkoxy group Chemical group 0.000 claims description 6
• 125000002883 imidazolyl group Chemical group 0.000 claims description 6
• 125000002541 furyl group Chemical group 0.000 claims description 5
• 238000002156 mixing Methods 0.000 claims description 5
• 125000000335 thiazolyl group Chemical group 0.000 claims description 5
• 238000004519 manufacturing process Methods 0.000 claims description 4
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
• 125000005530 alkylenedioxy group Chemical group 0.000 claims description 3
• 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
• 125000004043 oxo group Chemical group O=* 0.000 claims description 3
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 2
• IYZTVUCAOUBGHK-UHFFFAOYSA-N 3-(2,3-dihydro-1-benzofuran-5-yl)-2-(5-pyridin-2-ylpyridin-2-yl)-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound C=1C=C2OCCC2=CC=1C1C=2NC3=CC=CC=C3C(=O)C=2CN1C(N=C1)=CC=C1C1=CC=CC=N1 IYZTVUCAOUBGHK-UHFFFAOYSA-N 0.000 claims description 2
• 125000004598 dihydrobenzofuryl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims description 2
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 2
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
• LIXPPXSXJKCWIR-UHFFFAOYSA-N pyridin-4-ylmethyl 3-(1,3-benzodioxol-5-yl)-9-oxo-3,4-dihydro-1h-pyrrolo[3,4-b]quinoline-2-carboxylate Chemical compound C1C(C(C2=CC=CC=C2N2)=O)=C2C(C=2C=C3OCOC3=CC=2)N1C(=O)OCC1=CC=NC=C1 LIXPPXSXJKCWIR-UHFFFAOYSA-N 0.000 claims description 2
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
• 125000001680 trimethoxyphenyl group Chemical group 0.000 claims description 2
• KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims 7
• 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims 5
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 5
• 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims 5
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims 4
• 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 4
• 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 4
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 4
• UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims 3
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims 3
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims 2
• UKTMVBPQNHUHGD-MUUNZHRXSA-N (3r)-3-(1,3-benzodioxol-5-yl)-2-[5-(3,4-dimethoxyphenyl)pyrimidin-2-yl]-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound C1=C(OC)C(OC)=CC=C1C1=CN=C(N2[C@@H](C3=C(C(C4=CC=CC=C4N3)=O)C2)C=2C=C3OCOC3=CC=2)N=C1 UKTMVBPQNHUHGD-MUUNZHRXSA-N 0.000 claims 1
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
• LIXPPXSXJKCWIR-HSZRJFAPSA-N pyridin-4-ylmethyl (3r)-3-(1,3-benzodioxol-5-yl)-9-oxo-3,4-dihydro-1h-pyrrolo[3,4-b]quinoline-2-carboxylate Chemical compound C1([C@H]2C=3C=C4OCOC4=CC=3)=NC3=CC=CC=C3C(O)=C1CN2C(=O)OCC1=CC=NC=C1 LIXPPXSXJKCWIR-HSZRJFAPSA-N 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 167
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 146
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 128
• 238000005160 1H NMR spectroscopy Methods 0.000 description 117
• 239000000047 product Substances 0.000 description 106
• 238000000034 method Methods 0.000 description 104
• 239000007787 solid Substances 0.000 description 101
• 239000000243 solution Substances 0.000 description 95
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 78
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 76
• 239000000203 mixture Substances 0.000 description 64
• 239000011541 reaction mixture Substances 0.000 description 64
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 60
• 235000019439 ethyl acetate Nutrition 0.000 description 60
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 47
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 44
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 40
• 201000001881 impotence Diseases 0.000 description 37
• 230000008569 process Effects 0.000 description 37
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
• 239000002904 solvent Substances 0.000 description 35
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 34
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 34
• 239000000741 silica gel Substances 0.000 description 33
• 229910002027 silica gel Inorganic materials 0.000 description 33
• 235000002639 sodium chloride Nutrition 0.000 description 33
• 208000010228 Erectile Dysfunction Diseases 0.000 description 32
• 239000000460 chlorine Substances 0.000 description 29
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
• 239000012267 brine Substances 0.000 description 28
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 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 27
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 26
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 25
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 25
• 238000011282 treatment Methods 0.000 description 25
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
• 239000003153 chemical reaction reagent Substances 0.000 description 22
• 239000003960 organic solvent Substances 0.000 description 22
• 238000002360 preparation method Methods 0.000 description 22
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 20
• 238000006243 chemical reaction Methods 0.000 description 20
• 239000002244 precipitate Substances 0.000 description 20
• 229910001882 dioxygen Inorganic materials 0.000 description 19
• 238000003818 flash chromatography Methods 0.000 description 19
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 18
• 238000000746 purification Methods 0.000 description 18
• 210000001519 tissue Anatomy 0.000 description 18
• 102000011016 Type 5 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 description 17
• 108010037581 Type 5 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 description 17
• 239000002253 acid Substances 0.000 description 17
• 239000003054 catalyst Substances 0.000 description 17
• 239000012044 organic layer Substances 0.000 description 16
• ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 15
• 238000004440 column chromatography Methods 0.000 description 15
• 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 14
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 14
• MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 14
• ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 14
• 238000012746 preparative thin layer chromatography Methods 0.000 description 14
• 239000000725 suspension Substances 0.000 description 14
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 13
• 239000000843 powder Substances 0.000 description 13
• 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 description 13
• 239000011780 sodium chloride Substances 0.000 description 13
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
• ORKUYZDMEWAUEZ-UHFFFAOYSA-N pyrrolo[3,2-b]pyridin-2-one Chemical class N1=CC=CC2=NC(=O)C=C21 ORKUYZDMEWAUEZ-UHFFFAOYSA-N 0.000 description 12
• 239000011734 sodium Substances 0.000 description 12
• 229910000104 sodium hydride Inorganic materials 0.000 description 12
• 102000004190 Enzymes Human genes 0.000 description 11
• 108090000790 Enzymes Proteins 0.000 description 11
• 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 11
• 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 11
• 230000015572 biosynthetic process Effects 0.000 description 11
• 239000004327 boric acid Substances 0.000 description 11
• 238000001914 filtration Methods 0.000 description 11
• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 11
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 10
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 10
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 10
• 208000035475 disorder Diseases 0.000 description 10
• 239000012312 sodium hydride Substances 0.000 description 10
• ZLIPDSSTFWTNLJ-UHFFFAOYSA-N 3-(1,3-benzodioxol-5-yl)-1,2,3,4-tetrahydropyrrolo[3,4-b]quinolin-9-one Chemical compound C1=C2OCOC2=CC(C2NCC=3C(C4=CC=CC=C4NC=32)=O)=C1 ZLIPDSSTFWTNLJ-UHFFFAOYSA-N 0.000 description 9
• 201000001880 Sexual dysfunction Diseases 0.000 description 9
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
• 239000003814 drug Substances 0.000 description 9
• 231100000872 sexual dysfunction Toxicity 0.000 description 9
• 238000006467 substitution reaction Methods 0.000 description 9
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
• 206010057671 Female sexual dysfunction Diseases 0.000 description 8
• 229940079593 drug Drugs 0.000 description 8
• 239000007789 gas Substances 0.000 description 8
• 239000007788 liquid Substances 0.000 description 8
• 239000002480 mineral oil Substances 0.000 description 8
• 235000010446 mineral oil Nutrition 0.000 description 8
• 239000012074 organic phase Substances 0.000 description 8
• 239000003826 tablet Substances 0.000 description 8
• 238000012360 testing method Methods 0.000 description 8
• DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical class CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 8
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 7
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 7
• 239000002585 base Substances 0.000 description 7
• KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical class OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 7
• 239000012458 free base Substances 0.000 description 7
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 7
• 239000007800 oxidant agent Substances 0.000 description 7
• 229920006395 saturated elastomer Polymers 0.000 description 7
• 239000007858 starting material Substances 0.000 description 7
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 6
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 6
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
• 206010019280 Heart failures Diseases 0.000 description 6
• CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 6
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
• 230000000694 effects Effects 0.000 description 6
• 230000003834 intracellular effect Effects 0.000 description 6
• 239000010410 layer Substances 0.000 description 6
• 238000002844 melting Methods 0.000 description 6
• 230000008018 melting Effects 0.000 description 6
• QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 6
• 239000003921 oil Substances 0.000 description 6
• 235000019198 oils Nutrition 0.000 description 6
• 229910052760 oxygen Inorganic materials 0.000 description 6
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [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 6
• YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 6
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
• XXQBEVHPUKOQEO-UHFFFAOYSA-N potassium peroxide Inorganic materials [K+].[K+].[O-][O-] XXQBEVHPUKOQEO-UHFFFAOYSA-N 0.000 description 6
• 208000002815 pulmonary hypertension Diseases 0.000 description 6
• 238000010992 reflux Methods 0.000 description 6
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 5
• 206010002383 Angina Pectoris Diseases 0.000 description 5
• 208000024172 Cardiovascular disease Diseases 0.000 description 5
• 206010020772 Hypertension Diseases 0.000 description 5
• 238000004458 analytical method Methods 0.000 description 5
• 125000003118 aryl group Chemical group 0.000 description 5
• 208000006673 asthma Diseases 0.000 description 5
• 230000017531 blood circulation Effects 0.000 description 5
• 239000002775 capsule Substances 0.000 description 5
• 150000001732 carboxylic acid derivatives Chemical group 0.000 description 5
• 210000005226 corpus cavernosum Anatomy 0.000 description 5
• 230000004064 dysfunction Effects 0.000 description 5
• 230000002401 inhibitory effect Effects 0.000 description 5
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 5
• 239000006187 pill Substances 0.000 description 5
• 230000001568 sexual effect Effects 0.000 description 5
• 229960003310 sildenafil Drugs 0.000 description 5
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 5
• RQPNZWNSBMSVKC-UHFFFAOYSA-N 3-(2,3-dihydro-1-benzofuran-5-yl)-1,2,3,4-tetrahydropyrrolo[3,4-b]quinolin-9-one Chemical compound C1=C2OCCC2=CC(C2NCC=3C(C4=CC=CC=C4NC=32)=O)=C1 RQPNZWNSBMSVKC-UHFFFAOYSA-N 0.000 description 4
• BTJIUGUIPKRLHP-UHFFFAOYSA-M 4-nitrophenolate Chemical group [O-]C1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-M 0.000 description 4
• XPGIBDJXEVAVTO-UHFFFAOYSA-N 5-bromo-2-chloropyrimidine Chemical compound ClC1=NC=C(Br)C=N1 XPGIBDJXEVAVTO-UHFFFAOYSA-N 0.000 description 4
• 201000001320 Atherosclerosis Diseases 0.000 description 4
• 208000002249 Diabetes Complications Diseases 0.000 description 4
• 208000005171 Dysmenorrhea Diseases 0.000 description 4
• 206010013935 Dysmenorrhoea Diseases 0.000 description 4
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
• 206010022562 Intermittent claudication Diseases 0.000 description 4
• 241001465754 Metazoa Species 0.000 description 4
• 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 4
• URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical group CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 description 4
• 208000007536 Thrombosis Diseases 0.000 description 4
• 229960000583 acetic acid Drugs 0.000 description 4
• 239000004480 active ingredient Substances 0.000 description 4
• 239000012300 argon atmosphere Substances 0.000 description 4
• 230000037396 body weight Effects 0.000 description 4
• 125000005619 boric acid group Chemical group 0.000 description 4
• 210000003029 clitoris Anatomy 0.000 description 4
• 239000012362 glacial acetic acid Substances 0.000 description 4
• 208000019622 heart disease Diseases 0.000 description 4
• 238000004128 high performance liquid chromatography Methods 0.000 description 4
• 150000002431 hydrogen Chemical class 0.000 description 4
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 4
• 239000007924 injection Substances 0.000 description 4
• 238000002347 injection Methods 0.000 description 4
• 208000021156 intermittent vascular claudication Diseases 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• 208000010125 myocardial infarction Diseases 0.000 description 4
• 239000001301 oxygen Substances 0.000 description 4
• 125000006239 protecting group Chemical group 0.000 description 4
• 239000000758 substrate Substances 0.000 description 4
• 238000003786 synthesis reaction Methods 0.000 description 4
• 210000001215 vagina Anatomy 0.000 description 4
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical class CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
• XASJMEVESBZEOO-UHFFFAOYSA-N 2-chloro-5-(4-methoxyphenyl)pyrimidine Chemical compound C1=CC(OC)=CC=C1C1=CN=C(Cl)N=C1 XASJMEVESBZEOO-UHFFFAOYSA-N 0.000 description 3
• UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical compound ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 description 3
• GCFPFWRHYINTRX-UHFFFAOYSA-N 2-hydroxy-4-methylbenzenesulfonic acid Chemical group CC1=CC=C(S(O)(=O)=O)C(O)=C1 GCFPFWRHYINTRX-UHFFFAOYSA-N 0.000 description 3
• MSNMTBLMABIHNJ-UHFFFAOYSA-N 3-(1,3-benzodioxol-5-yl)-2-(5-bromopyrimidin-2-yl)-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound N1=CC(Br)=CN=C1N1C(C=2C=C3OCOC3=CC=2)C(NC=2C(=CC=CC=2)C2=O)=C2C1 MSNMTBLMABIHNJ-UHFFFAOYSA-N 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
• 241000416162 Astragalus gummifer Species 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 3
• 206010012655 Diabetic complications Diseases 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 3
• 240000007472 Leucaena leucocephala Species 0.000 description 3
• 229920001615 Tragacanth Polymers 0.000 description 3
• 150000001412 amines Chemical class 0.000 description 3
• 239000000908 ammonium hydroxide Substances 0.000 description 3
• 230000037007 arousal Effects 0.000 description 3
• 238000003556 assay Methods 0.000 description 3
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
• 239000011230 binding agent Substances 0.000 description 3
• 125000004432 carbon atom Chemical group C* 0.000 description 3
• 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 3
• 239000000969 carrier Substances 0.000 description 3
• 229910052801 chlorine Inorganic materials 0.000 description 3
• 239000012043 crude product Substances 0.000 description 3
• 239000000706 filtrate Substances 0.000 description 3
• 125000005842 heteroatom Chemical group 0.000 description 3
• 239000004615 ingredient Substances 0.000 description 3
• 230000005764 inhibitory process Effects 0.000 description 3
• 230000000302 ischemic effect Effects 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
• 235000019341 magnesium sulphate Nutrition 0.000 description 3
• 239000000463 material Substances 0.000 description 3
• 229920000609 methyl cellulose Polymers 0.000 description 3
• 239000001923 methylcellulose Substances 0.000 description 3
• 235000010981 methylcellulose Nutrition 0.000 description 3
• 238000012986 modification Methods 0.000 description 3
• 230000004048 modification Effects 0.000 description 3
• 230000018052 penile erection Effects 0.000 description 3
• 239000002571 phosphodiesterase inhibitor Substances 0.000 description 3
• 229910000027 potassium carbonate Inorganic materials 0.000 description 3
• 238000001556 precipitation Methods 0.000 description 3
• 230000002028 premature Effects 0.000 description 3
• 239000011347 resin Substances 0.000 description 3
• 229920005989 resin Polymers 0.000 description 3
• 238000010898 silica gel chromatography Methods 0.000 description 3
• 239000012258 stirred mixture Substances 0.000 description 3
• 239000006228 supernatant Substances 0.000 description 3
• 239000000375 suspending agent Substances 0.000 description 3
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
• 235000010487 tragacanth Nutrition 0.000 description 3
• 239000000196 tragacanth Substances 0.000 description 3
• 229940116362 tragacanth Drugs 0.000 description 3
• KYILORDWJFEQBS-RMKNXTFCSA-N (2e)-2-benzylidenebutanedioic acid Chemical compound OC(=O)C\C(C(O)=O)=C/C1=CC=CC=C1 KYILORDWJFEQBS-RMKNXTFCSA-N 0.000 description 2
• RQPNZWNSBMSVKC-QGZVFWFLSA-N (3r)-3-(2,3-dihydro-1-benzofuran-5-yl)-1,2,3,4-tetrahydropyrrolo[3,4-b]quinolin-9-one Chemical compound C1=C2OCCC2=CC([C@H]2NCC=3C(C4=CC=CC=C4NC=32)=O)=C1 RQPNZWNSBMSVKC-QGZVFWFLSA-N 0.000 description 2
• YFYUIURGBVQUBL-UNTBIKODSA-N (3r)-3-(2,3-dihydro-1-benzofuran-5-yl)-1,2,3,4-tetrahydropyrrolo[3,4-b]quinolin-9-one;hydrochloride Chemical compound Cl.C1=C2OCCC2=CC([C@H]2NCC=3C(C4=CC=CC=C4NC=32)=O)=C1 YFYUIURGBVQUBL-UNTBIKODSA-N 0.000 description 2
• MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 2
• SQJDLBYYQQIVSB-UHFFFAOYSA-N 1-methyl-5-pyridin-2-ylpyrimidin-2-one Chemical compound C1=NC(=O)N(C)C=C1C1=CC=CC=N1 SQJDLBYYQQIVSB-UHFFFAOYSA-N 0.000 description 2
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
• YFJZTISMEVURGQ-UHFFFAOYSA-N 2-[5-(3-benzylimidazol-4-yl)pyridin-2-yl]-3-(2,3-dihydro-1-benzofuran-5-yl)-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound C=1C=C2OCCC2=CC=1C1C=2NC3=CC=CC=C3C(=O)C=2CN1C(N=C1)=CC=C1C1=CN=CN1CC1=CC=CC=C1 YFJZTISMEVURGQ-UHFFFAOYSA-N 0.000 description 2
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
• VIYBNMCRHNVHRW-UHFFFAOYSA-N 2-benzyl-3-(2,3-dihydro-1-benzofuran-5-yl)-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound C=1C=C2OCCC2=CC=1C1C=2NC3=CC=CC=C3C(=O)C=2CN1CC1=CC=CC=C1 VIYBNMCRHNVHRW-UHFFFAOYSA-N 0.000 description 2
• ZVGGKATULXUPCL-UHFFFAOYSA-N 2-chloro-5-(3-methylimidazol-4-yl)pyridine Chemical compound CN1C=NC=C1C1=CC=C(Cl)N=C1 ZVGGKATULXUPCL-UHFFFAOYSA-N 0.000 description 2
• QKHVYVWUZZAQBC-UHFFFAOYSA-N 2-chloro-5-pyridin-2-ylpyrimidine Chemical compound C1=NC(Cl)=NC=C1C1=CC=CC=N1 QKHVYVWUZZAQBC-UHFFFAOYSA-N 0.000 description 2
• UHFATFSNMZKPNP-UHFFFAOYSA-N 3-(1,3-benzodioxol-5-yl)-1,2,3,4-tetrahydropyrrolo[3,4-b]quinolin-9-one hydrochloride Chemical compound Cl.O=c1c2CNC(c2[nH]c2ccccc12)c1ccc2OCOc2c1 UHFATFSNMZKPNP-UHFFFAOYSA-N 0.000 description 2
• BYZNVDZRIPNYSS-UHFFFAOYSA-N 3-(1,3-benzodioxol-5-yl)-2-[5-(4-nitrophenyl)furan-2-carbonyl]-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound C1=CC([N+](=O)[O-])=CC=C1C1=CC=C(C(=O)N2C(C3=C(C(C4=CC=CC=C4N3)=O)C2)C=2C=C3OCOC3=CC=2)O1 BYZNVDZRIPNYSS-UHFFFAOYSA-N 0.000 description 2
• KGENQSVKAHPEBR-UHFFFAOYSA-N 3-(1,3-benzodioxol-5-yl)-2-benzyl-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound C=1C=C2OCOC2=CC=1C1C=2NC3=CC=CC=C3C(=O)C=2CN1CC1=CC=CC=C1 KGENQSVKAHPEBR-UHFFFAOYSA-N 0.000 description 2
• OFCFRIBTCIXCPK-UHFFFAOYSA-N 3-(1,3-benzodioxol-5-yl)-2-pyrimidin-2-yl-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound C=1C=C2OCOC2=CC=1C1C=2NC3=CC=CC=C3C(=O)C=2CN1C1=NC=CC=N1 OFCFRIBTCIXCPK-UHFFFAOYSA-N 0.000 description 2
• LZIMQRPTGQTCJP-UHFFFAOYSA-N 3-(2,3-dihydro-1-benzofuran-5-yl)-2-[5-(3-methylimidazol-4-yl)pyridin-2-yl]-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound CN1C=NC=C1C1=CC=C(N2C(C3=C(C(C4=CC=CC=C4N3)=O)C2)C=2C=C3CCOC3=CC=2)N=C1 LZIMQRPTGQTCJP-UHFFFAOYSA-N 0.000 description 2
• NPQHDOLBQQVPMG-UHFFFAOYSA-N 3-(2,3-dihydro-1-benzofuran-5-yl)-2-pyridin-2-yl-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound C=1C=C2OCCC2=CC=1C1C=2NC3=CC=CC=C3C(=O)C=2CN1C1=CC=CC=N1 NPQHDOLBQQVPMG-UHFFFAOYSA-N 0.000 description 2
• QLVNUZPODFIOGC-UHFFFAOYSA-N 5-bromofuran-2-carbonyl chloride Chemical compound ClC(=O)C1=CC=C(Br)O1 QLVNUZPODFIOGC-UHFFFAOYSA-N 0.000 description 2
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
• DHMYULZVFHHEHE-UHFFFAOYSA-N 9h-fluoren-9-ylmethyl n-(sulfanylidenemethylidene)carbamate Chemical compound C1=CC=C2C(COC(=O)N=C=S)C3=CC=CC=C3C2=C1 DHMYULZVFHHEHE-UHFFFAOYSA-N 0.000 description 2
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• 201000000057 Coronary Stenosis Diseases 0.000 description 2
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• 108010078321 Guanylate Cyclase Proteins 0.000 description 2
• 102000014469 Guanylate cyclase Human genes 0.000 description 2
• 239000007995 HEPES buffer Substances 0.000 description 2
• 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 2
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
• 206010057672 Male sexual dysfunction Diseases 0.000 description 2
• 101000909851 Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) cAMP/cGMP dual specificity phosphodiesterase Rv0805 Proteins 0.000 description 2
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical group CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
• 241000272108 Ophiophagus hannah Species 0.000 description 2
• 241000283973 Oryctolagus cuniculus Species 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
• 229920002472 Starch Polymers 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• 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 2
• 150000001299 aldehydes Chemical class 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• 239000007900 aqueous suspension Substances 0.000 description 2
• 239000012298 atmosphere Substances 0.000 description 2
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 2
• 238000009835 boiling Methods 0.000 description 2
• 229940098773 bovine serum albumin Drugs 0.000 description 2
• 125000001246 bromo group Chemical group Br* 0.000 description 2
• GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
• 230000005587 bubbling Effects 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• 239000011575 calcium Substances 0.000 description 2
• 229910052791 calcium Inorganic materials 0.000 description 2
• 230000015556 catabolic process Effects 0.000 description 2
• 239000003795 chemical substances by application Substances 0.000 description 2
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
• 238000000576 coating method Methods 0.000 description 2
• 125000004122 cyclic group Chemical group 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• 206010012601 diabetes mellitus Diseases 0.000 description 2
• 201000010099 disease Diseases 0.000 description 2
• 239000007884 disintegrant Substances 0.000 description 2
• 239000002270 dispersing agent Substances 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• 238000001035 drying Methods 0.000 description 2
• 229940009662 edetate Drugs 0.000 description 2
• 238000000921 elemental analysis Methods 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 230000003511 endothelial effect Effects 0.000 description 2
• 239000012055 enteric layer Substances 0.000 description 2
• 150000002148 esters Chemical class 0.000 description 2
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
• 235000003599 food sweetener Nutrition 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
• 239000008187 granular material Substances 0.000 description 2
• 125000000623 heterocyclic group Chemical group 0.000 description 2
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
• 150000003840 hydrochlorides Chemical class 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 239000002502 liposome Substances 0.000 description 2
• 239000000314 lubricant Substances 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• 238000005259 measurement Methods 0.000 description 2
• RVJDAPFIUIWETP-MDWZMJQESA-N methyl 4-[(e)-3-[3-(1,3-benzodioxol-5-yl)-9-oxo-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-2-yl]-3-oxoprop-1-enyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1\C=C\C(=O)N1C(C=2C=C3OCOC3=CC=2)C(NC=2C(=CC=CC=2)C2=O)=C2C1 RVJDAPFIUIWETP-MDWZMJQESA-N 0.000 description 2
• 150000004702 methyl esters Chemical class 0.000 description 2
• 125000002950 monocyclic group Chemical group 0.000 description 2
• 125000001624 naphthyl group Chemical group 0.000 description 2
• 229920001206 natural gum Polymers 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 239000002777 nucleoside Substances 0.000 description 2
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
• 230000001590 oxidative effect Effects 0.000 description 2
• 229910052763 palladium Inorganic materials 0.000 description 2
• XQYZDYMELSJDRZ-UHFFFAOYSA-N papaverine Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 description 2
• 238000007911 parenteral administration Methods 0.000 description 2
• 239000002831 pharmacologic agent Substances 0.000 description 2
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
• 229920000642 polymer Polymers 0.000 description 2
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
• 235000011181 potassium carbonates Nutrition 0.000 description 2
• 230000003389 potentiating effect Effects 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• 230000001107 psychogenic effect Effects 0.000 description 2
• ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical compound OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 0.000 description 2
• 238000001953 recrystallisation Methods 0.000 description 2
• 239000002002 slurry Substances 0.000 description 2
• 239000003998 snake venom Substances 0.000 description 2
• 239000001632 sodium acetate Substances 0.000 description 2
• 235000017281 sodium acetate Nutrition 0.000 description 2
• 239000012453 solvate Substances 0.000 description 2
• 239000008107 starch Substances 0.000 description 2
• 235000019698 starch Nutrition 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 229910052717 sulfur Inorganic materials 0.000 description 2
• 239000003765 sweetening agent Substances 0.000 description 2
• 208000024891 symptom Diseases 0.000 description 2
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
• 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
• 238000001665 trituration Methods 0.000 description 2
• APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 2
• 239000002691 unilamellar liposome Substances 0.000 description 2
• 230000001196 vasorelaxation Effects 0.000 description 2
• WJUFSDZVCOTFON-UHFFFAOYSA-N veratraldehyde Chemical compound COC1=CC=C(C=O)C=C1OC WJUFSDZVCOTFON-UHFFFAOYSA-N 0.000 description 2
• KHWYSUBVXWWBRB-UHFFFAOYSA-N (+/-)-n-ethyl-1-phenyl-2-butylamine Chemical compound CCNC(CC)CC1=CC=CC=C1 KHWYSUBVXWWBRB-UHFFFAOYSA-N 0.000 description 1
• SFUIGUOONHIVLG-UHFFFAOYSA-N (2-nitrophenyl)boronic acid Chemical compound OB(O)C1=CC=CC=C1[N+]([O-])=O SFUIGUOONHIVLG-UHFFFAOYSA-N 0.000 description 1
• CMIBUZBMZCBCAT-HZPDHXFCSA-N (2r,3r)-2,3-bis[(4-methylbenzoyl)oxy]butanedioic acid Chemical compound C1=CC(C)=CC=C1C(=O)O[C@@H](C(O)=O)[C@H](C(O)=O)OC(=O)C1=CC=C(C)C=C1 CMIBUZBMZCBCAT-HZPDHXFCSA-N 0.000 description 1
• LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
• UHFATFSNMZKPNP-PKLMIRHRSA-N (3R)-3-(1,3-benzodioxol-5-yl)-1,2,3,4-tetrahydropyrrolo[3,4-b]quinolin-2-ium-9-one chloride Chemical compound [Cl-].C1=C2OCOC2=CC([C@H]2[NH2+]CC=3C(C4=CC=CC=C4NC=32)=O)=C1 UHFATFSNMZKPNP-PKLMIRHRSA-N 0.000 description 1
• VIYBNMCRHNVHRW-RUZDIDTESA-N (3r)-2-benzyl-3-(2,3-dihydro-1-benzofuran-5-yl)-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound C=1([C@H]2C=3C=C4CCOC4=CC=3)NC3=CC=CC=C3C(=O)C=1CN2CC1=CC=CC=C1 VIYBNMCRHNVHRW-RUZDIDTESA-N 0.000 description 1
• ZLIPDSSTFWTNLJ-MRXNPFEDSA-N (3r)-3-(1,3-benzodioxol-5-yl)-1,2,3,4-tetrahydropyrrolo[3,4-b]quinolin-9-one Chemical compound C1=C2OCOC2=CC([C@H]2NCC=3C(C4=CC=CC=C4NC=32)=O)=C1 ZLIPDSSTFWTNLJ-MRXNPFEDSA-N 0.000 description 1
• KGENQSVKAHPEBR-XMMPIXPASA-N (3r)-3-(1,3-benzodioxol-5-yl)-2-benzyl-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound C=1([C@H]2C=3C=C4OCOC4=CC=3)NC3=CC=CC=C3C(=O)C=1CN2CC1=CC=CC=C1 KGENQSVKAHPEBR-XMMPIXPASA-N 0.000 description 1
• DOZQLWGGJAEEKM-PDGVMRLRSA-N (3r)-3-(2,3,3a,4-tetrahydro-1-benzofuran-2-yl)-2-(5-pyridin-2-ylpyrimidin-2-yl)-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound C=1([C@@H]2C3OC4=CC=CCC4C3)NC3=CC=CC=C3C(=O)C=1CN2C(N=C1)=NC=C1C1=CC=CC=N1 DOZQLWGGJAEEKM-PDGVMRLRSA-N 0.000 description 1
• RSCXZLXGFCEIEG-LBDPGJCZSA-N (3r)-3-(2,3,3a,4-tetrahydro-1-benzofuran-2-yl)-2-[5-(4-methoxyphenyl)pyrimidin-2-yl]-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound C1=CC(OC)=CC=C1C1=CN=C(N2[C@H](C3=C(C(C4=CC=CC=C4N3)=O)C2)C2OC3=CC=CCC3C2)N=C1 RSCXZLXGFCEIEG-LBDPGJCZSA-N 0.000 description 1
• UKTMVBPQNHUHGD-NDEPHWFRSA-N (3s)-3-(1,3-benzodioxol-5-yl)-2-[5-(3,4-dimethoxyphenyl)pyrimidin-2-yl]-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound C1=C(OC)C(OC)=CC=C1C1=CN=C(N2[C@H](C3=C(C(C4=CC=CC=C4N3)=O)C2)C=2C=C3OCOC3=CC=2)N=C1 UKTMVBPQNHUHGD-NDEPHWFRSA-N 0.000 description 1
• CEBAHYWORUOILU-UHFFFAOYSA-N (4-cyanophenyl)boronic acid Chemical compound OB(O)C1=CC=C(C#N)C=C1 CEBAHYWORUOILU-UHFFFAOYSA-N 0.000 description 1
• BIWQNIMLAISTBV-UHFFFAOYSA-N (4-methylphenyl)boronic acid Chemical compound CC1=CC=C(B(O)O)C=C1 BIWQNIMLAISTBV-UHFFFAOYSA-N 0.000 description 1
• IVUHTLFKBDDICS-UHFFFAOYSA-N (4-methylsulfanylphenyl)boronic acid Chemical compound CSC1=CC=C(B(O)O)C=C1 IVUHTLFKBDDICS-UHFFFAOYSA-N 0.000 description 1
• NXLNNXIXOYSCMB-UHFFFAOYSA-N (4-nitrophenyl) carbonochloridate Chemical compound [O-][N+](=O)C1=CC=C(OC(Cl)=O)C=C1 NXLNNXIXOYSCMB-UHFFFAOYSA-N 0.000 description 1
• GMVPRGQOIOIIMI-UHFFFAOYSA-N (8R,11R,12R,13E,15S)-11,15-Dihydroxy-9-oxo-13-prostenoic acid Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CCCCCCC(O)=O GMVPRGQOIOIIMI-UHFFFAOYSA-N 0.000 description 1
• GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
• PVHMYONDAPXJSB-QPJJXVBHSA-N (e)-3-(4-methoxycarbonylphenyl)prop-2-enoic acid Chemical compound COC(=O)C1=CC=C(\C=C\C(O)=O)C=C1 PVHMYONDAPXJSB-QPJJXVBHSA-N 0.000 description 1
• GIWQSPITLQVMSG-UHFFFAOYSA-N 1,2-dimethylimidazole Chemical compound CC1=NC=CN1C GIWQSPITLQVMSG-UHFFFAOYSA-N 0.000 description 1
• LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-Bis(diphenylphosphino)propane Substances C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 1
• CMHPUBKZZPSUIQ-UHFFFAOYSA-N 1,3-benzodioxol-5-ylboronic acid Chemical compound OB(O)C1=CC=C2OCOC2=C1 CMHPUBKZZPSUIQ-UHFFFAOYSA-N 0.000 description 1
• FRYOOYJVTXUICA-UHFFFAOYSA-N 1-(2-bromophenyl)-2-(4-methoxyphenyl)ethanone Chemical compound C1=CC(OC)=CC=C1CC(=O)C1=CC=CC=C1Br FRYOOYJVTXUICA-UHFFFAOYSA-N 0.000 description 1
• PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
• 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
• XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 1
• XWIYUCRMWCHYJR-UHFFFAOYSA-N 1h-pyrrolo[3,2-b]pyridine Chemical group C1=CC=C2NC=CC2=N1 XWIYUCRMWCHYJR-UHFFFAOYSA-N 0.000 description 1
• WEBVDBDZSOJGPB-UHFFFAOYSA-N 2,3-dihydro-1-benzofuran-5-carbaldehyde Chemical compound O=CC1=CC=C2OCCC2=C1 WEBVDBDZSOJGPB-UHFFFAOYSA-N 0.000 description 1
• ZHXUWDPHUQHFOV-UHFFFAOYSA-N 2,5-dibromopyridine Chemical compound BrC1=CC=C(Br)N=C1 ZHXUWDPHUQHFOV-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
• DSHDAYCKUUJXPF-UHFFFAOYSA-N 2-[5-(3-benzyl-2-methylimidazol-4-yl)pyrimidin-2-yl]-3-(2,3-dihydro-1-benzofuran-5-yl)-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound CC1=NC=C(C=2C=NC(=NC=2)N2C(C3=C(C(C4=CC=CC=C4N3)=O)C2)C=2C=C3CCOC3=CC=2)N1CC1=CC=CC=C1 DSHDAYCKUUJXPF-UHFFFAOYSA-N 0.000 description 1
• HGIOVTCKDHJSNW-UHFFFAOYSA-N 2-[5-(4-aminophenyl)furan-2-carbonyl]-3-(1,3-benzodioxol-5-yl)-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound C1=CC(N)=CC=C1C1=CC=C(C(=O)N2C(C3=C(C(C4=CC=CC=C4N3)=O)C2)C=2C=C3OCOC3=CC=2)O1 HGIOVTCKDHJSNW-UHFFFAOYSA-N 0.000 description 1
• DYUISZMTIFUJKR-UHFFFAOYSA-N 2-benzyl-3-(3,4,5-trimethoxyphenyl)-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound COC1=C(OC)C(OC)=CC(C2C3=C(C(C4=CC=CC=C4N3)=O)CN2CC=2C=CC=CC=2)=C1 DYUISZMTIFUJKR-UHFFFAOYSA-N 0.000 description 1
• IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 description 1
• KJKIPRQNFDUULB-UHFFFAOYSA-N 2-chloro-4-iodopyridine Chemical compound ClC1=CC(I)=CC=N1 KJKIPRQNFDUULB-UHFFFAOYSA-N 0.000 description 1
• RDMNYPLXDBCPFB-UHFFFAOYSA-N 2-chloro-5-(3,4-dimethoxyphenyl)pyrimidine Chemical compound C1=C(OC)C(OC)=CC=C1C1=CN=C(Cl)N=C1 RDMNYPLXDBCPFB-UHFFFAOYSA-N 0.000 description 1
• RBCLQILHUJWWQP-UHFFFAOYSA-N 2-chloro-5-(3,5-dimethoxyphenyl)pyrimidine Chemical compound COC1=CC(OC)=CC(C=2C=NC(Cl)=NC=2)=C1 RBCLQILHUJWWQP-UHFFFAOYSA-N 0.000 description 1
• BQEPTIIJSKEJMX-UHFFFAOYSA-N 2-chloro-5-(4-chlorophenyl)pyrimidine Chemical compound C1=CC(Cl)=CC=C1C1=CN=C(Cl)N=C1 BQEPTIIJSKEJMX-UHFFFAOYSA-N 0.000 description 1
• AXBSAMHKWMWOKP-UHFFFAOYSA-N 2-chloro-5-(4-methylphenyl)pyrimidine Chemical compound C1=CC(C)=CC=C1C1=CN=C(Cl)N=C1 AXBSAMHKWMWOKP-UHFFFAOYSA-N 0.000 description 1
• CCZWSTFVHJPCEM-UHFFFAOYSA-N 2-iodopyridine Chemical compound IC1=CC=CC=N1 CCZWSTFVHJPCEM-UHFFFAOYSA-N 0.000 description 1
• 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
• 125000005916 2-methylpentyl group Chemical group 0.000 description 1
• YFLMNOXPPJOBCJ-UHFFFAOYSA-N 3-(1,3-benzodioxol-5-yl)-2-(4-imidazol-1-ylphenyl)-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound C=1C=C2OCOC2=CC=1C1C=2NC3=CC=CC=C3C(=O)C=2CN1C(C=C1)=CC=C1N1C=CN=C1 YFLMNOXPPJOBCJ-UHFFFAOYSA-N 0.000 description 1
• YZZBCBSZVRMZDN-UHFFFAOYSA-N 3-(1,3-benzodioxol-5-yl)-2-(5-bromofuran-2-carbonyl)-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound O1C(Br)=CC=C1C(=O)N1C(C=2C=C3OCOC3=CC=2)C(NC=2C(=CC=CC=2)C2=O)=C2C1 YZZBCBSZVRMZDN-UHFFFAOYSA-N 0.000 description 1
• AKRKBCPZPCYVPG-UHFFFAOYSA-N 3-(1,3-benzodioxol-5-yl)-2-(5-pyridin-3-ylpyrimidin-2-yl)-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound C=1C=C2OCOC2=CC=1C1C=2NC3=CC=CC=C3C(=O)C=2CN1C(N=C1)=NC=C1C1=CC=CN=C1 AKRKBCPZPCYVPG-UHFFFAOYSA-N 0.000 description 1
• IPWFKVRWJQVIKA-UHFFFAOYSA-N 3-(1,3-benzodioxol-5-yl)-2-(5-pyridin-4-ylpyrimidin-2-yl)-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound C=1C=C2OCOC2=CC=1C1C=2NC3=CC=CC=C3C(=O)C=2CN1C(N=C1)=NC=C1C1=CC=NC=C1 IPWFKVRWJQVIKA-UHFFFAOYSA-N 0.000 description 1
• RISQKYKOQGWYDC-UHFFFAOYSA-N 3-(1,3-benzodioxol-5-yl)-2-(6-hydroxy-1-benzofuran-2-carbonyl)-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound C1=C2OCOC2=CC(C2C3=C(C(C4=CC=CC=C4N3)=O)CN2C(=O)C2=CC3=CC=C(C=C3O2)O)=C1 RISQKYKOQGWYDC-UHFFFAOYSA-N 0.000 description 1
• YDPMNOXHNRTSNS-UHFFFAOYSA-N 3-(1,3-benzodioxol-5-yl)-2-(imidazole-1-carbothioyl)-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound C=1C=C2OCOC2=CC=1C1C=2NC3=CC=CC=C3C(=O)C=2CN1C(=S)N1C=CN=C1 YDPMNOXHNRTSNS-UHFFFAOYSA-N 0.000 description 1
• VJWHHFHPEDZHTP-UHFFFAOYSA-N 3-(1,3-benzodioxol-5-yl)-2-[5-(2-morpholin-4-ylethoxy)-1-benzofuran-2-carbonyl]-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound C1C(C(C2=CC=CC=C2N2)=O)=C2C(C=2C=C3OCOC3=CC=2)N1C(=O)C(OC1=CC=2)=CC1=CC=2OCCN1CCOCC1 VJWHHFHPEDZHTP-UHFFFAOYSA-N 0.000 description 1
• UKTMVBPQNHUHGD-UHFFFAOYSA-N 3-(1,3-benzodioxol-5-yl)-2-[5-(3,4-dimethoxyphenyl)pyrimidin-2-yl]-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound C1=C(OC)C(OC)=CC=C1C1=CN=C(N2C(C3=C(C(C4=CC=CC=C4N3)=O)C2)C=2C=C3OCOC3=CC=2)N=C1 UKTMVBPQNHUHGD-UHFFFAOYSA-N 0.000 description 1
• FMOZDELGJWKWRP-UHFFFAOYSA-N 3-(1,3-benzodioxol-5-yl)-2-[5-(4-hydroxyphenyl)furan-2-carbonyl]-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound C1=CC(O)=CC=C1C1=CC=C(C(=O)N2C(C3=C(C(C4=CC=CC=C4N3)=O)C2)C=2C=C3OCOC3=CC=2)O1 FMOZDELGJWKWRP-UHFFFAOYSA-N 0.000 description 1
• MQVTTZZNSGJGES-UHFFFAOYSA-N 3-(1,3-benzodioxol-5-yl)-2-[5-(4-methoxyphenyl)furan-2-carbonyl]-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound C1=CC(OC)=CC=C1C1=CC=C(C(=O)N2C(C3=C(C(C4=CC=CC=C4N3)=O)C2)C=2C=C3OCOC3=CC=2)O1 MQVTTZZNSGJGES-UHFFFAOYSA-N 0.000 description 1
• HRLBCKSHWMHNGK-UHFFFAOYSA-N 3-(1,3-benzodioxol-5-yl)-2-[5-(4-methoxyphenyl)pyrimidin-2-yl]-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound C1=CC(OC)=CC=C1C1=CN=C(N2C(C3=C(C(C4=CC=CC=C4N3)=O)C2)C=2C=C3OCOC3=CC=2)N=C1 HRLBCKSHWMHNGK-UHFFFAOYSA-N 0.000 description 1
• DTVQHOVWOLPNJL-UHFFFAOYSA-N 3-(1,3-benzodioxol-5-yl)-2-[5-[3-(trifluoromethyl)phenyl]furan-2-carbonyl]-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound FC(F)(F)C1=CC=CC(C=2OC(=CC=2)C(=O)N2C(C3=C(C(C4=CC=CC=C4N3)=O)C2)C=2C=C3OCOC3=CC=2)=C1 DTVQHOVWOLPNJL-UHFFFAOYSA-N 0.000 description 1
• YLQCRBXVRGQUBV-UHFFFAOYSA-N 3-(1-benzofuran-5-yl)-2-(5-pyridin-2-ylpyrimidin-2-yl)-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound C=1C=C2OC=CC2=CC=1C1C2=NC3=CC=CC=C3C(O)=C2CN1C(N=C1)=NC=C1C1=CC=CC=N1 YLQCRBXVRGQUBV-UHFFFAOYSA-N 0.000 description 1
• DOZQLWGGJAEEKM-UHFFFAOYSA-N 3-(2,3,3a,4-tetrahydro-1-benzofuran-2-yl)-2-(5-pyridin-2-ylpyrimidin-2-yl)-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound C1C2CC=CC=C2OC1C1C=2NC3=CC=CC=C3C(=O)C=2CN1C(N=C1)=NC=C1C1=CC=CC=N1 DOZQLWGGJAEEKM-UHFFFAOYSA-N 0.000 description 1
• RSCXZLXGFCEIEG-UHFFFAOYSA-N 3-(2,3,3a,4-tetrahydro-1-benzofuran-2-yl)-2-[5-(4-methoxyphenyl)pyrimidin-2-yl]-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound C1=CC(OC)=CC=C1C1=CN=C(N2C(C3=C(C(C4=CC=CC=C4N3)=O)C2)C2OC3=CC=CCC3C2)N=C1 RSCXZLXGFCEIEG-UHFFFAOYSA-N 0.000 description 1
• SBKKOPSSICKPQX-UHFFFAOYSA-N 3-(2,3-dihydro-1-benzofuran-5-yl)-2,3,4,9-tetrahydropyrrolo[3,4-b]quinolin-1-one Chemical compound C1=C2OCCC2=CC(C2NC(C3=C2NC2=CC=CC=C2C3)=O)=C1 SBKKOPSSICKPQX-UHFFFAOYSA-N 0.000 description 1
• YNUXXMJVZSTPFZ-UHFFFAOYSA-N 3-(2,3-dihydro-1-benzofuran-5-yl)-2-[5-(2,3-dimethylimidazol-4-yl)pyrimidin-2-yl]-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound CN1C(C)=NC=C1C1=CN=C(N2C(C3=C(C(C4=CC=CC=C4N3)=O)C2)C=2C=C3CCOC3=CC=2)N=C1 YNUXXMJVZSTPFZ-UHFFFAOYSA-N 0.000 description 1
• QIGGFIKIKKJPLQ-UHFFFAOYSA-N 3-(2,3-dihydro-1-benzofuran-5-yl)-2-[5-(2-methyl-1h-imidazol-5-yl)pyrimidin-2-yl]-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound N1C(C)=NC=C1C1=CN=C(N2C(C3=C(C(C4=CC=CC=C4N3)=O)C2)C=2C=C3CCOC3=CC=2)N=C1 QIGGFIKIKKJPLQ-UHFFFAOYSA-N 0.000 description 1
• DTTHOWQLCVTQCM-UHFFFAOYSA-N 3-(2,3-dihydro-1-benzofuran-5-yl)-2-pyrimidin-2-yl-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-9-one Chemical compound C=1C=C2OCCC2=CC=1C1C=2NC3=CC=CC=C3C(=O)C=2CN1C1=NC=CC=N1 DTTHOWQLCVTQCM-UHFFFAOYSA-N 0.000 description 1
• YDRSZUKCUVBUTH-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-1,2,3,4-tetrahydropyrrolo[3,4-b]quinolin-9-one Chemical compound C1=C(OC)C(OC)=CC=C1C1C(NC=2C(=CC=CC=2)C2=O)=C2CN1 YDRSZUKCUVBUTH-UHFFFAOYSA-N 0.000 description 1
• PHGIQGMOIGZMRU-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-1-[5-(3,4-dimethoxyphenyl)pyrimidin-2-yl]-1,2,3,4-tetrahydropyrrolo[3,4-b]quinolin-9-one Chemical compound C1=C(OC)C(OC)=CC=C1C1C(NC=2C(=CC=CC=2)C2=O)=C2C(C=2N=CC(=CN=2)C=2C=C(OC)C(OC)=CC=2)N1 PHGIQGMOIGZMRU-UHFFFAOYSA-N 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
• ALKYHXVLJMQRLQ-UHFFFAOYSA-M 3-carboxynaphthalen-2-olate Chemical compound C1=CC=C2C=C(C([O-])=O)C(O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-M 0.000 description 1
• MCSXGCZMEPXKIW-UHFFFAOYSA-N 3-hydroxy-4-[(4-methyl-2-nitrophenyl)diazenyl]-N-(3-nitrophenyl)naphthalene-2-carboxamide Chemical group Cc1ccc(N=Nc2c(O)c(cc3ccccc23)C(=O)Nc2cccc(c2)[N+]([O-])=O)c(c1)[N+]([O-])=O MCSXGCZMEPXKIW-UHFFFAOYSA-N 0.000 description 1
• ZDHKVKPZQKYREU-UHFFFAOYSA-N 4-(chloromethyl)pyridine;hydron;chloride Chemical compound Cl.ClCC1=CC=NC=C1 ZDHKVKPZQKYREU-UHFFFAOYSA-N 0.000 description 1
• BFVNITUTOZIFGP-MDWZMJQESA-N 4-[(e)-3-[3-(1,3-benzodioxol-5-yl)-4-methyl-9-oxo-1,3-dihydropyrrolo[3,4-b]quinolin-2-yl]-3-oxoprop-1-enyl]benzoic acid Chemical compound C1C=2C(=O)C3=CC=CC=C3N(C)C=2C(C=2C=C3OCOC3=CC=2)N1C(=O)\C=C\C1=CC=C(C(O)=O)C=C1 BFVNITUTOZIFGP-MDWZMJQESA-N 0.000 description 1
• OECGSQLNNYLLNB-MDWZMJQESA-N 4-[(e)-3-[3-(1,3-benzodioxol-5-yl)-9-methoxy-1,3,4,9-tetrahydropyrrolo[3,4-b]quinolin-2-yl]-3-oxoprop-1-enyl]benzoic acid Chemical compound N1C2=CC=CC=C2C(OC)C(C2)=C1C(C=1C=C3OCOC3=CC=1)N2C(=O)\C=C\C1=CC=C(C(O)=O)C=C1 OECGSQLNNYLLNB-MDWZMJQESA-N 0.000 description 1
• YYEVBHKCKXHPGR-KPKJPENVSA-N 4-[(e)-3-[3-(1,3-benzodioxol-5-yl)-9-oxo-3,4-dihydro-1h-pyrrolo[3,4-b]quinolin-2-yl]-3-oxoprop-1-enyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1\C=C\C(=O)N1C(C=2C=C3OCOC3=CC=2)C(NC=2C(=CC=CC=2)C2=O)=C2C1 YYEVBHKCKXHPGR-KPKJPENVSA-N 0.000 description 1
• UWCZSTHYLRBLJW-UHFFFAOYSA-N 4-[5-[3-(1,3-benzodioxol-5-yl)-9-oxo-3,4-dihydro-1h-pyrrolo[3,4-b]quinoline-2-carbonyl]furan-2-yl]benzaldehyde Chemical compound C1=CC(C=O)=CC=C1C1=CC=C(C(=O)N2C(C3=C(C(C4=CC=CC=C4N3)=O)C2)C=2C=C3OCOC3=CC=2)O1 UWCZSTHYLRBLJW-UHFFFAOYSA-N 0.000 description 1
• SIAVMDKGVRXFAX-UHFFFAOYSA-N 4-carboxyphenylboronic acid Chemical compound OB(O)C1=CC=C(C(O)=O)C=C1 SIAVMDKGVRXFAX-UHFFFAOYSA-N 0.000 description 1
• ICGLPKIVTVWCFT-UHFFFAOYSA-N 4-methylbenzenesulfonohydrazide Chemical compound CC1=CC=C(S(=O)(=O)NN)C=C1 ICGLPKIVTVWCFT-UHFFFAOYSA-N 0.000 description 1
• WOURWODWGFMUQA-UHFFFAOYSA-N 5-(3-benzylimidazol-4-yl)-2-chloropyridine Chemical compound C1=NC(Cl)=CC=C1C1=CN=CN1CC1=CC=CC=C1 WOURWODWGFMUQA-UHFFFAOYSA-N 0.000 description 1
• HMIDRMDGUSXDTP-UHFFFAOYSA-N 5-(4-methylphenyl)pyrimidine Chemical compound C1=CC(C)=CC=C1C1=CN=CN=C1 HMIDRMDGUSXDTP-UHFFFAOYSA-N 0.000 description 1
• PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
• YVQBMJRTSYWMFD-UHFFFAOYSA-N 6-hydroxy-1-benzofuran-2-carboxylic acid Chemical compound C1=C(O)C=C2OC(C(=O)O)=CC2=C1 YVQBMJRTSYWMFD-UHFFFAOYSA-N 0.000 description 1
• WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-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
• BPMFPOGUJAAYHL-UHFFFAOYSA-N 9H-Pyrido[2,3-b]indole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=N1 BPMFPOGUJAAYHL-UHFFFAOYSA-N 0.000 description 1
• 229930008281 A03AD01 - Papaverine Natural products 0.000 description 1
• 229920001817 Agar Polymers 0.000 description 1
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
• BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 206010007559 Cardiac failure congestive Diseases 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 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
• HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 1
• 244000060011 Cocos nucifera Species 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 201000000054 Coronary Restenosis Diseases 0.000 description 1
• 206010056489 Coronary artery restenosis Diseases 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• 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
• 229920002307 Dextran Polymers 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
• 206010016654 Fibrosis Diseases 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
• 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
• 206010019233 Headaches Diseases 0.000 description 1
• 206010060800 Hot flush Diseases 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-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
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical compound O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• RKOTXQYWCBGZLP-UHFFFAOYSA-N N-[(2,4-difluorophenyl)methyl]-2-ethyl-9-hydroxy-3-methoxy-1,8-dioxospiro[3H-pyrido[1,2-a]pyrazine-4,3'-oxolane]-7-carboxamide Chemical compound CCN1C(OC)C2(CCOC2)N2C=C(C(=O)NCC3=C(F)C=C(F)C=C3)C(=O)C(O)=C2C1=O RKOTXQYWCBGZLP-UHFFFAOYSA-N 0.000 description 1
• XGEGHDBEHXKFPX-UHFFFAOYSA-N N-methylthiourea Natural products CNC(N)=O XGEGHDBEHXKFPX-UHFFFAOYSA-N 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
• FDJUUGUUBBAPOC-UHFFFAOYSA-N O1CCC2=C1C=CC(=C2)C1N(CC2=C1NC=1C=CC=CC=1C2=O)C1=NC=C(C=C1)C=1NC=NC=1 Chemical compound O1CCC2=C1C=CC(=C2)C1N(CC2=C1NC=1C=CC=CC=1C2=O)C1=NC=C(C=C1)C=1NC=NC=1 FDJUUGUUBBAPOC-UHFFFAOYSA-N 0.000 description 1
• REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 208000031481 Pathologic Constriction Diseases 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 206010070656 Penile haematoma Diseases 0.000 description 1
• 206010034310 Penile pain Diseases 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• 108010039918 Polylysine Proteins 0.000 description 1
• 229920001710 Polyorthoester Polymers 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 208000006399 Premature Obstetric Labor Diseases 0.000 description 1
• 206010036600 Premature labour Diseases 0.000 description 1
• 102000001708 Protein Isoforms Human genes 0.000 description 1
• 108010029485 Protein Isoforms Proteins 0.000 description 1
• YDWKSSWZGXRQET-UHFFFAOYSA-N Pyrrolidine, 1-[2-(4-bromophenoxy)ethyl]- Chemical compound C1=CC(Br)=CC=C1OCCN1CCCC1 YDWKSSWZGXRQET-UHFFFAOYSA-N 0.000 description 1
• 101100183887 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) MHT1 gene Proteins 0.000 description 1
• 244000000231 Sesamum indicum Species 0.000 description 1
• 229920001800 Shellac Polymers 0.000 description 1
• 229910004298 SiO 2 Inorganic materials 0.000 description 1
• BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 229920002253 Tannate Polymers 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
• 240000008042 Zea mays Species 0.000 description 1
• 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
• 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
• HGTDLKXUWVKLQX-UHFFFAOYSA-N [3-(hydroxymethyl)phenyl]boronic acid Chemical compound OCC1=CC=CC(B(O)O)=C1 HGTDLKXUWVKLQX-UHFFFAOYSA-N 0.000 description 1
• PIPXKGQBEOMBKE-UHFFFAOYSA-N [4-(2-pyrrolidin-1-ylethoxy)phenoxy]boronic acid Chemical compound B(O)(O)OC1=CC=C(C=C1)OCCN2CCCC2 PIPXKGQBEOMBKE-UHFFFAOYSA-N 0.000 description 1
• RIIPFHVHLXPMHQ-UHFFFAOYSA-N [4-(dimethylamino)phenyl]boronic acid Chemical compound CN(C)C1=CC=C(B(O)O)C=C1 RIIPFHVHLXPMHQ-UHFFFAOYSA-N 0.000 description 1
• PZRPBPMLSSNFOM-UHFFFAOYSA-N [4-(hydroxymethyl)phenyl]boronic acid Chemical compound OCC1=CC=C(B(O)O)C=C1 PZRPBPMLSSNFOM-UHFFFAOYSA-N 0.000 description 1
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
• 229940081735 acetylcellulose Drugs 0.000 description 1
• 239000003377 acid catalyst Substances 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 230000006978 adaptation Effects 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 235000010419 agar Nutrition 0.000 description 1
• 229940072056 alginate Drugs 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 150000001335 aliphatic alkanes Chemical class 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 150000001336 alkenes Chemical class 0.000 description 1
• 125000003342 alkenyl group Chemical group 0.000 description 1
• 150000001345 alkine derivatives Chemical class 0.000 description 1
• 125000000304 alkynyl group Chemical group 0.000 description 1
• 201000009961 allergic asthma Diseases 0.000 description 1
• 229960000711 alprostadil Drugs 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 238000005349 anion exchange Methods 0.000 description 1
• 239000004004 anti-anginal agent Substances 0.000 description 1
• 229940124345 antianginal agent Drugs 0.000 description 1
• 239000000935 antidepressant agent Substances 0.000 description 1
• 229940005513 antidepressants Drugs 0.000 description 1
• 239000002220 antihypertensive agent Substances 0.000 description 1
• 229940030600 antihypertensive agent Drugs 0.000 description 1
• 239000002249 anxiolytic agent Substances 0.000 description 1
• 230000000949 anxiolytic effect Effects 0.000 description 1
• 229940005530 anxiolytics Drugs 0.000 description 1
• 230000004872 arterial blood pressure Effects 0.000 description 1
• 229940090047 auto-injector Drugs 0.000 description 1
• OISFUZRUIGGTSD-LJTMIZJLSA-N azane;(2r,3r,4r,5s)-6-(methylamino)hexane-1,2,3,4,5-pentol Chemical compound N.CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO OISFUZRUIGGTSD-LJTMIZJLSA-N 0.000 description 1
• AAMATCKFMHVIDO-UHFFFAOYSA-N azane;1h-pyrrole Chemical compound N.C=1C=CNC=1 AAMATCKFMHVIDO-UHFFFAOYSA-N 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 239000000440 bentonite Substances 0.000 description 1
• 229910000278 bentonite Inorganic materials 0.000 description 1
• 235000012216 bentonite Nutrition 0.000 description 1
• SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
• 229940077388 benzenesulfonate Drugs 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
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000005605 benzo group Chemical group 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• 125000005874 benzothiadiazolyl group Chemical group 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• BSLYOZMGLNSOKO-UHFFFAOYSA-N benzyl 3-(1,3-benzodioxol-5-yl)-9-oxo-3,4-dihydro-1h-pyrrolo[3,4-b]quinoline-2-carboxylate Chemical compound C1C(C(C2=CC=CC=C2N2)=O)=C2C(C=2C=C3OCOC3=CC=2)N1C(=O)OCC1=CC=CC=C1 BSLYOZMGLNSOKO-UHFFFAOYSA-N 0.000 description 1
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
• HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
• 125000002619 bicyclic group Chemical group 0.000 description 1
• 229920002988 biodegradable polymer Polymers 0.000 description 1
• 239000004621 biodegradable polymer Substances 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 229920001400 block copolymer Polymers 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 239000001506 calcium phosphate Substances 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
• 239000007894 caplet Substances 0.000 description 1
• 229910052799 carbon Inorganic materials 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• ZFTFAPZRGNKQPU-UHFFFAOYSA-L carboxylato carbonate Chemical compound [O-]C(=O)OC([O-])=O ZFTFAPZRGNKQPU-UHFFFAOYSA-L 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 229920002301 cellulose acetate Polymers 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• 229960000541 cetyl alcohol Drugs 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 238000004296 chiral HPLC Methods 0.000 description 1
• NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 1
• 235000012000 cholesterol Nutrition 0.000 description 1
• 238000013375 chromatographic separation Methods 0.000 description 1
• 229940090805 clavulanate Drugs 0.000 description 1
• HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 1
• 239000003240 coconut oil Substances 0.000 description 1
• 235000019864 coconut oil Nutrition 0.000 description 1
• 229910052681 coesite Inorganic materials 0.000 description 1
• 230000004456 color vision Effects 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000007906 compression Methods 0.000 description 1
• 230000006835 compression Effects 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 229920001577 copolymer Polymers 0.000 description 1
• 235000005822 corn Nutrition 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 235000012343 cottonseed oil Nutrition 0.000 description 1
• 239000002385 cottonseed oil Substances 0.000 description 1
• 229910052906 cristobalite Inorganic materials 0.000 description 1
• 239000013058 crude material Substances 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 125000000753 cycloalkyl group Chemical group 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical class CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 1
• 230000007423 decrease Effects 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• 239000003405 delayed action preparation Substances 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• RAFNCPHFRHZCPS-UHFFFAOYSA-N di(imidazol-1-yl)methanethione Chemical compound C1=CN=CN1C(=S)N1C=CN=C1 RAFNCPHFRHZCPS-UHFFFAOYSA-N 0.000 description 1
• NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
• 229940038472 dicalcium phosphate Drugs 0.000 description 1
• 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
• LCSNDSFWVKMJCT-UHFFFAOYSA-N dicyclohexyl-(2-phenylphenyl)phosphane Chemical compound C1CCCCC1P(C=1C(=CC=CC=1)C=1C=CC=CC=1)C1CCCCC1 LCSNDSFWVKMJCT-UHFFFAOYSA-N 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• 230000010339 dilation Effects 0.000 description 1
• 239000001177 diphosphate Substances 0.000 description 1
• XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
• 235000011180 diphosphates Nutrition 0.000 description 1
• CNXMDTWQWLGCPE-UHFFFAOYSA-N ditert-butyl-(2-phenylphenyl)phosphane Chemical compound CC(C)(C)P(C(C)(C)C)C1=CC=CC=C1C1=CC=CC=C1 CNXMDTWQWLGCPE-UHFFFAOYSA-N 0.000 description 1
• POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 210000001198 duodenum Anatomy 0.000 description 1
• 239000000975 dye Substances 0.000 description 1
• 239000008157 edible vegetable oil Substances 0.000 description 1
• 230000002526 effect on cardiovascular system Effects 0.000 description 1
• 238000010828 elution Methods 0.000 description 1
• 229950005627 embonate Drugs 0.000 description 1
• 210000003038 endothelium Anatomy 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 238000001952 enzyme assay Methods 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 230000004761 fibrosis Effects 0.000 description 1
• 239000012054 flavored emulsion Substances 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 235000020375 flavoured syrup Nutrition 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 238000009472 formulation Methods 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 229940050411 fumarate Drugs 0.000 description 1
• 230000006870 function Effects 0.000 description 1
• 229960001731 gluceptate Drugs 0.000 description 1
• KWMLJOLKUYYJFJ-VFUOTHLCSA-N glucoheptonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)C(O)=O KWMLJOLKUYYJFJ-VFUOTHLCSA-N 0.000 description 1
• 229940050410 gluconate Drugs 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 229930195712 glutamate Natural products 0.000 description 1
• 229940049906 glutamate Drugs 0.000 description 1
• 125000000350 glycoloyl group Chemical group O=C([*])C([H])([H])O[H] 0.000 description 1
• RQFCJASXJCIDSX-UUOKFMHZSA-N guanosine 5'-monophosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O RQFCJASXJCIDSX-UUOKFMHZSA-N 0.000 description 1
• 231100000869 headache Toxicity 0.000 description 1
• 210000002216 heart Anatomy 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 239000008240 homogeneous mixture Substances 0.000 description 1
• XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 239000000017 hydrogel Substances 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• 239000005457 ice water Substances 0.000 description 1
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
• 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• 238000009413 insulation Methods 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 230000037041 intracellular level Effects 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000010255 intramuscular injection Methods 0.000 description 1
• 239000007927 intramuscular injection Substances 0.000 description 1
• 238000007915 intraurethral administration Methods 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• 208000028867 ischemia Diseases 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 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
• 229940070765 laurate Drugs 0.000 description 1
• 238000012417 linear regression Methods 0.000 description 1
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical class [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 229940049920 malate Drugs 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 229940118019 malondialdehyde Drugs 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
• 230000001404 mediated effect Effects 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• MLSKXPOBNQFGHW-UHFFFAOYSA-N methoxy(dioxido)borane Chemical compound COB([O-])[O-] MLSKXPOBNQFGHW-UHFFFAOYSA-N 0.000 description 1
• UIWAWEHKXPOTBJ-UHFFFAOYSA-N methyl 4-[5-[3-(1,3-benzodioxol-5-yl)-9-oxo-3,4-dihydro-1h-pyrrolo[3,4-b]quinoline-2-carbonyl]furan-2-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=CC=C(C(=O)N2C(C3=C(C(C4=CC=CC=C4N3)=O)C2)C=2C=C3OCOC3=CC=2)O1 UIWAWEHKXPOTBJ-UHFFFAOYSA-N 0.000 description 1
• XSWDPIQGBIWAPT-UHFFFAOYSA-N methyl 6-methoxy-1-benzofuran-2-carboxylate Chemical compound C1=C(OC)C=C2OC(C(=O)OC)=CC2=C1 XSWDPIQGBIWAPT-UHFFFAOYSA-N 0.000 description 1
• 229940102396 methyl bromide Drugs 0.000 description 1
• LRMHVVPPGGOAJQ-UHFFFAOYSA-N methyl nitrate Chemical compound CO[N+]([O-])=O LRMHVVPPGGOAJQ-UHFFFAOYSA-N 0.000 description 1
• JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
• XGEGHDBEHXKFPX-NJFSPNSNSA-N methylurea Chemical compound [14CH3]NC(N)=O XGEGHDBEHXKFPX-NJFSPNSNSA-N 0.000 description 1
• 201000006417 multiple sclerosis Diseases 0.000 description 1
• 210000002464 muscle smooth vascular Anatomy 0.000 description 1
• 208000031225 myocardial ischemia Diseases 0.000 description 1
• PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
• WWFOKSZOIZQRIE-UHFFFAOYSA-N n-[2-(1h-indol-3-yl)ethyl]-1-naphthalen-1-ylethanamine Chemical compound C1=CC=C2C(C(NCCC=3C4=CC=CC=C4NC=3)C)=CC=CC2=C1 WWFOKSZOIZQRIE-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 210000005036 nerve Anatomy 0.000 description 1
• 230000001129 nonadrenergic effect Effects 0.000 description 1
• 230000002536 noncholinergic effect Effects 0.000 description 1
• 125000003835 nucleoside group Chemical group 0.000 description 1
• 239000002773 nucleotide Substances 0.000 description 1
• 125000003729 nucleotide group Chemical group 0.000 description 1
• 229940078552 o-xylene Drugs 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 239000012053 oil suspension Substances 0.000 description 1
• 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
• 150000007530 organic bases Chemical class 0.000 description 1
• 239000013110 organic ligand Substances 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 230000003647 oxidation Effects 0.000 description 1
• 238000007254 oxidation reaction Methods 0.000 description 1
• LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
• 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 229940014662 pantothenate Drugs 0.000 description 1
• 235000019161 pantothenic acid Nutrition 0.000 description 1
• 239000011713 pantothenic acid Substances 0.000 description 1
• 229960001789 papaverine Drugs 0.000 description 1
• 239000003182 parenteral nutrition solution Substances 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 210000003899 penis Anatomy 0.000 description 1
• 210000001428 peripheral nervous system Anatomy 0.000 description 1
• 239000008177 pharmaceutical agent Substances 0.000 description 1
• 239000008024 pharmaceutical diluent Substances 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• 229940124531 pharmaceutical excipient Drugs 0.000 description 1
• MRBDMNSDAVCSSF-UHFFFAOYSA-N phentolamine Chemical compound C1=CC(C)=CC=C1N(C=1C=C(O)C=CC=1)CC1=NCCN1 MRBDMNSDAVCSSF-UHFFFAOYSA-N 0.000 description 1
• 229960001999 phentolamine Drugs 0.000 description 1
• HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 1
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
• 150000003904 phospholipids Chemical class 0.000 description 1
• UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 239000000902 placebo Substances 0.000 description 1
• 229940068196 placebo Drugs 0.000 description 1
• 229910052697 platinum Inorganic materials 0.000 description 1
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
• 239000002798 polar solvent Substances 0.000 description 1
• 229920000747 poly(lactic acid) Polymers 0.000 description 1
• 229920002721 polycyanoacrylate Polymers 0.000 description 1
• 239000004626 polylactic acid Substances 0.000 description 1
• 229920000656 polylysine Polymers 0.000 description 1
• 229920006324 polyoxymethylene Polymers 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 235000015320 potassium carbonate Nutrition 0.000 description 1
• 159000000001 potassium salts Chemical class 0.000 description 1
• CLSKHAYBTFRDOV-UHFFFAOYSA-N potassium;molecular oxygen Chemical compound [K+].O=O CLSKHAYBTFRDOV-UHFFFAOYSA-N 0.000 description 1
• 208000026440 premature labor Diseases 0.000 description 1
• 238000004237 preparative chromatography Methods 0.000 description 1
• 201000011264 priapism Diseases 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• GMVPRGQOIOIIMI-DWKJAMRDSA-N prostaglandin E1 Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(O)=O GMVPRGQOIOIIMI-DWKJAMRDSA-N 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• 230000002685 pulmonary effect Effects 0.000 description 1
• 239000012264 purified product Substances 0.000 description 1
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• PTMBWNZJOQBTBK-UHFFFAOYSA-N pyridin-4-ylmethanol Chemical compound OCC1=CC=NC=C1 PTMBWNZJOQBTBK-UHFFFAOYSA-N 0.000 description 1
• NKTOXZJPCGMHBV-UHFFFAOYSA-N pyridin-4-ylmethyl 3-(2,3-dihydro-1-benzofuran-5-yl)-9-oxo-3,4-dihydro-1h-pyrrolo[3,4-b]quinoline-2-carboxylate Chemical compound C1C(C(C2=CC=CC=C2N2)=O)=C2C(C=2C=C3CCOC3=CC=2)N1C(=O)OCC1=CC=NC=C1 NKTOXZJPCGMHBV-UHFFFAOYSA-N 0.000 description 1
• VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
• LMTJWEYARSZOSQ-UHFFFAOYSA-N pyrrolo[3,4-b]quinolin-1-one Chemical compound C1=CC=C2C=C3C(=O)N=CC3=NC2=C1 LMTJWEYARSZOSQ-UHFFFAOYSA-N 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
• LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
• 229930185107 quinolinone Natural products 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 150000007660 quinolones Chemical class 0.000 description 1
• 238000011472 radical prostatectomy Methods 0.000 description 1
• 230000008929 regeneration Effects 0.000 description 1
• 238000011069 regeneration method Methods 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 230000004648 relaxation of smooth muscle Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 210000001525 retina Anatomy 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
• 238000007127 saponification reaction Methods 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 229940125723 sedative agent Drugs 0.000 description 1
• 239000000932 sedative agent Substances 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 230000036299 sexual function Effects 0.000 description 1
• 239000004208 shellac Substances 0.000 description 1
• ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
• 229940113147 shellac Drugs 0.000 description 1
• 235000013874 shellac Nutrition 0.000 description 1
• 239000000377 silicon dioxide Substances 0.000 description 1
• 235000012239 silicon dioxide Nutrition 0.000 description 1
• 210000002027 skeletal muscle Anatomy 0.000 description 1
• 210000002460 smooth muscle Anatomy 0.000 description 1
• 235000015424 sodium Nutrition 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
• 239000004299 sodium benzoate Substances 0.000 description 1
• 235000010234 sodium benzoate Nutrition 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• RPACBEVZENYWOL-XFULWGLBSA-M sodium;(2r)-2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate Chemical compound [Na+].C=1C=C(Cl)C=CC=1OCCCCCC[C@]1(C(=O)[O-])CO1 RPACBEVZENYWOL-XFULWGLBSA-M 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 235000010356 sorbitol Nutrition 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical compound [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 1
• 229910000080 stannane Inorganic materials 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 230000036262 stenosis Effects 0.000 description 1
• 208000037804 stenosis Diseases 0.000 description 1
• 239000008174 sterile solution Substances 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 238000003756 stirring Methods 0.000 description 1
• 229910052682 stishovite Inorganic materials 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 125000003107 substituted aryl group Chemical group 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 238000001356 surgical procedure Methods 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
• 239000012730 sustained-release form Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• 229950002757 teoclate Drugs 0.000 description 1
• MFPWEWYKQYMWRO-UHFFFAOYSA-N tert-butyl carboxy carbonate Chemical compound CC(C)(C)OC(=O)OC(O)=O MFPWEWYKQYMWRO-UHFFFAOYSA-N 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 238000004809 thin layer chromatography Methods 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
• QNMBSXGYAQZCTN-UHFFFAOYSA-N thiophen-3-ylboronic acid Chemical compound OB(O)C=1C=CSC=1 QNMBSXGYAQZCTN-UHFFFAOYSA-N 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 230000037317 transdermal delivery Effects 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• GYUURHMITDQTRU-UHFFFAOYSA-N tributyl(pyridin-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CC=N1 GYUURHMITDQTRU-UHFFFAOYSA-N 0.000 description 1
• UNEPXPMBVGDXGH-UHFFFAOYSA-N tributyl(pyridin-4-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=NC=C1 UNEPXPMBVGDXGH-UHFFFAOYSA-N 0.000 description 1
• 229910052905 tridymite Inorganic materials 0.000 description 1
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
• WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
• 238000003828 vacuum filtration Methods 0.000 description 1
• 229940070710 valerate Drugs 0.000 description 1
• NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
• 210000000264 venule Anatomy 0.000 description 1
• 229940094720 viagra Drugs 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 230000003442 weekly effect Effects 0.000 description 1
• 239000000230 xanthan gum Substances 0.000 description 1
• 229920001285 xanthan gum Polymers 0.000 description 1
• 235000010493 xanthan gum Nutrition 0.000 description 1
• 229940082509 xanthan gum Drugs 0.000 description 1
• PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 description 1