RU2728783C2 - ИНГИБИТОРЫ ФАКТОРА XIa - Google Patents
ИНГИБИТОРЫ ФАКТОРА XIa Download PDFInfo
- Publication number
- RU2728783C2 RU2728783C2 RU2018119015A RU2018119015A RU2728783C2 RU 2728783 C2 RU2728783 C2 RU 2728783C2 RU 2018119015 A RU2018119015 A RU 2018119015A RU 2018119015 A RU2018119015 A RU 2018119015A RU 2728783 C2 RU2728783 C2 RU 2728783C2
- Authority
- RU
- Russia
- Prior art keywords
- mmol
- mixture
- stirred
- halogen
- compound
- Prior art date
Links
- 239000003112 inhibitor Substances 0.000 title claims abstract description 26
- 150000001875 compounds Chemical class 0.000 claims abstract description 534
- -1 cyano, cyclopropyl Chemical group 0.000 claims abstract description 226
- 238000000034 method Methods 0.000 claims abstract description 74
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 72
- 150000002367 halogens Chemical class 0.000 claims abstract description 70
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 64
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 56
- 239000001257 hydrogen Substances 0.000 claims abstract description 56
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 52
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 48
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 38
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 33
- 108010080805 Factor XIa Proteins 0.000 claims abstract description 30
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 30
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 27
- 208000007536 Thrombosis Diseases 0.000 claims abstract description 26
- 239000003814 drug Substances 0.000 claims abstract description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 24
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 23
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 22
- 125000004429 atom Chemical group 0.000 claims abstract description 17
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 14
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 12
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 10
- 229910052760 oxygen Chemical group 0.000 claims abstract description 10
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 9
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 6
- 206010014522 Embolism venous Diseases 0.000 claims abstract description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- 208000004043 venous thromboembolism Diseases 0.000 claims abstract description 5
- 206010051055 Deep vein thrombosis Diseases 0.000 claims abstract description 4
- 206010047249 Venous thrombosis Diseases 0.000 claims abstract description 4
- 208000010378 Pulmonary Embolism Diseases 0.000 claims abstract description 3
- 206010043647 Thrombotic Stroke Diseases 0.000 claims abstract description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract 4
- 239000001301 oxygen Chemical group 0.000 claims abstract 4
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims abstract 3
- 239000000203 mixture Substances 0.000 claims description 325
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical group [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 59
- 150000003839 salts Chemical class 0.000 claims description 54
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
- 241000124008 Mammalia Species 0.000 claims description 21
- 125000001424 substituent group Chemical group 0.000 claims description 18
- 239000000460 chlorine Substances 0.000 claims description 13
- 125000002947 alkylene group Chemical group 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 108090000190 Thrombin Proteins 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 229960004072 thrombin Drugs 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 230000035602 clotting Effects 0.000 claims description 4
- 239000011737 fluorine Chemical group 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims 3
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims 2
- 229940126051 coagulation factor XIa Drugs 0.000 claims 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000008280 blood Substances 0.000 abstract description 13
- 210000004369 blood Anatomy 0.000 abstract description 13
- 230000000694 effects Effects 0.000 abstract description 4
- 102000015081 Blood Coagulation Factors Human genes 0.000 abstract description 3
- 108010039209 Blood Coagulation Factors Proteins 0.000 abstract description 3
- 239000003114 blood coagulation factor Substances 0.000 abstract description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 453
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 261
- 235000019439 ethyl acetate Nutrition 0.000 description 195
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 193
- 239000000243 solution Substances 0.000 description 170
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 153
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 150
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 147
- 230000002829 reductive effect Effects 0.000 description 136
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 107
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 106
- 239000012044 organic layer Substances 0.000 description 100
- 229910052938 sodium sulfate Inorganic materials 0.000 description 95
- 235000011152 sodium sulphate Nutrition 0.000 description 95
- 238000010898 silica gel chromatography Methods 0.000 description 93
- 238000005481 NMR spectroscopy Methods 0.000 description 87
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 72
- 239000012267 brine Substances 0.000 description 71
- 239000000543 intermediate Substances 0.000 description 71
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 71
- 239000003208 petroleum Substances 0.000 description 67
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 64
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 64
- 239000011541 reaction mixture Substances 0.000 description 58
- 229920006395 saturated elastomer Polymers 0.000 description 55
- 239000000706 filtrate Substances 0.000 description 54
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 50
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 47
- 238000010828 elution Methods 0.000 description 47
- 238000003786 synthesis reaction Methods 0.000 description 47
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 42
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 41
- 239000002904 solvent Substances 0.000 description 39
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 34
- 238000003818 flash chromatography Methods 0.000 description 31
- 235000019270 ammonium chloride Nutrition 0.000 description 30
- 239000012258 stirred mixture Substances 0.000 description 30
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 29
- 239000007787 solid Substances 0.000 description 27
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 24
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 24
- 239000012299 nitrogen atmosphere Substances 0.000 description 23
- 239000000523 sample Substances 0.000 description 23
- 239000000741 silica gel Substances 0.000 description 23
- 229910002027 silica gel Inorganic materials 0.000 description 23
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 22
- 102000003827 Plasma Kallikrein Human genes 0.000 description 21
- 108090000113 Plasma Kallikrein Proteins 0.000 description 21
- 125000003118 aryl group Chemical group 0.000 description 21
- 238000004007 reversed phase HPLC Methods 0.000 description 21
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 20
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 20
- 235000017557 sodium bicarbonate Nutrition 0.000 description 20
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 20
- 239000000047 product Substances 0.000 description 19
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 18
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 17
- 239000002585 base Substances 0.000 description 17
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 17
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 17
- 238000000926 separation method Methods 0.000 description 17
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 16
- 239000003054 catalyst Substances 0.000 description 16
- 238000001914 filtration Methods 0.000 description 16
- 238000000746 purification Methods 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000013543 active substance Substances 0.000 description 15
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- 230000004913 activation Effects 0.000 description 14
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 14
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 14
- 239000003146 anticoagulant agent Substances 0.000 description 13
- 229940079593 drug Drugs 0.000 description 13
- 150000002148 esters Chemical class 0.000 description 13
- 239000012071 phase Substances 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 239000012298 atmosphere Substances 0.000 description 12
- 229910052799 carbon Inorganic materials 0.000 description 12
- 230000037361 pathway Effects 0.000 description 12
- 239000011734 sodium Substances 0.000 description 12
- 238000011282 treatment Methods 0.000 description 12
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 12
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
- 229940002612 prodrug Drugs 0.000 description 11
- 239000000651 prodrug Substances 0.000 description 11
- 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 10
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 10
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 229940127219 anticoagulant drug Drugs 0.000 description 10
- 125000000753 cycloalkyl group Chemical group 0.000 description 10
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical class [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 description 10
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 10
- 239000007858 starting material Substances 0.000 description 10
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 9
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 9
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 9
- 125000004432 carbon atom Chemical group C* 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
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 9
- 239000003643 water by type Substances 0.000 description 9
- YYLBDBOSXXSZQQ-UHFFFAOYSA-N 5-chloropyridine-2-carbaldehyde Chemical compound ClC1=CC=C(C=O)N=C1 YYLBDBOSXXSZQQ-UHFFFAOYSA-N 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- 208000005189 Embolism Diseases 0.000 description 8
- 108010080865 Factor XII Proteins 0.000 description 8
- 102000000429 Factor XII Human genes 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 239000003480 eluent Substances 0.000 description 8
- LJQKCYFTNDAAPC-UHFFFAOYSA-N ethanol;ethyl acetate Chemical compound CCO.CCOC(C)=O LJQKCYFTNDAAPC-UHFFFAOYSA-N 0.000 description 8
- 239000005457 ice water Substances 0.000 description 8
- 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 8
- 229940062627 tribasic potassium phosphate Drugs 0.000 description 8
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 7
- 102100035792 Kininogen-1 Human genes 0.000 description 7
- 239000007868 Raney catalyst Substances 0.000 description 7
- 229910000564 Raney nickel Inorganic materials 0.000 description 7
- 238000006161 Suzuki-Miyaura coupling reaction Methods 0.000 description 7
- 208000001435 Thromboembolism Diseases 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 229940127218 antiplatelet drug Drugs 0.000 description 7
- 125000002619 bicyclic group Chemical group 0.000 description 7
- 230000023555 blood coagulation Effects 0.000 description 7
- PVEOYINWKBTPIZ-UHFFFAOYSA-N but-3-enoic acid Chemical compound OC(=O)CC=C PVEOYINWKBTPIZ-UHFFFAOYSA-N 0.000 description 7
- 230000015271 coagulation Effects 0.000 description 7
- 238000005345 coagulation Methods 0.000 description 7
- 239000003527 fibrinolytic agent Substances 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 7
- 235000011056 potassium acetate Nutrition 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 239000012453 solvate Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
- 108010074864 Factor XI Proteins 0.000 description 6
- 239000007821 HATU Substances 0.000 description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- 229940127379 Kallikrein Inhibitors Drugs 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 229910004298 SiO 2 Inorganic materials 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 6
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 239000006196 drop Substances 0.000 description 6
- 230000009977 dual effect Effects 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 150000002500 ions Chemical class 0.000 description 6
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- 229960000103 thrombolytic agent Drugs 0.000 description 6
- GJYJWUDHKGKGGR-UHFFFAOYSA-N 1-azido-2-bromo-4-chlorobenzene Chemical compound ClC1=CC=C(N=[N+]=[N-])C(Br)=C1 GJYJWUDHKGKGGR-UHFFFAOYSA-N 0.000 description 5
- BPXKZEMBEZGUAH-UHFFFAOYSA-N 2-(chloromethoxy)ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCCl BPXKZEMBEZGUAH-UHFFFAOYSA-N 0.000 description 5
- 108010071241 Factor XIIa Proteins 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 206010019860 Hereditary angioedema Diseases 0.000 description 5
- 108010000487 High-Molecular-Weight Kininogen Proteins 0.000 description 5
- 125000004450 alkenylene group Chemical group 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 5
- 230000001269 cardiogenic effect Effects 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 125000004122 cyclic group Chemical group 0.000 description 5
- 230000002950 deficient Effects 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 239000012458 free base Substances 0.000 description 5
- 210000002216 heart Anatomy 0.000 description 5
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 229910000160 potassium phosphate Inorganic materials 0.000 description 5
- 235000011009 potassium phosphates Nutrition 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 235000010288 sodium nitrite Nutrition 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 5
- YXIWHUQXZSMYRE-UHFFFAOYSA-N 1,3-benzothiazole-2-thiol Chemical compound C1=CC=C2SC(S)=NC2=C1 YXIWHUQXZSMYRE-UHFFFAOYSA-N 0.000 description 4
- MLOSJPZSZWUDSK-UHFFFAOYSA-N 4-carboxybutyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCCC(=O)O)C1=CC=CC=C1 MLOSJPZSZWUDSK-UHFFFAOYSA-N 0.000 description 4
- 239000002083 C09CA01 - Losartan Substances 0.000 description 4
- 102000009123 Fibrin Human genes 0.000 description 4
- 108010073385 Fibrin Proteins 0.000 description 4
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 4
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 4
- 150000001413 amino acids Chemical group 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(i) oxide Chemical compound [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 description 4
- 206010012601 diabetes mellitus Diseases 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 229950003499 fibrin Drugs 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 125000004404 heteroalkyl group Chemical group 0.000 description 4
- USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 239000011630 iodine Substances 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 229910052742 iron Inorganic materials 0.000 description 4
- 150000002576 ketones Chemical class 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- 230000001732 thrombotic effect Effects 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 4
- MPJYFSPMHBSROY-UHFFFAOYSA-N (3-bromophenyl)-(5-chloropyridin-2-yl)methanone Chemical compound BrC=1C=C(C=CC=1)C(=O)C1=NC=C(C=C1)Cl MPJYFSPMHBSROY-UHFFFAOYSA-N 0.000 description 3
- VYCOMMCTMLXDDL-UHFFFAOYSA-N (5-chloropyridin-2-yl)-(5-fluoro-4-iodopyridin-2-yl)methanone Chemical compound ClC=1C=CC(=NC=1)C(=O)C1=NC=C(C(=C1)I)F VYCOMMCTMLXDDL-UHFFFAOYSA-N 0.000 description 3
- MNIPVWXWSPXERA-IDNZQHFXSA-N (6r,7r)-1-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-4,7-dihydroxy-6-(11-phenoxyundecanoyloxy)-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CCC12[C@@H]([C@@H](OC(=O)CCCCCCCCCCOC=3C=CC=CC=3)C(O1)(C(O)=O)C(O)(C(O2)C(O)=O)C(O)=O)O)C1=CC=CC=C1 MNIPVWXWSPXERA-IDNZQHFXSA-N 0.000 description 3
- 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 3
- CMPNNGSZNMJRES-UHFFFAOYSA-N 1-(4-chloro-2-iodophenyl)-4-(difluoromethyl)triazole Chemical compound ClC1=CC(=C(C=C1)N1N=NC(=C1)C(F)F)I CMPNNGSZNMJRES-UHFFFAOYSA-N 0.000 description 3
- PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 3
- STPUUBCHYCYFBQ-UHFFFAOYSA-N 3-bromo-1-chloro-2,4-difluorobenzene Chemical compound FC1=CC=C(Cl)C(F)=C1Br STPUUBCHYCYFBQ-UHFFFAOYSA-N 0.000 description 3
- VPWARUVASBJSPY-UHFFFAOYSA-N 3-bromo-n-methoxy-n-methylbenzamide Chemical compound CON(C)C(=O)C1=CC=CC(Br)=C1 VPWARUVASBJSPY-UHFFFAOYSA-N 0.000 description 3
- NKKSUZCCSQAZGI-UHFFFAOYSA-N 4-carboxypentyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCC(C)C(O)=O)C1=CC=CC=C1 NKKSUZCCSQAZGI-UHFFFAOYSA-N 0.000 description 3
- GVJZHGCVSYBPIM-UHFFFAOYSA-N 4-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC(Cl)=CC=C1N GVJZHGCVSYBPIM-UHFFFAOYSA-N 0.000 description 3
- QRAMJYALSQDAKN-UHFFFAOYSA-N 6-[(3-chlorophenyl)methyl]pyridin-3-ol Chemical compound ClC=1C=C(CC2=CC=C(C=N2)O)C=CC=1 QRAMJYALSQDAKN-UHFFFAOYSA-N 0.000 description 3
- DHLUJPLHLZJUBW-UHFFFAOYSA-N 6-methylpyridin-3-ol Chemical compound CC1=CC=C(O)C=N1 DHLUJPLHLZJUBW-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- 206010003178 Arterial thrombosis Diseases 0.000 description 3
- OELCYQKBFKDKHN-UHFFFAOYSA-N BrC=1N(C(=CN=1)C(=O)C1=NC=C(C=C1)Cl)COCC[Si](C)(C)C Chemical compound BrC=1N(C(=CN=1)C(=O)C1=NC=C(C=C1)Cl)COCC[Si](C)(C)C OELCYQKBFKDKHN-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- GHOSNRCGJFBJIB-UHFFFAOYSA-N Candesartan cilexetil Chemical compound C=12N(CC=3C=CC(=CC=3)C=3C(=CC=CC=3)C3=NNN=N3)C(OCC)=NC2=CC=CC=1C(=O)OC(C)OC(=O)OC1CCCCC1 GHOSNRCGJFBJIB-UHFFFAOYSA-N 0.000 description 3
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 3
- 229940126650 Compound 3f Drugs 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 3
- 229910004373 HOAc Inorganic materials 0.000 description 3
- 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 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- 150000001204 N-oxides Chemical class 0.000 description 3
- 101150003085 Pdcl gene Proteins 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 229940122388 Thrombin inhibitor Drugs 0.000 description 3
- 208000007814 Unstable Angina Diseases 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 229940024606 amino acid Drugs 0.000 description 3
- 239000012378 ammonium molybdate tetrahydrate Substances 0.000 description 3
- 239000003524 antilipemic agent Substances 0.000 description 3
- FIXLYHHVMHXSCP-UHFFFAOYSA-H azane;dihydroxy(dioxo)molybdenum;trioxomolybdenum;tetrahydrate Chemical compound N.N.N.N.N.N.O.O.O.O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O[Mo](O)(=O)=O.O[Mo](O)(=O)=O.O[Mo](O)(=O)=O FIXLYHHVMHXSCP-UHFFFAOYSA-H 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 230000004087 circulation Effects 0.000 description 3
- 229940000425 combination drug Drugs 0.000 description 3
- 208000029078 coronary artery disease Diseases 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 3
- OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 description 3
- 239000012065 filter cake Substances 0.000 description 3
- 150000004677 hydrates Chemical class 0.000 description 3
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 3
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 3
- 125000002883 imidazolyl group Chemical group 0.000 description 3
- 208000027866 inflammatory disease Diseases 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 230000000155 isotopic effect Effects 0.000 description 3
- 150000002678 macrocyclic compounds Chemical class 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 3
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 3
- 239000012046 mixed solvent Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- 208000010125 myocardial infarction Diseases 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 125000002524 organometallic group Chemical group 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 239000012026 peptide coupling reagents Substances 0.000 description 3
- 239000012041 precatalyst Substances 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 125000003226 pyrazolyl group Chemical group 0.000 description 3
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 3
- MFFMDFFZMYYVKS-SECBINFHSA-N sitagliptin Chemical compound C([C@H](CC(=O)N1CC=2N(C(=NN=2)C(F)(F)F)CC1)N)C1=CC(F)=C(F)C=C1F MFFMDFFZMYYVKS-SECBINFHSA-N 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
- 235000019345 sodium thiosulphate Nutrition 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 239000003868 thrombin inhibitor 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
- 230000002792 vascular Effects 0.000 description 3
- UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 3
- WZTAIOAXAOLTDT-UHFFFAOYSA-N (2-bromo-1H-imidazol-5-yl)-(5-chloropyridin-2-yl)methanone Chemical compound BrC=1NC(=CN=1)C(=O)C1=NC=C(C=C1)Cl WZTAIOAXAOLTDT-UHFFFAOYSA-N 0.000 description 2
- GCGGDXVAQPQLIH-UHFFFAOYSA-N (2-bromopyridin-4-yl)-(5-chloropyridin-2-yl)methanol Chemical compound BrC1=NC=CC(=C1)C(O)C1=NC=C(C=C1)Cl GCGGDXVAQPQLIH-UHFFFAOYSA-N 0.000 description 2
- ONKHDHRIVOKILQ-UHFFFAOYSA-N (2-bromopyridin-4-yl)-(5-chloropyridin-2-yl)methanone Chemical compound BrC1=NC=CC(=C1)C(=O)C1=NC=C(C=C1)Cl ONKHDHRIVOKILQ-UHFFFAOYSA-N 0.000 description 2
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 2
- FOLCUFKJHSQMEL-BIXPGCQOSA-N (4-butylcyclohexyl) N-[(2S)-4-methyl-1-oxo-1-[[(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]pentan-2-yl]carbamate Chemical compound CCCCC1CCC(CC1)OC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C[C@@H]2CCNC2=O)C=O FOLCUFKJHSQMEL-BIXPGCQOSA-N 0.000 description 2
- FUHSVZIIUAMSOB-UHFFFAOYSA-N (4-chloro-2-iodophenyl)-diazonioazanide Chemical compound ClC1=CC=C(N=[N+]=[N-])C(I)=C1 FUHSVZIIUAMSOB-UHFFFAOYSA-N 0.000 description 2
- QCPULHGNQFWBCM-UHFFFAOYSA-N (5-chloropyridin-2-yl)-(5-fluoro-4-iodopyridin-2-yl)methanol Chemical compound ClC=1C=CC(=NC=1)C(O)C1=NC=C(C(=C1)I)F QCPULHGNQFWBCM-UHFFFAOYSA-N 0.000 description 2
- DDPPKSGKJXTMRH-UHFFFAOYSA-N (5-chloropyridin-2-yl)-(5-fluoropyridin-2-yl)methanone Chemical compound ClC=1C=CC(=NC=1)C(=O)C1=NC=C(C=C1)F DDPPKSGKJXTMRH-UHFFFAOYSA-N 0.000 description 2
- OOFKCRCWBCCGPA-UHFFFAOYSA-N (5-chloropyridin-2-yl)-(6-chloropyrimidin-4-yl)methanone Chemical compound ClC=1C=CC(=NC=1)C(=O)C1=NC=NC(=C1)Cl OOFKCRCWBCCGPA-UHFFFAOYSA-N 0.000 description 2
- VGNCBRNRHXEODV-XXVHXNRLSA-N (6r,7r)-1-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-6-dodecoxy-4,7-dihydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CCC12[C@H](O)[C@H](C(O2)(C(O)=O)C(O)(C(O1)C(O)=O)C(O)=O)OCCCCCCCCCCCC)C1=CC=CC=C1 VGNCBRNRHXEODV-XXVHXNRLSA-N 0.000 description 2
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 description 2
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 2
- SMGXHVWYXQYMNN-UHFFFAOYSA-N 1,3-dibromo-2-methylpropane Chemical compound BrCC(C)CBr SMGXHVWYXQYMNN-UHFFFAOYSA-N 0.000 description 2
- VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 2
- IPVLHIMLMPFFDL-UHFFFAOYSA-N 1-(2-bromo-4-chlorophenyl)-4-(difluoromethyl)triazole Chemical compound BrC1=C(C=CC(=C1)Cl)N1N=NC(=C1)C(F)F IPVLHIMLMPFFDL-UHFFFAOYSA-N 0.000 description 2
- GNXOJFOZMMNMHH-UHFFFAOYSA-N 1-(2-bromo-4-chlorophenyl)triazole-4-carbaldehyde Chemical compound BrC1=CC(Cl)=CC=C1N1N=NC(C=O)=C1 GNXOJFOZMMNMHH-UHFFFAOYSA-N 0.000 description 2
- YPSQTTRCBKFQSM-UHFFFAOYSA-N 1-(4-chloro-2-iodophenyl)triazole-4-carbaldehyde Chemical compound ClC1=CC(I)=C(C=C1)N1C=C(C=O)N=N1 YPSQTTRCBKFQSM-UHFFFAOYSA-N 0.000 description 2
- HYUYHWMOTBVGRX-UHFFFAOYSA-N 1-(4-chloro-3-fluoro-2-iodophenyl)-4-(trifluoromethyl)triazole Chemical compound ClC1=C(C(=C(C=C1)N1N=NC(=C1)C(F)(F)F)I)F HYUYHWMOTBVGRX-UHFFFAOYSA-N 0.000 description 2
- KWLCKTQXXQBJHQ-UHFFFAOYSA-N 1-[3-(1,3-benzothiazol-2-ylsulfanyl)propyl]cyclopropane-1-carboxylic acid Chemical compound S1C(=NC2=C1C=CC=C2)SCCCC1(CC1)C(=O)O KWLCKTQXXQBJHQ-UHFFFAOYSA-N 0.000 description 2
- QRADKVYIJIAENZ-UHFFFAOYSA-N 1-[[bromo(difluoro)methyl]-ethoxyphosphoryl]oxyethane Chemical compound CCOP(=O)(C(F)(F)Br)OCC QRADKVYIJIAENZ-UHFFFAOYSA-N 0.000 description 2
- MBVIIOFOGJEFBP-UHFFFAOYSA-N 1-azido-4-chloro-3-fluoro-2-iodobenzene Chemical compound N(=[N+]=[N-])C1=C(C(=C(C=C1)Cl)F)I MBVIIOFOGJEFBP-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- NFDGMTLLHGCGET-UHFFFAOYSA-N 2-[(2-bromoimidazol-1-yl)methoxy]ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCN1C=CN=C1Br NFDGMTLLHGCGET-UHFFFAOYSA-N 0.000 description 2
- RHFIAUKMKYHHFA-UHFFFAOYSA-N 2-[[6-(3,3-difluoropyrrolidin-1-yl)-4-[1-(oxetan-3-yl)piperidin-4-yl]pyridin-2-yl]amino]pyridine-4-carbonitrile Chemical compound C1C(F)(F)CCN1C1=CC(C2CCN(CC2)C2COC2)=CC(NC=2N=CC=C(C=2)C#N)=N1 RHFIAUKMKYHHFA-UHFFFAOYSA-N 0.000 description 2
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 2
- HRGNVARTBYIBSA-UHFFFAOYSA-N 2-bromo-1-fluoro-3,5-dinitrobenzene Chemical compound [O-][N+](=O)C1=CC(F)=C(Br)C([N+]([O-])=O)=C1 HRGNVARTBYIBSA-UHFFFAOYSA-N 0.000 description 2
- XUQJWVKFSVDGPP-UHFFFAOYSA-N 2-bromo-3,4-difluorophenol Chemical compound OC1=CC=C(F)C(F)=C1Br XUQJWVKFSVDGPP-UHFFFAOYSA-N 0.000 description 2
- ZZVVBYKBHDBUFV-UHFFFAOYSA-N 2-bromo-4-chloro-n-methoxy-n-methylbenzamide Chemical compound CON(C)C(=O)C1=CC=C(Cl)C=C1Br ZZVVBYKBHDBUFV-UHFFFAOYSA-N 0.000 description 2
- SYTBIFURTZACKR-UHFFFAOYSA-N 2-bromo-4-chloroaniline Chemical compound NC1=CC=C(Cl)C=C1Br SYTBIFURTZACKR-UHFFFAOYSA-N 0.000 description 2
- AJOAHIKYBSZIEV-UHFFFAOYSA-N 2-bromo-4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C(Br)=C1 AJOAHIKYBSZIEV-UHFFFAOYSA-N 0.000 description 2
- RCABZWNZVXSCDJ-UHFFFAOYSA-N 2-bromo-5-chloro-4-methoxypyridine Chemical compound COC1=CC(Br)=NC=C1Cl RCABZWNZVXSCDJ-UHFFFAOYSA-N 0.000 description 2
- BZUUVQCSPHPUQA-UHFFFAOYSA-N 2-bromo-5-chloropyridine Chemical compound ClC1=CC=C(Br)N=C1 BZUUVQCSPHPUQA-UHFFFAOYSA-N 0.000 description 2
- 150000005762 2-bromopyridine Chemical class 0.000 description 2
- GCFZQMCJLYJALN-UHFFFAOYSA-N 2-fluoro-4,6-dinitrophenol Chemical compound OC1=C(F)C=C([N+]([O-])=O)C=C1[N+]([O-])=O GCFZQMCJLYJALN-UHFFFAOYSA-N 0.000 description 2
- XKKSFCAMJLJEEA-UHFFFAOYSA-N 3-bromo-1,2-difluoro-4-(methoxymethoxy)benzene Chemical compound BrC1=C(C=CC(=C1F)F)OCOC XKKSFCAMJLJEEA-UHFFFAOYSA-N 0.000 description 2
- GRFNBEZIAWKNCO-UHFFFAOYSA-N 3-pyridinol Chemical compound OC1=CC=CN=C1 GRFNBEZIAWKNCO-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- KDEJQUNODYXYBJ-UHFFFAOYSA-N 4-(trifluoromethyl)-1h-pyrazole Chemical compound FC(F)(F)C=1C=NNC=1 KDEJQUNODYXYBJ-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- UBAXKQNQQZKDEM-UHFFFAOYSA-N 4-bromo-3-fluoro-5-nitroaniline Chemical compound NC1=CC(F)=C(Br)C([N+]([O-])=O)=C1 UBAXKQNQQZKDEM-UHFFFAOYSA-N 0.000 description 2
- PITHQPMZWKZGRZ-UHFFFAOYSA-N 4-bromo-3-nitroaniline Chemical compound NC1=CC=C(Br)C([N+]([O-])=O)=C1 PITHQPMZWKZGRZ-UHFFFAOYSA-N 0.000 description 2
- YKQGANWRJDKVAD-UHFFFAOYSA-N 4-iodo-5-methyl-1h-imidazole Chemical compound CC=1NC=NC=1I YKQGANWRJDKVAD-UHFFFAOYSA-N 0.000 description 2
- XLSZMDLNRCVEIJ-UHFFFAOYSA-N 4-methylimidazole Chemical compound CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 description 2
- VLFQFWXTXSXGGW-UHFFFAOYSA-N 5-(1,3-benzothiazol-2-ylsulfanyl)-2,2-dimethylpentanoic acid Chemical compound C1=CC=C2SC(SCCCC(C)(C)C(O)=O)=NC2=C1 VLFQFWXTXSXGGW-UHFFFAOYSA-N 0.000 description 2
- MOSJHOUGBVYKSE-UHFFFAOYSA-N 5-(1,3-benzothiazol-2-ylsulfanyl)-4-methylpentanoic acid Chemical compound S1C(=NC2=C1C=CC=C2)SCC(CCC(=O)O)C MOSJHOUGBVYKSE-UHFFFAOYSA-N 0.000 description 2
- OZVHBLUEPSKPBZ-UHFFFAOYSA-N 5-(1,3-benzothiazol-2-ylsulfonyl)-2,2-dimethylpentanoic acid Chemical compound S1C(=NC2=C1C=CC=C2)S(=O)(=O)CCCC(C(=O)O)(C)C OZVHBLUEPSKPBZ-UHFFFAOYSA-N 0.000 description 2
- WGTFNNXPENOZDM-UHFFFAOYSA-N 5-(1-phenyltetrazol-5-yl)sulfanylpentanoic acid Chemical compound OC(=O)CCCCSC1=NN=NN1C1=CC=CC=C1 WGTFNNXPENOZDM-UHFFFAOYSA-N 0.000 description 2
- ZLUVCPFHXCSKTK-UHFFFAOYSA-N 5-(1-phenyltetrazol-5-yl)sulfonylpentanoic acid Chemical compound C1(=CC=CC=C1)N1N=NN=C1S(=O)(=O)CCCCC(=O)O ZLUVCPFHXCSKTK-UHFFFAOYSA-N 0.000 description 2
- HGEQCXOCMDGILJ-UHFFFAOYSA-N 5-(2-bromo-4-chlorophenyl)-1,3-oxazole Chemical compound BrC1=C(C=CC(=C1)Cl)C1=CN=CO1 HGEQCXOCMDGILJ-UHFFFAOYSA-N 0.000 description 2
- GDYGMDZCBUYAIK-UHFFFAOYSA-N 5-bromo-2-methylpentanoic acid Chemical compound OC(=O)C(C)CCCBr GDYGMDZCBUYAIK-UHFFFAOYSA-N 0.000 description 2
- DCDCGYCMMJLNKE-UHFFFAOYSA-N 5-bromo-4-methylpentanoic acid Chemical compound BrCC(C)CCC(O)=O DCDCGYCMMJLNKE-UHFFFAOYSA-N 0.000 description 2
- YQUKLNVJRGVRKM-UHFFFAOYSA-N 5-bromo-n-methoxy-n-methylpyridine-2-carboxamide Chemical compound CON(C)C(=O)C1=CC=C(Br)C=N1 YQUKLNVJRGVRKM-UHFFFAOYSA-N 0.000 description 2
- MQMLJTNHVCTZML-UHFFFAOYSA-N 5-chloro-2-[1-(difluoromethyl)pyrazol-4-yl]phenol Chemical compound ClC=1C=CC(=C(C=1)O)C=1C=NN(C=1)C(F)F MQMLJTNHVCTZML-UHFFFAOYSA-N 0.000 description 2
- OAVVPDNRDVPTOK-UHFFFAOYSA-N 5-chloro-n-methoxy-n-methylpyridine-2-carboxamide Chemical compound CON(C)C(=O)C1=CC=C(Cl)C=N1 OAVVPDNRDVPTOK-UHFFFAOYSA-N 0.000 description 2
- FAJZIXITZFFSPC-UHFFFAOYSA-N 6-chloropyrimidine-4-carbonyl chloride Chemical compound ClC(=O)C1=CC(Cl)=NC=N1 FAJZIXITZFFSPC-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- 239000005695 Ammonium acetate Substances 0.000 description 2
- 102000004411 Antithrombin III Human genes 0.000 description 2
- 108090000935 Antithrombin III Proteins 0.000 description 2
- 206010003210 Arteriosclerosis Diseases 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 206010003658 Atrial Fibrillation Diseases 0.000 description 2
- 239000005485 Azilsartan Substances 0.000 description 2
- RYHTVJBJPQHXLC-UHFFFAOYSA-N BrC=1N(C(=CN=1)C(O)C1=NC=C(C=C1)Cl)COCC[Si](C)(C)C Chemical compound BrC=1N(C(=CN=1)C(O)C1=NC=C(C=C1)Cl)COCC[Si](C)(C)C RYHTVJBJPQHXLC-UHFFFAOYSA-N 0.000 description 2
- 101800004538 Bradykinin Proteins 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- VUWBMXNMKRWSEI-UHFFFAOYSA-N C1(CCCCC1)P(C1=C(C=CC=C1)C1=C(C=C(C=C1C(C)C)C(C)C)C(C)C)C1CCCCC1.[Cl] Chemical group C1(CCCCC1)P(C1=C(C=CC=C1)C1=C(C=C(C=C1C(C)C)C(C)C)C(C)C)C1CCCCC1.[Cl] VUWBMXNMKRWSEI-UHFFFAOYSA-N 0.000 description 2
- IWJYEHAMTLIBNB-UHFFFAOYSA-N CCCP1OP(CCC)(C(O)=O)OP(CCC)O1 Chemical compound CCCP1OP(CCC)(C(O)=O)OP(CCC)O1 IWJYEHAMTLIBNB-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- WDJWISUGZHCVNB-UHFFFAOYSA-N ClC1=CC(=C(C=C1)C1=CN=CO1)B1OC(C(O1)(C)C)(C)C Chemical compound ClC1=CC(=C(C=C1)C1=CN=CO1)B1OC(C(O1)(C)C)(C)C WDJWISUGZHCVNB-UHFFFAOYSA-N 0.000 description 2
- ROSYRYINTRJITE-UHFFFAOYSA-N ClC1=CC(=C(C=C1)N1N=NC(=C1)C(F)F)[Sn](C)(C)C Chemical compound ClC1=CC(=C(C=C1)N1N=NC(=C1)C(F)F)[Sn](C)(C)C ROSYRYINTRJITE-UHFFFAOYSA-N 0.000 description 2
- IHMLGWHZRUCPJP-UHFFFAOYSA-N ClC=1C=CC(=NC=1)C(=O)C1=CC(=CC=C1)B1OC(C(O1)(C)C)(C)C Chemical compound ClC=1C=CC(=NC=1)C(=O)C1=CC(=CC=C1)B1OC(C(O1)(C)C)(C)C IHMLGWHZRUCPJP-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 2
- 206010012688 Diabetic retinal oedema Diseases 0.000 description 2
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 2
- 206010014498 Embolic stroke Diseases 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- RPTUSVTUFVMDQK-UHFFFAOYSA-N Hidralazin Chemical compound C1=CC=C2C(NN)=NN=CC2=C1 RPTUSVTUFVMDQK-UHFFFAOYSA-N 0.000 description 2
- 239000005909 Kieselgur Substances 0.000 description 2
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 description 2
- 229930182821 L-proline Natural products 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
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- NOOXQXQMOACVBP-UHFFFAOYSA-N NC=1C=C(C=CC=1B1OC(C(O1)(C)C)(C)C)NC(OC)=O Chemical compound NC=1C=C(C=CC=1B1OC(C(O1)(C)C)(C)C)NC(OC)=O NOOXQXQMOACVBP-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 108700010041 Nicotinic acid receptor Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 108010001014 Plasminogen Activators Proteins 0.000 description 2
- 102000001938 Plasminogen Activators Human genes 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical compound [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 description 2
- 241000720974 Protium Species 0.000 description 2
- 206010038563 Reocclusion Diseases 0.000 description 2
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 2
- 229940124639 Selective inhibitor Drugs 0.000 description 2
- 102000012479 Serine Proteases Human genes 0.000 description 2
- 108010022999 Serine Proteases Proteins 0.000 description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 2
- 206010052428 Wound Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 239000012391 XPhos Pd G2 Substances 0.000 description 2
- PZQKQOSYWWTPSY-UHFFFAOYSA-N [1-(2-bromo-4-chlorophenyl)triazol-4-yl]-tributylstannane Chemical compound BrC1=C(C=CC(=C1)Cl)N1N=NC(=C1)[Sn](CCCC)(CCCC)CCCC PZQKQOSYWWTPSY-UHFFFAOYSA-N 0.000 description 2
- YEWNXSNUHBHUNY-UHFFFAOYSA-N [1-(2-bromo-4-chlorophenyl)triazol-4-yl]methanol Chemical compound N1=NC(CO)=CN1C1=CC=C(Cl)C=C1Br YEWNXSNUHBHUNY-UHFFFAOYSA-N 0.000 description 2
- PPXFAFBKPUFJGF-UHFFFAOYSA-N [1-(4-chloro-2-iodophenyl)triazol-4-yl]methanol Chemical compound OCC1=CN(N=N1)C1=C(I)C=C(Cl)C=C1 PPXFAFBKPUFJGF-UHFFFAOYSA-N 0.000 description 2
- NSAXQHOQNOXKHN-UHFFFAOYSA-N [Br-].BrC=1C=CC(=NC=1)C(=O)C=1N(C=C(N=1)C1=C(C=C(C=C1)NC(=O)OC)NC(CCCC[P+](C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1)=O)COCC[Si](C)(C)C Chemical compound [Br-].BrC=1C=CC(=NC=1)C(=O)C=1N(C=C(N=1)C1=C(C=C(C=C1)NC(=O)OC)NC(CCCC[P+](C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1)=O)COCC[Si](C)(C)C NSAXQHOQNOXKHN-UHFFFAOYSA-N 0.000 description 2
- XIPUIGPNIDKXJU-UHFFFAOYSA-N [CH]1CC1 Chemical class [CH]1CC1 XIPUIGPNIDKXJU-UHFFFAOYSA-N 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- OQIQSTLJSLGHID-WNWIJWBNSA-N aflatoxin B1 Chemical compound C=1([C@@H]2C=CO[C@@H]2OC=1C=C(C1=2)OC)C=2OC(=O)C2=C1CCC2=O OQIQSTLJSLGHID-WNWIJWBNSA-N 0.000 description 2
- 238000005937 allylation reaction Methods 0.000 description 2
- 235000019257 ammonium acetate Nutrition 0.000 description 2
- 229940043376 ammonium acetate Drugs 0.000 description 2
- 238000002399 angioplasty Methods 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 229940127090 anticoagulant agent Drugs 0.000 description 2
- 239000002220 antihypertensive agent Substances 0.000 description 2
- 229960005348 antithrombin iii Drugs 0.000 description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- 150000001502 aryl halides Chemical class 0.000 description 2
- 150000007514 bases Chemical class 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 239000012472 biological sample Substances 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 230000036770 blood supply Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 2
- 150000001649 bromium compounds Chemical class 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
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 159000000007 calcium salts Chemical class 0.000 description 2
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 2
- RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 2
- 208000026106 cerebrovascular disease Diseases 0.000 description 2
- NMMPMZWIIQCZBA-UHFFFAOYSA-M chloropalladium(1+);dicyclohexyl-[2-[2,4,6-tri(propan-2-yl)phenyl]phenyl]phosphane;2-phenylethanamine Chemical compound [Pd+]Cl.NCCC1=CC=CC=[C-]1.CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 NMMPMZWIIQCZBA-UHFFFAOYSA-M 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 2
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 2
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 2
- 238000007887 coronary angioplasty Methods 0.000 description 2
- 239000006184 cosolvent Substances 0.000 description 2
- IBAHLNWTOIHLKE-UHFFFAOYSA-N cyano cyanate Chemical group N#COC#N IBAHLNWTOIHLKE-UHFFFAOYSA-N 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 230000005595 deprotonation Effects 0.000 description 2
- 238000010537 deprotonation reaction Methods 0.000 description 2
- 229910052805 deuterium Inorganic materials 0.000 description 2
- 201000011190 diabetic macular edema Diseases 0.000 description 2
- HVCGZCMANWMJFJ-UHFFFAOYSA-N diethyl 2-(3-bromopropyl)-2-methylpropanedioate Chemical compound CCOC(=O)C(C)(CCCBr)C(=O)OCC HVCGZCMANWMJFJ-UHFFFAOYSA-N 0.000 description 2
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 2
- DBPFRRFGLYGEJI-UHFFFAOYSA-N ethyl glyoxylate Chemical compound CCOC(=O)C=O DBPFRRFGLYGEJI-UHFFFAOYSA-N 0.000 description 2
- 229960000815 ezetimibe Drugs 0.000 description 2
- 239000002319 fibrinogen receptor antagonist Substances 0.000 description 2
- 230000003176 fibrotic effect Effects 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- 210000003709 heart valve Anatomy 0.000 description 2
- 230000023597 hemostasis Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 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 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 150000004694 iodide salts Chemical class 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- AHFWIQIYAXSLBA-RQXATKFSSA-N ipragliflozin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=CC=C(F)C(CC=2SC3=CC=CC=C3C=2)=C1 AHFWIQIYAXSLBA-RQXATKFSSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- PSIFNNKUMBGKDQ-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2NN=NN=2)C=C1 PSIFNNKUMBGKDQ-UHFFFAOYSA-N 0.000 description 2
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 2
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 2
- 229960003105 metformin Drugs 0.000 description 2
- MLMGRETXAWUMKM-UHFFFAOYSA-N methyl 5-(1,3-benzothiazol-2-ylsulfanyl)-2,2-dimethylpentanoate Chemical compound S1C(=NC2=C1C=CC=C2)SCCCC(C(=O)OC)(C)C MLMGRETXAWUMKM-UHFFFAOYSA-N 0.000 description 2
- ZAFPMRDLEZWXSA-UHFFFAOYSA-N methyl 5-(1,3-benzothiazol-2-ylsulfanyl)-2-methylpentanoate Chemical compound S1C(=NC2=C1C=CC=C2)SCCCC(C(=O)OC)C ZAFPMRDLEZWXSA-UHFFFAOYSA-N 0.000 description 2
- AGVXQDGXRYWFPO-UHFFFAOYSA-N methyl 5-(1,3-benzothiazol-2-ylsulfanyl)-4-methylpentanoate Chemical compound S1C(=NC2=C1C=CC=C2)SCC(CCC(=O)OC)C AGVXQDGXRYWFPO-UHFFFAOYSA-N 0.000 description 2
- BSPOOZOFDFOBNM-UHFFFAOYSA-N methyl 5-bromo-4-methylpentanoate Chemical compound COC(=O)CCC(C)CBr BSPOOZOFDFOBNM-UHFFFAOYSA-N 0.000 description 2
- CUJZAGNIPMKYQK-UHFFFAOYSA-N methyl n-(3-amino-4-bromophenyl)carbamate Chemical compound COC(=O)NC1=CC=C(Br)C(N)=C1 CUJZAGNIPMKYQK-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 229960003512 nicotinic acid Drugs 0.000 description 2
- 235000001968 nicotinic acid Nutrition 0.000 description 2
- 239000011664 nicotinic acid Substances 0.000 description 2
- VTRAEEWXHOVJFV-UHFFFAOYSA-N olmesartan Chemical compound CCCC1=NC(C(C)(C)O)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C=2NN=NN=2)C=C1 VTRAEEWXHOVJFV-UHFFFAOYSA-N 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 2
- HVAMZGADVCBITI-UHFFFAOYSA-M pent-4-enoate Chemical compound [O-]C(=O)CCC=C HVAMZGADVCBITI-UHFFFAOYSA-M 0.000 description 2
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 2
- 229940127126 plasminogen activator Drugs 0.000 description 2
- 229920000728 polyester Polymers 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 238000012746 preparative thin layer chromatography Methods 0.000 description 2
- 229960002429 proline Drugs 0.000 description 2
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000002797 proteolythic effect Effects 0.000 description 2
- 210000001147 pulmonary artery Anatomy 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- 125000002098 pyridazinyl group Chemical group 0.000 description 2
- ZRNDSLLIAOLRJS-UHFFFAOYSA-N pyridin-3-yl trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC1=CC=CN=C1 ZRNDSLLIAOLRJS-UHFFFAOYSA-N 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 239000000018 receptor agonist Substances 0.000 description 2
- 229940044601 receptor agonist Drugs 0.000 description 2
- 230000000306 recurrent effect Effects 0.000 description 2
- RWWYLEGWBNMMLJ-YSOARWBDSA-N remdesivir Chemical compound NC1=NC=NN2C1=CC=C2[C@]1([C@@H]([C@@H]([C@H](O1)CO[P@](=O)(OC1=CC=CC=C1)N[C@H](C(=O)OCC(CC)CC)C)O)O)C#N RWWYLEGWBNMMLJ-YSOARWBDSA-N 0.000 description 2
- 208000037803 restenosis Diseases 0.000 description 2
- 230000002207 retinal effect Effects 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 229960002855 simvastatin Drugs 0.000 description 2
- 229960004034 sitagliptin Drugs 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 description 2
- RIZHSLFDFUZPJJ-UHFFFAOYSA-N tert-butyl n-(4-bromo-3-nitrophenyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=C(Br)C([N+]([O-])=O)=C1 RIZHSLFDFUZPJJ-UHFFFAOYSA-N 0.000 description 2
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 230000009424 thromboembolic effect Effects 0.000 description 2
- 201000005665 thrombophilia Diseases 0.000 description 2
- 230000003558 thrombophilic effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 125000001425 triazolyl group Chemical group 0.000 description 2
- YEMJHNYABQHWHL-UHFFFAOYSA-N tributyl(ethynyl)stannane Chemical group CCCC[Sn](CCCC)(CCCC)C#C YEMJHNYABQHWHL-UHFFFAOYSA-N 0.000 description 2
- YLGRTLMDMVAFNI-UHFFFAOYSA-N tributyl(prop-2-enyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)CC=C YLGRTLMDMVAFNI-UHFFFAOYSA-N 0.000 description 2
- SNWQEQMYYXQBBX-UHFFFAOYSA-N triethyl 4-bromo-3-methylbutane-1,1,1-tricarboxylate Chemical compound BrCC(CC(C(=O)OCC)(C(=O)OCC)C(=O)OCC)C SNWQEQMYYXQBBX-UHFFFAOYSA-N 0.000 description 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-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
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
- 230000008728 vascular permeability Effects 0.000 description 2
- 230000025033 vasoconstriction Effects 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 2
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
- LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- XPYOMXGWCAUYCL-UHFFFAOYSA-N (2-bromo-5-fluoropyridin-4-yl)-(5-chloropyridin-2-yl)methanol Chemical compound BrC1=NC=C(C(=C1)C(O)C1=NC=C(C=C1)Cl)F XPYOMXGWCAUYCL-UHFFFAOYSA-N 0.000 description 1
- QLTDFLQBNKHEAR-UHFFFAOYSA-N (2-bromo-5-fluoropyridin-4-yl)-(5-chloropyridin-2-yl)methanone Chemical compound BrC1=NC=C(C(=C1)C(=O)C1=NC=C(C=C1)Cl)F QLTDFLQBNKHEAR-UHFFFAOYSA-N 0.000 description 1
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 1
- OJRHUICOVVSGSY-RXMQYKEDSA-N (2s)-2-chloro-3-methylbutan-1-ol Chemical compound CC(C)[C@H](Cl)CO OJRHUICOVVSGSY-RXMQYKEDSA-N 0.000 description 1
- QKDRXGFQVGOQKS-CRSSMBPESA-N (2s,3r,4r,5s,6r)-2-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-6-methylsulfanyloxane-3,4,5-triol Chemical compound C1=CC(OCC)=CC=C1CC1=CC([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](SC)O2)O)=CC=C1Cl QKDRXGFQVGOQKS-CRSSMBPESA-N 0.000 description 1
- BIDNLKIUORFRQP-XYGFDPSESA-N (2s,4s)-4-cyclohexyl-1-[2-[[(1s)-2-methyl-1-propanoyloxypropoxy]-(4-phenylbutyl)phosphoryl]acetyl]pyrrolidine-2-carboxylic acid Chemical compound C([P@@](=O)(O[C@H](OC(=O)CC)C(C)C)CC(=O)N1[C@@H](C[C@H](C1)C1CCCCC1)C(O)=O)CCCC1=CC=CC=C1 BIDNLKIUORFRQP-XYGFDPSESA-N 0.000 description 1
- XJEJCCKWUPDYRK-UHFFFAOYSA-N (3-bromophenyl)-(5-chloro-4-methoxypyridin-2-yl)methanone Chemical compound BrC=1C=C(C=CC=1)C(=O)C1=NC=C(C(=C1)OC)Cl XJEJCCKWUPDYRK-UHFFFAOYSA-N 0.000 description 1
- IYZRFOAPEUBNQP-JPZLKUPGSA-N (3s)-n-[(2s)-1-[[(5s)-5-amino-6-hydroxyhexyl]amino]-4-methyl-1-oxopentan-2-yl]-3-hydroxy-4-[[3-(1h-imidazol-5-yl)-2-[[3-naphthalen-1-yl-2-(naphthalen-1-ylmethyl)propanoyl]amino]propanoyl]amino]-6-methylheptanamide;dihydrochloride Chemical compound Cl.Cl.C=1C=CC2=CC=CC=C2C=1CC(CC=1C2=CC=CC=C2C=CC=1)C(=O)NC(C(=O)NC(CC(C)C)[C@@H](O)CC(=O)N[C@@H](CC(C)C)C(=O)NCCCC[C@H](N)CO)CC1=CN=CN1 IYZRFOAPEUBNQP-JPZLKUPGSA-N 0.000 description 1
- SYPWPWUSXPWLKW-ZQWQDMLBSA-N (3s,4s)-5-cyclohexyl-n-hexyl-3-hydroxy-4-[[(2s)-2-[[(2s)-2-[(2-morpholin-4-ylacetyl)amino]-3-naphthalen-1-ylpropanoyl]amino]-3-(1,3-thiazol-4-yl)propanoyl]amino]pentanamide Chemical compound C([C@@H]([C@@H](O)CC(=O)NCCCCCC)NC(=O)[C@H](CC=1N=CSC=1)NC(=O)[C@H](CC=1C2=CC=CC=C2C=CC=1)NC(=O)CN1CCOCC1)C1CCCCC1 SYPWPWUSXPWLKW-ZQWQDMLBSA-N 0.000 description 1
- WRIVAYRTTUMTKX-UHFFFAOYSA-N (4-bromopyridin-2-yl)-(5-chloropyridin-2-yl)methanone Chemical compound BrC1=CC(=NC=C1)C(=O)C1=NC=C(C=C1)Cl WRIVAYRTTUMTKX-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
- METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 description 1
- TWBNMYSKRDRHAT-RCWTXCDDSA-N (S)-timolol hemihydrate Chemical compound O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 TWBNMYSKRDRHAT-RCWTXCDDSA-N 0.000 description 1
- QRDAPCMJAOQZSU-KQQUZDAGSA-N (e)-3-[4-[(e)-3-(3-fluorophenyl)-3-oxoprop-1-enyl]-1-methylpyrrol-2-yl]-n-hydroxyprop-2-enamide Chemical compound C1=C(\C=C\C(=O)NO)N(C)C=C1\C=C\C(=O)C1=CC=CC(F)=C1 QRDAPCMJAOQZSU-KQQUZDAGSA-N 0.000 description 1
- IGVKWAAPMVVTFX-BUHFOSPRSA-N (e)-octadec-5-en-7,9-diynoic acid Chemical compound CCCCCCCCC#CC#C\C=C\CCCC(O)=O IGVKWAAPMVVTFX-BUHFOSPRSA-N 0.000 description 1
- VAVHMEQFYYBAPR-ITWZMISCSA-N (e,3r,5s)-7-[4-(4-fluorophenyl)-1-phenyl-2-propan-2-ylpyrrol-3-yl]-3,5-dihydroxyhept-6-enoic acid Chemical compound CC(C)C1=C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)C(C=2C=CC(F)=CC=2)=CN1C1=CC=CC=C1 VAVHMEQFYYBAPR-ITWZMISCSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- COONSELKYZNNQC-UHFFFAOYSA-N 1,2-difluoro-4-(methoxymethoxy)benzene Chemical compound COCOC1=CC=C(F)C(F)=C1 COONSELKYZNNQC-UHFFFAOYSA-N 0.000 description 1
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 1
- UPYMLXKJNVYVFS-UHFFFAOYSA-N 1-(2-bromo-4-chlorophenyl)-4-(trifluoromethyl)triazole Chemical compound BrC1=C(C=CC(=C1)Cl)N1N=NC(=C1)C(F)(F)F UPYMLXKJNVYVFS-UHFFFAOYSA-N 0.000 description 1
- AMYQYJADPCROFX-UHFFFAOYSA-N 1-(2-bromo-4-chlorophenyl)-4-chlorotriazole Chemical compound N1=NC(Cl)=CN1C1=CC=C(Cl)C=C1Br AMYQYJADPCROFX-UHFFFAOYSA-N 0.000 description 1
- BQXROZQUDCJBBY-UHFFFAOYSA-N 1-(2-bromo-5-fluorophenyl)ethanone Chemical compound CC(=O)C1=CC(F)=CC=C1Br BQXROZQUDCJBBY-UHFFFAOYSA-N 0.000 description 1
- AHVDHUTVNSIIPD-UHFFFAOYSA-N 1-(4-chloro-3-fluoro-2-iodophenyl)-4-(trifluoromethyl)pyrazole Chemical compound ClC1=C(C(=C(C=C1)N1N=CC(=C1)C(F)(F)F)I)F AHVDHUTVNSIIPD-UHFFFAOYSA-N 0.000 description 1
- MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 1
- SACVSUQLLHEZLY-UHFFFAOYSA-N 1-(difluoromethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole Chemical compound O1C(C)(C)C(C)(C)OB1C1=CN(C(F)F)N=C1 SACVSUQLLHEZLY-UHFFFAOYSA-N 0.000 description 1
- GGZHVNZHFYCSEV-UHFFFAOYSA-N 1-Phenyl-5-mercaptotetrazole Chemical compound SC1=NN=NN1C1=CC=CC=C1 GGZHVNZHFYCSEV-UHFFFAOYSA-N 0.000 description 1
- LEFVGZQNSCHOMA-UHFFFAOYSA-N 1-[3-(1,3-benzothiazol-2-ylsulfonyl)propyl]cyclopropane-1-carboxylic acid Chemical compound S1C(=NC2=C1C=CC=C2)S(=O)(=O)CCCC1(CC1)C(=O)O LEFVGZQNSCHOMA-UHFFFAOYSA-N 0.000 description 1
- VVQPBMDNYWURGL-UHFFFAOYSA-N 1-chloro-2,4-difluoro-3-iodobenzene Chemical compound FC1=CC=C(Cl)C(F)=C1I VVQPBMDNYWURGL-UHFFFAOYSA-N 0.000 description 1
- AJCSNHQKXUSMMY-UHFFFAOYSA-N 1-chloro-2,4-difluorobenzene Chemical compound FC1=CC=C(Cl)C(F)=C1 AJCSNHQKXUSMMY-UHFFFAOYSA-N 0.000 description 1
- ICUOPRHOUZCMIM-UHFFFAOYSA-M 1-chloro-3-methanidylbenzene;chlorozinc(1+) Chemical compound [Zn+]Cl.[CH2-]C1=CC=CC(Cl)=C1 ICUOPRHOUZCMIM-UHFFFAOYSA-M 0.000 description 1
- VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical compound CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
- VUQPJRPDRDVQMN-UHFFFAOYSA-N 1-chlorooctadecane Chemical class CCCCCCCCCCCCCCCCCCCl VUQPJRPDRDVQMN-UHFFFAOYSA-N 0.000 description 1
- IVVNZDGDKPTYHK-JTQLQIEISA-N 1-cyano-2-[(2s)-3,3-dimethylbutan-2-yl]-3-pyridin-4-ylguanidine Chemical compound CC(C)(C)[C@H](C)N=C(NC#N)NC1=CC=NC=C1 IVVNZDGDKPTYHK-JTQLQIEISA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- NUGZBVBZIDWZAD-UHFFFAOYSA-N 1h-pyrazole-4-carbonitrile Chemical compound N#CC=1C=NNC=1 NUGZBVBZIDWZAD-UHFFFAOYSA-N 0.000 description 1
- ZKWTVVXHWYTWJT-UHFFFAOYSA-N 2,4-dibromo-5-fluoropyridine Chemical compound FC1=CN=C(Br)C=C1Br ZKWTVVXHWYTWJT-UHFFFAOYSA-N 0.000 description 1
- PCMMSLVJMKQWMQ-UHFFFAOYSA-N 2,4-dibromopyridine Chemical compound BrC1=CC=NC(Br)=C1 PCMMSLVJMKQWMQ-UHFFFAOYSA-N 0.000 description 1
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
- OTVHUEBCKRVBIT-UHFFFAOYSA-N 2-(3-chloro-2,6-difluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound ClC=1C(=C(C(=CC=1)F)B1OC(C(O1)(C)C)(C)C)F OTVHUEBCKRVBIT-UHFFFAOYSA-N 0.000 description 1
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
- BVOHFHIEDQSTKD-UHFFFAOYSA-N 2-[(4-iodoimidazol-1-yl)methoxy]ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCN1C=NC(I)=C1 BVOHFHIEDQSTKD-UHFFFAOYSA-N 0.000 description 1
- JMEBYHAQUUWVBS-UHFFFAOYSA-N 2-[1-[5-(2-bromo-5-fluorophenyl)-1H-imidazol-2-yl]but-3-enyl]-5-[(4-methoxyphenyl)methoxy]pyridine Chemical compound COc1ccc(COc2ccc(nc2)C(CC=C)c2ncc([nH]2)-c2cc(F)ccc2Br)cc1 JMEBYHAQUUWVBS-UHFFFAOYSA-N 0.000 description 1
- WBCLNYMZPBFELG-UHFFFAOYSA-N 2-[5-[(4-methoxyphenyl)methoxy]pyridin-2-yl]pent-4-enoic acid Chemical compound COC1=CC=C(COC=2C=CC(=NC=2)C(C(=O)O)CC=C)C=C1 WBCLNYMZPBFELG-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 1
- QLVGHFBUSGYCCG-UHFFFAOYSA-N 2-amino-n-(1-cyano-2-phenylethyl)acetamide Chemical compound NCC(=O)NC(C#N)CC1=CC=CC=C1 QLVGHFBUSGYCCG-UHFFFAOYSA-N 0.000 description 1
- NYXFGTZHLKBZIL-UHFFFAOYSA-N 2-bromo-1-(2-bromo-5-fluorophenyl)ethanone Chemical compound FC1=CC=C(Br)C(C(=O)CBr)=C1 NYXFGTZHLKBZIL-UHFFFAOYSA-N 0.000 description 1
- OXLATYXOXMAMPP-UHFFFAOYSA-N 2-bromo-1-(difluoromethoxy)-3,4-difluorobenzene Chemical compound BrC1=C(C=CC(=C1F)F)OC(F)F OXLATYXOXMAMPP-UHFFFAOYSA-N 0.000 description 1
- BRIPPFBRTQDCPT-UHFFFAOYSA-N 2-bromo-1-(difluoromethyl)-3-fluorobenzene Chemical compound FC(F)C1=CC=CC(F)=C1Br BRIPPFBRTQDCPT-UHFFFAOYSA-N 0.000 description 1
- AXHRGVJWDJDYPO-UHFFFAOYSA-N 2-bromo-1h-imidazole Chemical compound BrC1=NC=CN1 AXHRGVJWDJDYPO-UHFFFAOYSA-N 0.000 description 1
- CYJBMGYWRHGZBR-UHFFFAOYSA-N 2-bromo-3-fluorobenzaldehyde Chemical compound FC1=CC=CC(C=O)=C1Br CYJBMGYWRHGZBR-UHFFFAOYSA-N 0.000 description 1
- LMFRSLRJXLATRL-UHFFFAOYSA-N 2-bromo-3-fluorophenol Chemical compound OC1=CC=CC(F)=C1Br LMFRSLRJXLATRL-UHFFFAOYSA-N 0.000 description 1
- YFFUYGSLQXVHMB-UHFFFAOYSA-N 2-bromo-4-chloro-1-fluorobenzene Chemical compound FC1=CC=C(Cl)C=C1Br YFFUYGSLQXVHMB-UHFFFAOYSA-N 0.000 description 1
- IOOHLHPTFHYPSD-UHFFFAOYSA-N 2-bromo-4-chloro-3-fluoroaniline Chemical compound BrC1=C(N)C=CC(=C1F)Cl IOOHLHPTFHYPSD-UHFFFAOYSA-N 0.000 description 1
- HBHBARSMRVAINH-UHFFFAOYSA-N 2-bromo-4-chloro-6-fluoroaniline Chemical compound NC1=C(F)C=C(Cl)C=C1Br HBHBARSMRVAINH-UHFFFAOYSA-N 0.000 description 1
- USMQLFCVCDEXAK-UHFFFAOYSA-N 2-bromo-4-chlorobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1Br USMQLFCVCDEXAK-UHFFFAOYSA-N 0.000 description 1
- ZIYRDJLAJYTELF-UHFFFAOYSA-N 2-bromo-4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1Br ZIYRDJLAJYTELF-UHFFFAOYSA-N 0.000 description 1
- YLMFXCIATJJKQL-UHFFFAOYSA-N 2-bromo-4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1Br YLMFXCIATJJKQL-UHFFFAOYSA-N 0.000 description 1
- CSRAUIQMWHYTRV-UHFFFAOYSA-N 2-bromo-5-chloro-1h-pyridin-4-one Chemical compound OC1=CC(Br)=NC=C1Cl CSRAUIQMWHYTRV-UHFFFAOYSA-N 0.000 description 1
- FMRKYXVZQWHGDA-UHFFFAOYSA-N 2-bromo-5-chlorophenol Chemical compound OC1=CC(Cl)=CC=C1Br FMRKYXVZQWHGDA-UHFFFAOYSA-N 0.000 description 1
- UODINHBLNPPDPD-UHFFFAOYSA-N 2-bromo-5-fluoropyridine Chemical compound FC1=CC=C(Br)N=C1 UODINHBLNPPDPD-UHFFFAOYSA-N 0.000 description 1
- RTWLIQFKXMWEJY-UHFFFAOYSA-N 2-bromopyridine-4-carbaldehyde Chemical compound BrC1=CC(C=O)=CC=N1 RTWLIQFKXMWEJY-UHFFFAOYSA-N 0.000 description 1
- YBTKGKVQEXAYEM-UHFFFAOYSA-N 2-bromopyridine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NC(Br)=C1 YBTKGKVQEXAYEM-UHFFFAOYSA-N 0.000 description 1
- UENGBOCGGKLVJJ-UHFFFAOYSA-N 2-chloro-1-(2,4-difluorophenyl)ethanone Chemical compound FC1=CC=C(C(=O)CCl)C(F)=C1 UENGBOCGGKLVJJ-UHFFFAOYSA-N 0.000 description 1
- OKDGRDCXVWSXDC-UHFFFAOYSA-N 2-chloropyridine Chemical group ClC1=CC=CC=N1 OKDGRDCXVWSXDC-UHFFFAOYSA-N 0.000 description 1
- UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical compound ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 description 1
- JBBKWIFIXPBQGZ-UHFFFAOYSA-N 2-diazonio-1-phenylmethoxyethenolate Chemical compound [N-]=[N+]=CC(=O)OCC1=CC=CC=C1 JBBKWIFIXPBQGZ-UHFFFAOYSA-N 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- 229940013085 2-diethylaminoethanol Drugs 0.000 description 1
- HFHFGHLXUCOHLN-UHFFFAOYSA-N 2-fluorophenol Chemical compound OC1=CC=CC=C1F HFHFGHLXUCOHLN-UHFFFAOYSA-N 0.000 description 1
- 102100027324 2-hydroxyacyl-CoA lyase 1 Human genes 0.000 description 1
- GQWNPIKWYPQUPI-UHFFFAOYSA-N 2-methylbut-3-enoic acid Chemical compound C=CC(C)C(O)=O GQWNPIKWYPQUPI-UHFFFAOYSA-N 0.000 description 1
- QWGRWMMWNDWRQN-UHFFFAOYSA-N 2-methylpropane-1,3-diol Chemical compound OCC(C)CO QWGRWMMWNDWRQN-UHFFFAOYSA-N 0.000 description 1
- WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical class BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
- AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical compound N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 description 1
- BNPWVUJOPCGHIK-UHFFFAOYSA-N 3,4-difluorophenol Chemical compound OC1=CC=C(F)C(F)=C1 BNPWVUJOPCGHIK-UHFFFAOYSA-N 0.000 description 1
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 1
- PBUNICLVOHJWRN-UHFFFAOYSA-N 3-bromo-4,5-difluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=C(F)C(Br)=C1 PBUNICLVOHJWRN-UHFFFAOYSA-N 0.000 description 1
- ONELILMJNOWXSA-UHFFFAOYSA-N 3-bromo-4-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C(Br)=C1 ONELILMJNOWXSA-UHFFFAOYSA-N 0.000 description 1
- KLSLJMGWUPAQGZ-UHFFFAOYSA-N 3-bromo-5-fluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=CC(Br)=C1 KLSLJMGWUPAQGZ-UHFFFAOYSA-N 0.000 description 1
- VOIZNVUXCQLQHS-UHFFFAOYSA-N 3-bromobenzoic acid Chemical compound OC(=O)C1=CC=CC(Br)=C1 VOIZNVUXCQLQHS-UHFFFAOYSA-N 0.000 description 1
- NYPYPOZNGOXYSU-UHFFFAOYSA-N 3-bromopyridine Chemical compound BrC1=CC=CN=C1 NYPYPOZNGOXYSU-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
- ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
- UIAGMCDKSXEBJQ-IBGZPJMESA-N 3-o-(2-methoxyethyl) 5-o-propan-2-yl (4s)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)[C@H]1C1=CC=CC([N+]([O-])=O)=C1 UIAGMCDKSXEBJQ-IBGZPJMESA-N 0.000 description 1
- JHNLZOVBAQWGQU-UHFFFAOYSA-N 380814_sial Chemical compound CS(O)(=O)=O.O=P(=O)OP(=O)=O JHNLZOVBAQWGQU-UHFFFAOYSA-N 0.000 description 1
- WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical compound C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 description 1
- SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical class COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 description 1
- GDWOMZZPEUVRDT-UHFFFAOYSA-N 4-[3-(5-chloropyridine-2-carbonyl)phenyl]-3-nitrobenzonitrile Chemical compound ClC=1C=CC(=NC=1)C(=O)C=1C=C(C=CC=1)C1=C(C=C(C=C1)C#N)[N+](=O)[O-] GDWOMZZPEUVRDT-UHFFFAOYSA-N 0.000 description 1
- PDNZCDDWSKYNTE-UHFFFAOYSA-N 4-bromo-2-fluoro-5-nitroaniline Chemical compound NC1=CC([N+]([O-])=O)=C(Br)C=C1F PDNZCDDWSKYNTE-UHFFFAOYSA-N 0.000 description 1
- FXRMUJPWDOLCLX-UHFFFAOYSA-N 4-bromo-3-nitrobenzonitrile Chemical compound [O-][N+](=O)C1=CC(C#N)=CC=C1Br FXRMUJPWDOLCLX-UHFFFAOYSA-N 0.000 description 1
- FLEJOBRWKBPUOX-UHFFFAOYSA-N 4-chloro-2-iodoaniline Chemical compound NC1=CC=C(Cl)C=C1I FLEJOBRWKBPUOX-UHFFFAOYSA-N 0.000 description 1
- PHRXRQKTLQGGHD-UHFFFAOYSA-N 4-chloro-3-fluoro-2-iodoaniline Chemical compound NC1=CC=C(Cl)C(F)=C1I PHRXRQKTLQGGHD-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 1
- RLUKWTHMONYTKG-UHFFFAOYSA-N 4-fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC(F)=CC=C1N RLUKWTHMONYTKG-UHFFFAOYSA-N 0.000 description 1
- QYGHXDAYBIFGKI-UHFFFAOYSA-N 4-oxo-1h-pyrimidine-6-carboxylic acid Chemical compound OC(=O)C1=CC(=O)N=CN1 QYGHXDAYBIFGKI-UHFFFAOYSA-N 0.000 description 1
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 1
- XZCQQQVMSMWHKL-UHFFFAOYSA-N 5-(1,3-benzothiazol-2-ylsulfonyl)-4-methylpentanoic acid Chemical compound S1C(=NC2=C1C=CC=C2)S(=O)(=O)CC(CCC(=O)O)C XZCQQQVMSMWHKL-UHFFFAOYSA-N 0.000 description 1
- JDVOEOFZQIKDAR-UHFFFAOYSA-N 5-(1,3-benzothiazol-2-ylsulfonyl)pentanoic acid Chemical compound S1C(=NC2=C1C=CC=C2)S(=O)(=O)CCCCC(=O)O JDVOEOFZQIKDAR-UHFFFAOYSA-N 0.000 description 1
- FNTDUMYXIRGUPV-UHFFFAOYSA-N 5-(2-chloro-5-nitrophenyl)oxolan-2-one Chemical compound [O-][N+](=O)C1=CC=C(Cl)C(C2OC(=O)CC2)=C1 FNTDUMYXIRGUPV-UHFFFAOYSA-N 0.000 description 1
- BEQLUULPDXSQBR-UHFFFAOYSA-N 5-[(4-methoxyphenyl)methoxy]-2-methylpyridine Chemical compound COC1=CC=C(COC2=CN=C(C)C=C2)C=C1 BEQLUULPDXSQBR-UHFFFAOYSA-N 0.000 description 1
- MNNQIBXLAHVDDL-UHFFFAOYSA-N 5-bromopyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(Br)C=N1 MNNQIBXLAHVDDL-UHFFFAOYSA-N 0.000 description 1
- KSBUTBXMRFVLND-UHFFFAOYSA-N 5-chloro-2-(trifluoromethoxy)aniline Chemical compound NC1=CC(Cl)=CC=C1OC(F)(F)F KSBUTBXMRFVLND-UHFFFAOYSA-N 0.000 description 1
- BHCMXJKPZOPRNN-UHFFFAOYSA-N 5-iodo-1h-imidazole Chemical compound IC1=CN=CN1 BHCMXJKPZOPRNN-UHFFFAOYSA-N 0.000 description 1
- RZTAMFZIAATZDJ-HNNXBMFYSA-N 5-o-ethyl 3-o-methyl (4s)-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-HNNXBMFYSA-N 0.000 description 1
- RAZCZHMSNADNPO-UHFFFAOYSA-N 6-[1-[3-(2-amino-5-fluorophenyl)phenyl]but-3-enyl]pyridin-3-ol Chemical compound NC1=C(C=C(C=C1)F)C1=CC(=CC=C1)C(CC=C)C1=CC=C(C=N1)O RAZCZHMSNADNPO-UHFFFAOYSA-N 0.000 description 1
- UVDJYBXHNFJTME-UHFFFAOYSA-N 6-bromo-5-fluoropyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(F)C(Br)=N1 UVDJYBXHNFJTME-UHFFFAOYSA-N 0.000 description 1
- PTEFNEALEPSHLC-UHFFFAOYSA-N 6-bromopyridin-3-ol Chemical compound OC1=CC=C(Br)N=C1 PTEFNEALEPSHLC-UHFFFAOYSA-N 0.000 description 1
- UIYUUEDFAMZISF-FTBISJDPSA-N 6-chloro-1,1-dioxo-3,4-dihydro-2h-1$l^{6},2,4-benzothiadiazine-7-sulfonamide;(2s)-3-methyl-2-[pentanoyl-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]amino]butanoic acid Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O.C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NNN=N1 UIYUUEDFAMZISF-FTBISJDPSA-N 0.000 description 1
- GBMIVDMAHNBPIH-UHFFFAOYSA-N 6-chloro-1,1-dioxo-3,4-dihydro-2h-1$l^{6},2,4-benzothiadiazine-7-sulfonamide;1-cyclohexyloxycarbonyloxyethyl 2-ethoxy-3-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]benzimidazole-4-carboxylate Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O.C=12N(CC=3C=CC(=CC=3)C=3C(=CC=CC=3)C3=NNN=N3)C(OCC)=NC2=CC=CC=1C(=O)OC(C)OC(=O)OC1CCCCC1 GBMIVDMAHNBPIH-UHFFFAOYSA-N 0.000 description 1
- MDUOYNYOCNXQGV-UHFFFAOYSA-N 6-chloro-n-methoxy-n-methylpyrimidine-4-carboxamide Chemical compound CON(C)C(=O)C1=CC(Cl)=NC=N1 MDUOYNYOCNXQGV-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
- 239000005541 ACE inhibitor Substances 0.000 description 1
- DJQOOSBJCLSSEY-UHFFFAOYSA-N Acipimox Chemical compound CC1=CN=C(C(O)=O)C=[N+]1[O-] DJQOOSBJCLSSEY-UHFFFAOYSA-N 0.000 description 1
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 1
- FHHHOYXPRDYHEZ-COXVUDFISA-N Alacepril Chemical compound CC(=O)SC[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 FHHHOYXPRDYHEZ-COXVUDFISA-N 0.000 description 1
- 229940123338 Aldosterone synthase inhibitor Drugs 0.000 description 1
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 1
- 102100033312 Alpha-2-macroglobulin Human genes 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
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 206010002388 Angina unstable Diseases 0.000 description 1
- 108050000824 Angiotensin II receptor Proteins 0.000 description 1
- 102000008873 Angiotensin II receptor Human genes 0.000 description 1
- 201000005657 Antithrombin III deficiency Diseases 0.000 description 1
- 241001553178 Arachis glabrata Species 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
- 239000005552 B01AC04 - Clopidogrel Substances 0.000 description 1
- 239000005465 B01AC22 - Prasugrel Substances 0.000 description 1
- XPCFTKFZXHTYIP-PMACEKPBSA-N Benazepril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 XPCFTKFZXHTYIP-PMACEKPBSA-N 0.000 description 1
- JXYACYYPACQCDM-UHFFFAOYSA-N Benzyl glycinate Chemical compound NCC(=O)OCC1=CC=CC=C1 JXYACYYPACQCDM-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 229940123208 Biguanide Drugs 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- USPNHBJGQRAMDU-UHFFFAOYSA-N BrC1=C(C=C(C=C1)F)C=1N=C(N(C=1)COCC[Si](C)(C)C)C(CC=C)C1=NC=C(C=C1)OCC1=CC=C(C=C1)OC Chemical compound BrC1=C(C=C(C=C1)F)C=1N=C(N(C=1)COCC[Si](C)(C)C)C(CC=C)C1=NC=C(C=C1)OCC1=CC=C(C=C1)OC USPNHBJGQRAMDU-UHFFFAOYSA-N 0.000 description 1
- NRWLTSNAVFEWMP-UHFFFAOYSA-N BrC=1C=CC(=NC=1)C(=O)C=1N(C=C(N=1)I)COCC[Si](C)(C)C Chemical compound BrC=1C=CC(=NC=1)C(=O)C=1N(C=C(N=1)I)COCC[Si](C)(C)C NRWLTSNAVFEWMP-UHFFFAOYSA-N 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- 239000002080 C09CA02 - Eprosartan Substances 0.000 description 1
- 239000004072 C09CA03 - Valsartan Substances 0.000 description 1
- 239000002947 C09CA04 - Irbesartan Substances 0.000 description 1
- 239000002053 C09CA06 - Candesartan Substances 0.000 description 1
- 239000005537 C09CA07 - Telmisartan Substances 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241001631457 Cannula Species 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical class [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- IFYLTXNCFVRALQ-OALUTQOASA-N Ceronapril Chemical compound O([C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)P(O)(=O)CCCCC1=CC=CC=C1 IFYLTXNCFVRALQ-OALUTQOASA-N 0.000 description 1
- 206010008479 Chest Pain Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 1
- RKWGIWYCVPQPMF-UHFFFAOYSA-N Chloropropamide Chemical compound CCCNC(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1 RKWGIWYCVPQPMF-UHFFFAOYSA-N 0.000 description 1
- 229940122502 Cholesterol absorption inhibitor Drugs 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- LFNCFZDQIGPVHM-UHFFFAOYSA-N ClC=1C=CC(=NC=1)C(=O)C=1N(C(=C(N=1)I)C)COCC[Si](C)(C)C Chemical compound ClC=1C=CC(=NC=1)C(=O)C=1N(C(=C(N=1)I)C)COCC[Si](C)(C)C LFNCFZDQIGPVHM-UHFFFAOYSA-N 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
- 102100029117 Coagulation factor X Human genes 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 229940126639 Compound 33 Drugs 0.000 description 1
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 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
- 229920004518 DION® Polymers 0.000 description 1
- JVHXJTBJCFBINQ-ADAARDCZSA-N Dapagliflozin Chemical compound C1=CC(OCC)=CC=C1CC1=CC([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=CC=C1Cl JVHXJTBJCFBINQ-ADAARDCZSA-N 0.000 description 1
- 238000006646 Dess-Martin oxidation reaction Methods 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
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- 102000003779 Dipeptidyl-peptidases and tripeptidyl-peptidases Human genes 0.000 description 1
- 108090000194 Dipeptidyl-peptidases and tripeptidyl-peptidases Proteins 0.000 description 1
- DVJAMEIQRSHVKC-BDAKNGLRSA-N Dutogliptin Chemical compound OB(O)[C@@H]1CCCN1C(=O)CN[C@H]1CNCC1 DVJAMEIQRSHVKC-BDAKNGLRSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 108010078772 ES 8891 Proteins 0.000 description 1
- 108010061435 Enalapril Proteins 0.000 description 1
- 108010066671 Enalaprilat Proteins 0.000 description 1
- 229940118365 Endothelin receptor antagonist Drugs 0.000 description 1
- 102000010911 Enzyme Precursors Human genes 0.000 description 1
- 108010062466 Enzyme Precursors Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- MCIACXAZCBVDEE-CUUWFGFTSA-N Ertugliflozin Chemical compound C1=CC(OCC)=CC=C1CC1=CC([C@@]23O[C@@](CO)(CO2)[C@@H](O)[C@H](O)[C@H]3O)=CC=C1Cl MCIACXAZCBVDEE-CUUWFGFTSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- HTQBXNHDCUEHJF-XWLPCZSASA-N Exenatide Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 HTQBXNHDCUEHJF-XWLPCZSASA-N 0.000 description 1
- RSKLVPDVJGMUQO-UHFFFAOYSA-N FC1=CC(=C(C=C1)NC(CC=C)=O)C=1N=C(N(C=1)COCC[Si](C)(C)C)C(CC=C)C1=NC=C(C=C1)OCC1=CC=C(C=C1)OC Chemical compound FC1=CC(=C(C=C1)NC(CC=C)=O)C=1N=C(N(C=1)COCC[Si](C)(C)C)C(CC=C)C1=NC=C(C=C1)OCC1=CC=C(C=C1)OC RSKLVPDVJGMUQO-UHFFFAOYSA-N 0.000 description 1
- WVPMUZZEKMPBFC-UHFFFAOYSA-N FC1=CC(=C(N)C=C1)C=1N=C(N(C=1)COCC[Si](C)(C)C)C(CC=C)C1=NC=C(C=C1)OCC1=CC=C(C=C1)OC Chemical compound FC1=CC(=C(N)C=C1)C=1N=C(N(C=1)COCC[Si](C)(C)C)C(CC=C)C1=NC=C(C=C1)OCC1=CC=C(C=C1)OC WVPMUZZEKMPBFC-UHFFFAOYSA-N 0.000 description 1
- 102000018711 Facilitative Glucose Transport Proteins Human genes 0.000 description 1
- 229940123849 Factor IXa inhibitor Drugs 0.000 description 1
- 206010058279 Factor V Leiden mutation Diseases 0.000 description 1
- 229940082863 Factor VIIa inhibitor Drugs 0.000 description 1
- 108010014173 Factor X Proteins 0.000 description 1
- 108010074860 Factor Xa Proteins 0.000 description 1
- 229940123583 Factor Xa inhibitor Drugs 0.000 description 1
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
- VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical compound [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- XQLWNAFCTODIRK-UHFFFAOYSA-N Gallopamil Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC(OC)=C(OC)C(OC)=C1 XQLWNAFCTODIRK-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- ZWPRRQZNBDYKLH-VIFPVBQESA-N Gemigliptin Chemical compound C([C@@H](N)CC(=O)N1CC2=C(C(=NC(=N2)C(F)(F)F)C(F)(F)F)CC1)N1CC(F)(F)CCC1=O ZWPRRQZNBDYKLH-VIFPVBQESA-N 0.000 description 1
- FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 description 1
- 108091052347 Glucose transporter family Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101001009252 Homo sapiens 2-hydroxyacyl-CoA lyase 1 Proteins 0.000 description 1
- 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 1
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- GVSQSDXMEOJZCU-UHFFFAOYSA-N IC1=C(N=CN1COCC[Si](C)(C)C)C Chemical compound IC1=C(N=CN1COCC[Si](C)(C)C)C GVSQSDXMEOJZCU-UHFFFAOYSA-N 0.000 description 1
- BOVQVWDWAIGZKE-UHFFFAOYSA-N IC=1N=CN(C=1C)COCC[Si](C)(C)C Chemical compound IC=1N=CN(C=1C)COCC[Si](C)(C)C BOVQVWDWAIGZKE-UHFFFAOYSA-N 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 229940122355 Insulin sensitizer Drugs 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- 108010093008 Kinins Proteins 0.000 description 1
- 102000002397 Kinins Human genes 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 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
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- LTXREWYXXSTFRX-QGZVFWFLSA-N Linagliptin Chemical compound N=1C=2N(C)C(=O)N(CC=3N=C4C=CC=CC4=C(C)N=3)C(=O)C=2N(CC#CC)C=1N1CCC[C@@H](N)C1 LTXREWYXXSTFRX-QGZVFWFLSA-N 0.000 description 1
- 108010007859 Lisinopril Proteins 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- WHSOLWOTCHFFBK-ZQGJOIPISA-N Luseogliflozin Chemical compound C1=CC(OCC)=CC=C1CC1=CC([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)S2)O)=C(OC)C=C1C WHSOLWOTCHFFBK-ZQGJOIPISA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- SPAGIJMPHSUYSE-UHFFFAOYSA-N Magnesium peroxide Chemical compound [Mg+2].[O-][O-] SPAGIJMPHSUYSE-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical compound OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 0.000 description 1
- ZFMITUMMTDLWHR-UHFFFAOYSA-N Minoxidil Chemical compound NC1=[N+]([O-])C(N)=CC(N2CCCCC2)=N1 ZFMITUMMTDLWHR-UHFFFAOYSA-N 0.000 description 1
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102000003729 Neprilysin Human genes 0.000 description 1
- 108090000028 Neprilysin Proteins 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 239000005480 Olmesartan Substances 0.000 description 1
- UQGKUQLKSCSZGY-UHFFFAOYSA-N Olmesartan medoxomil Chemical compound C=1C=C(C=2C(=CC=CC=2)C2=NNN=N2)C=CC=1CN1C(CCC)=NC(C(C)(C)O)=C1C(=O)OCC=1OC(=O)OC=1C UQGKUQLKSCSZGY-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 101800001589 Plasma kallikrein light chain Proteins 0.000 description 1
- 102400001128 Plasma kallikrein light chain Human genes 0.000 description 1
- 102000013566 Plasminogen Human genes 0.000 description 1
- 108010051456 Plasminogen Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
- 108010015078 Pregnancy-Associated alpha 2-Macroglobulins Proteins 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 201000005660 Protein C Deficiency Diseases 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 206010051292 Protein S Deficiency Diseases 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- PNUZDKCDAWUEGK-CYZMBNFOSA-N Sitafloxacin Chemical compound C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1 PNUZDKCDAWUEGK-CYZMBNFOSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 108010023197 Streptokinase Proteins 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- 235000019486 Sunflower oil Nutrition 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- 239000000219 Sympatholytic Substances 0.000 description 1
- 229920002253 Tannate Polymers 0.000 description 1
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 1
- 229940123464 Thiazolidinedione Drugs 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
- 108010036928 Thiorphan Proteins 0.000 description 1
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 1
- ZXOCGDDVNPDRIW-NHFZGCSJSA-N Tofogliflozin Chemical compound O.C1=CC(CC)=CC=C1CC1=CC=C(CO[C@@]23[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)C2=C1 ZXOCGDDVNPDRIW-NHFZGCSJSA-N 0.000 description 1
- JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 1
- VXFJYXUZANRPDJ-WTNASJBWSA-N Trandopril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@H]2CCCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 VXFJYXUZANRPDJ-WTNASJBWSA-N 0.000 description 1
- 208000032109 Transient ischaemic attack Diseases 0.000 description 1
- FNYLWPVRPXGIIP-UHFFFAOYSA-N Triamterene Chemical compound NC1=NC2=NC(N)=NC(N)=C2N=C1C1=CC=CC=C1 FNYLWPVRPXGIIP-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
- 206010053648 Vascular occlusion Diseases 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- JCEUYYVXBDARNN-UHFFFAOYSA-N [2-(2-amino-5-fluorophenyl)-5-fluoropyridin-4-yl]-(5-chloropyridin-2-yl)methanone Chemical compound NC1=C(C=C(C=C1)F)C1=NC=C(C(=C1)C(=O)C1=NC=C(C=C1)Cl)F JCEUYYVXBDARNN-UHFFFAOYSA-N 0.000 description 1
- DZIMTBNIKSEWHY-UHFFFAOYSA-N [3-(2-amino-5-fluorophenyl)phenyl]-(5-chloropyridin-2-yl)methanone Chemical compound NC1=C(C=C(C=C1)F)C1=CC(=CC=C1)C(=O)C1=NC=C(C=C1)Cl DZIMTBNIKSEWHY-UHFFFAOYSA-N 0.000 description 1
- OGXAMOSYHUNWPP-UHFFFAOYSA-N [3-amino-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl] carbamate Chemical compound C(N)(OC1=CC(=C(C=C1)B1OC(C(O1)(C)C)(C)C)N)=O OGXAMOSYHUNWPP-UHFFFAOYSA-N 0.000 description 1
- ZEYQOYCGCUZADJ-UHFFFAOYSA-N [5-[2-[2-(5-bromopyridine-2-carbonyl)-1-(2-trimethylsilylethoxymethyl)imidazol-4-yl]-5-(methoxycarbonylamino)anilino]-4-methyl-5-oxopentyl]-triphenylphosphanium bromide Chemical compound [Br-].BrC=1C=CC(=NC=1)C(=O)C=1N(C=C(N=1)C1=C(C=C(C=C1)NC(=O)OC)NC(C(CCC[P+](C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1)C)=O)COCC[Si](C)(C)C ZEYQOYCGCUZADJ-UHFFFAOYSA-N 0.000 description 1
- UGTQXPURJRZQIA-UHFFFAOYSA-N [5-[2-[3-(5-chloropyridine-2-carbonyl)-5-fluorophenyl]-5-(methoxycarbonylamino)anilino]-5-oxopentyl]-triphenylphosphanium bromide Chemical compound [Br-].ClC=1C=CC(=NC=1)C(=O)C=1C=C(C=C(C=1)F)C1=C(C=C(C=C1)NC(=O)OC)NC(CCCC[P+](C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1)=O UGTQXPURJRZQIA-UHFFFAOYSA-N 0.000 description 1
- ZPZRNVFDBAMBHP-UHFFFAOYSA-N [5-[2-[3-(5-chloropyridine-2-carbonyl)phenyl]-5-(methoxycarbonylamino)anilino]-4-methyl-5-oxopentyl]-triphenylphosphanium bromide Chemical compound [Br-].ClC=1C=CC(=NC=1)C(=O)C=1C=C(C=CC=1)C1=C(C=C(C=C1)NC(=O)OC)NC(C(CCC[P+](C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1)C)=O ZPZRNVFDBAMBHP-UHFFFAOYSA-N 0.000 description 1
- IRQMFCXQURMEKJ-UHFFFAOYSA-N [5-[2-[3-(5-chloropyridine-2-carbonyl)phenyl]-5-(methoxycarbonylamino)anilino]-5-oxopentyl]-triphenylphosphanium bromide Chemical compound [Br-].ClC=1C=CC(=NC=1)C(=O)C=1C=C(C=CC=1)C1=C(C=C(C=C1)NC(=O)OC)NC(CCCC[P+](C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1)=O IRQMFCXQURMEKJ-UHFFFAOYSA-N 0.000 description 1
- OCBFFGCSTGGPSQ-UHFFFAOYSA-N [CH2]CC Chemical class [CH2]CC OCBFFGCSTGGPSQ-UHFFFAOYSA-N 0.000 description 1
- DSVGQVZAZSZEEX-UHFFFAOYSA-N [C].[Pt] Chemical class [C].[Pt] DSVGQVZAZSZEEX-UHFFFAOYSA-N 0.000 description 1
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical class [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 1
- XNZVFTMTDZVZLR-UHFFFAOYSA-N [Si](C1=CC=CC=C1)(C1=CC=CC=C1)(C(C)(C)C)OC=1C=CC(=NC=1)C(CC=C)C=1C=C(C=CC=1)C1=C(C=CC(=C1)F)NC(CC=C)=O Chemical compound [Si](C1=CC=CC=C1)(C1=CC=CC=C1)(C(C)(C)C)OC=1C=CC(=NC=1)C(CC=C)C=1C=C(C=CC=1)C1=C(C=CC(=C1)F)NC(CC=C)=O XNZVFTMTDZVZLR-UHFFFAOYSA-N 0.000 description 1
- ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229960002632 acarbose Drugs 0.000 description 1
- 108010063628 acarboxyprothrombin Proteins 0.000 description 1
- XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 1
- 229960002122 acebutolol Drugs 0.000 description 1
- GOEMGAFJFRBGGG-UHFFFAOYSA-N acebutolol Chemical compound CCCC(=O)NC1=CC=C(OCC(O)CNC(C)C)C(C(C)=O)=C1 GOEMGAFJFRBGGG-UHFFFAOYSA-N 0.000 description 1
- AUALQMFGWLZREY-UHFFFAOYSA-N acetonitrile;methanol Chemical compound OC.CC#N AUALQMFGWLZREY-UHFFFAOYSA-N 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- DFDGRKNOFOJBAJ-UHFFFAOYSA-N acifran Chemical compound C=1C=CC=CC=1C1(C)OC(C(O)=O)=CC1=O DFDGRKNOFOJBAJ-UHFFFAOYSA-N 0.000 description 1
- 229950000146 acifran Drugs 0.000 description 1
- 229960003526 acipimox Drugs 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000695 adrenergic alpha-agonist Substances 0.000 description 1
- 229950007884 alacepril Drugs 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 239000002170 aldosterone antagonist Substances 0.000 description 1
- 229940083712 aldosterone antagonist Drugs 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
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- ZSBOMTDTBDDKMP-OAHLLOKOSA-N alogliptin Chemical compound C=1C=CC=C(C#N)C=1CN1C(=O)N(C)C(=O)C=C1N1CCC[C@@H](N)C1 ZSBOMTDTBDDKMP-OAHLLOKOSA-N 0.000 description 1
- 229960001667 alogliptin Drugs 0.000 description 1
- SRVFFFJZQVENJC-IHRRRGAJSA-N aloxistatin Chemical compound CCOC(=O)[C@H]1O[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)NCCC(C)C SRVFFFJZQVENJC-IHRRRGAJSA-N 0.000 description 1
- 239000003888 alpha glucosidase inhibitor Substances 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- CJCSPKMFHVPWAR-JTQLQIEISA-N alpha-methyl-L-dopa Chemical compound OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1 CJCSPKMFHVPWAR-JTQLQIEISA-N 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 238000010976 amide bond formation reaction Methods 0.000 description 1
- 229960002576 amiloride Drugs 0.000 description 1
- LTKVFMLMEYCWMK-UHFFFAOYSA-N amiloride hydrochloride dihydrate Chemical compound [H+].O.O.[Cl-].NC(=N)NC(=O)C1=NC(Cl)=C(N)N=C1N LTKVFMLMEYCWMK-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 150000008064 anhydrides Chemical group 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000000879 anti-atherosclerotic effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000002429 anti-coagulating effect Effects 0.000 description 1
- 239000000883 anti-obesity agent Substances 0.000 description 1
- 239000003416 antiarrhythmic agent Substances 0.000 description 1
- 229940125708 antidiabetic agent Drugs 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 229940127088 antihypertensive drug Drugs 0.000 description 1
- 229940125710 antiobesity agent Drugs 0.000 description 1
- 229960004676 antithrombotic agent Drugs 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229940058087 atacand Drugs 0.000 description 1
- 229940112147 atacand hct Drugs 0.000 description 1
- 229960002274 atenolol Drugs 0.000 description 1
- 229960005370 atorvastatin Drugs 0.000 description 1
- FQCKMBLVYCEXJB-MNSAWQCASA-L atorvastatin calcium Chemical compound [Ca+2].C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1.C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 FQCKMBLVYCEXJB-MNSAWQCASA-L 0.000 description 1
- 229960001770 atorvastatin calcium Drugs 0.000 description 1
- 229940000201 avapro 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
- YEESUBCSWGVPCE-UHFFFAOYSA-N azanylidyneoxidanium iron(2+) pentacyanide Chemical compound [Fe++].[C-]#N.[C-]#N.[C-]#N.[C-]#N.[C-]#N.N#[O+] YEESUBCSWGVPCE-UHFFFAOYSA-N 0.000 description 1
- KGSXMPPBFPAXLY-UHFFFAOYSA-N azilsartan Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NOC(=O)N1 KGSXMPPBFPAXLY-UHFFFAOYSA-N 0.000 description 1
- 229960002731 azilsartan Drugs 0.000 description 1
- IHWFKDWIUSZLCJ-UHFFFAOYSA-M azilsartan kamedoxomil Chemical compound [K+].C=12N(CC=3C=CC(=CC=3)C=3C(=CC=CC=3)C=3[N-]C(=O)ON=3)C(OCC)=NC2=CC=CC=1C(=O)OCC=1OC(=O)OC=1C IHWFKDWIUSZLCJ-UHFFFAOYSA-M 0.000 description 1
- 201000005008 bacterial sepsis Diseases 0.000 description 1
- 229960004530 benazepril Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229940055053 benicar Drugs 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
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004601 benzofurazanyl group Chemical group N1=C2C(=NO1)C(=CC=C2)* 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=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
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- FCDPQMAOJARMTG-UHFFFAOYSA-L benzylidene-[1,3-bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene]-dichlororuthenium;tricyclohexylphosphane Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1.CC1=CC(C)=CC(C)=C1N(CCN1C=2C(=CC(C)=CC=2C)C)C1=[Ru](Cl)(Cl)=CC1=CC=CC=C1 FCDPQMAOJARMTG-UHFFFAOYSA-L 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 229960004324 betaxolol Drugs 0.000 description 1
- NWIUTZDMDHAVTP-UHFFFAOYSA-N betaxolol Chemical compound C1=CC(OCC(O)CNC(C)C)=CC=C1CCOCC1CC1 NWIUTZDMDHAVTP-UHFFFAOYSA-N 0.000 description 1
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
- 150000004283 biguanides Chemical class 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000012455 biphasic mixture Substances 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 229960002781 bisoprolol Drugs 0.000 description 1
- VHYCDWMUTMEGQY-UHFFFAOYSA-N bisoprolol Chemical compound CC(C)NCC(O)COC1=CC=C(COCCOC(C)C)C=C1 VHYCDWMUTMEGQY-UHFFFAOYSA-N 0.000 description 1
- 239000010836 blood and blood product Substances 0.000 description 1
- 229940125691 blood product Drugs 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- OZVBMTJYIDMWIL-AYFBDAFISA-N bromocriptine Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=C(Br)NC3=C1 OZVBMTJYIDMWIL-AYFBDAFISA-N 0.000 description 1
- 229960002802 bromocriptine Drugs 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229940009550 c1 esterase inhibitor Drugs 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 229960001713 canagliflozin Drugs 0.000 description 1
- VHOFTEAWFCUTOS-TUGBYPPCSA-N canagliflozin hydrate Chemical compound O.CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1.CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1 VHOFTEAWFCUTOS-TUGBYPPCSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 229960000932 candesartan Drugs 0.000 description 1
- 229960004349 candesartan cilexetil Drugs 0.000 description 1
- 229960001080 cangrelor Drugs 0.000 description 1
- COWWROCHWNGJHQ-OPKBHZIBSA-J cangrelor tetrasodium Chemical compound [Na+].[Na+].[Na+].[Na+].C1=NC=2C(NCCSC)=NC(SCCC(F)(F)F)=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)C(Cl)(Cl)P([O-])([O-])=O)[C@@H](O)[C@H]1O COWWROCHWNGJHQ-OPKBHZIBSA-J 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229960000830 captopril Drugs 0.000 description 1
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 125000004623 carbolinyl group Chemical group 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 206010061592 cardiac fibrillation Diseases 0.000 description 1
- 210000004413 cardiac myocyte Anatomy 0.000 description 1
- 238000013130 cardiovascular surgery Methods 0.000 description 1
- NPAKNKYSJIDKMW-UHFFFAOYSA-N carvedilol Chemical compound COC1=CC=CC=C1OCCNCC(O)COC1=CC=CC2=NC3=CC=C[CH]C3=C12 NPAKNKYSJIDKMW-UHFFFAOYSA-N 0.000 description 1
- 229960004195 carvedilol Drugs 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000004640 cellular pathway Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229940083181 centrally acting adntiadrenergic agent methyldopa Drugs 0.000 description 1
- 229950005749 ceronapril Drugs 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- TZRFSLHOCZEXCC-HIVFKXHNSA-N chembl2219536 Chemical compound N1([C@H]2C[C@@H]([C@H](O2)COP(O)(=O)S[C@@H]2[C@H](O[C@H](C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)S[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)S[C@@H]2[C@H](O[C@H](C2)N2C(N=C(N)C(C)=C2)=O)COP(O)(=O)S[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)S[C@@H]2[C@H](O[C@H](C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)S[C@@H]2[C@H](O[C@H](C2)N2C3=NC=NC(N)=C3N=C2)COP(O)(=O)S[C@H]2[C@H]([C@@H](O[C@@H]2COP(O)(=O)S[C@H]2[C@H]([C@@H](O[C@@H]2COP(O)(=O)S[C@H]2[C@H]([C@@H](O[C@@H]2COP(O)(=O)S[C@H]2[C@H]([C@@H](O[C@@H]2COP(O)(=O)S[C@H]2[C@H]([C@@H](O[C@@H]2CO)N2C3=C(C(NC(N)=N3)=O)N=C2)OCCOC)N2C(N=C(N)C(C)=C2)=O)OCCOC)N2C(N=C(N)C(C)=C2)=O)OCCOC)N2C(NC(=O)C(C)=C2)=O)OCCOC)N2C(N=C(N)C(C)=C2)=O)OCCOC)SP(O)(=O)OC[C@H]2O[C@H](C[C@@H]2SP(O)(=O)OC[C@H]2O[C@H](C[C@@H]2SP(O)(=O)OC[C@H]2O[C@H](C[C@@H]2SP(O)(=O)OC[C@@H]2[C@H]([C@H]([C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OCCOC)SP(O)(=O)OC[C@H]2[C@@H]([C@@H]([C@H](O2)N2C(N=C(N)C(C)=C2)=O)OCCOC)SP(O)(=O)OC[C@H]2[C@@H]([C@@H]([C@H](O2)N2C3=NC=NC(N)=C3N=C2)OCCOC)SP(O)(=O)OC[C@H]2[C@@H]([C@@H]([C@H](O2)N2C(N=C(N)C(C)=C2)=O)OCCOC)SP(O)(=O)OC[C@H]2[C@H](O)[C@@H]([C@H](O2)N2C(N=C(N)C(C)=C2)=O)OCCOC)N2C(N=C(N)C(C)=C2)=O)N2C(NC(=O)C(C)=C2)=O)N2C(NC(=O)C(C)=C2)=O)C=C(C)C(N)=NC1=O TZRFSLHOCZEXCC-HIVFKXHNSA-N 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229960001761 chlorpropamide Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- HHHKFGXWKKUNCY-FHWLQOOXSA-N cilazapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N2[C@@H](CCCN2CCC1)C(O)=O)=O)CC1=CC=CC=C1 HHHKFGXWKKUNCY-FHWLQOOXSA-N 0.000 description 1
- 229960005025 cilazapril Drugs 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 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
- GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 1
- GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 description 1
- 229960003009 clopidogrel Drugs 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 229940105756 coagulation factor x Drugs 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 235000012716 cod liver oil Nutrition 0.000 description 1
- 239000003026 cod liver oil Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 229940125846 compound 25 Drugs 0.000 description 1
- 229940125796 compound 3d Drugs 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910000365 copper sulfate Inorganic materials 0.000 description 1
- 229910000366 copper(II) sulfate Inorganic materials 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 229940097499 cozaar Drugs 0.000 description 1
- 229940066901 crestor Drugs 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([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
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- QKYLHOOIOJOCIQ-UHFFFAOYSA-N cyclopropyl hydrogen carbonate Chemical compound OC(=O)OC1CC1 QKYLHOOIOJOCIQ-UHFFFAOYSA-N 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 229960003850 dabigatran Drugs 0.000 description 1
- YBSJFWOBGCMAKL-UHFFFAOYSA-N dabigatran Chemical compound N=1C2=CC(C(=O)N(CCC(O)=O)C=3N=CC=CC=3)=CC=C2N(C)C=1CNC1=CC=C(C(N)=N)C=C1 YBSJFWOBGCMAKL-UHFFFAOYSA-N 0.000 description 1
- 229960003834 dapagliflozin Drugs 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 229960005227 delapril Drugs 0.000 description 1
- WOUOLAUOZXOLJQ-MBSDFSHPSA-N delapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N(CC(O)=O)C1CC2=CC=CC=C2C1)CC1=CC=CC=C1 WOUOLAUOZXOLJQ-MBSDFSHPSA-N 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 150000008050 dialkyl sulfates Chemical class 0.000 description 1
- 229960004042 diazoxide Drugs 0.000 description 1
- 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 description 1
- 125000005435 dihydrobenzoxazolyl group Chemical group O1C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000001070 dihydroindolyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000005044 dihydroquinolinyl group Chemical group N1(CC=CC2=CC=CC=C12)* 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 1
- 229960004166 diltiazem Drugs 0.000 description 1
- SPCNPOWOBZQWJK-UHFFFAOYSA-N dimethoxy-(2-propan-2-ylsulfanylethylsulfanyl)-sulfanylidene-$l^{5}-phosphane Chemical compound COP(=S)(OC)SCCSC(C)C SPCNPOWOBZQWJK-UHFFFAOYSA-N 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229940074620 diovan hct Drugs 0.000 description 1
- GAFRWLVTHPVQGK-UHFFFAOYSA-N dipentyl sulfate Chemical class CCCCCOS(=O)(=O)OCCCCC GAFRWLVTHPVQGK-UHFFFAOYSA-N 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
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 208000009190 disseminated intravascular coagulation Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- LZWLLMFYVGUUAL-UHFFFAOYSA-L ditert-butyl(cyclopenta-1,3-dien-1-yl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.CC(C)(C)P(C(C)(C)C)C1=CC=C[CH-]1.CC(C)(C)P(C(C)(C)C)C1=CC=C[CH-]1 LZWLLMFYVGUUAL-UHFFFAOYSA-L 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- YRIUSKIDOIARQF-UHFFFAOYSA-N dodecyl benzenesulfonate Chemical compound CCCCCCCCCCCCOS(=O)(=O)C1=CC=CC=C1 YRIUSKIDOIARQF-UHFFFAOYSA-N 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229940071161 dodecylbenzenesulfonate Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- RUZYUOTYCVRMRZ-UHFFFAOYSA-N doxazosin Chemical compound C1OC2=CC=CC=C2OC1C(=O)N(CC1)CCN1C1=NC(N)=C(C=C(C(OC)=C2)OC)C2=N1 RUZYUOTYCVRMRZ-UHFFFAOYSA-N 0.000 description 1
- 229960001389 doxazosin Drugs 0.000 description 1
- 229950003693 dutogliptin Drugs 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 108010011867 ecallantide Proteins 0.000 description 1
- 229940009662 edetate Drugs 0.000 description 1
- 229960000622 edoxaban Drugs 0.000 description 1
- PSMMNJNZVZZNOI-SJILXJHISA-N edoxaban tosylate hydrate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1.N([C@H]1CC[C@@H](C[C@H]1NC(=O)C=1SC=2CN(C)CCC=2N=1)C(=O)N(C)C)C(=O)C(=O)NC1=CC=C(Cl)C=N1 PSMMNJNZVZZNOI-SJILXJHISA-N 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 238000000132 electrospray ionisation Methods 0.000 description 1
- 229950005627 embonate Drugs 0.000 description 1
- 229960003345 empagliflozin Drugs 0.000 description 1
- OBWASQILIWPZMG-QZMOQZSNSA-N empagliflozin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=CC=C(Cl)C(CC=2C=CC(O[C@@H]3COCC3)=CC=2)=C1 OBWASQILIWPZMG-QZMOQZSNSA-N 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 229960000873 enalapril Drugs 0.000 description 1
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 1
- 229960002680 enalaprilat Drugs 0.000 description 1
- MZYVOFLIPYDBGD-MLZQUWKJSA-N enalaprilat dihydrate Chemical compound O.O.C([C@H](N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 MZYVOFLIPYDBGD-MLZQUWKJSA-N 0.000 description 1
- 239000002308 endothelin receptor antagonist Substances 0.000 description 1
- 229960004563 eprosartan Drugs 0.000 description 1
- OROAFUQRIXKEMV-LDADJPATSA-N eprosartan Chemical compound C=1C=C(C(O)=O)C=CC=1CN1C(CCCC)=NC=C1\C=C(C(O)=O)/CC1=CC=CS1 OROAFUQRIXKEMV-LDADJPATSA-N 0.000 description 1
- 229960000573 eprosartan mesylate Drugs 0.000 description 1
- DJSLTDBPKHORNY-XMMWENQYSA-N eprosartan methanesulfonate Chemical compound CS(O)(=O)=O.C=1C=C(C(O)=O)C=CC=1CN1C(CCCC)=NC=C1\C=C(C(O)=O)/CC1=CC=CS1 DJSLTDBPKHORNY-XMMWENQYSA-N 0.000 description 1
- 229960003133 ergot alkaloid Drugs 0.000 description 1
- 229950006535 ertugliflozin Drugs 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 229950000206 estolate Drugs 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- KWFADUNOPOSMIJ-UHFFFAOYSA-N ethyl 3-chloro-3-oxopropanoate Chemical compound CCOC(=O)CC(Cl)=O KWFADUNOPOSMIJ-UHFFFAOYSA-N 0.000 description 1
- AFRWBGJRWRHQOV-UHFFFAOYSA-N ethyl 5-bromopentanoate Chemical compound CCOC(=O)CCCCBr AFRWBGJRWRHQOV-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
- NPTDXPDGUHAFKC-UHFFFAOYSA-N ethynylcyclopropane Chemical group C#CC1CC1 NPTDXPDGUHAFKC-UHFFFAOYSA-N 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 229960003580 felodipine Drugs 0.000 description 1
- 230000002600 fibrillogenic effect Effects 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 230000020764 fibrinolysis Effects 0.000 description 1
- 230000003480 fibrinolytic effect Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 229960003765 fluvastatin Drugs 0.000 description 1
- RIKMMFOAQPJVMX-UHFFFAOYSA-N fomepizole Chemical compound CC=1C=NNC=1 RIKMMFOAQPJVMX-UHFFFAOYSA-N 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 229960002490 fosinopril Drugs 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 229960000457 gallopamil Drugs 0.000 description 1
- 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229960002458 gemigliptin Drugs 0.000 description 1
- 230000008570 general process Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 229960004580 glibenclamide Drugs 0.000 description 1
- WIGIZIANZCJQQY-RUCARUNLSA-N glimepiride Chemical compound O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)N[C@@H]2CC[C@@H](C)CC2)C=C1 WIGIZIANZCJQQY-RUCARUNLSA-N 0.000 description 1
- 229960004346 glimepiride Drugs 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
- 229960002442 glucosamine Drugs 0.000 description 1
- 230000004190 glucose uptake Effects 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- 208000033666 hereditary antithrombin deficiency Diseases 0.000 description 1
- 208000013746 hereditary thrombophilia due to congenital protein C deficiency Diseases 0.000 description 1
- 150000002390 heteroarenes Chemical class 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 230000009997 humoral pathway Effects 0.000 description 1
- 229960002474 hydralazine Drugs 0.000 description 1
- 229960002003 hydrochlorothiazide Drugs 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 229940090022 hyzaar Drugs 0.000 description 1
- 229960001195 imidapril Drugs 0.000 description 1
- KLZWOWYOHUKJIG-BPUTZDHNSA-N imidapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1C(N(C)C[C@H]1C(O)=O)=O)CC1=CC=CC=C1 KLZWOWYOHUKJIG-BPUTZDHNSA-N 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 229950000991 ipragliflozin Drugs 0.000 description 1
- 229960002198 irbesartan Drugs 0.000 description 1
- YOSHYTLCDANDAN-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2NN=NN=2)C(CCCC)=NC21CCCC2 YOSHYTLCDANDAN-UHFFFAOYSA-N 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 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
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 229940103445 janumet Drugs 0.000 description 1
- 229940090473 januvia Drugs 0.000 description 1
- VBGWSQKGUZHFPS-VGMMZINCSA-N kalbitor Chemical compound C([C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]2C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=3C=CC=CC=3)C(=O)N[C@H](C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)NCC(=O)NCC(=O)N[C@H]3CSSC[C@H](NC(=O)[C@@H]4CCCN4C(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CO)NC(=O)[C@H](CC=4NC=NC=4)NC(=O)[C@H](CCSC)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(O)=O)CSSC[C@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC3=O)CSSC2)C(=O)N[C@@H]([C@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=2NC=NC=2)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N1)[C@@H](C)CC)[C@H](C)O)=O)[C@@H](C)CC)C1=CC=CC=C1 VBGWSQKGUZHFPS-VGMMZINCSA-N 0.000 description 1
- 229940018902 kalbitor Drugs 0.000 description 1
- 230000003907 kidney function Effects 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
- 150000002596 lactones Chemical class 0.000 description 1
- NXFFJDQHYLNEJK-CYBMUJFWSA-N laropiprant Chemical compound C=1([C@@H](CC(O)=O)CCC=1C=1C=C(F)C=C(C2=1)S(=O)(=O)C)N2CC1=CC=C(Cl)C=C1 NXFFJDQHYLNEJK-CYBMUJFWSA-N 0.000 description 1
- 229950008292 laropiprant Drugs 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 229940095570 lescol Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229960002397 linagliptin Drugs 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 229940002661 lipitor Drugs 0.000 description 1
- 229960002394 lisinopril Drugs 0.000 description 1
- CZRQXSDBMCMPNJ-ZUIPZQNBSA-N lisinopril dihydrate Chemical compound O.O.C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 CZRQXSDBMCMPNJ-ZUIPZQNBSA-N 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 description 1
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- UTEFBSAVJNEPTR-RGEXLXHISA-N loprazolam Chemical compound C1CN(C)CCN1\C=C/1C(=O)N2C3=CC=C([N+]([O-])=O)C=C3C(C=3C(=CC=CC=3)Cl)=NCC2=N\1 UTEFBSAVJNEPTR-RGEXLXHISA-N 0.000 description 1
- 229960003019 loprazolam Drugs 0.000 description 1
- 229960004773 losartan Drugs 0.000 description 1
- 229960000519 losartan potassium Drugs 0.000 description 1
- 229960004844 lovastatin Drugs 0.000 description 1
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229950004397 luseogliflozin Drugs 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229950004994 meglitinide Drugs 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 238000005649 metathesis reaction Methods 0.000 description 1
- OETHQSJEHLVLGH-UHFFFAOYSA-N metformin hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N OETHQSJEHLVLGH-UHFFFAOYSA-N 0.000 description 1
- MJOQXIXZHYEHQH-UHFFFAOYSA-N methyl 4-amino-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate Chemical compound COC(=O)C1=CC=C(N)C(B2OC(C)(C)C(C)(C)O2)=C1 MJOQXIXZHYEHQH-UHFFFAOYSA-N 0.000 description 1
- AIUWAOALZYWQBX-UHFFFAOYSA-N methyl 4-amino-3-bromobenzoate Chemical compound COC(=O)C1=CC=C(N)C(Br)=C1 AIUWAOALZYWQBX-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
- ZIYVHBGGAOATLY-UHFFFAOYSA-N methylmalonic acid Chemical compound OC(=O)C(C)C(O)=O ZIYVHBGGAOATLY-UHFFFAOYSA-N 0.000 description 1
- 229960002237 metoprolol Drugs 0.000 description 1
- IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 description 1
- 229960001300 metoprolol tartrate Drugs 0.000 description 1
- 229940099246 mevacor Drugs 0.000 description 1
- 229960001110 miglitol Drugs 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 229960003632 minoxidil Drugs 0.000 description 1
- 229960004778 mipomersen Drugs 0.000 description 1
- 108091060283 mipomersen Proteins 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([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
- ACTNHJDHMQSOGL-UHFFFAOYSA-N n',n'-dibenzylethane-1,2-diamine Chemical compound C=1C=CC=CC=1CN(CCN)CC1=CC=CC=C1 ACTNHJDHMQSOGL-UHFFFAOYSA-N 0.000 description 1
- KRKPYFLIYNGWTE-UHFFFAOYSA-N n,o-dimethylhydroxylamine Chemical compound CNOC KRKPYFLIYNGWTE-UHFFFAOYSA-N 0.000 description 1
- QAPTWHXHEYAIKG-RCOXNQKVSA-N n-[(1r,2s,5r)-5-(tert-butylamino)-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](NC(C)(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 QAPTWHXHEYAIKG-RCOXNQKVSA-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
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- VWPOSFSPZNDTMJ-UCWKZMIHSA-N nadolol Chemical compound C1[C@@H](O)[C@@H](O)CC2=C1C=CC=C2OCC(O)CNC(C)(C)C VWPOSFSPZNDTMJ-UCWKZMIHSA-N 0.000 description 1
- 229960004255 nadolol Drugs 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 150000005054 naphthyridines Chemical class 0.000 description 1
- 229960000698 nateglinide Drugs 0.000 description 1
- OELFLUMRDSZNSF-BRWVUGGUSA-N nateglinide Chemical compound C1C[C@@H](C(C)C)CC[C@@H]1C(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 OELFLUMRDSZNSF-BRWVUGGUSA-N 0.000 description 1
- 229960001783 nicardipine Drugs 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- LBHIOVVIQHSOQN-UHFFFAOYSA-N nicorandil Chemical compound [O-][N+](=O)OCCNC(=O)C1=CC=CN=C1 LBHIOVVIQHSOQN-UHFFFAOYSA-N 0.000 description 1
- 229960002497 nicorandil Drugs 0.000 description 1
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
- 229960001597 nifedipine Drugs 0.000 description 1
- VZWXXKDFACOXNT-UHFFFAOYSA-N niludipine Chemical compound CCCOCCOC(=O)C1=C(C)NC(C)=C(C(=O)OCCOCCC)C1C1=CC=CC([N+]([O-])=O)=C1 VZWXXKDFACOXNT-UHFFFAOYSA-N 0.000 description 1
- 229950000109 niludipine Drugs 0.000 description 1
- 229960000715 nimodipine Drugs 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229960002460 nitroprusside Drugs 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 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
- 229960005117 olmesartan Drugs 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 125000002734 organomagnesium group Chemical group 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 238000004806 packaging method and process Methods 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
- 230000036961 partial effect Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- IPWFJLQDVFKJDU-UHFFFAOYSA-N pentanamide Chemical compound CCCCC(N)=O IPWFJLQDVFKJDU-UHFFFAOYSA-N 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000000810 peripheral vasodilating agent Substances 0.000 description 1
- 229960002116 peripheral vasodilator Drugs 0.000 description 1
- 210000003800 pharynx Anatomy 0.000 description 1
- GRJHONXDTNBDTC-UHFFFAOYSA-N phenyl trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC1=CC=CC=C1 GRJHONXDTNBDTC-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
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 1
- 229960002310 pinacidil Drugs 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229940126155 plasma kallikrein inhibitor Drugs 0.000 description 1
- 229940012957 plasmin Drugs 0.000 description 1
- 230000010118 platelet activation Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000004036 potassium channel stimulating agent Substances 0.000 description 1
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical class [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
- 239000003286 potassium sparing diuretic agent Substances 0.000 description 1
- 229940097241 potassium-sparing diuretic Drugs 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- TZIRZGBAFTZREM-MKAGXXMWSA-N pramlintide Chemical compound C([C@@H](C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H]1NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CCCCN)CSSC1)[C@@H](C)O)C(C)C)C1=CC=CC=C1 TZIRZGBAFTZREM-MKAGXXMWSA-N 0.000 description 1
- 229960003611 pramlintide Drugs 0.000 description 1
- 108010029667 pramlintide Proteins 0.000 description 1
- DTGLZDAWLRGWQN-UHFFFAOYSA-N prasugrel Chemical compound C1CC=2SC(OC(=O)C)=CC=2CN1C(C=1C(=CC=CC=1)F)C(=O)C1CC1 DTGLZDAWLRGWQN-UHFFFAOYSA-N 0.000 description 1
- 229960004197 prasugrel Drugs 0.000 description 1
- 229940089484 pravachol Drugs 0.000 description 1
- 229960002965 pravastatin Drugs 0.000 description 1
- IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 1
- 229960001289 prazosin Drugs 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000000019 pro-fibrinolytic effect Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- UZQBKCWYZBHBOW-UHFFFAOYSA-N propan-2-yl 4-cyclohexyl-2-hydroxy-3-[[3-methylsulfanyl-2-[[2-(morpholine-4-carbonylamino)-3-phenylpropanoyl]amino]propanoyl]amino]butanoate Chemical compound C1CCCCC1CC(C(O)C(=O)OC(C)C)NC(=O)C(CSC)NC(=O)C(NC(=O)N1CCOCC1)CC1=CC=CC=C1 UZQBKCWYZBHBOW-UHFFFAOYSA-N 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 229960003401 ramipril Drugs 0.000 description 1
- HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000020964 regulation of blood coagulation Effects 0.000 description 1
- 239000002461 renin inhibitor Substances 0.000 description 1
- 229940086526 renin-inhibitors Drugs 0.000 description 1
- 229960002354 repaglinide Drugs 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 239000013037 reversible inhibitor Substances 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- ITDJKCJYYAQMRO-UHFFFAOYSA-L rhodium(2+);diacetate Chemical compound [Rh+2].CC([O-])=O.CC([O-])=O ITDJKCJYYAQMRO-UHFFFAOYSA-L 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 229960001148 rivaroxaban Drugs 0.000 description 1
- KGFYHTZWPPHNLQ-AWEZNQCLSA-N rivaroxaban Chemical compound S1C(Cl)=CC=C1C(=O)NC[C@@H]1OC(=O)N(C=2C=CC(=CC=2)N2C(COCC2)=O)C1 KGFYHTZWPPHNLQ-AWEZNQCLSA-N 0.000 description 1
- 238000011808 rodent model Methods 0.000 description 1
- 229960004586 rosiglitazone Drugs 0.000 description 1
- 229960000672 rosuvastatin Drugs 0.000 description 1
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 description 1
- LALFOYNTGMUKGG-BGRFNVSISA-L rosuvastatin calcium Chemical compound [Ca+2].CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O.CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O LALFOYNTGMUKGG-BGRFNVSISA-L 0.000 description 1
- 238000001896 rotating frame Overhauser effect spectroscopy Methods 0.000 description 1
- 229910052707 ruthenium Inorganic materials 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
- 229960004937 saxagliptin Drugs 0.000 description 1
- QGJUIPDUBHWZPV-SGTAVMJGSA-N saxagliptin Chemical compound C1C(C2)CC(C3)CC2(O)CC13[C@H](N)C(=O)N1[C@H](C#N)C[C@@H]2C[C@@H]21 QGJUIPDUBHWZPV-SGTAVMJGSA-N 0.000 description 1
- 108010033693 saxagliptin Proteins 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
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000002210 silicon-based material Substances 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 1
- 235000010378 sodium ascorbate Nutrition 0.000 description 1
- 229960005055 sodium ascorbate Drugs 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 1
- ZBMZVLHSJCTVON-UHFFFAOYSA-N sotalol Chemical compound CC(C)NCC(O)C1=CC=C(NS(C)(=O)=O)C=C1 ZBMZVLHSJCTVON-UHFFFAOYSA-N 0.000 description 1
- 229960002370 sotalol Drugs 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 229960002909 spirapril Drugs 0.000 description 1
- HRWCVUIFMSZDJS-SZMVWBNQSA-N spirapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2(C1)SCCS2)C(O)=O)CC1=CC=CC=C1 HRWCVUIFMSZDJS-SZMVWBNQSA-N 0.000 description 1
- 108700035424 spirapril Proteins 0.000 description 1
- LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 1
- 229960002256 spironolactone Drugs 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229960005202 streptokinase Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000002600 sunflower oil Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000000948 sympatholitic effect Effects 0.000 description 1
- 239000011885 synergistic combination Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- 229960005187 telmisartan Drugs 0.000 description 1
- 229960004084 temocapril Drugs 0.000 description 1
- FIQOFIRCTOWDOW-BJLQDIEVSA-N temocapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C[C@H](SC1)C=1SC=CC=1)=O)CC1=CC=CC=C1 FIQOFIRCTOWDOW-BJLQDIEVSA-N 0.000 description 1
- 108010069247 terlakiren Proteins 0.000 description 1
- WUBVEMGCQRSBBT-UHFFFAOYSA-N tert-butyl 4-(trifluoromethylsulfonyloxy)-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(OS(=O)(=O)C(F)(F)F)=CC1 WUBVEMGCQRSBBT-UHFFFAOYSA-N 0.000 description 1
- NGASWKRTXGWPNN-UHFFFAOYSA-N tert-butyl but-3-enoate Chemical compound CC(C)(C)OC(=O)CC=C NGASWKRTXGWPNN-UHFFFAOYSA-N 0.000 description 1
- FTEAAYMAQFBUJJ-UHFFFAOYSA-N tert-butyl cyclopropanecarboxylate Chemical compound CC(C)(C)OC(=O)C1CC1 FTEAAYMAQFBUJJ-UHFFFAOYSA-N 0.000 description 1
- RFQBPWDUTRKBLH-UHFFFAOYSA-N tert-butyl n-(3-amino-4-bromophenyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=C(Br)C(N)=C1 RFQBPWDUTRKBLH-UHFFFAOYSA-N 0.000 description 1
- MHYGQXWCZAYSLJ-UHFFFAOYSA-N tert-butyl-chloro-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](Cl)(C(C)(C)C)C1=CC=CC=C1 MHYGQXWCZAYSLJ-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 239000005458 thiazide-like diuretic Substances 0.000 description 1
- 150000001467 thiazolidinediones Chemical class 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- LJJKNPQAGWVLDQ-SNVBAGLBSA-N thiorphan Chemical compound OC(=O)CNC(=O)[C@@H](CS)CC1=CC=CC=C1 LJJKNPQAGWVLDQ-SNVBAGLBSA-N 0.000 description 1
- 239000003856 thrombin receptor antagonist Substances 0.000 description 1
- OEKWJQXRCDYSHL-FNOIDJSQSA-N ticagrelor Chemical compound C1([C@@H]2C[C@H]2NC=2N=C(N=C3N([C@H]4[C@@H]([C@H](O)[C@@H](OCCO)C4)O)N=NC3=2)SCCC)=CC=C(F)C(F)=C1 OEKWJQXRCDYSHL-FNOIDJSQSA-N 0.000 description 1
- 229960002528 ticagrelor Drugs 0.000 description 1
- 229960004605 timolol Drugs 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- 229960000187 tissue plasminogen activator Drugs 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 229950006667 tofogliflozin Drugs 0.000 description 1
- 229960005371 tolbutamide Drugs 0.000 description 1
- CFOAUYCPAUGDFF-UHFFFAOYSA-N tosmic Chemical compound CC1=CC=C(S(=O)(=O)C[N+]#[C-])C=C1 CFOAUYCPAUGDFF-UHFFFAOYSA-N 0.000 description 1
- 229960002051 trandolapril Drugs 0.000 description 1
- 201000010875 transient cerebral ischemia Diseases 0.000 description 1
- 229960001288 triamterene Drugs 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- AGZPNUZBDCYTBB-UHFFFAOYSA-N triethyl methanetricarboxylate Chemical compound CCOC(=O)C(C(=O)OCC)C(=O)OCC AGZPNUZBDCYTBB-UHFFFAOYSA-N 0.000 description 1
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 1
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 1
- CCRMAATUKBYMPA-UHFFFAOYSA-N trimethyltin Chemical compound C[Sn](C)C.C[Sn](C)C CCRMAATUKBYMPA-UHFFFAOYSA-N 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 108010036927 trypsin-like serine protease Proteins 0.000 description 1
- 229960004699 valsartan Drugs 0.000 description 1
- SJSNUMAYCRRIOM-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 description 1
- 230000003966 vascular damage Effects 0.000 description 1
- 208000021331 vascular occlusion disease Diseases 0.000 description 1
- 230000006439 vascular pathology Effects 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 description 1
- 229960001254 vildagliptin Drugs 0.000 description 1
- ZBGXUVOIWDMMJE-QHNZEKIYSA-N vorapaxar Chemical compound C(/[C@@H]1[C@H]2[C@H](C(O[C@@H]2C)=O)C[C@H]2[C@H]1CC[C@H](C2)NC(=O)OCC)=C\C(N=C1)=CC=C1C1=CC=CC(F)=C1 ZBGXUVOIWDMMJE-QHNZEKIYSA-N 0.000 description 1
- 229960005044 vorapaxar Drugs 0.000 description 1
- PNAMDJVUJCJOIX-XVZWKFLSSA-N vytorin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1.N1([C@@H]([C@H](C1=O)CC[C@@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 PNAMDJVUJCJOIX-XVZWKFLSSA-N 0.000 description 1
- 229940009349 vytorin Drugs 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
- 229940051223 zetia Drugs 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229940072168 zocor Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/08—Bridged systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562248075P | 2015-10-29 | 2015-10-29 | |
| US62/248,075 | 2015-10-29 | ||
| PCT/US2016/058362 WO2017074832A1 (en) | 2015-10-29 | 2016-10-24 | FACTOR XIa INHIBITORS |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| RU2018119015A RU2018119015A (ru) | 2019-11-29 |
| RU2018119015A3 RU2018119015A3 (enExample) | 2020-02-18 |
| RU2728783C2 true RU2728783C2 (ru) | 2020-07-31 |
Family
ID=58631804
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2018119015A RU2728783C2 (ru) | 2015-10-29 | 2016-10-24 | ИНГИБИТОРЫ ФАКТОРА XIa |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US10214512B2 (enExample) |
| EP (1) | EP3368036B1 (enExample) |
| JP (1) | JP6892858B2 (enExample) |
| KR (1) | KR102727485B1 (enExample) |
| CN (1) | CN108430471B (enExample) |
| AU (1) | AU2016344476B2 (enExample) |
| BR (1) | BR112018008506B8 (enExample) |
| CA (1) | CA2998902C (enExample) |
| MA (1) | MA43128A (enExample) |
| MX (1) | MX387515B (enExample) |
| RU (1) | RU2728783C2 (enExample) |
| WO (1) | WO2017074832A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2819271C1 (ru) * | 2023-04-28 | 2024-05-16 | федеральное государственное бюджетное образовательное учреждение высшего образования "Воронежский государственный университет" (ФГБОУ ВО "ВГУ") | Применение замещенных 2-(2-(4,4,6-триметил-2-оксо-4н-пирроло[3,2,1-ij]хинолин-1(2н)-илиден)гидразинил)тиазол-4(5н)-онов в качестве ингибиторов факторов свертывания крови xa и xia и способ их получения |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US12344616B2 (en) | 2018-10-25 | 2025-07-01 | Merck Sharp & Dohme Llc | Factor XIa inhibitors |
| ES2974842T3 (es) * | 2018-11-13 | 2024-07-01 | Novartis Ag | Compuestos y composiciones para el tratamiento de afecciones asociadas a la actividad de nlrp |
| US12018027B2 (en) | 2019-04-16 | 2024-06-25 | China Resources Biopharmaceutical Company Limited | Macrocyclic derivatives acting as XIa factor inhibitor |
| JP7286001B2 (ja) * | 2019-07-23 | 2023-06-02 | メッドシャイン ディスカバリー インコーポレイテッド | 第ＸＩａ因子阻害剤としての大環状誘導体 |
| US12528786B2 (en) | 2020-07-10 | 2026-01-20 | Merck Sharp & Dohme Llc | Plasma kallikrein inhibitors |
| CA3206548A1 (en) * | 2021-01-28 | 2022-08-04 | John S. Debenham | Factor xia inhibitors |
| US11845748B2 (en) | 2021-03-18 | 2023-12-19 | Janssen Pharmaceutica Nv | Bicyclic pyridine N-oxide derivatives useful as a factor XIa inhibitors |
| US11814364B2 (en) | 2021-03-18 | 2023-11-14 | Janssen Pharmaceutica Nv | Pyridine N-oxide derivatives useful as factor XIa inhibitors |
| US11919881B2 (en) | 2021-03-18 | 2024-03-05 | Janssen Pharmaceutica Nv | Substituted pyridine N-oxide derivatives useful as a factor XIa inhibitors |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014022767A1 (en) * | 2012-08-03 | 2014-02-06 | Bristol-Myers Squibb Company | Dihydropyridone p1 as factor xia inhibitors |
| US20150290194A1 (en) * | 2014-04-11 | 2015-10-15 | The University Of North Carolina At Chapel Hill | Therapeutic uses of selected pyrimidine compounds with anti-mer tyrosine kinase activity |
Family Cites Families (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HUP0303901A2 (hu) | 2000-11-07 | 2004-03-01 | Bristol-Myers Squibb Co. | Szerin proteáz inhibitorokként alkalmazható savszármazékok és ezeket tartalmazó gyógyszerkészítmények |
| CA2428191A1 (en) | 2000-11-07 | 2002-05-30 | Bristol-Myers Squibb Company | Acid derivatives useful as serine protease inhibitors |
| HUP0304058A2 (hu) | 2001-01-30 | 2004-04-28 | Bristol-Myers Squibb Company | Xa faktor szulfonamid-laktám inhibitorok és alkalmazásuk és ezeket tartalmazó gyógyszerkészítmények |
| US6825208B2 (en) | 2001-08-20 | 2004-11-30 | Bristol-Myers Squibb Pharma Company | Tetrahydroquinoline derivatives as antithrombotic agents |
| EP1523483A4 (en) | 2002-06-26 | 2006-03-08 | Bristol Myers Squibb Co | AMINO-BICYCLIC PYRAZINONE AND PYRIDINONE FOR INHIBITING THE COOKING OF SERIN PROTEASE |
| US20040180855A1 (en) | 2003-02-19 | 2004-09-16 | Schumacher William A. | Methods of treating thrombosis with reduced risk of increased bleeding times |
| US7138412B2 (en) | 2003-03-11 | 2006-11-21 | Bristol-Myers Squibb Company | Tetrahydroquinoline derivatives useful as serine protease inhibitors |
| US7129264B2 (en) | 2003-04-16 | 2006-10-31 | Bristol-Myers Squibb Company | Biarylmethyl indolines and indoles as antithromboembolic agents |
| US7417063B2 (en) | 2004-04-13 | 2008-08-26 | Bristol-Myers Squibb Company | Bicyclic heterocycles useful as serine protease inhibitors |
| US7453002B2 (en) | 2004-06-15 | 2008-11-18 | Bristol-Myers Squibb Company | Five-membered heterocycles useful as serine protease inhibitors |
| US7429604B2 (en) | 2004-06-15 | 2008-09-30 | Bristol Myers Squibb Company | Six-membered heterocycles useful as serine protease inhibitors |
| US20060074103A1 (en) | 2004-10-06 | 2006-04-06 | Corte James R | Cyclic beta-amino acid derivatives as factor Xa inhibitors |
| ATE405553T1 (de) | 2004-12-08 | 2008-09-15 | Bristol Myers Squibb Co | Heterocyclische verbindungen als inhibitoren von faktor viia |
| ATE479676T1 (de) | 2005-01-10 | 2010-09-15 | Bristol Myers Squibb Co | Als antikoagulanzien verwendbare phenylglycinamid-derivate |
| JP5236293B2 (ja) | 2005-01-13 | 2013-07-17 | ブリストル−マイヤーズ スクイブ カンパニー | Ｘｉａ因子阻害剤としての置換ビアリール化合物 |
| US20060183771A1 (en) | 2005-02-17 | 2006-08-17 | Seiffert Dietmar A | Novel combination of selective factor VIIa and/or factor XIa inhibitors and selective plasma kallikrein inhibitors |
| WO2006115652A1 (en) * | 2005-04-20 | 2006-11-02 | Janssen Pharmaceutica, N.V. | Fluorinated pyridine n-oxide thrombin modulators and process for n-oxidation of nitrogen containing heteroaryls |
| US8466295B2 (en) | 2005-12-14 | 2013-06-18 | Bristol-Myers Squibb Company | Thiophene derivatives as factor XIa inhibitors |
| AU2006325746A1 (en) | 2005-12-14 | 2007-06-21 | Bristol-Myers Squibb Company | Six-membered heterocycles useful as serine protease inhibitors |
| EP1981854B1 (en) | 2005-12-14 | 2011-06-01 | Bristol-Myers Squibb Company | Arylpropionamide, arylacrylamide, arylpropynamide, or arylmethylurea analogs as factor xia inhibitors |
| WO2007109459A2 (en) * | 2006-03-21 | 2007-09-27 | Janssen Pharmaceutica, Nv | Pyridines and pyridine n-oxides as modulators of thrombin |
| EP2102189B1 (en) | 2006-12-15 | 2015-07-29 | Bristol-Myers Squibb Company | Arylpropionamide, arylacrylamide, arylpropynamide, or arylmethylurea analogs as factor xia inhibitors |
| EP2152664B1 (en) * | 2007-06-13 | 2014-09-03 | Bristol-Myers Squibb Company | Dipeptide analogs as coagulation factor inhibitors |
| EP2265601B1 (en) | 2008-03-13 | 2012-02-01 | Bristol-Myers Squibb Company | Pyridazine derivatives as factor xia inhibitors |
| CA2789622C (en) | 2010-02-11 | 2018-04-03 | Bristol-Myers Squibb Company | Macrocycles as factor xia inhibitors |
| TW201311689A (zh) * | 2011-08-05 | 2013-03-16 | 必治妥美雅史谷比公司 | 作為因子ｘｉａ抑制劑之新穎巨環化合物 |
| TW201319068A (zh) * | 2011-08-05 | 2013-05-16 | 必治妥美雅史谷比公司 | 作為ｘｉａ因子抑制劑之環狀ｐ１接合劑 |
| SI2766346T1 (sl) | 2011-10-14 | 2017-05-31 | Bristol-Myers Squibb Company | Substituirane tetrahidroizokinolinske spojine kot faktor xia inhibitorji |
| WO2013056034A1 (en) | 2011-10-14 | 2013-04-18 | Bristol-Myers Squibb Company | Substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| EP2899183B1 (en) | 2011-10-14 | 2018-09-19 | Bristol-Myers Squibb Company | Substituted Tetrahydroisoquinoline Compounds as Factor Xia Inhibitors |
| DK2794597T3 (en) | 2011-12-21 | 2018-01-15 | Ono Pharmaceutical Co | PYRIDINON AND PYRIMIDINON DERIVATIVES AS FACTOR XIA INHIBITORS |
| JP2015083542A (ja) | 2012-02-08 | 2015-04-30 | 大日本住友製薬株式会社 | ３位置換プロリン誘導体 |
| LT2882734T (lt) * | 2012-08-03 | 2016-12-12 | Bristol-Myers Squibb Company | Dihidropiridonai, kaip xia faktoriaus slopikliai |
| US9809545B2 (en) | 2013-03-27 | 2017-11-07 | Merck Sharp & Dohme Corp. | Factor XIa inhibitors |
| KR20240017118A (ko) * | 2014-01-31 | 2024-02-06 | 브리스톨-마이어스 스큅 컴퍼니 | 인자 XIa 억제제로서의 헤테로시클릭 P2' 기를 갖는 마크로사이클 |
| NO2760821T3 (enExample) * | 2014-01-31 | 2018-03-10 | ||
| EP3104701B1 (en) * | 2014-02-11 | 2019-01-30 | Merck Sharp & Dohme Corp. | Factor xia inhibitors |
| US9453018B2 (en) * | 2014-10-01 | 2016-09-27 | Bristol-Myers Squibb Company | Pyrimidinones as factor XIa inhibitors |
| US20180162821A1 (en) * | 2016-12-14 | 2018-06-14 | Bristol-Myers Squibb Company | Factor xia macrocycles with novel p1 groups |
-
2016
- 2016-10-24 MX MX2018005045A patent/MX387515B/es unknown
- 2016-10-24 JP JP2018521211A patent/JP6892858B2/ja active Active
- 2016-10-24 KR KR1020187013433A patent/KR102727485B1/ko active Active
- 2016-10-24 WO PCT/US2016/058362 patent/WO2017074832A1/en not_active Ceased
- 2016-10-24 MA MA043128A patent/MA43128A/fr unknown
- 2016-10-24 AU AU2016344476A patent/AU2016344476B2/en active Active
- 2016-10-24 CA CA2998902A patent/CA2998902C/en active Active
- 2016-10-24 CN CN201680059577.7A patent/CN108430471B/zh active Active
- 2016-10-24 US US15/771,538 patent/US10214512B2/en active Active
- 2016-10-24 RU RU2018119015A patent/RU2728783C2/ru active
- 2016-10-24 EP EP16860556.6A patent/EP3368036B1/en active Active
- 2016-10-24 BR BR112018008506A patent/BR112018008506B8/pt active IP Right Grant
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014022767A1 (en) * | 2012-08-03 | 2014-02-06 | Bristol-Myers Squibb Company | Dihydropyridone p1 as factor xia inhibitors |
| EA028581B1 (ru) * | 2012-08-03 | 2017-12-29 | Бристол-Маерс Сквибб Компани | ДИГИДРОПИРИДОН Р1 В КАЧЕСТВЕ ИНГИБИТОРОВ ФАКТОРА XIa |
| US20150290194A1 (en) * | 2014-04-11 | 2015-10-15 | The University Of North Carolina At Chapel Hill | Therapeutic uses of selected pyrimidine compounds with anti-mer tyrosine kinase activity |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2819271C1 (ru) * | 2023-04-28 | 2024-05-16 | федеральное государственное бюджетное образовательное учреждение высшего образования "Воронежский государственный университет" (ФГБОУ ВО "ВГУ") | Применение замещенных 2-(2-(4,4,6-триметил-2-оксо-4н-пирроло[3,2,1-ij]хинолин-1(2н)-илиден)гидразинил)тиазол-4(5н)-онов в качестве ингибиторов факторов свертывания крови xa и xia и способ их получения |
| RU2819897C1 (ru) * | 2023-04-28 | 2024-05-28 | федеральное государственное бюджетное образовательное учреждение высшего образования "Воронежский государственный университет" (ФГБОУ ВО "ВГУ") | Применение гидрированных производных пирроло[3,2,1-ij]хинолин-1-илиден-2-тиоксотиазолидин-4-онов в качестве ингибиторов факторов свертывания крови xa и xia |
Also Published As
| Publication number | Publication date |
|---|---|
| BR112018008506B8 (pt) | 2023-12-05 |
| AU2016344476B2 (en) | 2020-08-13 |
| EP3368036B1 (en) | 2022-07-20 |
| KR20180073602A (ko) | 2018-07-02 |
| JP6892858B2 (ja) | 2021-06-23 |
| RU2018119015A3 (enExample) | 2020-02-18 |
| US20180339977A1 (en) | 2018-11-29 |
| WO2017074832A1 (en) | 2017-05-04 |
| CN108430471A (zh) | 2018-08-21 |
| CN108430471B (zh) | 2021-07-09 |
| EP3368036A1 (en) | 2018-09-05 |
| AU2016344476A1 (en) | 2018-03-08 |
| CA2998902C (en) | 2024-03-26 |
| RU2018119015A (ru) | 2019-11-29 |
| EP3368036A4 (en) | 2019-04-17 |
| US10214512B2 (en) | 2019-02-26 |
| MA43128A (fr) | 2018-09-05 |
| MX387515B (es) | 2025-03-18 |
| KR102727485B1 (ko) | 2024-11-06 |
| JP2018531954A (ja) | 2018-11-01 |
| CA2998902A1 (en) | 2017-05-04 |
| MX2018005045A (es) | 2018-08-01 |
| BR112018008506A2 (pt) | 2018-10-23 |
| BR112018008506B1 (pt) | 2023-11-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR102727485B1 (ko) | 인자 XIa 억제제 | |
| EP3134408B1 (en) | FACTOR XIa INHIBITORS | |
| EP3283464B1 (en) | Factor xia inhibitors | |
| EP3180327B1 (en) | FACTOR XIa INHIBITORS | |
| EP3148542B1 (en) | Factor xia inhibitors | |
| EP3180317B1 (en) | FACTOR XIa INHIBITORS | |
| EP3049435A1 (en) | Factor xia inhibitors | |
| EP3180325B1 (en) | FACTOR XIa INHIBITORS | |
| EP3383847B1 (en) | FACTOR XIa INHIBITORS | |
| JP2018502137A (ja) | 第ＸＩａ因子阻害剤 | |
| CN116157154A (zh) | 血浆激肽释放酶抑制剂 | |
| RU2849957C1 (ru) | Ингибиторы калликреина плазмы | |
| WO2022164735A1 (en) | Factor xia inhibitors |