OA12080A - Sodium-hydrogen exchanger type 1 inhibitor crystals. - Google Patents

Sodium-hydrogen exchanger type 1 inhibitor crystals. Download PDF

Info

Publication number: OA12080A
Authority: OA; OAPI
Prior art keywords: recited; daim; tissue; rel; crystal
Prior art date: 1999-10-29

Application number

OA1200200128A

Other languages

English (en)

Inventor

Lyle Robinson Brostrom

Terrence Joseph Connolly

Jane Li Zheng

Susan Lee Orrill

Bharat Kiritkumar Shah

Original Assignee

Pfizer Prod Inc

Priority date (The priority date 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 date listed.)

1999-10-29

Filing date

2000-10-09

Publication date

2003-08-25

2000-10-09 Application filed by Pfizer Prod Inc filed Critical Pfizer Prod Inc

2003-08-25 Publication of OA12080A publication Critical patent/OA12080A/en

Links

239000013078 crystal Substances 0.000 title claims abstract description 101
239000003112 inhibitor Substances 0.000 title abstract description 14
102000052126 Sodium-Hydrogen Exchangers Human genes 0.000 title description 3
108091006672 Sodium–hydrogen antiporter Proteins 0.000 title description 3
238000000034 method Methods 0.000 claims abstract description 51
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 23
230000000451 tissue damage Effects 0.000 claims abstract description 21
231100000827 tissue damage Toxicity 0.000 claims abstract description 21
208000028867 ischemia Diseases 0.000 claims abstract description 13
150000001875 compounds Chemical class 0.000 claims description 53
239000000203 mixture Substances 0.000 claims description 33
210000001519 tissue Anatomy 0.000 claims description 31
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 26
239000003085 diluting agent Substances 0.000 claims description 17
238000001356 surgical procedure Methods 0.000 claims description 16
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 14
238000007675 cardiac surgery Methods 0.000 claims description 13
239000003937 drug carrier Substances 0.000 claims description 13
230000006378 damage Effects 0.000 claims description 12
GDXBRVCQGGKXJY-UHFFFAOYSA-N 5-cyclopropyl-n-(diaminomethylidene)-1-quinolin-5-ylpyrazole-4-carboxamide Chemical compound NC(N)=NC(=O)C=1C=NN(C=2C3=CC=CN=C3C=CC=2)C=1C1CC1 GDXBRVCQGGKXJY-UHFFFAOYSA-N 0.000 claims description 11
239000003981 vehicle Substances 0.000 claims description 11
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 10
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 8
238000002441 X-ray diffraction Methods 0.000 claims description 8
230000001603 reducing effect Effects 0.000 claims description 8
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 7
SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 7
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
230000000747 cardiac effect Effects 0.000 claims description 6
238000009499 grossing Methods 0.000 claims description 6
238000002054 transplantation Methods 0.000 claims description 6
208000027418 Wounds and injury Diseases 0.000 claims description 5
208000014674 injury Diseases 0.000 claims description 5
229940098779 methanesulfonic acid Drugs 0.000 claims description 4
210000004556 brain Anatomy 0.000 claims description 3
210000001525 retina Anatomy 0.000 claims description 3
238000001816 cooling Methods 0.000 claims description 2
230000000968 intestinal effect Effects 0.000 claims description 2
210000000952 spleen Anatomy 0.000 claims description 2
SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 24
206010021143 Hypoxia Diseases 0.000 claims 2
230000007954 hypoxia Effects 0.000 claims 2
210000003205 muscle Anatomy 0.000 claims 2
241000711981 Sais Species 0.000 claims 1
210000005013 brain tissue Anatomy 0.000 claims 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
229960004592 isopropanol Drugs 0.000 claims 1
210000005036 nerve Anatomy 0.000 claims 1
210000005084 renal tissue Anatomy 0.000 claims 1
102100030980 Sodium/hydrogen exchanger 1 Human genes 0.000 abstract description 7
108010093115 growth factor-activatable Na-H exchanger NHE-1 Proteins 0.000 abstract description 7
241000124008 Mammalia Species 0.000 description 31
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 20
FUQOTYRCMBZFOL-UHFFFAOYSA-N 5-chloro-1H-indole-2-carboxylic acid Chemical compound ClC1=CC=C2NC(C(=O)O)=CC2=C1 FUQOTYRCMBZFOL-UHFFFAOYSA-N 0.000 description 18
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
239000000243 solution Substances 0.000 description 18
239000003795 chemical substances by application Substances 0.000 description 16
201000010099 disease Diseases 0.000 description 15
230000004224 protection Effects 0.000 description 14
239000007787 solid Substances 0.000 description 14
239000002904 solvent Substances 0.000 description 14
238000009472 formulation Methods 0.000 description 13
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
239000000047 product Substances 0.000 description 12
208000010125 myocardial infarction Diseases 0.000 description 11
239000002253 acid Substances 0.000 description 10
235000019439 ethyl acetate Nutrition 0.000 description 10
229960004198 guanidine Drugs 0.000 description 10
210000000056 organ Anatomy 0.000 description 10
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
239000003288 aldose reductase inhibitor Substances 0.000 description 9
-1 captoprîl Chemical compound 0.000 description 9
239000002552 dosage form Substances 0.000 description 9
239000003826 tablet Substances 0.000 description 9
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
ROJNYKZWTOHRNU-UHFFFAOYSA-N 2-chloro-4,5-difluoro-n-[[2-methoxy-5-(methylcarbamoylamino)phenyl]carbamoyl]benzamide Chemical compound CNC(=O)NC1=CC=C(OC)C(NC(=O)NC(=O)C=2C(=CC(F)=C(F)C=2)Cl)=C1 ROJNYKZWTOHRNU-UHFFFAOYSA-N 0.000 description 7
229940118148 Aldose reductase inhibitor Drugs 0.000 description 7
238000006243 chemical reaction Methods 0.000 description 7
230000002107 myocardial effect Effects 0.000 description 7
230000001225 therapeutic effect Effects 0.000 description 7
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
239000007864 aqueous solution Substances 0.000 description 6
239000003153 chemical reaction reagent Substances 0.000 description 6
238000000634 powder X-ray diffraction Methods 0.000 description 6
239000011734 sodium Substances 0.000 description 6
239000000725 suspension Substances 0.000 description 6
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 5
229920002472 Starch Polymers 0.000 description 5
238000004458 analytical method Methods 0.000 description 5
206010003119 arrhythmia Diseases 0.000 description 5
230000006793 arrhythmia Effects 0.000 description 5
238000003556 assay Methods 0.000 description 5
208000029078 coronary artery disease Diseases 0.000 description 5
239000007822 coupling agent Substances 0.000 description 5
208000035475 disorder Diseases 0.000 description 5
238000001914 filtration Methods 0.000 description 5
230000008569 process Effects 0.000 description 5
239000002002 slurry Substances 0.000 description 5
229910052708 sodium Inorganic materials 0.000 description 5
239000008107 starch Substances 0.000 description 5
235000019698 starch Nutrition 0.000 description 5
206010002388 Angina unstable Diseases 0.000 description 4
102000007390 Glycogen Phosphorylase Human genes 0.000 description 4
108010046163 Glycogen Phosphorylase Proteins 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
206010061216 Infarction Diseases 0.000 description 4
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
208000007814 Unstable Angina Diseases 0.000 description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
239000002327 cardiovascular agent Substances 0.000 description 4
229940125692 cardiovascular agent Drugs 0.000 description 4
210000004027 cell Anatomy 0.000 description 4
230000001684 chronic effect Effects 0.000 description 4
230000000694 effects Effects 0.000 description 4
229940093499 ethyl acetate Drugs 0.000 description 4
239000008187 granular material Substances 0.000 description 4
230000001939 inductive effect Effects 0.000 description 4
239000012442 inert solvent Substances 0.000 description 4
230000007574 infarction Effects 0.000 description 4
239000000543 intermediate Substances 0.000 description 4
201000004332 intermediate coronary syndrome Diseases 0.000 description 4
238000001990 intravenous administration Methods 0.000 description 4
238000002844 melting Methods 0.000 description 4
230000008018 melting Effects 0.000 description 4
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
239000000546 pharmaceutical excipient Substances 0.000 description 4
239000000843 powder Substances 0.000 description 4
AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 4
238000010992 reflux Methods 0.000 description 4
235000011121 sodium hydroxide Nutrition 0.000 description 4
239000007858 starting material Substances 0.000 description 4
239000000126 substance Substances 0.000 description 4
239000000829 suppository Substances 0.000 description 4
238000007631 vascular surgery Methods 0.000 description 4
206010002383 Angina Pectoris Diseases 0.000 description 3
206010007572 Cardiac hypertrophy Diseases 0.000 description 3
208000006029 Cardiomegaly Diseases 0.000 description 3
VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 description 3
206010019280 Heart failures Diseases 0.000 description 3
241000282412 Homo Species 0.000 description 3
206010020772 Hypertension Diseases 0.000 description 3
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
230000005961 cardioprotection Effects 0.000 description 3
238000007887 coronary angioplasty Methods 0.000 description 3
210000004351 coronary vessel Anatomy 0.000 description 3
230000004064 dysfunction Effects 0.000 description 3
239000000796 flavoring agent Substances 0.000 description 3
239000007903 gelatin capsule Substances 0.000 description 3
238000010438 heat treatment Methods 0.000 description 3
206010020718 hyperplasia Diseases 0.000 description 3
239000010410 layer Substances 0.000 description 3
238000000386 microscopy Methods 0.000 description 3
238000002156 mixing Methods 0.000 description 3
208000031225 myocardial ischemia Diseases 0.000 description 3
239000001301 oxygen Substances 0.000 description 3
229910052760 oxygen Inorganic materials 0.000 description 3
239000001267 polyvinylpyrrolidone Substances 0.000 description 3
229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
208000005069 pulmonary fibrosis Diseases 0.000 description 3
230000010410 reperfusion Effects 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
230000002537 thrombolytic effect Effects 0.000 description 3
NXWGWUVGUSFQJC-GFCCVEGCSA-N (2r)-1-[(2-methyl-1h-indol-4-yl)oxy]-3-(propan-2-ylamino)propan-2-ol Chemical compound CC(C)NC[C@@H](O)COC1=CC=CC2=C1C=C(C)N2 NXWGWUVGUSFQJC-GFCCVEGCSA-N 0.000 description 2
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 2
PVHUJELLJLJGLN-INIZCTEOSA-N (S)-nitrendipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC([N+]([O-])=O)=C1 PVHUJELLJLJGLN-INIZCTEOSA-N 0.000 description 2
UUOJIACWOAYWEZ-UHFFFAOYSA-N 1-(tert-butylamino)-3-[(2-methyl-1H-indol-4-yl)oxy]propan-2-yl benzoate Chemical compound C1=CC=C2NC(C)=CC2=C1OCC(CNC(C)(C)C)OC(=O)C1=CC=CC=C1 UUOJIACWOAYWEZ-UHFFFAOYSA-N 0.000 description 2
PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 2
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 2
SGUAFYQXFOLMHL-UHFFFAOYSA-N 2-hydroxy-5-{1-hydroxy-2-[(4-phenylbutan-2-yl)amino]ethyl}benzamide Chemical compound C=1C=C(O)C(C(N)=O)=CC=1C(O)CNC(C)CCC1=CC=CC=C1 SGUAFYQXFOLMHL-UHFFFAOYSA-N 0.000 description 2
BCSVCWVQNOXFGL-UHFFFAOYSA-N 3,4-dihydro-4-oxo-3-((5-trifluoromethyl-2-benzothiazolyl)methyl)-1-phthalazine acetic acid Chemical group O=C1C2=CC=CC=C2C(CC(=O)O)=NN1CC1=NC2=CC(C(F)(F)F)=CC=C2S1 BCSVCWVQNOXFGL-UHFFFAOYSA-N 0.000 description 2
208000004476 Acute Coronary Syndrome Diseases 0.000 description 2
BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
239000005711 Benzoic acid Substances 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
206010007559 Cardiac failure congestive Diseases 0.000 description 2
208000024172 Cardiovascular disease Diseases 0.000 description 2
PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 2
GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 2
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
208000002249 Diabetes Complications Diseases 0.000 description 2
206010012655 Diabetic complications Diseases 0.000 description 2
LTMHDMANZUZIPE-AMTYYWEZSA-N Digoxin Natural products O([C@H]1[C@H](C)O[C@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@](C)([C@H](O)C4)[C@H](C4=CC(=O)OC4)CC5)CC3)CC2)C[C@@H]1O)[C@H]1O[C@H](C)[C@@H](O[C@H]2O[C@@H](C)[C@H](O)[C@@H](O)C2)[C@@H](O)C1 LTMHDMANZUZIPE-AMTYYWEZSA-N 0.000 description 2
GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 2
108010061435 Enalapril Proteins 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
206010020880 Hypertrophy Diseases 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
206010028851 Necrosis Diseases 0.000 description 2
SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 2
UJEWTUDSLQGTOA-UHFFFAOYSA-N Piretanide Chemical compound C=1C=CC=CC=1OC=1C(S(=O)(=O)N)=CC(C(O)=O)=CC=1N1CCCC1 UJEWTUDSLQGTOA-UHFFFAOYSA-N 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
229960001138 acetylsalicylic acid Drugs 0.000 description 2
230000001154 acute effect Effects 0.000 description 2
OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
239000002593 adenosine A3 receptor agonist Substances 0.000 description 2
238000013019 agitation Methods 0.000 description 2
229940090865 aldose reductase inhibitors used in diabetes Drugs 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
150000008064 anhydrides Chemical class 0.000 description 2
239000000010 aprotic solvent Substances 0.000 description 2
229960002274 atenolol Drugs 0.000 description 2
125000004429 atom Chemical group 0.000 description 2
235000010233 benzoic acid Nutrition 0.000 description 2
239000002876 beta blocker Substances 0.000 description 2
229940097320 beta blocking agent Drugs 0.000 description 2
210000004369 blood Anatomy 0.000 description 2
239000008280 blood Substances 0.000 description 2
230000017531 blood circulation Effects 0.000 description 2
210000004204 blood vessel Anatomy 0.000 description 2
229960001035 bopindolol Drugs 0.000 description 2
239000000480 calcium channel blocker Substances 0.000 description 2
239000002775 capsule Substances 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
229960002896 clonidine Drugs 0.000 description 2
239000006184 cosolvent Substances 0.000 description 2
230000008878 coupling Effects 0.000 description 2
238000010168 coupling process Methods 0.000 description 2
238000005859 coupling reaction Methods 0.000 description 2
238000004807 desolvation Methods 0.000 description 2
206010012601 diabetes mellitus Diseases 0.000 description 2
LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 description 2
229960005156 digoxin Drugs 0.000 description 2
LTMHDMANZUZIPE-UHFFFAOYSA-N digoxine Natural products C1C(O)C(O)C(C)OC1OC1C(C)OC(OC2C(OC(OC3CC4C(C5C(C6(CCC(C6(C)C(O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)CC2O)C)CC1O LTMHDMANZUZIPE-UHFFFAOYSA-N 0.000 description 2
IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 description 2
229960002768 dipyridamole Drugs 0.000 description 2
230000008034 disappearance Effects 0.000 description 2
239000002934 diuretic Substances 0.000 description 2
229940030606 diuretics Drugs 0.000 description 2
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 2
229960000873 enalapril Drugs 0.000 description 2
230000002255 enzymatic effect Effects 0.000 description 2
235000019634 flavors Nutrition 0.000 description 2
239000007789 gas Substances 0.000 description 2
210000001035 gastrointestinal tract Anatomy 0.000 description 2
230000001434 glomerular Effects 0.000 description 2
MNQZXJOMYWMBOU-UHFFFAOYSA-N glyceraldehyde Chemical compound OCC(O)C=O MNQZXJOMYWMBOU-UHFFFAOYSA-N 0.000 description 2
229960003711 glyceryl trinitrate Drugs 0.000 description 2
229930182470 glycoside Natural products 0.000 description 2
150000002338 glycosides Chemical class 0.000 description 2
229960000789 guanidine hydrochloride Drugs 0.000 description 2
PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 2
210000002216 heart Anatomy 0.000 description 2
208000019622 heart disease Diseases 0.000 description 2
210000005003 heart tissue Anatomy 0.000 description 2
229960002003 hydrochlorothiazide Drugs 0.000 description 2
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
230000001771 impaired effect Effects 0.000 description 2
239000012535 impurity Substances 0.000 description 2
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 2
229960004569 indapamide Drugs 0.000 description 2
238000001802 infusion Methods 0.000 description 2
238000007918 intramuscular administration Methods 0.000 description 2
MOYKHGMNXAOIAT-JGWLITMVSA-N isosorbide dinitrate Chemical compound [O-][N+](=O)O[C@H]1CO[C@@H]2[C@H](O[N+](=O)[O-])CO[C@@H]21 MOYKHGMNXAOIAT-JGWLITMVSA-N 0.000 description 2
229960000201 isosorbide dinitrate Drugs 0.000 description 2
229960003827 isosorbide mononitrate Drugs 0.000 description 2
YWXYYJSYQOXTPL-SLPGGIOYSA-N isosorbide mononitrate Chemical compound [O-][N+](=O)O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 YWXYYJSYQOXTPL-SLPGGIOYSA-N 0.000 description 2
210000003734 kidney Anatomy 0.000 description 2
210000004185 liver Anatomy 0.000 description 2
210000004072 lung Anatomy 0.000 description 2
239000000463 material Substances 0.000 description 2
239000002609 medium Substances 0.000 description 2
229960003134 mepindolol Drugs 0.000 description 2
VKQFCGNPDRICFG-UHFFFAOYSA-N methyl 2-methylpropyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCC(C)C)C1C1=CC=CC=C1[N+]([O-])=O VKQFCGNPDRICFG-UHFFFAOYSA-N 0.000 description 2
UOWBHNVPNLWAEH-UHFFFAOYSA-N methyl 5-cyclopropyl-1-quinolin-5-ylpyrazole-4-carboxylate Chemical compound COC(=O)C=1C=NN(C=2C3=CC=CN=C3C=CC=2)C=1C1CC1 UOWBHNVPNLWAEH-UHFFFAOYSA-N 0.000 description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
229960004255 nadolol Drugs 0.000 description 2
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 2
230000017074 necrotic cell death Effects 0.000 description 2
201000009925 nephrosclerosis Diseases 0.000 description 2
229960001597 nifedipine Drugs 0.000 description 2
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 2
229960000227 nisoldipine Drugs 0.000 description 2
150000002823 nitrates Chemical class 0.000 description 2
229960005425 nitrendipine Drugs 0.000 description 2
230000010412 perfusion Effects 0.000 description 2
239000008024 pharmaceutical diluent Substances 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
229960001085 piretanide Drugs 0.000 description 2
239000000106 platelet aggregation inhibitor Substances 0.000 description 2
239000001103 potassium chloride Substances 0.000 description 2
235000011164 potassium chloride Nutrition 0.000 description 2
229960002816 potassium chloride Drugs 0.000 description 2
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 2
229960001289 prazosin Drugs 0.000 description 2
229960003712 propranolol Drugs 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
230000002829 reductive effect Effects 0.000 description 2
229940107685 reopro Drugs 0.000 description 2
150000003839 salts Chemical class 0.000 description 2
230000035939 shock Effects 0.000 description 2
210000002027 skeletal muscle Anatomy 0.000 description 2
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
229940083608 sodium hydroxide Drugs 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
229960002370 sotalol Drugs 0.000 description 2
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 2
238000012289 standard assay Methods 0.000 description 2
238000003756 stirring Methods 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
239000007916 tablet composition Substances 0.000 description 2
239000000454 talc Substances 0.000 description 2
229910052623 talc Inorganic materials 0.000 description 2
IMCGHZIGRANKHV-AJNGGQMLSA-N tert-butyl (3s,5s)-2-oxo-5-[(2s,4s)-5-oxo-4-propan-2-yloxolan-2-yl]-3-propan-2-ylpyrrolidine-1-carboxylate Chemical compound O1C(=O)[C@H](C(C)C)C[C@H]1[C@H]1N(C(=O)OC(C)(C)C)C(=O)[C@H](C(C)C)C1 IMCGHZIGRANKHV-AJNGGQMLSA-N 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
229960000103 thrombolytic agent Drugs 0.000 description 2
230000009092 tissue dysfunction Effects 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
229960001722 verapamil Drugs 0.000 description 2
MTZBBNMLMNBNJL-UHFFFAOYSA-N xipamide Chemical compound CC1=CC=CC(C)=C1NC(=O)C1=CC(S(N)(=O)=O)=C(Cl)C=C1O MTZBBNMLMNBNJL-UHFFFAOYSA-N 0.000 description 2
229960000537 xipamide Drugs 0.000 description 2
229950005346 zopolrestat Drugs 0.000 description 2
BFCDFTHTSVTWOG-PXNSSMCTSA-N (1r,2s)-2-(octylamino)-1-(4-propan-2-ylsulfanylphenyl)propan-1-ol Chemical compound CCCCCCCCN[C@@H](C)[C@H](O)C1=CC=C(SC(C)C)C=C1 BFCDFTHTSVTWOG-PXNSSMCTSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
KWCPQPFOPUCWPH-UHFFFAOYSA-N 1-(oxomethylidene)guanidine Chemical group NC(=N)N=C=O KWCPQPFOPUCWPH-UHFFFAOYSA-N 0.000 description 1
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
AVGBKIPAXGXJQH-SYDPRGILSA-N 2-amino-1-[(3S,4R)-3,4-dihydroxypyrrolidin-1-yl]ethanone Chemical compound NCC(=O)N1C[C@H](O)[C@H](O)C1 AVGBKIPAXGXJQH-SYDPRGILSA-N 0.000 description 1
YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
RIIVBOIBIOLLPO-UHFFFAOYSA-N 2-phthalazin-1-ylacetic acid Chemical compound C1=CC=C2C(CC(=O)O)=NN=CC2=C1 RIIVBOIBIOLLPO-UHFFFAOYSA-N 0.000 description 1
PITVZRMNFBGRFW-UHFFFAOYSA-N 5,6-dichloro-1h-indole-2-carboxylic acid Chemical compound ClC1=C(Cl)C=C2NC(C(=O)O)=CC2=C1 PITVZRMNFBGRFW-UHFFFAOYSA-N 0.000 description 1
KLLOIWZUJAJGPU-IBGZPJMESA-N 5-chloro-n-[(2s)-1-(3-hydroxyazetidin-1-yl)-1-oxo-3-phenylpropan-2-yl]-1h-indole-2-carboxamide Chemical compound C1C(O)CN1C(=O)[C@@H](NC(=O)C=1NC2=CC=C(Cl)C=C2C=1)CC1=CC=CC=C1 KLLOIWZUJAJGPU-IBGZPJMESA-N 0.000 description 1
DVXQIHZTVBIXDY-NRFANRHFSA-N 5-chloro-n-[(2s)-1-(4-hydroxyiminopiperidin-1-yl)-1-oxo-3-phenylpropan-2-yl]-1h-indole-2-carboxamide Chemical compound C1CC(=NO)CCN1C(=O)[C@@H](NC(=O)C=1NC2=CC=C(Cl)C=C2C=1)CC1=CC=CC=C1 DVXQIHZTVBIXDY-NRFANRHFSA-N 0.000 description 1
TWYFEHONZYASQG-UHFFFAOYSA-N 5-chloro-n-[2-oxo-2-(1,3-thiazolidin-3-yl)ethyl]-1h-indole-2-carboxamide Chemical compound C=1C2=CC(Cl)=CC=C2NC=1C(=O)NCC(=O)N1CCSC1 TWYFEHONZYASQG-UHFFFAOYSA-N 0.000 description 1
WSLKLYKPUZWAQW-UHFFFAOYSA-N 5-cyclopropyl-1-quinolin-5-ylpyrazole-4-carboxylic acid Chemical compound OC(=O)C=1C=NN(C=2C3=CC=CN=C3C=CC=2)C=1C1CC1 WSLKLYKPUZWAQW-UHFFFAOYSA-N 0.000 description 1
239000005541 ACE inhibitor Substances 0.000 description 1
102000016912 Aldehyde Reductase Human genes 0.000 description 1
108010053754 Aldehyde reductase Proteins 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
206010003210 Arteriosclerosis Diseases 0.000 description 1
239000002126 C01EB10 - Adenosine Substances 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
206010007556 Cardiac failure acute Diseases 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
208000007342 Diabetic Nephropathies Diseases 0.000 description 1
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
206010016654 Fibrosis Diseases 0.000 description 1
KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 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
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
229920002527 Glycogen Polymers 0.000 description 1
206010019668 Hepatic fibrosis Diseases 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
240000003183 Manihot esculenta Species 0.000 description 1
235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 1
206010030113 Oedema Diseases 0.000 description 1
235000019502 Orange oil Nutrition 0.000 description 1
102000004316 Oxidoreductases Human genes 0.000 description 1
108090000854 Oxidoreductases Proteins 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
208000031481 Pathologic Constriction Diseases 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
229940127315 Potassium Channel Openers Drugs 0.000 description 1
208000023146 Pre-existing disease Diseases 0.000 description 1
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
206010063837 Reperfusion injury Diseases 0.000 description 1
206010040070 Septic Shock Diseases 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
244000061456 Solanum tuberosum Species 0.000 description 1
235000002595 Solanum tuberosum Nutrition 0.000 description 1
229930006000 Sucrose Natural products 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
206010042434 Sudden death Diseases 0.000 description 1
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
150000001241 acetals Chemical class 0.000 description 1
239000003377 acid catalyst Substances 0.000 description 1
230000009471 action Effects 0.000 description 1
239000013543 active substance Substances 0.000 description 1
229960005305 adenosine Drugs 0.000 description 1
230000002411 adverse Effects 0.000 description 1
HXXFSFRBOHSIMQ-VFUOTHLCSA-N alpha-D-glucose 1-phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(O)=O)[C@H](O)[C@@H](O)[C@@H]1O HXXFSFRBOHSIMQ-VFUOTHLCSA-N 0.000 description 1
150000001408 amides Chemical class 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
238000002399 angioplasty Methods 0.000 description 1
229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
230000003288 anthiarrhythmic effect Effects 0.000 description 1
230000003466 anti-cipated effect Effects 0.000 description 1
239000003416 antiarrhythmic agent Substances 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
208000011775 arteriosclerosis disease Diseases 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
230000002051 biphasic effect Effects 0.000 description 1
239000012455 biphasic mixture Substances 0.000 description 1
229910000019 calcium carbonate Inorganic materials 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
229960000830 captopril Drugs 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
238000006555 catalytic reaction Methods 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
208000026106 cerebrovascular disease Diseases 0.000 description 1
210000000038 chest Anatomy 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
230000004087 circulation Effects 0.000 description 1
239000003086 colorant Substances 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
VMKJWLXVLHBJNK-UHFFFAOYSA-N cyanuric fluoride Chemical compound FC1=NC(F)=NC(F)=N1 VMKJWLXVLHBJNK-UHFFFAOYSA-N 0.000 description 1
230000002939 deleterious effect Effects 0.000 description 1
238000011161 development Methods 0.000 description 1
208000033679 diabetic kidney disease Diseases 0.000 description 1
VLNZUSMTOFYNPS-UHFFFAOYSA-N diethylphosphorylformonitrile Chemical compound CCP(=O)(CC)C#N VLNZUSMTOFYNPS-UHFFFAOYSA-N 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003814 drug Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000002526 effect on cardiovascular system Effects 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
210000002950 fibroblast Anatomy 0.000 description 1
230000004761 fibrosis Effects 0.000 description 1
230000003176 fibrotic effect Effects 0.000 description 1
239000000945 filler Substances 0.000 description 1
238000011049 filling Methods 0.000 description 1
239000012065 filter cake Substances 0.000 description 1
230000009969 flowable effect Effects 0.000 description 1
239000012530 fluid Substances 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
230000014509 gene expression Effects 0.000 description 1
239000008103 glucose Substances 0.000 description 1
229950010772 glucose-1-phosphate Drugs 0.000 description 1
125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
229940096919 glycogen Drugs 0.000 description 1
230000004116 glycogenolysis Effects 0.000 description 1
230000036541 health Effects 0.000 description 1
125000001072 heteroaryl group Chemical group 0.000 description 1
239000008241 heterogeneous mixture Substances 0.000 description 1
OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 1
BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
238000005462 in vivo assay Methods 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
229910052816 inorganic phosphate Inorganic materials 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000007788 liquid Substances 0.000 description 1
210000005228 liver tissue Anatomy 0.000 description 1
238000011068 loading method Methods 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
RIJWDPRXCXJDPK-UHFFFAOYSA-N methyl 3-cyclopropyl-3-oxopropanoate Chemical compound COC(=O)CC(=O)C1CC1 RIJWDPRXCXJDPK-UHFFFAOYSA-N 0.000 description 1
IYJMSDVSVHDVGT-PEQKVOOWSA-N metildigoxin Chemical compound O1[C@H](C)[C@@H](OC)[C@@H](O)C[C@@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O IYJMSDVSVHDVGT-PEQKVOOWSA-N 0.000 description 1
229960003746 metildigoxin Drugs 0.000 description 1
230000003680 myocardial damage Effects 0.000 description 1
208000037891 myocardial injury Diseases 0.000 description 1
210000004165 myocardium Anatomy 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
238000002638 palliative care Methods 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
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
239000006187 pill Substances 0.000 description 1
229960002508 pindolol Drugs 0.000 description 1
PHUTUTUABXHXLW-UHFFFAOYSA-N pindolol Chemical compound CC(C)NCC(O)COC1=CC=CC2=NC=C[C]12 PHUTUTUABXHXLW-UHFFFAOYSA-N 0.000 description 1
239000000902 placebo Substances 0.000 description 1
229940068196 placebo Drugs 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920001296 polysiloxane Polymers 0.000 description 1
BITYAPCSNKJESK-UHFFFAOYSA-N potassiosodium Chemical compound [Na].[K] BITYAPCSNKJESK-UHFFFAOYSA-N 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
AMMGCGVWJMRTQI-UHFFFAOYSA-N prop-1-en-2-yl carbonochloridate Chemical compound CC(=C)OC(Cl)=O AMMGCGVWJMRTQI-UHFFFAOYSA-N 0.000 description 1
239000003380 propellant Substances 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
210000002307 prostate Anatomy 0.000 description 1
239000008213 purified water Substances 0.000 description 1
239000003379 purinergic P1 receptor agonist Substances 0.000 description 1
YZKWEHGEHPCODG-UHFFFAOYSA-N quinolin-5-ylhydrazine Chemical compound C1=CC=C2C(NN)=CC=CC2=N1 YZKWEHGEHPCODG-UHFFFAOYSA-N 0.000 description 1
238000011160 research Methods 0.000 description 1
150000004760 silicates Chemical class 0.000 description 1
210000000329 smooth muscle myocyte Anatomy 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
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000011973 solid acid Substances 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
210000001032 spinal nerve Anatomy 0.000 description 1
229910001220 stainless steel Inorganic materials 0.000 description 1
239000010935 stainless steel Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
UJJLJRQIPMGXEZ-UHFFFAOYSA-N tetrahydro-2-furoic acid Chemical compound OC(=O)C1CCCO1 UJJLJRQIPMGXEZ-UHFFFAOYSA-N 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
239000006211 transdermal dosage form Substances 0.000 description 1
210000005166 vasculature Anatomy 0.000 description 1
238000010792 warming Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
- 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

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Diabetes (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Physical Education & Sports Medicine (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Surgery (AREA)
Emergency Medicine (AREA)
Endocrinology (AREA)
Hematology (AREA)
Obesity (AREA)
Neurology (AREA)
Orthopedic Medicine & Surgery (AREA)
Toxicology (AREA)
Pulmonology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Treatment Of Water By Ion Exchange (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Plural Heterocyclic Compounds (AREA)

OA1200200128A 1999-10-29 2000-10-09 Sodium-hydrogen exchanger type 1 inhibitor crystals. OA12080A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US16237499P	1999-10-29	1999-10-29

Publications (1)

Publication Number	Publication Date
OA12080A true OA12080A (en)	2003-08-25

Family

ID=22585355

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA1200200128A OA12080A (en)	1999-10-29	2000-10-09	Sodium-hydrogen exchanger type 1 inhibitor crystals.

Country Status (44)

Country	Link
EP (1)	EP1224179B1 (de)
JP (1)	JP2003512455A (de)
KR (1)	KR100464526B1 (de)
CN (2)	CN1205205C (de)
AP (1)	AP2002002493A0 (de)
AR (1)	AR029402A1 (de)
AT (1)	ATE271047T1 (de)
AU (1)	AU778573B2 (de)
BG (1)	BG106729A (de)
BR (1)	BR0015275A (de)
CA (1)	CA2389020A1 (de)
CO (1)	CO5271714A1 (de)
CZ (1)	CZ20021332A3 (de)
DE (1)	DE60012208T2 (de)
DK (1)	DK1224179T3 (de)
DZ (1)	DZ3463A1 (de)
EA (1)	EA004937B1 (de)
EE (1)	EE200200227A (de)
ES (1)	ES2222923T3 (de)
GE (1)	GEP20043222B (de)
GT (1)	GT200000180A (de)
HK (1)	HK1048472B (de)
HR (1)	HRP20020366B1 (de)
HU (1)	HUP0204009A3 (de)
IL (1)	IL148581A0 (de)
IS (1)	IS6302A (de)
MA (1)	MA26840A1 (de)
MX (1)	MXPA02004358A (de)
NO (1)	NO20021821L (de)
NZ (1)	NZ517738A (de)
OA (1)	OA12080A (de)
PA (1)	PA8505501A1 (de)
PE (1)	PE20010764A1 (de)
PL (1)	PL354869A1 (de)
PT (1)	PT1224179E (de)
SI (1)	SI1224179T1 (de)
SK (1)	SK5312002A3 (de)
SV (1)	SV2002000209A (de)
TN (1)	TNSN00210A1 (de)
TR (1)	TR200201167T2 (de)
UA (1)	UA72002C2 (de)
WO (1)	WO2001030759A2 (de)
YU (1)	YU31502A (de)
ZA (1)	ZA200203295B (de)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6441176B1 (en)	1999-10-29	2002-08-27	Pfizer Inc.	Method for preparing sodium-hydrogen exchanger type 1 inhibitor
CA2436539A1 (en) *	2001-01-31	2002-08-08	Pfizer Products Inc.	Ethanolates of sodium-hydrogen exchanger type-1 inhibitor
EP1472242A1 (de) *	2002-01-30	2004-11-03	Pfizer Products Inc.	Pharmazeutische zusammensetzungen, zoniporide mesylat enthaltend und prozesse zur verbesserung der löslichkeit von zoniporide
EP1499317A1 (de) *	2002-05-02	2005-01-26	Pfizer Products Inc.	Verwendung von nhe-1 inhibitoren zur behandlung der zuckerkrankheit und der begleitskrankheiten

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP2002504546A (ja) *	1998-02-27	2002-02-12	ファイザー・プロダクツ・インク	虚血の治療のためのｎ−［（置換５員ジもしくはトリアザ二不飽和環）カルボニル］グアニジン誘導体

2000
- 2000-09-10 UA UA2002043503A patent/UA72002C2/uk unknown
- 2000-10-09 TR TR2002/01167T patent/TR200201167T2/xx unknown
- 2000-10-09 SK SK531-2002A patent/SK5312002A3/sk unknown
- 2000-10-09 HU HU0204009A patent/HUP0204009A3/hu unknown
- 2000-10-09 BR BR0015275-7A patent/BR0015275A/pt not_active IP Right Cessation
- 2000-10-09 SI SI200030449T patent/SI1224179T1/xx unknown
- 2000-10-09 EP EP00962776A patent/EP1224179B1/de not_active Expired - Lifetime
- 2000-10-09 CN CNB008146748A patent/CN1205205C/zh not_active Expired - Fee Related
- 2000-10-09 EE EEP200200227A patent/EE200200227A/xx unknown
- 2000-10-09 NZ NZ517738A patent/NZ517738A/en unknown
- 2000-10-09 PT PT00962776T patent/PT1224179E/pt unknown
- 2000-10-09 AU AU74415/00A patent/AU778573B2/en not_active Ceased
- 2000-10-09 OA OA1200200128A patent/OA12080A/en unknown
- 2000-10-09 HK HK03100504.6A patent/HK1048472B/zh not_active IP Right Cessation
- 2000-10-09 PL PL00354869A patent/PL354869A1/xx not_active Application Discontinuation
- 2000-10-09 DZ DZ003463A patent/DZ3463A1/fr active
- 2000-10-09 CA CA002389020A patent/CA2389020A1/en not_active Abandoned
- 2000-10-09 DE DE60012208T patent/DE60012208T2/de not_active Expired - Fee Related
- 2000-10-09 ES ES00962776T patent/ES2222923T3/es not_active Expired - Lifetime
- 2000-10-09 GE GEAP20006430A patent/GEP20043222B/en unknown
- 2000-10-09 YU YU31502A patent/YU31502A/sh unknown
- 2000-10-09 KR KR10-2002-7005366A patent/KR100464526B1/ko not_active Expired - Fee Related
- 2000-10-09 MX MXPA02004358A patent/MXPA02004358A/es active IP Right Grant
- 2000-10-09 JP JP2001533113A patent/JP2003512455A/ja active Pending
- 2000-10-09 WO PCT/IB2000/001460 patent/WO2001030759A2/en not_active Ceased
- 2000-10-09 AT AT00962776T patent/ATE271047T1/de not_active IP Right Cessation
- 2000-10-09 CN CNA200410094665XA patent/CN1636991A/zh active Pending
- 2000-10-09 EA EA200200416A patent/EA004937B1/ru not_active IP Right Cessation
- 2000-10-09 CZ CZ20021332A patent/CZ20021332A3/cs unknown
- 2000-10-09 IL IL14858100A patent/IL148581A0/xx unknown
- 2000-10-09 AP APAP/P/2002/002493A patent/AP2002002493A0/en unknown
- 2000-10-09 DK DK00962776T patent/DK1224179T3/da active
- 2000-10-09 HR HR20020366A patent/HRP20020366B1/xx not_active IP Right Cessation
- 2000-10-18 GT GT200000180A patent/GT200000180A/es unknown
- 2000-10-20 PA PA20008505501A patent/PA8505501A1/es unknown
- 2000-10-25 CO CO00081375A patent/CO5271714A1/es not_active Application Discontinuation
- 2000-10-26 PE PE2000001145A patent/PE20010764A1/es not_active Application Discontinuation
- 2000-10-27 TN TNTNSN00210A patent/TNSN00210A1/fr unknown
- 2000-10-27 SV SV2000000209A patent/SV2002000209A/es unknown
- 2000-10-27 AR ARP000105700A patent/AR029402A1/es unknown
2002
- 2002-03-15 IS IS6302A patent/IS6302A/is unknown
- 2002-04-18 NO NO20021821A patent/NO20021821L/no not_active Application Discontinuation
- 2002-04-22 MA MA26615A patent/MA26840A1/fr unknown
- 2002-04-25 ZA ZA200203295A patent/ZA200203295B/xx unknown
- 2002-05-20 BG BG106729A patent/BG106729A/bg unknown

Also Published As

Publication number	Publication date
HK1048472B (zh)	2005-09-16
SV2002000209A (es)	2002-07-16
EA200200416A1 (ru)	2002-10-31
ATE271047T1 (de)	2004-07-15
SK5312002A3 (en)	2003-01-09
NO20021821D0 (no)	2002-04-18
GT200000180A (es)	2002-04-11
TNSN00210A1 (fr)	2005-11-10
ES2222923T3 (es)	2005-02-16
HUP0204009A3 (en)	2004-07-28
EE200200227A (et)	2003-06-16
JP2003512455A (ja)	2003-04-02
AR029402A1 (es)	2003-06-25
AP2002002493A0 (en)	2002-06-30
PL354869A1 (en)	2004-03-08
DE60012208D1 (de)	2004-08-19
NZ517738A (en)	2005-06-24
CA2389020A1 (en)	2001-05-03
HK1048472A1 (en)	2003-04-04
MXPA02004358A (es)	2002-11-07
IL148581A0 (en)	2002-09-12
HRP20020366B1 (en)	2005-04-30
ZA200203295B (en)	2003-06-25
SI1224179T1 (en)	2004-10-31
DZ3463A1 (fr)	2001-05-03
EP1224179B1 (de)	2004-07-14
EA004937B1 (ru)	2004-10-28
BG106729A (bg)	2002-12-29
CN1636991A (zh)	2005-07-13
HRP20020366A2 (en)	2004-02-29
AU7441500A (en)	2001-05-08
CN1205205C (zh)	2005-06-08
CZ20021332A3 (cs)	2002-10-16
PE20010764A1 (es)	2001-07-23
BR0015275A (pt)	2002-07-16
TR200201167T2 (tr)	2002-08-21
KR100464526B1 (ko)	2005-01-03
DK1224179T3 (da)	2004-10-25
DE60012208T2 (de)	2005-07-21
EP1224179A2 (de)	2002-07-24
PA8505501A1 (es)	2003-09-05
NO20021821L (no)	2002-04-18
WO2001030759A3 (en)	2001-09-13
WO2001030759A2 (en)	2001-05-03
KR20020040918A (ko)	2002-05-30
HUP0204009A2 (hu)	2003-03-28
IS6302A (is)	2002-03-15
UA72002C2 (en)	2005-01-17
AU778573B2 (en)	2004-12-09
CN1384829A (zh)	2002-12-11
GEP20043222B (en)	2004-04-26
PT1224179E (pt)	2004-10-29
YU31502A (sh)	2004-12-31
CO5271714A1 (es)	2003-04-30
MA26840A1 (fr)	2004-12-20

Publication	Publication Date	Title
JP4075064B2 (ja)	2008-04-16	４，４−ジフルオロ−１，２，３，４−テトラヒドロ−５ｈ−１−ベンゾアゼピン誘導体又はその塩
EA021025B1 (ru)	2015-03-31	Соединения, эффективные в качестве ингибиторов ксантиноксидазы, способ их получения и содержащая их фармацевтическая композиция
LV11614B (en)	1997-04-20	Substituted n-(indole-2-carbonyl)-©-alaninamides and derivatives as antidiabetic agents
EP1224179B1 (de)	2004-07-14	Type 1 inhibitorkristalle als inhibitoren des natrium-protonen austauschs
OA12256A (en)	2003-11-06	Sodium-hydrogen exchanger type 1 inhibitor (NHE-1).
TWI221152B (en)	2004-09-21	Method for preparing sodium-hydrogen exchanger type 1 inhibitor
JP2005187449A (ja)	2005-07-14	４，４−ジフルオロ−１，２，３，４−テトラヒドロ−５ｈ−１−ベンゾアゼピン誘導体又はその塩
US20010051634A1 (en)	2001-12-13	Sodium-hydrogen exchanger type 1 inhibitor
AU2005201428A1 (en)	2005-04-28	Method for preparing sodium-hydrogen exchanger type 1 inhibitor