JP2005531516A - 選択的ｅｐ４受容体アゴニストによる治療方法 - Google Patents
選択的ｅｐ４受容体アゴニストによる治療方法 Download PDFInfo
- Publication number
- JP2005531516A JP2005531516A JP2003575963A JP2003575963A JP2005531516A JP 2005531516 A JP2005531516 A JP 2005531516A JP 2003575963 A JP2003575963 A JP 2003575963A JP 2003575963 A JP2003575963 A JP 2003575963A JP 2005531516 A JP2005531516 A JP 2005531516A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- oxopyrrolidin
- propyl
- mmol
- alkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 238000000034 method Methods 0.000 title claims abstract description 142
- 229940044601 receptor agonist Drugs 0.000 title claims abstract description 67
- 239000000018 receptor agonist Substances 0.000 title claims abstract description 67
- 238000011282 treatment Methods 0.000 title claims description 43
- 101150109738 Ptger4 gene Proteins 0.000 title 1
- 229940002612 prodrug Drugs 0.000 claims abstract description 94
- 239000000651 prodrug Substances 0.000 claims abstract description 94
- 239000000203 mixture Substances 0.000 claims abstract description 69
- 150000003839 salts Chemical class 0.000 claims abstract description 69
- 206010020772 Hypertension Diseases 0.000 claims abstract description 26
- 208000010412 Glaucoma Diseases 0.000 claims abstract description 21
- 206010019663 Hepatic failure Diseases 0.000 claims abstract description 20
- 231100000835 liver failure Toxicity 0.000 claims abstract description 20
- 208000007903 liver failure Diseases 0.000 claims abstract description 20
- 206010030043 Ocular hypertension Diseases 0.000 claims abstract description 19
- 150000001875 compounds Chemical class 0.000 claims description 282
- -1 aminocarbonylamino, sulfonamido Chemical class 0.000 claims description 217
- 229910052757 nitrogen Chemical group 0.000 claims description 70
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 44
- 125000001424 substituent group Chemical group 0.000 claims description 32
- 229920006395 saturated elastomer Polymers 0.000 claims description 23
- 159000000000 sodium salts Chemical class 0.000 claims description 23
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 19
- 125000001153 fluoro group Chemical group F* 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 18
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 18
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 11
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- 239000011593 sulfur Chemical group 0.000 claims description 11
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 8
- 125000006598 aminocarbonylamino group Chemical group 0.000 claims description 8
- 125000002619 bicyclic group Chemical group 0.000 claims description 8
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 125000004043 oxo group Chemical group O=* 0.000 claims description 8
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 7
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 7
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 7
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 7
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 7
- 125000003282 alkyl amino group Chemical group 0.000 claims description 7
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 7
- 125000001589 carboacyl group Chemical group 0.000 claims description 7
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 7
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 6
- 125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 125000002950 monocyclic group Chemical group 0.000 claims description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- WCXWPBVAQVZCJK-UHFFFAOYSA-N (carbamoylamino)sulfamic acid Chemical class NC(=O)NNS(O)(=O)=O WCXWPBVAQVZCJK-UHFFFAOYSA-N 0.000 claims description 2
- 125000005871 1,3-benzodioxolyl group Chemical group 0.000 claims description 2
- 241001024304 Mino Species 0.000 claims description 2
- 150000001735 carboxylic acids Chemical class 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 2
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 2
- 125000003396 thiol group Chemical class [H]S* 0.000 claims 3
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 claims 2
- 239000000556 agonist Substances 0.000 abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 381
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 347
- 235000019439 ethyl acetate Nutrition 0.000 description 171
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 145
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 142
- 239000000460 chlorine Substances 0.000 description 126
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 102
- 239000000243 solution Substances 0.000 description 92
- 238000004587 chromatography analysis Methods 0.000 description 88
- 239000002609 medium Substances 0.000 description 87
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 69
- 238000000746 purification Methods 0.000 description 69
- 102000005962 receptors Human genes 0.000 description 67
- 108020003175 receptors Proteins 0.000 description 67
- 238000002360 preparation method Methods 0.000 description 63
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 58
- 239000011541 reaction mixture Substances 0.000 description 58
- 235000002639 sodium chloride Nutrition 0.000 description 55
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 45
- 239000012044 organic layer Substances 0.000 description 41
- 239000002904 solvent Substances 0.000 description 38
- 210000004027 cell Anatomy 0.000 description 37
- 239000002585 base Substances 0.000 description 35
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- 238000012360 testing method Methods 0.000 description 33
- 239000012442 inert solvent Substances 0.000 description 32
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 29
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 28
- 230000002829 reductive effect Effects 0.000 description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
- 101000929803 Rattus norvegicus Acyl-CoA-binding protein Proteins 0.000 description 26
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 230000004872 arterial blood pressure Effects 0.000 description 23
- 238000007920 subcutaneous administration Methods 0.000 description 22
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 20
- 239000010410 layer Substances 0.000 description 20
- 238000010992 reflux Methods 0.000 description 20
- 239000002253 acid Substances 0.000 description 19
- 238000001990 intravenous administration Methods 0.000 description 19
- 229910000104 sodium hydride Inorganic materials 0.000 description 19
- 150000001450 anions Chemical class 0.000 description 18
- 210000002216 heart Anatomy 0.000 description 18
- 238000001727 in vivo Methods 0.000 description 18
- 229910052739 hydrogen Inorganic materials 0.000 description 17
- 101000929799 Homo sapiens Acyl-CoA-binding protein Proteins 0.000 description 16
- 239000012267 brine Substances 0.000 description 16
- 239000003921 oil Substances 0.000 description 16
- 235000019198 oils Nutrition 0.000 description 16
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 15
- 239000003054 catalyst Substances 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 14
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 14
- VMKAFJQFKBASMU-QGZVFWFLSA-N (r)-2-methyl-cbs-oxazaborolidine Chemical group C([C@@H]12)CCN1B(C)OC2(C=1C=CC=CC=1)C1=CC=CC=C1 VMKAFJQFKBASMU-QGZVFWFLSA-N 0.000 description 13
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 13
- 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 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 239000002775 capsule Substances 0.000 description 12
- 239000002552 dosage form Substances 0.000 description 12
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 12
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 12
- 125000006239 protecting group Chemical group 0.000 description 12
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 12
- 239000007858 starting material Substances 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- 241000282693 Cercopithecidae Species 0.000 description 11
- 239000003153 chemical reaction reagent Substances 0.000 description 11
- 229940079593 drug Drugs 0.000 description 11
- 239000003814 drug Substances 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 11
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
- 239000002168 alkylating agent Substances 0.000 description 10
- 229940100198 alkylating agent Drugs 0.000 description 10
- 230000027455 binding Effects 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- 238000007254 oxidation reaction Methods 0.000 description 10
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 10
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 10
- 239000003039 volatile agent Substances 0.000 description 10
- 230000003276 anti-hypertensive effect Effects 0.000 description 9
- 229940030600 antihypertensive agent Drugs 0.000 description 9
- 239000002220 antihypertensive agent Substances 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 9
- 210000000170 cell membrane Anatomy 0.000 description 9
- 239000003638 chemical reducing agent Substances 0.000 description 9
- 239000003085 diluting agent Substances 0.000 description 9
- 125000000524 functional group Chemical group 0.000 description 9
- 230000007062 hydrolysis Effects 0.000 description 9
- 238000006460 hydrolysis reaction Methods 0.000 description 9
- 230000003647 oxidation Effects 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 9
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 8
- 241000283973 Oryctolagus cuniculus Species 0.000 description 8
- 235000011054 acetic acid Nutrition 0.000 description 8
- 210000000988 bone and bone Anatomy 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 238000001802 infusion Methods 0.000 description 8
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 8
- 239000002243 precursor Substances 0.000 description 8
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 7
- 208000006386 Bone Resorption Diseases 0.000 description 7
- 230000024279 bone resorption Effects 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- VFURZFXINHLLBT-GFCCVEGCSA-N ethyl 7-[(2r)-2-formyl-5-oxopyrrolidin-1-yl]heptanoate Chemical compound CCOC(=O)CCCCCCN1[C@@H](C=O)CCC1=O VFURZFXINHLLBT-GFCCVEGCSA-N 0.000 description 7
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 7
- VMHPVAWXMHRICK-UHFFFAOYSA-N methyl 4-(3-bromopropyl)benzoate Chemical compound COC(=O)C1=CC=C(CCCBr)C=C1 VMHPVAWXMHRICK-UHFFFAOYSA-N 0.000 description 7
- TYGXITCKYVKKFC-SNVBAGLBSA-N methyl 5-[3-[(2r)-2-formyl-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)CC[C@@H]1C=O TYGXITCKYVKKFC-SNVBAGLBSA-N 0.000 description 7
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 7
- 150000003536 tetrazoles Chemical class 0.000 description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 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 6
- 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 6
- 239000005711 Benzoic acid Substances 0.000 description 6
- 241000288906 Primates Species 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 150000001298 alcohols Chemical class 0.000 description 6
- 150000001299 aldehydes Chemical class 0.000 description 6
- 150000001350 alkyl halides Chemical class 0.000 description 6
- 150000008052 alkyl sulfonates Chemical class 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 229960005370 atorvastatin Drugs 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
- ZDQWVKDDJDIVAL-UHFFFAOYSA-N catecholborane Chemical group C1=CC=C2O[B]OC2=C1 ZDQWVKDDJDIVAL-UHFFFAOYSA-N 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 239000003937 drug carrier Substances 0.000 description 6
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Natural products O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- 239000011777 magnesium Substances 0.000 description 6
- 150000002825 nitriles Chemical class 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- 229920003023 plastic Polymers 0.000 description 6
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 6
- 238000012746 preparative thin layer chromatography Methods 0.000 description 6
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
- 108091026890 Coding region Proteins 0.000 description 5
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 150000001347 alkyl bromides Chemical class 0.000 description 5
- 235000019270 ammonium chloride Nutrition 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 239000000010 aprotic solvent Substances 0.000 description 5
- 239000011575 calcium Substances 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 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 5
- 239000002934 diuretic Substances 0.000 description 5
- 229940030606 diuretics Drugs 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 239000011888 foil Substances 0.000 description 5
- 238000005984 hydrogenation reaction Methods 0.000 description 5
- 150000002500 ions Chemical class 0.000 description 5
- 150000002576 ketones Chemical class 0.000 description 5
- 210000003734 kidney Anatomy 0.000 description 5
- 210000004185 liver Anatomy 0.000 description 5
- 150000004702 methyl esters Chemical class 0.000 description 5
- UMFJAHHVKNCGLG-UHFFFAOYSA-N n-Nitrosodimethylamine Chemical compound CN(C)N=O UMFJAHHVKNCGLG-UHFFFAOYSA-N 0.000 description 5
- 239000004033 plastic Substances 0.000 description 5
- 238000011809 primate model Methods 0.000 description 5
- 150000003180 prostaglandins Chemical class 0.000 description 5
- 238000011555 rabbit model Methods 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 230000000699 topical effect Effects 0.000 description 5
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
- MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- PPVVRGQUTZDTFU-NQCNTLBGSA-N 7-[(2r)-2-[3-hydroxy-4-(3-phenoxyphenyl)but-1-enyl]-5-oxopyrrolidin-1-yl]heptanoic acid Chemical compound C([C@@H]1N(C(=O)CC1)CCCCCCC(O)=O)=CC(O)CC(C=1)=CC=CC=1OC1=CC=CC=C1 PPVVRGQUTZDTFU-NQCNTLBGSA-N 0.000 description 4
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 4
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 238000010240 RT-PCR analysis Methods 0.000 description 4
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 125000006241 alcohol protecting group Chemical group 0.000 description 4
- 150000001351 alkyl iodides Chemical class 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 4
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 4
- 230000008878 coupling Effects 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- 229940095074 cyclic amp Drugs 0.000 description 4
- 238000007405 data analysis Methods 0.000 description 4
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 4
- 239000002158 endotoxin Substances 0.000 description 4
- TVQGDYNRXLTQAP-UHFFFAOYSA-N ethyl heptanoate Chemical compound CCCCCCC(=O)OCC TVQGDYNRXLTQAP-UHFFFAOYSA-N 0.000 description 4
- 238000005755 formation reaction Methods 0.000 description 4
- 150000004820 halides Chemical class 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 229920006008 lipopolysaccharide Polymers 0.000 description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
- 229910052749 magnesium Inorganic materials 0.000 description 4
- 239000007758 minimum essential medium Substances 0.000 description 4
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 4
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 235000009518 sodium iodide Nutrition 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 150000003573 thiols Chemical class 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 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 3
- GLVJOHLPQHQJMH-UHFFFAOYSA-N 1-dimethoxyphosphoryl-3-naphthalen-2-ylpropan-2-one Chemical compound C1=CC=CC2=CC(CC(=O)CP(=O)(OC)OC)=CC=C21 GLVJOHLPQHQJMH-UHFFFAOYSA-N 0.000 description 3
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 3
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 3
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 3
- VYASUBHPACQVFC-UHFFFAOYSA-N 5-(3-hydroxy-4-phenylbutyl)pyrrolidin-2-one Chemical compound C=1C=CC=CC=1CC(O)CCC1CCC(=O)N1 VYASUBHPACQVFC-UHFFFAOYSA-N 0.000 description 3
- ZCBNQGIWWKNBCL-UHFFFAOYSA-N 5-(3-oxo-4-phenylbutyl)pyrrolidin-2-one Chemical compound C=1C=CC=CC=1CC(=O)CCC1CCC(=O)N1 ZCBNQGIWWKNBCL-UHFFFAOYSA-N 0.000 description 3
- REMRSWNHASHECZ-UHFFFAOYSA-N 5-[3-oxo-4-[3-(trifluoromethyl)phenyl]butyl]pyrrolidin-2-one Chemical compound FC(F)(F)C1=CC=CC(CC(=O)CCC2NC(=O)CC2)=C1 REMRSWNHASHECZ-UHFFFAOYSA-N 0.000 description 3
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 3
- 108010082126 Alanine transaminase Proteins 0.000 description 3
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 3
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 208000002330 Congenital Heart Defects Diseases 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- 239000007818 Grignard reagent Substances 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
- 208000008238 Muscle Spasticity Diseases 0.000 description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 3
- AJLFOPYRIVGYMJ-UHFFFAOYSA-N SJ000287055 Natural products C12C(OC(=O)C(C)CC)CCC=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 AJLFOPYRIVGYMJ-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 150000001348 alkyl chlorides Chemical class 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 229940006133 antiglaucoma drug and miotics carbonic anhydrase inhibitors Drugs 0.000 description 3
- 150000001502 aryl halides Chemical class 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 239000002876 beta blocker Substances 0.000 description 3
- 229940097320 beta blocking agent Drugs 0.000 description 3
- 230000007883 bronchodilation Effects 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 239000003489 carbonate dehydratase inhibitor Substances 0.000 description 3
- 150000001733 carboxylic acid esters Chemical class 0.000 description 3
- 125000002091 cationic group Chemical group 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- JGFBRKRYDCGYKD-UHFFFAOYSA-N dibutyl(oxo)tin Chemical compound CCCC[Sn](=O)CCCC JGFBRKRYDCGYKD-UHFFFAOYSA-N 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 150000004795 grignard reagents Chemical class 0.000 description 3
- 230000000004 hemodynamic effect Effects 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 150000004678 hydrides Chemical class 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- 229960002003 hydrochlorothiazide Drugs 0.000 description 3
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000004410 intraocular pressure Effects 0.000 description 3
- 239000007928 intraperitoneal injection Substances 0.000 description 3
- 238000001638 lipofection Methods 0.000 description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- KZRAAPTWXAMZHQ-UHFFFAOYSA-N methoxymethanamine Chemical class COCN KZRAAPTWXAMZHQ-UHFFFAOYSA-N 0.000 description 3
- QFLBWNWKBXCHKS-UHFFFAOYSA-N methyl 4-(3-hydroxyprop-1-ynyl)benzoate Chemical compound COC(=O)C1=CC=C(C#CCO)C=C1 QFLBWNWKBXCHKS-UHFFFAOYSA-N 0.000 description 3
- ARNGRGQYXABYAT-UHFFFAOYSA-N methyl 4-(3-hydroxypropyl)benzoate Chemical compound COC(=O)C1=CC=C(CCCO)C=C1 ARNGRGQYXABYAT-UHFFFAOYSA-N 0.000 description 3
- LBISABYSBNAOHO-SFHVURJKSA-N methyl 5-[3-[(2r)-2-[4-(3-chlorophenyl)-3-oxobut-1-enyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)CC[C@@H]1C=CC(=O)CC1=CC=CC(Cl)=C1 LBISABYSBNAOHO-SFHVURJKSA-N 0.000 description 3
- IPZKLECZSIHAFM-SFHVURJKSA-N methyl 5-[3-[(2r)-2-[4-(3-fluorophenyl)-3-oxobut-1-enyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)CC[C@@H]1C=CC(=O)CC1=CC=CC(F)=C1 IPZKLECZSIHAFM-SFHVURJKSA-N 0.000 description 3
- VJWSUSVBKUEDJR-SFHVURJKSA-N methyl 5-[3-[(2r)-2-[4-(4-fluorophenyl)-3-oxobut-1-enyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)CC[C@@H]1C=CC(=O)CC1=CC=C(F)C=C1 VJWSUSVBKUEDJR-SFHVURJKSA-N 0.000 description 3
- HYILSLDFAUEGMG-HNNXBMFYSA-N methyl 5-[3-[(5r)-2-oxo-5-(3-oxo-4-thiophen-2-ylbut-1-enyl)pyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)CC[C@@H]1C=CC(=O)CC1=CC=CS1 HYILSLDFAUEGMG-HNNXBMFYSA-N 0.000 description 3
- AJLFOPYRIVGYMJ-INTXDZFKSA-N mevastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=CCC[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 AJLFOPYRIVGYMJ-INTXDZFKSA-N 0.000 description 3
- 229950009116 mevastatin Drugs 0.000 description 3
- BOZILQFLQYBIIY-UHFFFAOYSA-N mevastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CCC=C21 BOZILQFLQYBIIY-UHFFFAOYSA-N 0.000 description 3
- CYMUETWUGMNGIO-UHFFFAOYSA-N n-methoxy-n-methyl-2-[3-(trifluoromethyl)phenyl]acetamide Chemical compound CON(C)C(=O)CC1=CC=CC(C(F)(F)F)=C1 CYMUETWUGMNGIO-UHFFFAOYSA-N 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 238000012856 packing Methods 0.000 description 3
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 3
- 239000011574 phosphorus Substances 0.000 description 3
- 229910052698 phosphorus Inorganic materials 0.000 description 3
- 238000003752 polymerase chain reaction Methods 0.000 description 3
- 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 3
- 239000003586 protic polar solvent Substances 0.000 description 3
- 238000003127 radioimmunoassay Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 230000004044 response Effects 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
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 208000018198 spasticity Diseases 0.000 description 3
- 230000010473 stable expression Effects 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 description 2
- ZGGHKIMDNBDHJB-RPQBTBOMSA-M (3S,5R)-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-RPQBTBOMSA-M 0.000 description 2
- VDSBXXDKCUBMQC-HNGSOEQISA-N (4r,6s)-6-[(e)-2-[2-(4-fluoro-3-methylphenyl)-4,4,6,6-tetramethylcyclohexen-1-yl]ethenyl]-4-hydroxyoxan-2-one Chemical compound C1=C(F)C(C)=CC(C=2CC(C)(C)CC(C)(C)C=2\C=C\[C@H]2OC(=O)C[C@H](O)C2)=C1 VDSBXXDKCUBMQC-HNGSOEQISA-N 0.000 description 2
- HOBJEFOCIRXQKH-SCSAIBSYSA-N (5r)-5-(hydroxymethyl)pyrrolidin-2-one Chemical compound OC[C@H]1CCC(=O)N1 HOBJEFOCIRXQKH-SCSAIBSYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- NYTJUSHDAHWGGT-UHFFFAOYSA-N 1-(3-bromophenyl)-3-dimethoxyphosphorylpropan-2-one Chemical compound COP(=O)(OC)CC(=O)CC1=CC=CC(Br)=C1 NYTJUSHDAHWGGT-UHFFFAOYSA-N 0.000 description 2
- OZFANVREVNSDJM-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-dimethoxyphosphorylpropan-2-one Chemical compound COP(=O)(OC)CC(=O)CC1=CC=CC(Cl)=C1 OZFANVREVNSDJM-UHFFFAOYSA-N 0.000 description 2
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 2
- NAWVLGFYFTWPBE-UHFFFAOYSA-N 1-diethoxyphosphoryl-3-(4-fluoro-3-methylphenyl)propan-2-ol Chemical compound CCOP(=O)(OCC)CC(O)CC1=CC=C(F)C(C)=C1 NAWVLGFYFTWPBE-UHFFFAOYSA-N 0.000 description 2
- RELPPYANIRFORI-UHFFFAOYSA-N 1-diethoxyphosphoryl-3-(4-fluoro-3-methylphenyl)propan-2-one Chemical compound CCOP(=O)(OCC)CC(=O)CC1=CC=C(F)C(C)=C1 RELPPYANIRFORI-UHFFFAOYSA-N 0.000 description 2
- PJEWIHPAWTUFGD-UHFFFAOYSA-N 1-diethoxyphosphoryl-3-[3-(methoxymethyl)phenyl]propan-2-one Chemical compound CCOP(=O)(OCC)CC(=O)CC1=CC=CC(COC)=C1 PJEWIHPAWTUFGD-UHFFFAOYSA-N 0.000 description 2
- HTTUPTMZPOGKEB-UHFFFAOYSA-N 1-dimethoxyphosphoryl-3-(3-fluorophenyl)propan-2-one Chemical compound COP(=O)(OC)CC(=O)CC1=CC=CC(F)=C1 HTTUPTMZPOGKEB-UHFFFAOYSA-N 0.000 description 2
- QNOXQOMRJZRWQU-UHFFFAOYSA-N 1-dimethoxyphosphoryl-3-(4-fluorophenyl)propan-2-one Chemical compound COP(=O)(OC)CC(=O)CC1=CC=C(F)C=C1 QNOXQOMRJZRWQU-UHFFFAOYSA-N 0.000 description 2
- FMEWANGHXVQRPI-UHFFFAOYSA-N 1-dimethoxyphosphoryl-3-[2-(trifluoromethyl)phenyl]propan-2-one Chemical compound COP(=O)(OC)CC(=O)CC1=CC=CC=C1C(F)(F)F FMEWANGHXVQRPI-UHFFFAOYSA-N 0.000 description 2
- RSEJVIDWZXYLGW-UHFFFAOYSA-N 1-dimethoxyphosphoryl-3-[3-(trifluoromethoxy)phenyl]propan-2-one Chemical compound COP(=O)(OC)CC(=O)CC1=CC=CC(OC(F)(F)F)=C1 RSEJVIDWZXYLGW-UHFFFAOYSA-N 0.000 description 2
- QUBZTBJWGAIXDN-UHFFFAOYSA-N 1-dimethoxyphosphoryl-3-[3-(trifluoromethyl)phenyl]propan-2-one Chemical compound COP(=O)(OC)CC(=O)CC1=CC=CC(C(F)(F)F)=C1 QUBZTBJWGAIXDN-UHFFFAOYSA-N 0.000 description 2
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- WRFWAYDBNCOWRA-UHFFFAOYSA-N 3,4-dichloro-1-(6-iodo-4-oxo-2-thiophen-2-ylquinazolin-3-yl)pyrrole-2,5-dione Chemical compound O=C1C(Cl)=C(Cl)C(=O)N1N1C(=O)C2=CC(I)=CC=C2N=C1C1=CC=CS1 WRFWAYDBNCOWRA-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- DQLDMXGXNPDHDY-UHFFFAOYSA-N 4-[3-[2-(3-hydroxy-4-phenylbutyl)-5-oxopyrrolidin-1-yl]propyl]benzoic acid Chemical compound C=1C=CC=CC=1CC(O)CCC1CCC(=O)N1CCCC1=CC=C(C(O)=O)C=C1 DQLDMXGXNPDHDY-UHFFFAOYSA-N 0.000 description 2
- WGVTVAQXBSHSQR-UHFFFAOYSA-N 4-[3-[2-(3-hydroxy-4-phenylbutyl)-5-oxopyrrolidin-1-yl]propyl]benzonitrile Chemical compound C=1C=CC=CC=1CC(O)CCC1CCC(=O)N1CCCC1=CC=C(C#N)C=C1 WGVTVAQXBSHSQR-UHFFFAOYSA-N 0.000 description 2
- VOGGIVIFFYJCQQ-UHFFFAOYSA-N 4-[3-[2-[3-[tert-butyl(dimethyl)silyl]oxy-4-(3-phenylphenyl)butyl]-5-oxopyrrolidin-1-yl]propyl]benzoic acid Chemical compound C=1C=CC(C=2C=CC=CC=2)=CC=1CC(O[Si](C)(C)C(C)(C)C)CCC1CCC(=O)N1CCCC1=CC=C(C(O)=O)C=C1 VOGGIVIFFYJCQQ-UHFFFAOYSA-N 0.000 description 2
- CILMWGKYOULOMR-UHFFFAOYSA-N 4-[3-[2-[4-(3-fluorophenyl)-3-hydroxybutyl]-5-oxopyrrolidin-1-yl]propyl]benzoic acid Chemical compound C=1C=CC(F)=CC=1CC(O)CCC1CCC(=O)N1CCCC1=CC=C(C(O)=O)C=C1 CILMWGKYOULOMR-UHFFFAOYSA-N 0.000 description 2
- UOGUMNDDVPYVGT-UHFFFAOYSA-N 5-(3-bromo-3-hydroxybutyl)pyrrolidin-2-one Chemical compound CC(O)(Br)CCC1CCC(=O)N1 UOGUMNDDVPYVGT-UHFFFAOYSA-N 0.000 description 2
- JLUPKRIHFCXUKH-UHFFFAOYSA-N 5-[3-[tert-butyl(dimethyl)silyl]oxy-4-(3-phenylphenyl)butyl]pyrrolidin-2-one Chemical compound C=1C=CC(C=2C=CC=CC=2)=CC=1CC(O[Si](C)(C)C(C)(C)C)CCC1CCC(=O)N1 JLUPKRIHFCXUKH-UHFFFAOYSA-N 0.000 description 2
- HVGRUOYWJYOTDJ-UHFFFAOYSA-N 5-[3-[tert-butyl(dimethyl)silyl]oxy-4-(4-fluorophenyl)butyl]pyrrolidin-2-one Chemical compound C=1C=C(F)C=CC=1CC(O[Si](C)(C)C(C)(C)C)CCC1CCC(=O)N1 HVGRUOYWJYOTDJ-UHFFFAOYSA-N 0.000 description 2
- IRQGUQFUNOFPKQ-UHFFFAOYSA-N 5-[3-[tert-butyl(dimethyl)silyl]oxy-4-[3-(trifluoromethyl)phenyl]butyl]pyrrolidin-2-one Chemical compound C=1C=CC(C(F)(F)F)=CC=1CC(O[Si](C)(C)C(C)(C)C)CCC1CCC(=O)N1 IRQGUQFUNOFPKQ-UHFFFAOYSA-N 0.000 description 2
- TXZWDQOLYJCSFG-UHFFFAOYSA-N 5-[3-[tert-butyl(dimethyl)silyl]oxy-4-phenylbutyl]pyrrolidin-2-one Chemical compound C=1C=CC=CC=1CC(O[Si](C)(C)C(C)(C)C)CCC1CCC(=O)N1 TXZWDQOLYJCSFG-UHFFFAOYSA-N 0.000 description 2
- VHWUOYZRNSJTEG-UHFFFAOYSA-N 5-[3-bromo-3-[tert-butyl(dimethyl)silyl]oxybutyl]pyrrolidin-2-one Chemical compound CC(C)(C)[Si](C)(C)OC(C)(Br)CCC1CCC(=O)N1 VHWUOYZRNSJTEG-UHFFFAOYSA-N 0.000 description 2
- RSMJOBRJNFOERO-UHFFFAOYSA-N 5-[3-hydroxy-4-[3-(trifluoromethyl)phenyl]butyl]pyrrolidin-2-one Chemical compound C=1C=CC(C(F)(F)F)=CC=1CC(O)CCC1CCC(=O)N1 RSMJOBRJNFOERO-UHFFFAOYSA-N 0.000 description 2
- HAELTGKNMSJGAK-UHFFFAOYSA-N 5-[3-oxo-4-(3-phenoxyphenyl)butyl]pyrrolidin-2-one Chemical compound C=1C=CC(OC=2C=CC=CC=2)=CC=1CC(=O)CCC1CCC(=O)N1 HAELTGKNMSJGAK-UHFFFAOYSA-N 0.000 description 2
- GNDPTVGVYYVVOT-UHFFFAOYSA-N 5-[4-(3-fluorophenyl)-3-oxobutyl]pyrrolidin-2-one Chemical compound FC1=CC=CC(CC(=O)CCC2NC(=O)CC2)=C1 GNDPTVGVYYVVOT-UHFFFAOYSA-N 0.000 description 2
- OATMWXXAHKMXFU-UHFFFAOYSA-N 5-[4-(4-fluorophenyl)-3-hydroxybutyl]pyrrolidin-2-one Chemical compound C=1C=C(F)C=CC=1CC(O)CCC1CCC(=O)N1 OATMWXXAHKMXFU-UHFFFAOYSA-N 0.000 description 2
- HMNYAEMFCADHKL-UHFFFAOYSA-N 5-[4-(4-fluorophenyl)-3-oxobutyl]pyrrolidin-2-one Chemical compound C1=CC(F)=CC=C1CC(=O)CCC1NC(=O)CC1 HMNYAEMFCADHKL-UHFFFAOYSA-N 0.000 description 2
- FRUMJWHHYIOBIT-LLVKDONJSA-N 7-[(2r)-2-(hydroxymethyl)-5-oxopyrrolidin-1-yl]heptanenitrile Chemical compound OC[C@H]1CCC(=O)N1CCCCCCC#N FRUMJWHHYIOBIT-LLVKDONJSA-N 0.000 description 2
- PDGDTFHFGWDBKI-NRFANRHFSA-N 7-[(2r)-2-[4-[3-(methoxymethyl)phenyl]-3-oxobut-1-enyl]-5-oxopyrrolidin-1-yl]heptanenitrile Chemical compound COCC1=CC=CC(CC(=O)C=C[C@@H]2N(C(=O)CC2)CCCCCCC#N)=C1 PDGDTFHFGWDBKI-NRFANRHFSA-N 0.000 description 2
- OUGXCQMOYWPHMR-LLVKDONJSA-N 7-[(2r)-2-formyl-5-oxopyrrolidin-1-yl]heptanenitrile Chemical compound O=C[C@H]1CCC(=O)N1CCCCCCC#N OUGXCQMOYWPHMR-LLVKDONJSA-N 0.000 description 2
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 229940127291 Calcium channel antagonist Drugs 0.000 description 2
- 239000005973 Carvone Substances 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 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 2
- 206010017076 Fracture Diseases 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 206010067125 Liver injury Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N Methyl benzoate Natural products COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-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
- 208000001132 Osteoporosis Diseases 0.000 description 2
- 208000001164 Osteoporotic Fractures Diseases 0.000 description 2
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 2
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 2
- 238000005835 Pfitzner-Moffat oxidation reaction Methods 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- CYLWJCABXYDINA-UHFFFAOYSA-N Polythiazide Polymers ClC1=C(S(N)(=O)=O)C=C2S(=O)(=O)N(C)C(CSCC(F)(F)F)NC2=C1 CYLWJCABXYDINA-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 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 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
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 238000006069 Suzuki reaction reaction Methods 0.000 description 2
- FNYLWPVRPXGIIP-UHFFFAOYSA-N Triamterene Chemical compound NC1=NC2=NC(N)=NC(N)=C2N=C1C1=CC=CC=C1 FNYLWPVRPXGIIP-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 231100000439 acute liver injury Toxicity 0.000 description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 description 2
- 150000001345 alkine derivatives Chemical class 0.000 description 2
- 125000005907 alkyl ester group Chemical group 0.000 description 2
- 229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 2
- 239000002160 alpha blocker Substances 0.000 description 2
- 229940124308 alpha-adrenoreceptor antagonist Drugs 0.000 description 2
- ACHKKGDWZVCSNH-UHFFFAOYSA-N amiloride hydrochloride Chemical compound Cl.NC(N)=NC(=O)C1=NC(Cl)=C(N)N=C1N ACHKKGDWZVCSNH-UHFFFAOYSA-N 0.000 description 2
- 229960004104 amiloride hydrochloride Drugs 0.000 description 2
- 125000000129 anionic group Chemical group 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 150000001499 aryl bromides Chemical class 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 150000001503 aryl iodides Chemical class 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 238000000065 atmospheric pressure chemical ionisation Methods 0.000 description 2
- 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 2
- 230000008901 benefit Effects 0.000 description 2
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 2
- RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 125000001743 benzylic group Chemical group 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].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 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 2
- 239000007844 bleaching agent Substances 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 229940124630 bronchodilator Drugs 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 239000000480 calcium channel blocker Substances 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 229960005110 cerivastatin Drugs 0.000 description 2
- SEERZIQQUAZTOL-ANMDKAQQSA-N cerivastatin Chemical compound COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 SEERZIQQUAZTOL-ANMDKAQQSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 238000011097 chromatography purification Methods 0.000 description 2
- 208000020832 chronic kidney disease Diseases 0.000 description 2
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 2
- 230000001886 ciliary effect Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 208000028831 congenital heart disease Diseases 0.000 description 2
- 229950003040 dalvastatin Drugs 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 229940043279 diisopropylamine Drugs 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 239000012039 electrophile Substances 0.000 description 2
- CNHISCQPKKGDPO-UHFFFAOYSA-N ethyl 2-bromo-1,3-thiazole-4-carboxylate Chemical compound CCOC(=O)C1=CSC(Br)=N1 CNHISCQPKKGDPO-UHFFFAOYSA-N 0.000 description 2
- FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 2
- YDARFNBVDDWMBQ-GFCCVEGCSA-N ethyl 7-[(2r)-2-(hydroxymethyl)-5-oxopyrrolidin-1-yl]heptanoate Chemical compound CCOC(=O)CCCCCCN1[C@@H](CO)CCC1=O YDARFNBVDDWMBQ-GFCCVEGCSA-N 0.000 description 2
- KPMNVWCCNVFESA-FQEVSTJZSA-N ethyl 7-[(2r)-2-[4-(3-bromophenyl)-3-oxobut-1-enyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound C1CC(=O)N(CCCCCCC(=O)OCC)[C@H]1C=CC(=O)CC1=CC=CC(Br)=C1 KPMNVWCCNVFESA-FQEVSTJZSA-N 0.000 description 2
- VQVAHSZEAAVATH-QHCPKHFHSA-N ethyl 7-[(2r)-2-[4-[3-(2-methoxyethyl)phenyl]-3-oxobut-1-enyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound C1CC(=O)N(CCCCCCC(=O)OCC)[C@H]1C=CC(=O)CC1=CC=CC(CCOC)=C1 VQVAHSZEAAVATH-QHCPKHFHSA-N 0.000 description 2
- QPHHYDVJIUJKPG-DEOSSOPVSA-N ethyl 7-[(5r)-2-oxo-5-[3-oxo-4-(3-phenoxyphenyl)but-1-enyl]pyrrolidin-1-yl]heptanoate Chemical compound C1CC(=O)N(CCCCCCC(=O)OCC)[C@H]1C=CC(=O)CC1=CC=CC(OC=2C=CC=CC=2)=C1 QPHHYDVJIUJKPG-DEOSSOPVSA-N 0.000 description 2
- QSFVVMNHHDLQCT-IBGZPJMESA-N ethyl 7-[(5r)-2-oxo-5-[3-oxo-4-[3-(trifluoromethoxy)phenyl]but-1-enyl]pyrrolidin-1-yl]heptanoate Chemical compound C1CC(=O)N(CCCCCCC(=O)OCC)[C@H]1C=CC(=O)CC1=CC=CC(OC(F)(F)F)=C1 QSFVVMNHHDLQCT-IBGZPJMESA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 230000001605 fetal effect Effects 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 229960003765 fluvastatin Drugs 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000027119 gastric acid secretion Effects 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 125000003106 haloaryl group Chemical group 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 2
- 230000001631 hypertensive effect Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 229910001502 inorganic halide Inorganic materials 0.000 description 2
- 229910017053 inorganic salt Inorganic materials 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 230000009545 invasion Effects 0.000 description 2
- 210000004731 jugular vein Anatomy 0.000 description 2
- 229940002661 lipitor Drugs 0.000 description 2
- 229910003002 lithium salt Inorganic materials 0.000 description 2
- 159000000002 lithium salts Chemical class 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
- 239000006166 lysate Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 2
- 229910052753 mercury Inorganic materials 0.000 description 2
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 2
- VKBCJIJGDJYNIP-UHFFFAOYSA-N methyl 2-(3-phenylphenyl)acetate Chemical compound COC(=O)CC1=CC=CC(C=2C=CC=CC=2)=C1 VKBCJIJGDJYNIP-UHFFFAOYSA-N 0.000 description 2
- DZBBOAWSQOJBOM-UHFFFAOYSA-N methyl 4-[3-[2-[3-[tert-butyl(dimethyl)silyl]oxy-4-(3-fluorophenyl)butyl]-5-oxopyrrolidin-1-yl]propyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CCCN1C(=O)CCC1CCC(O[Si](C)(C)C(C)(C)C)CC1=CC=CC(F)=C1 DZBBOAWSQOJBOM-UHFFFAOYSA-N 0.000 description 2
- LVTSZIGODZVGPE-UHFFFAOYSA-N methyl 4-[3-[2-[3-[tert-butyl(dimethyl)silyl]oxy-4-(4-fluorophenyl)butyl]-5-oxopyrrolidin-1-yl]propyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CCCN1C(=O)CCC1CCC(O[Si](C)(C)C(C)(C)C)CC1=CC=C(F)C=C1 LVTSZIGODZVGPE-UHFFFAOYSA-N 0.000 description 2
- DEPYBYOWEDPGQC-UHFFFAOYSA-N methyl 4-[3-[2-[3-hydroxy-4-(3-phenylphenyl)butyl]-5-oxopyrrolidin-1-yl]propyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CCCN1C(=O)CCC1CCC(O)CC1=CC=CC(C=2C=CC=CC=2)=C1 DEPYBYOWEDPGQC-UHFFFAOYSA-N 0.000 description 2
- SMHJOMDRJSDQOM-UHFFFAOYSA-N methyl 4-[3-[2-[4-(3-chlorophenyl)-3-hydroxybutyl]-5-oxopyrrolidin-1-yl]propyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CCCN1C(=O)CCC1CCC(O)CC1=CC=CC(Cl)=C1 SMHJOMDRJSDQOM-UHFFFAOYSA-N 0.000 description 2
- RICGXCUZOSIQNC-UHFFFAOYSA-N methyl 4-[3-[2-[4-(3-fluorophenyl)-3-hydroxybutyl]-5-oxopyrrolidin-1-yl]propyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CCCN1C(=O)CCC1CCC(O)CC1=CC=CC(F)=C1 RICGXCUZOSIQNC-UHFFFAOYSA-N 0.000 description 2
- MGBXTCJYKMJGCS-SNVBAGLBSA-N methyl 5-[3-[(2r)-2-(hydroxymethyl)-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)CC[C@@H]1CO MGBXTCJYKMJGCS-SNVBAGLBSA-N 0.000 description 2
- ICXPKOBEJSYAMN-SFHVURJKSA-N methyl 5-[3-[(2r)-2-[4-(4-chlorophenyl)-3-oxobut-1-enyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)CC[C@@H]1C=CC(=O)CC1=CC=C(Cl)C=C1 ICXPKOBEJSYAMN-SFHVURJKSA-N 0.000 description 2
- FSPSYONJMSWYIU-OAHLLOKOSA-N methyl 5-[3-[(2r)-2-[[tert-butyl(dimethyl)silyl]oxymethyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)CC[C@@H]1CO[Si](C)(C)C(C)(C)C FSPSYONJMSWYIU-OAHLLOKOSA-N 0.000 description 2
- MGWIFQZFPLGPJQ-KRWDZBQOSA-N methyl 5-[3-[(5r)-2-oxo-5-[3-oxo-4-[2-(trifluoromethyl)phenyl]but-1-enyl]pyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)CC[C@@H]1C=CC(=O)CC1=CC=CC=C1C(F)(F)F MGWIFQZFPLGPJQ-KRWDZBQOSA-N 0.000 description 2
- 229940095102 methyl benzoate Drugs 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 229910000510 noble metal Inorganic materials 0.000 description 2
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 2
- 239000011087 paperboard Substances 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 229960001412 pentobarbital Drugs 0.000 description 2
- 230000010412 perfusion Effects 0.000 description 2
- 208000028169 periodontal disease Diseases 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 230000001766 physiological effect Effects 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 229910003446 platinum oxide Inorganic materials 0.000 description 2
- 229960005483 polythiazide Drugs 0.000 description 2
- 229920000046 polythiazide Polymers 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229960002965 pravastatin Drugs 0.000 description 2
- 238000004237 preparative chromatography Methods 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 229950010131 puromycin Drugs 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- NRTYMEPCRDJMPZ-UHFFFAOYSA-N pyridine;2,2,2-trifluoroacetic acid Chemical compound C1=CC=NC=C1.OC(=O)C(F)(F)F NRTYMEPCRDJMPZ-UHFFFAOYSA-N 0.000 description 2
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 2
- 230000006340 racemization Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- DHNUAKOQUGJUGA-UHFFFAOYSA-N silicon;sulfane Chemical compound [Si].S DHNUAKOQUGJUGA-UHFFFAOYSA-N 0.000 description 2
- 229960002855 simvastatin Drugs 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000008247 solid mixture Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
- 229940095064 tartrate Drugs 0.000 description 2
- 238000003419 tautomerization reaction Methods 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
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 229960001288 triamterene Drugs 0.000 description 2
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 2
- SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 210000005166 vasculature Anatomy 0.000 description 2
- 230000024883 vasodilation Effects 0.000 description 2
- 230000003313 weakening effect Effects 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- 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
- 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
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- 125000005862 (C1-C6)alkanoyl group Chemical group 0.000 description 1
- 125000004209 (C1-C8) alkyl group Chemical group 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
- KJTLQQUUPVSXIM-ZCFIWIBFSA-N (R)-mevalonic acid Chemical compound OCC[C@](O)(C)CC(O)=O KJTLQQUUPVSXIM-ZCFIWIBFSA-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
- 0 *CC(*)CCCCC(CC1)N(CC**O)C1=O Chemical compound *CC(*)CCCCC(CC1)N(CC**O)C1=O 0.000 description 1
- JCIIKRHCWVHVFF-UHFFFAOYSA-N 1,2,4-thiadiazol-5-amine;hydrochloride Chemical compound Cl.NC1=NC=NS1 JCIIKRHCWVHVFF-UHFFFAOYSA-N 0.000 description 1
- YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 description 1
- JORYTEOEUYNAJL-UHFFFAOYSA-N 1-(1,3-benzodioxol-5-yl)-3-dimethoxyphosphorylpropan-2-one Chemical compound COP(=O)(OC)CC(=O)CC1=CC=C2OCOC2=C1 JORYTEOEUYNAJL-UHFFFAOYSA-N 0.000 description 1
- YIPWQAHTCKALEO-UHFFFAOYSA-N 1-(4-chlorophenyl)-3-dimethoxyphosphorylpropan-2-one Chemical compound COP(=O)(OC)CC(=O)CC1=CC=C(Cl)C=C1 YIPWQAHTCKALEO-UHFFFAOYSA-N 0.000 description 1
- XGASTRVQNVVYIZ-UHFFFAOYSA-N 1-(chloromethyl)-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC(CCl)=C1 XGASTRVQNVVYIZ-UHFFFAOYSA-N 0.000 description 1
- QUYVTGFWFHQVRO-UHFFFAOYSA-N 1-(chloromethyl)-3-phenoxybenzene Chemical compound ClCC1=CC=CC(OC=2C=CC=CC=2)=C1 QUYVTGFWFHQVRO-UHFFFAOYSA-N 0.000 description 1
- WHINIPISJNSYGE-UHFFFAOYSA-N 1-[3-[tert-butyl(dimethyl)silyl]oxy-4-(3-fluorophenyl)butyl]pyrrolidin-2-one Chemical compound C=1C=CC(F)=CC=1CC(O[Si](C)(C)C(C)(C)C)CCN1CCCC1=O WHINIPISJNSYGE-UHFFFAOYSA-N 0.000 description 1
- USYQKCQEVBFJRP-UHFFFAOYSA-N 1-bromo-3-phenylbenzene Chemical group BrC1=CC=CC(C=2C=CC=CC=2)=C1 USYQKCQEVBFJRP-UHFFFAOYSA-N 0.000 description 1
- OILPPNKWYFAORW-UHFFFAOYSA-N 1-cyclohexyl-3-dimethoxyphosphorylpropan-2-one Chemical compound COP(=O)(OC)CC(=O)CC1CCCCC1 OILPPNKWYFAORW-UHFFFAOYSA-N 0.000 description 1
- IWQISEXIPZPFGG-UHFFFAOYSA-N 1-diethoxyphosphoryl-3-(4-ethylphenyl)propan-2-one Chemical compound CCOP(=O)(OCC)CC(=O)CC1=CC=C(CC)C=C1 IWQISEXIPZPFGG-UHFFFAOYSA-N 0.000 description 1
- UFETWGZWAUALTN-UHFFFAOYSA-N 1-diethoxyphosphoryl-3-[3-(2-methoxyethyl)phenyl]propan-2-one Chemical compound CCOP(=O)(OCC)CC(=O)CC1=CC=CC(CCOC)=C1 UFETWGZWAUALTN-UHFFFAOYSA-N 0.000 description 1
- MUNPYKGLTLFKBE-UHFFFAOYSA-N 1-dimethoxyphosphoryl-3-(3-phenoxyphenyl)propan-2-one Chemical compound COP(=O)(OC)CC(=O)CC1=CC=CC(OC=2C=CC=CC=2)=C1 MUNPYKGLTLFKBE-UHFFFAOYSA-N 0.000 description 1
- KHKYLTTZTQTAGN-UHFFFAOYSA-N 1-dimethoxyphosphoryl-3-(3-phenylphenyl)propan-2-one Chemical compound COP(=O)(OC)CC(=O)CC1=CC=CC(C=2C=CC=CC=2)=C1 KHKYLTTZTQTAGN-UHFFFAOYSA-N 0.000 description 1
- HQJAUSGLWRLGOI-UHFFFAOYSA-N 1-dimethoxyphosphoryl-3-phenylpropan-2-one Chemical compound COP(=O)(OC)CC(=O)CC1=CC=CC=C1 HQJAUSGLWRLGOI-UHFFFAOYSA-N 0.000 description 1
- QYLFCMNVRZLGOZ-UHFFFAOYSA-N 1-dimethoxyphosphoryl-3-thiophen-2-ylpropan-2-one Chemical compound COP(=O)(OC)CC(=O)CC1=CC=CS1 QYLFCMNVRZLGOZ-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
- CGEVLDYWZUAHBK-RRKGBCIJSA-N 2-[(2R)-2-formyl-5-oxopyrrolidin-1-yl]heptanenitrile Chemical compound C(=O)[C@@H]1N(C(CC1)=O)C(C#N)CCCCC CGEVLDYWZUAHBK-RRKGBCIJSA-N 0.000 description 1
- BLXXCCIBGGBDHI-UHFFFAOYSA-N 2-[3-(trifluoromethyl)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(C(F)(F)F)=C1 BLXXCCIBGGBDHI-UHFFFAOYSA-N 0.000 description 1
- JIVPVXMEBJLZRO-CQSZACIVSA-N 2-chloro-5-[(1r)-1-hydroxy-3-oxo-2h-isoindol-1-yl]benzenesulfonamide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC([C@@]2(O)C3=CC=CC=C3C(=O)N2)=C1 JIVPVXMEBJLZRO-CQSZACIVSA-N 0.000 description 1
- UUCSJRADVBQCCV-UHFFFAOYSA-N 2-diethoxyphosphoryloxirane Chemical compound CCOP(=O)(OCC)C1CO1 UUCSJRADVBQCCV-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- APIXJSLKIYYUKG-UHFFFAOYSA-N 3 Isobutyl 1 methylxanthine Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N=CN2 APIXJSLKIYYUKG-UHFFFAOYSA-N 0.000 description 1
- WGCICQJXVYFFCA-UHFFFAOYSA-N 3-iodoprop-1-yne Chemical compound ICC#C WGCICQJXVYFFCA-UHFFFAOYSA-N 0.000 description 1
- BTDDPWYXRFJJIY-UHFFFAOYSA-N 4-[3-[2-[3-[tert-butyl(dimethyl)silyl]oxy-4-(3-chlorophenyl)butyl]-5-oxopyrrolidin-1-yl]propyl]benzoic acid Chemical compound C=1C=CC(Cl)=CC=1CC(O[Si](C)(C)C(C)(C)C)CCC1CCC(=O)N1CCCC1=CC=C(C(O)=O)C=C1 BTDDPWYXRFJJIY-UHFFFAOYSA-N 0.000 description 1
- UQDUSJYYEMFVGI-UHFFFAOYSA-N 4-[3-[2-[3-[tert-butyl(dimethyl)silyl]oxy-4-(3-fluorophenyl)butyl]-5-oxopyrrolidin-1-yl]propyl]benzoic acid Chemical compound C=1C=CC(F)=CC=1CC(O[Si](C)(C)C(C)(C)C)CCC1CCC(=O)N1CCCC1=CC=C(C(O)=O)C=C1 UQDUSJYYEMFVGI-UHFFFAOYSA-N 0.000 description 1
- WFWOBSSUWMMSCU-UHFFFAOYSA-N 4-[3-[2-[3-[tert-butyl(dimethyl)silyl]oxy-4-(4-fluorophenyl)butyl]-5-oxopyrrolidin-1-yl]propyl]benzoic acid Chemical compound C=1C=C(F)C=CC=1CC(O[Si](C)(C)C(C)(C)C)CCC1CCC(=O)N1CCCC1=CC=C(C(O)=O)C=C1 WFWOBSSUWMMSCU-UHFFFAOYSA-N 0.000 description 1
- SDEZJSYVFCHZOB-UHFFFAOYSA-N 4-[3-[2-[3-hydroxy-4-(3-phenoxyphenyl)butyl]-5-oxopyrrolidin-1-yl]propyl]benzoic acid Chemical compound C=1C=CC(OC=2C=CC=CC=2)=CC=1CC(O)CCC1CCC(=O)N1CCCC1=CC=C(C(O)=O)C=C1 SDEZJSYVFCHZOB-UHFFFAOYSA-N 0.000 description 1
- FBSYWZQEXIMEQD-UHFFFAOYSA-N 4-[3-[2-[3-hydroxy-4-(3-phenylphenyl)butyl]-5-oxopyrrolidin-1-yl]propyl]benzoic acid Chemical compound C=1C=CC(C=2C=CC=CC=2)=CC=1CC(O)CCC1CCC(=O)N1CCCC1=CC=C(C(O)=O)C=C1 FBSYWZQEXIMEQD-UHFFFAOYSA-N 0.000 description 1
- SRSAPNTYWCSITR-UHFFFAOYSA-N 4-[3-[2-[3-hydroxy-4-[3-(trifluoromethyl)phenyl]butyl]-5-oxopyrrolidin-1-yl]propyl]benzoic acid Chemical compound C=1C=CC(C(F)(F)F)=CC=1CC(O)CCC1CCC(=O)N1CCCC1=CC=C(C(O)=O)C=C1 SRSAPNTYWCSITR-UHFFFAOYSA-N 0.000 description 1
- APXHYSJSTXRVDF-UHFFFAOYSA-N 4-[3-[2-[4-(3-chlorophenyl)-3-hydroxybutyl]-5-oxopyrrolidin-1-yl]propyl]benzoic acid Chemical compound C=1C=CC(Cl)=CC=1CC(O)CCC1CCC(=O)N1CCCC1=CC=C(C(O)=O)C=C1 APXHYSJSTXRVDF-UHFFFAOYSA-N 0.000 description 1
- ZSPAEDJDADQTKU-UHFFFAOYSA-N 4-[3-[2-[4-(4-fluorophenyl)-3-hydroxybutyl]-5-oxopyrrolidin-1-yl]propyl]benzoic acid Chemical compound C=1C=C(F)C=CC=1CC(O)CCC1CCC(=O)N1CCCC1=CC=C(C(O)=O)C=C1 ZSPAEDJDADQTKU-UHFFFAOYSA-N 0.000 description 1
- HQSCPPCMBMFJJN-UHFFFAOYSA-N 4-bromobenzonitrile Chemical compound BrC1=CC=C(C#N)C=C1 HQSCPPCMBMFJJN-UHFFFAOYSA-N 0.000 description 1
- DMJFXAPTBPHPAN-UHFFFAOYSA-N 5-(3-hydroxy-4-phenylbutyl)-1-[3-[4-(2h-tetrazol-5-yl)phenyl]propyl]pyrrolidin-2-one Chemical compound C=1C=CC=CC=1CC(O)CCC1CCC(=O)N1CCCC(C=C1)=CC=C1C=1N=NNN=1 DMJFXAPTBPHPAN-UHFFFAOYSA-N 0.000 description 1
- DDFHBQSCUXNBSA-UHFFFAOYSA-N 5-(5-carboxythiophen-2-yl)thiophene-2-carboxylic acid Chemical compound S1C(C(=O)O)=CC=C1C1=CC=C(C(O)=O)S1 DDFHBQSCUXNBSA-UHFFFAOYSA-N 0.000 description 1
- OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 1
- ZZBMOSXMXZEBIV-UHFFFAOYSA-N 5-[3-[tert-butyl(dimethyl)silyl]oxy-4-(3-chlorophenyl)butyl]pyrrolidin-2-one Chemical compound C=1C=CC(Cl)=CC=1CC(O[Si](C)(C)C(C)(C)C)CCC1CCC(=O)N1 ZZBMOSXMXZEBIV-UHFFFAOYSA-N 0.000 description 1
- NNKQTVQXEWLWJP-UHFFFAOYSA-N 5-[3-[tert-butyl(dimethyl)silyl]oxy-4-(3-fluorophenyl)butyl]pyrrolidin-2-one Chemical compound C=1C=CC(F)=CC=1CC(O[Si](C)(C)C(C)(C)C)CCC1CCC(=O)N1 NNKQTVQXEWLWJP-UHFFFAOYSA-N 0.000 description 1
- REKLGDRSMJUJBR-UHFFFAOYSA-N 5-[3-[tert-butyl(dimethyl)silyl]oxy-4-(3-phenoxyphenyl)butyl]pyrrolidin-2-one Chemical compound C=1C=CC(OC=2C=CC=CC=2)=CC=1CC(O[Si](C)(C)C(C)(C)C)CCC1CCC(=O)N1 REKLGDRSMJUJBR-UHFFFAOYSA-N 0.000 description 1
- WDXOZILVSFKBRL-UHFFFAOYSA-N 5-[3-hydroxy-4-(3-phenoxyphenyl)butyl]pyrrolidin-2-one Chemical compound C=1C=CC(OC=2C=CC=CC=2)=CC=1CC(O)CCC1CCC(=O)N1 WDXOZILVSFKBRL-UHFFFAOYSA-N 0.000 description 1
- FZCUPEHZVHFFEK-UHFFFAOYSA-N 5-[4-(3-chlorophenyl)-3-hydroxybutyl]pyrrolidin-2-one Chemical compound C=1C=CC(Cl)=CC=1CC(O)CCC1CCC(=O)N1 FZCUPEHZVHFFEK-UHFFFAOYSA-N 0.000 description 1
- YTRBMRZOSVXYNE-UHFFFAOYSA-N 5-[4-(3-fluorophenyl)-3-hydroxybutyl]pyrrolidin-2-one Chemical compound C=1C=CC(F)=CC=1CC(O)CCC1CCC(=O)N1 YTRBMRZOSVXYNE-UHFFFAOYSA-N 0.000 description 1
- COWZPSUDTMGBAT-UHFFFAOYSA-N 5-bromothiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(Br)S1 COWZPSUDTMGBAT-UHFFFAOYSA-N 0.000 description 1
- HNLAFWZKHCUIMC-UHFFFAOYSA-N 6-chloro-1,1-dioxo-3,4-dihydro-2h-1$l^{6},2,4-benzothiadiazine-7-sulfonamide;hydrochloride Chemical compound Cl.C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O HNLAFWZKHCUIMC-UHFFFAOYSA-N 0.000 description 1
- XZJHMLFAEMPMGH-WTQRLHSKSA-N 7-[(2r)-2-(3-hydroxy-4-naphthalen-2-ylbutyl)-5-oxopyrrolidin-1-yl]heptanoic acid Chemical compound C=1C=C2C=CC=CC2=CC=1CC(O)CC[C@@H]1CCC(=O)N1CCCCCCC(O)=O XZJHMLFAEMPMGH-WTQRLHSKSA-N 0.000 description 1
- VRQWHBXJTBXEBA-ZENAZSQFSA-N 7-[(2r)-2-[4-(1,3-benzodioxol-5-yl)-3-hydroxybut-1-enyl]-5-oxopyrrolidin-1-yl]heptanoic acid Chemical compound C=1C=C2OCOC2=CC=1CC(O)C=C[C@H]1CCC(=O)N1CCCCCCC(O)=O VRQWHBXJTBXEBA-ZENAZSQFSA-N 0.000 description 1
- QHCYYZKVGMZKHT-UHFFFAOYSA-N 7-bromo-2-ethylheptanenitrile Chemical compound C(C)C(C#N)CCCCCBr QHCYYZKVGMZKHT-UHFFFAOYSA-N 0.000 description 1
- WXWQOKAQXAVJMG-UHFFFAOYSA-N 7-bromo-2-ethylheptanoic acid Chemical compound CCC(C(O)=O)CCCCCBr WXWQOKAQXAVJMG-UHFFFAOYSA-N 0.000 description 1
- HVVQSKCGHAPHMV-UHFFFAOYSA-N 7-bromoheptanenitrile Chemical compound BrCCCCCCC#N HVVQSKCGHAPHMV-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- WRDABNWSWOHGMS-UHFFFAOYSA-N AEBSF hydrochloride Chemical compound Cl.NCCC1=CC=C(S(F)(=O)=O)C=C1 WRDABNWSWOHGMS-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000010444 Acidosis Diseases 0.000 description 1
- 208000009304 Acute Kidney Injury Diseases 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
- XYLJNLCSTIOKRM-UHFFFAOYSA-N Alphagan Chemical compound C1=CC2=NC=CN=C2C(Br)=C1NC1=NCCN1 XYLJNLCSTIOKRM-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 102000008873 Angiotensin II receptor Human genes 0.000 description 1
- 108050000824 Angiotensin II receptor Proteins 0.000 description 1
- 108010087765 Antipain Proteins 0.000 description 1
- 208000031104 Arterial Occlusive disease Diseases 0.000 description 1
- 240000000850 Astartea fascicularis Species 0.000 description 1
- 208000037157 Azotemia Diseases 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
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 208000010392 Bone Fractures Diseases 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 238000009010 Bradford assay Methods 0.000 description 1
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 1
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- NUUQRWANWXQPGE-UHFFFAOYSA-N C(C)OC(C1=C(C=CC=C1)OCCN1C(CCC1=O)CCC(CC1=CC=CC=C1)O)=O Chemical compound C(C)OC(C1=C(C=CC=C1)OCCN1C(CCC1=O)CCC(CC1=CC=CC=C1)O)=O NUUQRWANWXQPGE-UHFFFAOYSA-N 0.000 description 1
- 239000002083 C09CA01 - Losartan Substances 0.000 description 1
- 239000004072 C09CA03 - Valsartan Substances 0.000 description 1
- 239000002947 C09CA04 - Irbesartan Substances 0.000 description 1
- 239000005537 C09CA07 - Telmisartan Substances 0.000 description 1
- NSXZCGVOXXQUIO-UHFFFAOYSA-N CC(C)(C)[Si](C)(C)OC(CCN1CCCC1=O)CC2=CC(=CC=C2)Cl Chemical compound CC(C)(C)[Si](C)(C)OC(CCN1CCCC1=O)CC2=CC(=CC=C2)Cl NSXZCGVOXXQUIO-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- WVUHHPQQQLBMOE-UHFFFAOYSA-N Cc1cnc(C)[s]1 Chemical compound Cc1cnc(C)[s]1 WVUHHPQQQLBMOE-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 206010009192 Circulatory collapse 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
- 241000043587 Collimonas fungivorans Species 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- NOTFZGFABLVTIG-UHFFFAOYSA-N Cyclohexylethyl acetate Chemical compound CC(=O)OCCC1CCCCC1 NOTFZGFABLVTIG-UHFFFAOYSA-N 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
- KJTLQQUUPVSXIM-UHFFFAOYSA-N DL-mevalonic acid Natural products OCCC(O)(C)CC(O)=O KJTLQQUUPVSXIM-UHFFFAOYSA-N 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- 108010061435 Enalapril Proteins 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- LHEKQFDKPKZZJF-UHFFFAOYSA-N FC=1C=C(C[Mg])C=CC1 Chemical compound FC=1C=C(C[Mg])C=CC1 LHEKQFDKPKZZJF-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 1
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 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 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 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
- 241000282567 Macaca fascicularis Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 1
- 206010027417 Metabolic acidosis Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- GMPKIPWJBDOURN-UHFFFAOYSA-N Methoxyamine Chemical compound CON GMPKIPWJBDOURN-UHFFFAOYSA-N 0.000 description 1
- CESYKOGBSMNBPD-UHFFFAOYSA-N Methyclothiazide Chemical compound ClC1=C(S(N)(=O)=O)C=C2S(=O)(=O)N(C)C(CCl)NC2=C1 CESYKOGBSMNBPD-UHFFFAOYSA-N 0.000 description 1
- PGBFYLVIMDQYMS-UHFFFAOYSA-N Methyl thiophene-2-carboxylate Chemical compound COC(=O)C1=CC=CS1 PGBFYLVIMDQYMS-UHFFFAOYSA-N 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-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
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-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
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229940127473 Prostaglandin Receptor Agonists Drugs 0.000 description 1
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
- 229940123934 Reductase inhibitor Drugs 0.000 description 1
- 208000033626 Renal failure acute Diseases 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 244000000231 Sesamum indicum Species 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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
- 238000006859 Swern oxidation reaction Methods 0.000 description 1
- 239000000150 Sympathomimetic Substances 0.000 description 1
- NGBFQHCMQULJNZ-UHFFFAOYSA-N Torsemide Chemical compound CC(C)NC(=O)NS(=O)(=O)C1=CN=CC=C1NC1=CC=CC(C)=C1 NGBFQHCMQULJNZ-UHFFFAOYSA-N 0.000 description 1
- 238000008050 Total Bilirubin Reagent Methods 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
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 208000036029 Uterine contractions during pregnancy Diseases 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- 206010047141 Vasodilatation Diseases 0.000 description 1
- BXBALPFLMRJKQD-UHFFFAOYSA-N [3-(4-chlorophenyl)-2-oxopropyl]phosphonic acid Chemical compound OP(O)(=O)CC(=O)CC1=CC=C(Cl)C=C1 BXBALPFLMRJKQD-UHFFFAOYSA-N 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 206010000210 abortion Diseases 0.000 description 1
- 231100000176 abortion Toxicity 0.000 description 1
- 238000010521 absorption reaction Methods 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
- 229960002122 acebutolol Drugs 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 229960004308 acetylcysteine Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 201000011040 acute kidney failure Diseases 0.000 description 1
- 208000012998 acute renal failure Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000003732 agents acting on the eye Substances 0.000 description 1
- 229950007884 alacepril Drugs 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- 238000010976 amide bond formation reaction Methods 0.000 description 1
- HTIQEAQVCYTUBX-UHFFFAOYSA-N amlodipine Chemical compound CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-UHFFFAOYSA-N 0.000 description 1
- 229960000528 amlodipine Drugs 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 210000002159 anterior chamber Anatomy 0.000 description 1
- 230000001262 anti-secretory effect Effects 0.000 description 1
- 230000002921 anti-spasmodic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- SDNYTAYICBFYFH-TUFLPTIASA-N antipain Chemical compound NC(N)=NCCC[C@@H](C=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 SDNYTAYICBFYFH-TUFLPTIASA-N 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 210000002376 aorta thoracic Anatomy 0.000 description 1
- 210000001742 aqueous humor Anatomy 0.000 description 1
- 230000004509 aqueous humor production Effects 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- 230000037007 arousal Effects 0.000 description 1
- 208000021328 arterial occlusion Diseases 0.000 description 1
- 150000001543 aryl boronic acids Chemical class 0.000 description 1
- 229960002274 atenolol Drugs 0.000 description 1
- 229960001770 atorvastatin calcium Drugs 0.000 description 1
- 238000010945 base-catalyzed hydrolysis reactiony Methods 0.000 description 1
- 229960004530 benazepril Drugs 0.000 description 1
- UPABQMWFWCMOFV-UHFFFAOYSA-N benethamine Chemical compound C=1C=CC=CC=1CNCCC1=CC=CC=C1 UPABQMWFWCMOFV-UHFFFAOYSA-N 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 229960004324 betaxolol Drugs 0.000 description 1
- CHDPSNLJFOQTRK-UHFFFAOYSA-N betaxolol hydrochloride Chemical compound [Cl-].C1=CC(OCC(O)C[NH2+]C(C)C)=CC=C1CCOCC1CC1 CHDPSNLJFOQTRK-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000012620 biological material Substances 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
- 229960002781 bisoprolol Drugs 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 229960003679 brimonidine Drugs 0.000 description 1
- HCRKCZRJWPKOAR-JTQLQIEISA-N brinzolamide Chemical compound CCN[C@H]1CN(CCCOC)S(=O)(=O)C2=C1C=C(S(N)(=O)=O)S2 HCRKCZRJWPKOAR-JTQLQIEISA-N 0.000 description 1
- 229960000722 brinzolamide Drugs 0.000 description 1
- 150000001649 bromium compounds Chemical group 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000000168 bronchodilator agent Substances 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 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
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 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
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- GPUADMRJQVPIAS-QCVDVZFFSA-M cerivastatin sodium Chemical compound [Na+].COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 GPUADMRJQVPIAS-QCVDVZFFSA-M 0.000 description 1
- JYFJNCCRKBBRKZ-UHFFFAOYSA-N chembl194764 Chemical compound C=1C=CC=C(F)C=1CCN1C(=O)C(CC)=C(C)N=C1C1=CC=CC=C1O JYFJNCCRKBBRKZ-UHFFFAOYSA-N 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 229960002155 chlorothiazide Drugs 0.000 description 1
- 229960001523 chlortalidone 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
- 229940117975 chromium trioxide Drugs 0.000 description 1
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 1
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 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
- 229950006523 cilexetil Drugs 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000005516 coenzyme A Substances 0.000 description 1
- 229940093530 coenzyme a Drugs 0.000 description 1
- 230000037319 collagen production Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000003433 contraceptive agent Substances 0.000 description 1
- 230000002254 contraceptive effect Effects 0.000 description 1
- 230000037020 contractile activity Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- VTDCYOLLYVAJSY-UHFFFAOYSA-N cyclohexyl propan-2-yl carbonate Chemical compound CC(C)OC(=O)OC1CCCCC1 VTDCYOLLYVAJSY-UHFFFAOYSA-N 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000001120 cytoprotective effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003247 decreasing effect 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
- 230000005595 deprotonation Effects 0.000 description 1
- 238000010537 deprotonation reaction Methods 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 150000001987 diarylethers Chemical class 0.000 description 1
- 238000011917 diastereoselective reduction Methods 0.000 description 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 1
- GJQPMPFPNINLKP-UHFFFAOYSA-N diclofenamide Chemical compound NS(=O)(=O)C1=CC(Cl)=C(Cl)C(S(N)(=O)=O)=C1 GJQPMPFPNINLKP-UHFFFAOYSA-N 0.000 description 1
- 229960005081 diclofenamide Drugs 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 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
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- IAVUPMFITXYVAF-XPUUQOCRSA-N dorzolamide Chemical compound CCN[C@H]1C[C@H](C)S(=O)(=O)C2=C1C=C(S(N)(=O)=O)S2 IAVUPMFITXYVAF-XPUUQOCRSA-N 0.000 description 1
- 229960003933 dorzolamide Drugs 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
- 239000006196 drop Substances 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 108010039262 elastatinal Proteins 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003995 emulsifying agent 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
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- AVOLMBLBETYQHX-UHFFFAOYSA-N etacrynic acid Chemical compound CCC(=C)C(=O)C1=CC=C(OCC(O)=O)C(Cl)=C1Cl AVOLMBLBETYQHX-UHFFFAOYSA-N 0.000 description 1
- 229960003199 etacrynic acid Drugs 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- CAERSDJFKGMKLY-UHFFFAOYSA-N ethyl 2-(3-bromophenyl)acetate Chemical compound CCOC(=O)CC1=CC=CC(Br)=C1 CAERSDJFKGMKLY-UHFFFAOYSA-N 0.000 description 1
- ZSNARLMEYXXCIK-OAHLLOKOSA-N ethyl 2-[3-[(2R)-2-(2-tert-butylsilyloxypropan-2-yl)-5-oxopyrrolidin-1-yl]prop-1-ynyl]-1,3-thiazole-4-carboxylate Chemical compound C(C)OC(=O)C=1N=C(SC=1)C#CCN1[C@H](CCC1=O)C(O[SiH2]C(C)(C)C)(C)C ZSNARLMEYXXCIK-OAHLLOKOSA-N 0.000 description 1
- HMXKDWBDNSGBNZ-OAHLLOKOSA-N ethyl 2-[3-[(2R)-2-(2-tert-butylsilyloxypropan-2-yl)-5-oxopyrrolidin-1-yl]propyl]-1,3-thiazole-4-carboxylate Chemical compound C(C)OC(=O)C=1N=C(SC=1)CCCN1[C@H](CCC1=O)C(O[SiH2]C(C)(C)C)(C)C HMXKDWBDNSGBNZ-OAHLLOKOSA-N 0.000 description 1
- PEPILSVZOINLHW-SNVBAGLBSA-N ethyl 2-[3-[(2r)-2-(hydroxymethyl)-5-oxopyrrolidin-1-yl]propyl]-1,3-thiazole-4-carboxylate Chemical compound CCOC(=O)C1=CSC(CCCN2C(CC[C@@H]2CO)=O)=N1 PEPILSVZOINLHW-SNVBAGLBSA-N 0.000 description 1
- KTYIFXLNIMPSKI-UHFFFAOYSA-N ethyl 2-bromo-1,3-thiazole-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(Br)S1 KTYIFXLNIMPSKI-UHFFFAOYSA-N 0.000 description 1
- DBSADESEDBCPFO-UHFFFAOYSA-N ethyl 2-cyclopentylacetate Chemical compound CCOC(=O)CC1CCCC1 DBSADESEDBCPFO-UHFFFAOYSA-N 0.000 description 1
- BZLVOUTZDHRJPD-UHFFFAOYSA-N ethyl 4-(2-bromoethoxy)benzoate Chemical compound CCOC(=O)C1=CC=C(OCCBr)C=C1 BZLVOUTZDHRJPD-UHFFFAOYSA-N 0.000 description 1
- GSPWDJRYCQDGPO-UHFFFAOYSA-N ethyl 4-[2-[2-(3-hydroxy-4-phenylbutyl)-5-oxopyrrolidin-1-yl]ethoxy]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1OCCN1C(=O)CCC1CCC(O)CC1=CC=CC=C1 GSPWDJRYCQDGPO-UHFFFAOYSA-N 0.000 description 1
- CSTGNEZQERQUCM-UHFFFAOYSA-N ethyl 4-[2-[2-[3-[tert-butyl(dimethyl)silyl]oxy-4-phenylbutyl]-5-oxopyrrolidin-1-yl]ethoxy]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1OCCN1C(=O)CCC1CCC(O[Si](C)(C)C(C)(C)C)CC1=CC=CC=C1 CSTGNEZQERQUCM-UHFFFAOYSA-N 0.000 description 1
- XZIAFENWXIQIKR-UHFFFAOYSA-N ethyl 4-bromobenzoate Chemical compound CCOC(=O)C1=CC=C(Br)C=C1 XZIAFENWXIQIKR-UHFFFAOYSA-N 0.000 description 1
- PZNHMXAOMDQLLE-UHFFFAOYSA-N ethyl 5-bromothiophene-2-carboxylate Chemical compound CCOC(=O)C1=CC=C(Br)S1 PZNHMXAOMDQLLE-UHFFFAOYSA-N 0.000 description 1
- GZHLKZARNGMNQT-XJDOXCRVSA-N ethyl 7-[(2r)-2-[4-(1,3-benzodioxol-5-yl)-3-hydroxybut-1-enyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound C1CC(=O)N(CCCCCCC(=O)OCC)[C@H]1C=CC(O)CC1=CC=C(OCO2)C2=C1 GZHLKZARNGMNQT-XJDOXCRVSA-N 0.000 description 1
- SRNNZHJXCPFTTJ-QFIPXVFZSA-N ethyl 7-[(2r)-2-[4-[3-(methoxymethyl)phenyl]-3-oxobut-1-enyl]-5-oxopyrrolidin-1-yl]heptanoate Chemical compound C1CC(=O)N(CCCCCCC(=O)OCC)[C@H]1C=CC(=O)CC1=CC=CC(COC)=C1 SRNNZHJXCPFTTJ-QFIPXVFZSA-N 0.000 description 1
- 125000006437 ethyl cyclopropyl group Chemical group 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 229960002490 fosinopril Drugs 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 229960003883 furosemide Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000004868 gas analysis Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 206010019692 hepatic necrosis Diseases 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- DMDGGSIALPNSEE-UHFFFAOYSA-N hydroflumethiazide Chemical compound C1=C(C(F)(F)F)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O DMDGGSIALPNSEE-UHFFFAOYSA-N 0.000 description 1
- 229960003313 hydroflumethiazide Drugs 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- DCPMPXBYPZGNDC-UHFFFAOYSA-N hydron;methanediimine;chloride Chemical compound Cl.N=C=N DCPMPXBYPZGNDC-UHFFFAOYSA-N 0.000 description 1
- USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 1
- RCBVKBFIWMOMHF-UHFFFAOYSA-L hydroxy-(hydroxy(dioxo)chromio)oxy-dioxochromium;pyridine Chemical compound C1=CC=NC=C1.C1=CC=NC=C1.O[Cr](=O)(=O)O[Cr](O)(=O)=O RCBVKBFIWMOMHF-UHFFFAOYSA-L 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 208000006575 hypertriglyceridemia Diseases 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- NDDAHWYSQHTHNT-UHFFFAOYSA-N indapamide Chemical compound CC1CC2=CC=CC=C2N1NC(=O)C1=CC=C(Cl)C(S(N)(=O)=O)=C1 NDDAHWYSQHTHNT-UHFFFAOYSA-N 0.000 description 1
- 229960004569 indapamide Drugs 0.000 description 1
- 238000007373 indentation Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 229960002198 irbesartan Drugs 0.000 description 1
- YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-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
- 238000002372 labelling Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- ZDXUKAKRHYTAKV-UHFFFAOYSA-N lercanidipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)(C)CN(C)CCC(C=2C=CC=CC=2)C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZDXUKAKRHYTAKV-UHFFFAOYSA-N 0.000 description 1
- 229960004294 lercanidipine Drugs 0.000 description 1
- 229940095570 lescol Drugs 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- 229960002394 lisinopril Drugs 0.000 description 1
- RLAWWYSOJDYHDC-BZSNNMDCSA-N lisinopril Chemical compound C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 RLAWWYSOJDYHDC-BZSNNMDCSA-N 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 231100000149 liver necrosis Toxicity 0.000 description 1
- 239000002171 loop diuretic Substances 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
- 210000004072 lung Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- JHMNJUQVLPODJN-UHFFFAOYSA-M magnesium;1-fluoro-4-methanidylbenzene;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C1=CC=C(F)C=C1 JHMNJUQVLPODJN-UHFFFAOYSA-M 0.000 description 1
- SCEZYJKGDJPHQO-UHFFFAOYSA-M magnesium;methanidylbenzene;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C1=CC=CC=C1 SCEZYJKGDJPHQO-UHFFFAOYSA-M 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000036244 malformation Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 description 1
- 210000003584 mesangial cell Anatomy 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229960003739 methyclothiazide Drugs 0.000 description 1
- ULSSGHADTSRELG-UHFFFAOYSA-N methyl 2-(3-bromophenyl)acetate Chemical compound COC(=O)CC1=CC=CC(Br)=C1 ULSSGHADTSRELG-UHFFFAOYSA-N 0.000 description 1
- HTBBVKFFDDQVER-UHFFFAOYSA-N methyl 2-(3-chlorophenyl)acetate Chemical compound COC(=O)CC1=CC=CC(Cl)=C1 HTBBVKFFDDQVER-UHFFFAOYSA-N 0.000 description 1
- PRRBXZOTQDDOFR-UHFFFAOYSA-N methyl 4-[3-[2-(3-hydroxy-4-phenylbutyl)-5-oxopyrrolidin-1-yl]propyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CCCN1C(=O)CCC1CCC(O)CC1=CC=CC=C1 PRRBXZOTQDDOFR-UHFFFAOYSA-N 0.000 description 1
- VLKOZGZVCUGVFQ-UHFFFAOYSA-N methyl 4-[3-[2-[3-[tert-butyl(dimethyl)silyl]oxy-4-(3-chlorophenyl)butyl]-5-oxopyrrolidin-1-yl]propyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CCCN1C(=O)CCC1CCC(O[Si](C)(C)C(C)(C)C)CC1=CC=CC(Cl)=C1 VLKOZGZVCUGVFQ-UHFFFAOYSA-N 0.000 description 1
- NEYMKEOVGOGHGL-UHFFFAOYSA-N methyl 4-[3-[2-[3-[tert-butyl(dimethyl)silyl]oxy-4-(3-phenoxyphenyl)butyl]-5-oxopyrrolidin-1-yl]propyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CCCN1C(=O)CCC1CCC(O[Si](C)(C)C(C)(C)C)CC1=CC=CC(OC=2C=CC=CC=2)=C1 NEYMKEOVGOGHGL-UHFFFAOYSA-N 0.000 description 1
- PTWCVVCCVILERF-UHFFFAOYSA-N methyl 4-[3-[2-[3-[tert-butyl(dimethyl)silyl]oxy-4-(3-phenylphenyl)butyl]-5-oxopyrrolidin-1-yl]propyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CCCN1C(=O)CCC1CCC(O[Si](C)(C)C(C)(C)C)CC1=CC=CC(C=2C=CC=CC=2)=C1 PTWCVVCCVILERF-UHFFFAOYSA-N 0.000 description 1
- YTINDJCONYNLHA-UHFFFAOYSA-N methyl 4-[3-[2-[4-(4-fluorophenyl)-3-hydroxybutyl]-5-oxopyrrolidin-1-yl]propyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CCCN1C(=O)CCC1CCC(O)CC1=CC=C(F)C=C1 YTINDJCONYNLHA-UHFFFAOYSA-N 0.000 description 1
- DYUWQWMXZHDZOR-UHFFFAOYSA-N methyl 4-iodobenzoate Chemical compound COC(=O)C1=CC=C(I)C=C1 DYUWQWMXZHDZOR-UHFFFAOYSA-N 0.000 description 1
- ZIXWMVGUJNUFSF-OAHLLOKOSA-N methyl 5-[3-[(2r)-2-[[tert-butyl(dimethyl)silyl]oxymethyl]-5-oxopyrrolidin-1-yl]prop-1-ynyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1C#CCN1C(=O)CC[C@@H]1CO[Si](C)(C)C(C)(C)C ZIXWMVGUJNUFSF-OAHLLOKOSA-N 0.000 description 1
- AWJFNOGSZPVOFP-SFHVURJKSA-N methyl 5-[3-[(5r)-2-oxo-5-[3-oxo-4-[3-(trifluoromethyl)phenyl]but-1-enyl]pyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)CC[C@@H]1C=CC(=O)CC1=CC=CC(C(F)(F)F)=C1 AWJFNOGSZPVOFP-SFHVURJKSA-N 0.000 description 1
- QLWUHAQCKDHUNL-UHFFFAOYSA-N methyl 5-bromothiophene-2-carboxylate Chemical compound COC(=O)C1=CC=C(Br)S1 QLWUHAQCKDHUNL-UHFFFAOYSA-N 0.000 description 1
- 125000006431 methyl cyclopropyl group Chemical group 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
- AQCHWTWZEMGIFD-UHFFFAOYSA-N metolazone Chemical compound CC1NC2=CC(Cl)=C(S(N)(=O)=O)C=C2C(=O)N1C1=CC=CC=C1C AQCHWTWZEMGIFD-UHFFFAOYSA-N 0.000 description 1
- 229960002817 metolazone Drugs 0.000 description 1
- 229940099246 mevacor Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000003547 miosis Effects 0.000 description 1
- 239000003604 miotic agent Substances 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- UHAAFJWANJYDIS-UHFFFAOYSA-N n,n'-diethylmethanediimine Chemical compound CCN=C=NCC UHAAFJWANJYDIS-UHFFFAOYSA-N 0.000 description 1
- KRKPYFLIYNGWTE-UHFFFAOYSA-N n,o-dimethylhydroxylamine Chemical compound CNOC KRKPYFLIYNGWTE-UHFFFAOYSA-N 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 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
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000011587 new zealand white rabbit Methods 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
- 229940124643 non-selective drug Drugs 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 229940125702 ophthalmic agent Drugs 0.000 description 1
- 239000002997 ophthalmic solution Substances 0.000 description 1
- 229940054534 ophthalmic solution Drugs 0.000 description 1
- 210000001328 optic nerve Anatomy 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 150000002924 oxiranes Chemical class 0.000 description 1
- 238000012858 packaging process Methods 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- QJPQVXSHYBGQGM-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 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 1
- 239000000123 paper Substances 0.000 description 1
- 239000000734 parasympathomimetic agent Substances 0.000 description 1
- 229940127242 parasympathomimetic drug Drugs 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- KQXKVJAGOJTNJS-HNNXBMFYSA-N penbutolol Chemical compound CC(C)(C)NC[C@H](O)COC1=CC=CC=C1C1CCCC1 KQXKVJAGOJTNJS-HNNXBMFYSA-N 0.000 description 1
- 229960002035 penbutolol Drugs 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 150000004686 pentahydrates Chemical class 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 108010091212 pepstatin Proteins 0.000 description 1
- 230000009984 peri-natal effect Effects 0.000 description 1
- 229960002582 perindopril Drugs 0.000 description 1
- IPVQLZZIHOAWMC-QXKUPLGCSA-N perindopril Chemical compound C1CCC[C@H]2C[C@@H](C(O)=O)N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@H]21 IPVQLZZIHOAWMC-QXKUPLGCSA-N 0.000 description 1
- 230000008855 peristalsis Effects 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 229960003424 phenylacetic acid Drugs 0.000 description 1
- 239000003279 phenylacetic acid Substances 0.000 description 1
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 1
- 229960001802 phenylephrine Drugs 0.000 description 1
- 229940067107 phenylethyl alcohol Drugs 0.000 description 1
- 229940096826 phenylmercuric acetate Drugs 0.000 description 1
- PDTFCHSETJBPTR-UHFFFAOYSA-N phenylmercuric nitrate Chemical compound [O-][N+](=O)O[Hg]C1=CC=CC=C1 PDTFCHSETJBPTR-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
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- ZPHBZEQOLSRPAK-XLCYBJAPSA-N phosphoramidon Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)P(O)(=O)O[C@@H]1O[C@@H](C)[C@H](O)[C@@H](O)[C@H]1O ZPHBZEQOLSRPAK-XLCYBJAPSA-N 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 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
- 229920001592 potato starch Polymers 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229940089484 pravachol Drugs 0.000 description 1
- 229960001289 prazosin 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
- WFXFYZULCQKPIP-UHFFFAOYSA-N prazosin hydrochloride Chemical compound [H+].[Cl-].N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 WFXFYZULCQKPIP-UHFFFAOYSA-N 0.000 description 1
- 229960002386 prazosin hydrochloride Drugs 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 239000013615 primer Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 1
- UOCCVDMCNJYVIW-UHFFFAOYSA-N prop-2-yne-1-sulfonic acid Chemical class OS(=O)(=O)CC#C UOCCVDMCNJYVIW-UHFFFAOYSA-N 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000002633 protecting effect Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000004088 pulmonary circulation Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 230000001179 pupillary effect Effects 0.000 description 1
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 229960001455 quinapril Drugs 0.000 description 1
- JSDRRTOADPPCHY-HSQYWUDLSA-N quinapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC=CC=C2C1)C(O)=O)CC1=CC=CC=C1 JSDRRTOADPPCHY-HSQYWUDLSA-N 0.000 description 1
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000002285 radioactive effect Effects 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
- 230000009257 reactivity Effects 0.000 description 1
- 230000004648 relaxation of smooth muscle Effects 0.000 description 1
- 230000008085 renal dysfunction Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 210000003752 saphenous vein Anatomy 0.000 description 1
- 238000013391 scatchard analysis Methods 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 206010040560 shock Diseases 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 230000007958 sleep Effects 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 229940001474 sodium thiosulfate Drugs 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 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
- 230000009870 specific binding 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
- 238000012289 standard assay Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 238000011916 stereoselective reduction Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 150000003871 sulfonates Chemical group 0.000 description 1
- 150000003458 sulfonic acid derivatives Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 229940127230 sympathomimetic drug Drugs 0.000 description 1
- 230000008337 systemic blood flow Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229960005187 telmisartan Drugs 0.000 description 1
- QHBINVDUJXFESZ-DEOSSOPVSA-N tert-butyl 5-[3-[(2r)-2-(4-naphthalen-2-yl-3-oxobut-1-enyl)-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC(C)(C)C)=CC=C1CCCN1C(=O)CC[C@@H]1C=CC(=O)CC1=CC=C(C=CC=C2)C2=C1 QHBINVDUJXFESZ-DEOSSOPVSA-N 0.000 description 1
- SZHIVWSUCCSBNX-GFCCVEGCSA-N tert-butyl 5-[3-[(2r)-2-formyl-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC(C)(C)C)=CC=C1CCCN1C(=O)CC[C@@H]1C=O SZHIVWSUCCSBNX-GFCCVEGCSA-N 0.000 description 1
- VSWLXYAZJZQIKA-UHFFFAOYSA-N tetrachloromethane;triphenylphosphane Chemical compound ClC(Cl)(Cl)Cl.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 VSWLXYAZJZQIKA-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000003451 thiazide diuretic agent Substances 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 229960004605 timolol Drugs 0.000 description 1
- 238000003354 tissue distribution assay Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 229960005461 torasemide Drugs 0.000 description 1
- 210000001585 trabecular meshwork Anatomy 0.000 description 1
- 229960002051 trandolapril Drugs 0.000 description 1
- 208000014903 transposition of the great arteries Diseases 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- CMSYDJVRTHCWFP-UHFFFAOYSA-N triphenylphosphane;hydrobromide Chemical compound Br.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 CMSYDJVRTHCWFP-UHFFFAOYSA-N 0.000 description 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 208000009852 uremia Diseases 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- ACWBQPMHZXGDFX-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=NN1 ACWBQPMHZXGDFX-QFIPXVFZSA-N 0.000 description 1
- 229960004699 valsartan Drugs 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
- 229940072168 zocor Drugs 0.000 description 1
- IAIDUHCBNLFXEF-MNEFBYGVSA-N zofenopril Chemical compound C([C@@H](C)C(=O)N1[C@@H](C[C@@H](C1)SC=1C=CC=CC=1)C(O)=O)SC(=O)C1=CC=CC=C1 IAIDUHCBNLFXEF-MNEFBYGVSA-N 0.000 description 1
- 229960002769 zofenopril Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4025—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Ophthalmology & Optometry (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36571102P | 2002-03-18 | 2002-03-18 | |
| PCT/IB2003/000844 WO2003077910A1 (en) | 2002-03-18 | 2003-03-06 | Methods of treatment with selective ep4 receptor agonists |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2005531516A true JP2005531516A (ja) | 2005-10-20 |
| JP2005531516A5 JP2005531516A5 (https=) | 2006-03-23 |
Family
ID=28042041
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2003575963A Withdrawn JP2005531516A (ja) | 2002-03-18 | 2003-03-06 | 選択的ｅｐ４受容体アゴニストによる治療方法 |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US7414071B2 (https=) |
| EP (1) | EP1487437B1 (https=) |
| JP (1) | JP2005531516A (https=) |
| AT (1) | ATE336247T1 (https=) |
| AU (1) | AU2003207900A1 (https=) |
| BR (1) | BR0308738A (https=) |
| CA (1) | CA2478653A1 (https=) |
| DE (1) | DE60307607T2 (https=) |
| ES (1) | ES2268327T3 (https=) |
| MX (1) | MXPA04005555A (https=) |
| TW (1) | TW200304816A (https=) |
| WO (1) | WO2003077910A1 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005530796A (ja) * | 2002-05-14 | 2005-10-13 | アラーガン、インコーポレイテッド | 眼圧降下剤としての８−アザプロスタグランジン類似体 |
Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE281432T1 (de) | 1999-03-05 | 2004-11-15 | Univ Duke | C-16 ungesätigte fp-selektive prostaglandin analoge |
| US20020013294A1 (en) | 2000-03-31 | 2002-01-31 | Delong Mitchell Anthony | Cosmetic and pharmaceutical compositions and methods using 2-decarboxy-2-phosphinico derivatives |
| US20020172693A1 (en) | 2000-03-31 | 2002-11-21 | Delong Michell Anthony | Compositions and methods for treating hair loss using non-naturally occurring prostaglandins |
| AU2011202937B2 (en) * | 2002-05-14 | 2012-06-07 | Allergan, Inc. | 8-azaprostaglandin analogs as agents for lowering intraocular pressure |
| GB0219143D0 (en) * | 2002-08-16 | 2002-09-25 | Univ Leicester | Modified tailed oligonucleotides |
| US7256211B1 (en) | 2003-01-21 | 2007-08-14 | Ono Pharmaceutical Co., Ltd. | 8-azaprostaglandin derivatives and medical use thereof |
| US6734206B1 (en) * | 2003-06-02 | 2004-05-11 | Allergan, Inc. | 3-oxa-8-azaprostaglandin analogs as agents for lowering intraocular pressure |
| JP2007512347A (ja) * | 2003-11-26 | 2007-05-17 | デューク・ユニバーシティー | 緑内障を予防するかまたは治療する方法 |
| DE602005025755D1 (de) | 2004-06-04 | 2011-02-17 | Teva Pharma | Irbesartan enthaltende pharmazeutische zusammensetzung |
| AU2005252171A1 (en) * | 2004-06-04 | 2005-12-22 | Allergan, Inc. | Piperidinyl prostaglandin analogs as ocular hypotensive agents |
| JP2008518013A (ja) * | 2004-10-26 | 2008-05-29 | アラーガン、インコーポレイテッド | プロスタグランジンｅｐ４アゴニストによる処置方法およびデリバリー方法 |
| WO2006052893A2 (en) | 2004-11-08 | 2006-05-18 | Allergan, Inc. | Substituted pyrrolidone compounds as ep4 agonists |
| ATE515263T1 (de) * | 2005-05-06 | 2011-07-15 | Allergan Inc | Substituierte beta-lactame und deren verwendung in der medizin |
| US7674786B2 (en) | 2005-05-06 | 2010-03-09 | Allergan, Inc. | Therapeutic β-lactams |
| WO2006121822A1 (en) * | 2005-05-06 | 2006-11-16 | Allergan, Inc. | USE OF β-LACTAMS FOR THE TREATMENTOF IBD AND GLAUCOMA |
| US7893107B2 (en) | 2005-11-30 | 2011-02-22 | Allergan, Inc. | Therapeutic methods using prostaglandin EP4 agonist components |
| UY30121A1 (es) | 2006-02-03 | 2007-08-31 | Glaxo Group Ltd | Nuevos compuestos |
| US20070232660A1 (en) * | 2006-04-04 | 2007-10-04 | Allergan, Inc. | Therapeutic and delivery methods of prostaglandin ep4 agonists |
| EP2269611B1 (en) | 2006-11-16 | 2016-03-23 | Gemmus Pharma Inc. | EP2 and EP4 agonists as agents for the treatment of influenza A viral infection |
| AU2007331471C1 (en) | 2006-12-15 | 2013-07-25 | Glaxo Group Limited | Benzamide derivatives as EP4 receptor agonists |
| GB0721611D0 (en) | 2007-11-02 | 2007-12-12 | Glaxo Group Ltd | Novel compounds |
| US8063033B2 (en) * | 2008-01-18 | 2011-11-22 | Allergan, Inc. | Therapeutic beta-lactams |
| US8202855B2 (en) | 2008-03-04 | 2012-06-19 | Allergan, Inc | Substituted beta-lactams |
| EP2149551A1 (de) | 2008-07-30 | 2010-02-03 | Bayer Schering Pharma AG | N-(Indol-3-ylalkyl)-(hetero)arylamidderivate als Modulatoren des EP2-Rezeptors |
| EP2149552A1 (de) | 2008-07-30 | 2010-02-03 | Bayer Schering Pharma AG | 5,6 substituierte Benzamid-Derivate als Modulatoren des EP2-Rezeptors |
| EP2149554A1 (de) | 2008-07-30 | 2010-02-03 | Bayer Schering Pharma Aktiengesellschaft | Indolylamide als Modulatoren des EP2-Rezeptors |
| US20110293549A1 (en) | 2009-02-03 | 2011-12-01 | Athena Cosmetics, Inc. | Composition, method and kit for enhancing hair |
| WO2010116270A1 (en) | 2009-04-10 | 2010-10-14 | Pfizer Inc. | Ep2/4 agonists |
| JO3296B1 (ar) * | 2012-06-29 | 2018-09-16 | Lilly Co Eli | مركبات فينوكسي إيثيل بيبريدين |
| CN107802623B (zh) | 2012-07-19 | 2020-10-30 | 开曼化学股份有限公司 | 用于ep4介导的骨相关疾病和病症的二氟内酰胺组合物 |
| WO2014144610A1 (en) | 2013-03-15 | 2014-09-18 | Cayman Chemical Company, Inc. | Lactam compounds as ep4 receptor-selective agonists for use in the treatment of ep4-mediated diseases and conditions |
| EP3235817B1 (en) | 2013-03-15 | 2018-12-12 | Cayman Chemical Company, Incorporated | Lactam compounds as ep4 receptor-selective agonists for use in the treatment of ep4-mediated diseases and conditions |
| JP6368351B2 (ja) | 2013-03-15 | 2018-08-01 | ケイマン ケミカル カンパニー， インコーポレーテッド | ジフルオロラクタムアナログを合成する方法 |
| JP2016527006A (ja) | 2013-07-19 | 2016-09-08 | ケイマン ケミカル カンパニー， インコーポレーテッド | 骨成長を促進するための方法、システム、及び組成物 |
| ME02896B (me) | 2013-12-17 | 2018-04-20 | Lilly Co Eli | Fenoksietilni derivati prstenastog amina i njihova aktivnost kao modulatora receptora ep4 |
| US9540357B1 (en) * | 2014-07-31 | 2017-01-10 | Allergan, Inc. | 15-aryl prostaglandins as EP4 agonists, and methods of use thereof |
| CN114259992B (zh) * | 2021-12-23 | 2023-06-27 | 复旦大学 | 正离子超分子有机框架固体材料在吸附生物毒素中的应用 |
| GB202211232D0 (en) | 2022-08-02 | 2022-09-14 | Heptares Therapeutics Ltd | Prostaglandin EP4 receptor agonist compounds |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4113873A (en) * | 1975-04-26 | 1978-09-12 | Tanabe Seiyaku Co. Ltd. | 8-azaprostanoic acid derivatives |
| DE2528664A1 (de) * | 1975-06-27 | 1977-01-13 | Hoechst Ag | Pyrrolidone und verfahren zu ihrer herstellung |
| US4177346A (en) * | 1976-08-06 | 1979-12-04 | Pfizer Inc. | 1,5-Disubstituted-2-pyrrolidones |
| CA1077948A (en) * | 1976-08-06 | 1980-05-20 | Albin J. Nelson | 1,-5 disubstituted-2-pyrrolidones and processes for their production |
| WO2000038667A2 (en) * | 1998-12-24 | 2000-07-06 | Alcon Laboratories, Inc. | Prostaglandin e agonists for treatment of glaucoma |
| WO2002024647A1 (en) * | 2000-09-21 | 2002-03-28 | Ono Pharmaceutical Co., Ltd. | Ep4 receptor agonists containing 8-azaprostaglandin derivatives as the active ingredient |
| PT1339678E (pt) * | 2000-11-27 | 2007-11-30 | Pfizer Prod Inc | Agonistas selectivos do receptor ep4 no tratamento de osteoporose |
| US20040254230A1 (en) * | 2001-12-03 | 2004-12-16 | Ogidigben Miller J. | Method for treating ocular hypertension |
-
2003
- 2003-03-06 CA CA002478653A patent/CA2478653A1/en not_active Abandoned
- 2003-03-06 WO PCT/IB2003/000844 patent/WO2003077910A1/en not_active Ceased
- 2003-03-06 JP JP2003575963A patent/JP2005531516A/ja not_active Withdrawn
- 2003-03-06 MX MXPA04005555A patent/MXPA04005555A/es unknown
- 2003-03-06 DE DE60307607T patent/DE60307607T2/de not_active Expired - Fee Related
- 2003-03-06 BR BR0308738A patent/BR0308738A/pt not_active IP Right Cessation
- 2003-03-06 AU AU2003207900A patent/AU2003207900A1/en not_active Abandoned
- 2003-03-06 AT AT03704902T patent/ATE336247T1/de not_active IP Right Cessation
- 2003-03-06 ES ES03704902T patent/ES2268327T3/es not_active Expired - Lifetime
- 2003-03-06 EP EP03704902A patent/EP1487437B1/en not_active Expired - Lifetime
- 2003-03-11 US US10/386,307 patent/US7414071B2/en not_active Expired - Fee Related
- 2003-03-17 TW TW092105829A patent/TW200304816A/zh unknown
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005530796A (ja) * | 2002-05-14 | 2005-10-13 | アラーガン、インコーポレイテッド | 眼圧降下剤としての８−アザプロスタグランジン類似体 |
| JP2011116768A (ja) * | 2002-05-14 | 2011-06-16 | Allergan Inc | 眼圧降下剤としての８−アザプロスタグランジン類似体 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2003077910A1 (en) | 2003-09-25 |
| US7414071B2 (en) | 2008-08-19 |
| BR0308738A (https=) | 2005-01-11 |
| EP1487437B1 (en) | 2006-08-16 |
| ATE336247T1 (de) | 2006-09-15 |
| ES2268327T3 (es) | 2007-03-16 |
| DE60307607D1 (de) | 2006-09-28 |
| CA2478653A1 (en) | 2003-09-25 |
| EP1487437A1 (en) | 2004-12-22 |
| MXPA04005555A (es) | 2005-05-16 |
| TW200304816A (en) | 2003-10-16 |
| DE60307607T2 (de) | 2007-08-09 |
| US20030207925A1 (en) | 2003-11-06 |
| AU2003207900A1 (en) | 2003-09-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2005531516A (ja) | 選択的ｅｐ４受容体アゴニストによる治療方法 | |
| JP3347330B2 (ja) | １，３―ジヘテロ環式メタロプロテアーゼ阻害剤類 | |
| JP4854511B2 (ja) | 糖尿病治療剤 | |
| CN108164513B (zh) | 取代的氧代吡啶衍生物及其在治疗心血管病症方面的用途 | |
| CA2649022C (en) | Cocrystal of c-glycoside derivative and l-proline | |
| JP3984164B2 (ja) | 骨粗鬆症治療用ｅｐ４受容体選択的アゴニスト | |
| CN101175724B (zh) | 吡咯烷衍生物或其盐 | |
| CN100430052C (zh) | 组织蛋白酶半胱氨酸蛋白酶抑制剂 | |
| CN1974596B (zh) | 丙型肝炎病毒抑制剂 | |
| JP3347331B2 (ja) | 複素環式メタロプロテアーゼ阻害剤 | |
| US8058305B2 (en) | Pyrrolidine derivatives as prostaglandin modulators | |
| US6861441B1 (en) | Use of EP4 receptor ligands in the treatment of neuropathic pain and colon cancer | |
| US20240158372A1 (en) | Bisamide sarcomere activating compounds and uses thereof | |
| TW542822B (en) | Benzamidine derivatives | |
| CN113292539A (zh) | 取代的氧代吡啶衍生物 | |
| KR100400507B1 (ko) | 치환 피롤리딘 히드록사메이트 메탈로프로테아제 억제제 | |
| JP2000514827A (ja) | ある種のプロスタグランジンアゴニストによる骨質量の減少の防止および回復 | |
| KR20040095311A (ko) | 프로스타글란딘 ｆ 수용체의 모듈레이터로서의 티아졸리딘카르복사미드 유도체 | |
| CZ62499A3 (cs) | Víceúčelové inhibitory metaloproteásy | |
| CA2256438C (en) | Aromatic amidine derivatives useful as selective thrombin inhibitors | |
| WO2006080323A1 (ja) | ヘテロ６員環化合物及びその用途 | |
| MXPA04009036A (es) | Uso de agonistas del receptor ep4 selectivos para el tratamiento de la insuficiencia hepatica, perdida de permeabilidad del ductus arterioso, glaucoma o hipertension ocular. | |
| EP1619185A1 (en) | 4,4-difluoro-1,2,3,4-tetrahydro-5h-1-benzazepine derivative or salt thereof | |
| JP5254007B2 (ja) | 置換β−ラクタム及び医薬におけるその使用 | |
| WO1999043318A1 (en) | Lp(a)-LOWERING AGENTS AND APOPROTEIN (a) PRODUCTION INHIBTORS |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20060206 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20060206 |
|
| RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7422 Effective date: 20071009 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20071009 |
|
| A761 | Written withdrawal of application |
Free format text: JAPANESE INTERMEDIATE CODE: A761 Effective date: 20090106 |