TWI257389B - Pharmaceutical compound - Google Patents
Pharmaceutical compound Download PDFInfo
- Publication number
- TWI257389B TWI257389B TW091112134A TW91112134A TWI257389B TW I257389 B TWI257389 B TW I257389B TW 091112134 A TW091112134 A TW 091112134A TW 91112134 A TW91112134 A TW 91112134A TW I257389 B TWI257389 B TW I257389B
- Authority
- TW
- Taiwan
- Prior art keywords
- phenylglycine
- carbonyl
- methylpiperidin
- pharmaceutically acceptable
- indol
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title description 14
- 239000013078 crystal Substances 0.000 claims description 18
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 claims description 3
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- ZGUNAGUHMKGQNY-SSDOTTSWSA-N D-alpha-phenylglycine Chemical compound OC(=O)[C@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-SSDOTTSWSA-N 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 230000003073 embolic effect Effects 0.000 claims 1
- 150000003839 salts Chemical class 0.000 abstract description 9
- 108010022999 Serine Proteases Proteins 0.000 abstract description 4
- 102000012479 Serine Proteases Human genes 0.000 abstract description 4
- 239000003112 inhibitor Substances 0.000 abstract description 4
- 108010074860 Factor Xa Proteins 0.000 abstract description 3
- OLCPTSBUDSMZCV-NNRSTJKISA-N (e)-but-2-enedioic acid;n-[(1r)-2-[4-(1-methylpiperidin-4-yl)piperazin-1-yl]-2-oxo-1-phenylethyl]-1h-indole-6-carboxamide Chemical group OC(=O)\C=C\C(O)=O.OC(=O)\C=C\C(O)=O.C1CN(C)CCC1N1CCN(C(=O)[C@H](NC(=O)C=2C=C3NC=CC3=CC=2)C=2C=CC=CC=2)CC1 OLCPTSBUDSMZCV-NNRSTJKISA-N 0.000 abstract 1
- 208000024172 Cardiovascular disease Diseases 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 229910001868 water Inorganic materials 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 239000002904 solvent Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- -1 Factor Vila Proteins 0.000 description 5
- 102000035195 Peptidases Human genes 0.000 description 5
- 108091005804 Peptidases Proteins 0.000 description 5
- 239000003146 anticoagulant agent Substances 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 239000004365 Protease Substances 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 229940127219 anticoagulant drug Drugs 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 238000000113 differential scanning calorimetry Methods 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000000825 pharmaceutical preparation Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 108010014173 Factor X Proteins 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 229940127557 pharmaceutical product Drugs 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000002411 thermogravimetry Methods 0.000 description 3
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 229940124639 Selective inhibitor Drugs 0.000 description 2
- 241000009298 Trigla lyra Species 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000002178 crystalline material Substances 0.000 description 2
- 239000001177 diphosphate Substances 0.000 description 2
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 2
- 235000011180 diphosphates Nutrition 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000002537 thrombolytic effect Effects 0.000 description 2
- HOBFSNNENNQQIU-SNVBAGLBSA-N (2r)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-2-phenylacetic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](C(O)=O)C1=CC=CC=C1 HOBFSNNENNQQIU-SNVBAGLBSA-N 0.000 description 1
- HMUNWXXNJPVALC-UHFFFAOYSA-N 1-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C(CN1CC2=C(CC1)NN=N2)=O HMUNWXXNJPVALC-UHFFFAOYSA-N 0.000 description 1
- GPASDLXNNAPVRX-UHFFFAOYSA-N 1-methyl-4-piperidin-1-ylpiperidine Chemical compound C1CN(C)CCC1N1CCCCC1 GPASDLXNNAPVRX-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- NFEVMRNCAGDLBK-UHFFFAOYSA-N 2-anilino-2-phenylacetic acid Chemical group C=1C=CC=CC=1C(C(=O)O)NC1=CC=CC=C1 NFEVMRNCAGDLBK-UHFFFAOYSA-N 0.000 description 1
- 108091005508 Acid proteases Proteins 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 108090000145 Bacillolysin Proteins 0.000 description 1
- HKMTVMBEALTRRR-UHFFFAOYSA-N Benzo[a]fluorene Chemical group C1=CC=CC2=C3CC4=CC=CC=C4C3=CC=C21 HKMTVMBEALTRRR-UHFFFAOYSA-N 0.000 description 1
- FDUMGWZHEBDQFZ-LLTODGECSA-N CC(C)(C)OC(=O)C1(CC=CC=C1)[C@H](C(=O)O)N Chemical group CC(C)(C)OC(=O)C1(CC=CC=C1)[C@H](C(=O)O)N FDUMGWZHEBDQFZ-LLTODGECSA-N 0.000 description 1
- 206010008088 Cerebral artery embolism Diseases 0.000 description 1
- 108090000317 Chymotrypsin Proteins 0.000 description 1
- 102000016917 Complement C1 Human genes 0.000 description 1
- 108010028774 Complement C1 Proteins 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 206010014513 Embolism arterial Diseases 0.000 description 1
- 108010048049 Factor IXa Proteins 0.000 description 1
- 241000270322 Lepidosauria Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- NPKSPKHJBVJUKB-UHFFFAOYSA-N N-phenylglycine Chemical compound OC(=O)CNC1=CC=CC=C1 NPKSPKHJBVJUKB-UHFFFAOYSA-N 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- 108091005507 Neutral proteases Proteins 0.000 description 1
- 102000035092 Neutral proteases Human genes 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- 102000016387 Pancreatic elastase Human genes 0.000 description 1
- 101710180012 Protease 7 Proteins 0.000 description 1
- 208000010378 Pulmonary Embolism Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 101710151386 Serine protease 3 Proteins 0.000 description 1
- 229910004489 SiLi Inorganic materials 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
- 108090000787 Subtilisin Proteins 0.000 description 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 102100034396 Trypsin-3 Human genes 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 206010053648 Vascular occlusion Diseases 0.000 description 1
- 206010047249 Venous thrombosis Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- FRDYCXQDNBSHAL-UHFFFAOYSA-N acetic acid;chloroform;ethyl acetate Chemical compound CC(O)=O.ClC(Cl)Cl.CCOC(C)=O FRDYCXQDNBSHAL-UHFFFAOYSA-N 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 238000000065 atmospheric pressure chemical ionisation Methods 0.000 description 1
- 229960005370 atorvastatin Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- UOKRBSXOBUKDGE-UHFFFAOYSA-N butylphosphonic acid Chemical compound CCCCP(O)(O)=O UOKRBSXOBUKDGE-UHFFFAOYSA-N 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 238000003490 calendering Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229960002376 chymotrypsin Drugs 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229960002380 dibutyl phthalate Drugs 0.000 description 1
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 239000003527 fibrinolytic agent Substances 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 210000000003 hoof Anatomy 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 201000010849 intracranial embolism Diseases 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000002132 lysosomal effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000007431 microscopic evaluation Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- YAOULQGDLCJSSG-UHFFFAOYSA-N perchloric acid hydrochloride Chemical compound Cl(=O)(=O)(=O)O.Cl YAOULQGDLCJSSG-UHFFFAOYSA-N 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- YFSSNCSFDCFTCP-UHFFFAOYSA-N phosphoric acid;propanenitrile Chemical compound CCC#N.OP(O)(O)=O YFSSNCSFDCFTCP-UHFFFAOYSA-N 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical class OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
- 229940012957 plasmin Drugs 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 239000012495 reaction gas Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 108010059841 serine carboxypeptidase Proteins 0.000 description 1
- 239000003001 serine protease inhibitor Substances 0.000 description 1
- 150000003355 serines Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002076 thermal analysis method Methods 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 229960000103 thrombolytic agent Drugs 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000563 toxic property Toxicity 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 208000021331 vascular occlusion disease Diseases 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 230000002087 whitening effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/GB2001/002553 WO2001096323A1 (en) | 2000-06-13 | 2001-06-12 | Serine protease inhibitors |
| US33929501P | 2001-12-12 | 2001-12-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TWI257389B true TWI257389B (en) | 2006-07-01 |
Family
ID=41210812
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW091112134A TWI257389B (en) | 2001-06-12 | 2002-06-05 | Pharmaceutical compound |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US20040162295A1 (enExample) |
| EP (1) | EP1397348B1 (enExample) |
| JP (1) | JP2004534062A (enExample) |
| AR (1) | AR036048A1 (enExample) |
| AT (1) | ATE305452T1 (enExample) |
| AU (1) | AU2002348501A1 (enExample) |
| DE (1) | DE60206376T2 (enExample) |
| ES (1) | ES2248618T3 (enExample) |
| MY (1) | MY137876A (enExample) |
| PE (1) | PE20030198A1 (enExample) |
| SV (1) | SV2003001085A (enExample) |
| TW (1) | TWI257389B (enExample) |
| WO (1) | WO2002100847A2 (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE384713T1 (de) * | 2001-07-26 | 2008-02-15 | Lilly Co Eli | 1-glycinyl-4-(1-methylpiperidin-4-yl)piperazine und -piperidine als faktor-xa-antagonisten |
| IL164018A0 (en) | 2002-04-01 | 2005-12-18 | Lilly Co Eli | Certain 1-(d-cyclopropylglycinyl)-4-(piperidin-4-yl)piperazine compounds as inhibitors of the serineprotease factor xa |
| EA010307B1 (ru) * | 2004-06-30 | 2008-08-29 | Эли Лилли Энд Компани | Фармацевтическое соединение |
| KR100849242B1 (ko) * | 2004-06-30 | 2008-07-29 | 일라이 릴리 앤드 캄파니 | 1(인돌-6-카르보닐-ｄ-페닐글리시닐)-4-(1-메틸피페리딘-4-일) 피페라진 ｄ-타르트레이트 |
| DE102007028407A1 (de) | 2007-06-20 | 2008-12-24 | Bayer Healthcare Ag | Substituierte Oxazolidinone und ihre Verwendung |
| DE102007028406A1 (de) | 2007-06-20 | 2008-12-24 | Bayer Healthcare Ag | Substituierte Oxazolidinone und ihre Verwendung |
| DE102007028319A1 (de) | 2007-06-20 | 2008-12-24 | Bayer Healthcare Ag | Substituierte Oxazolidinone und ihre Verwendung |
| EP2875020B1 (en) * | 2012-07-19 | 2017-09-06 | Boehringer Ingelheim International GmbH | Process for the preparation of a fumaric acid salt of 9-[4-(3-chloro-2-fluoro-phenylamino)-7-methoxy- chinazolin-6-yloxy]-1,4-diaza-spiro[5.5]undecan-5-one |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1192132B1 (en) * | 1999-06-14 | 2005-09-07 | Eli Lilly And Company | Serine protease inhibitors |
| GB0030304D0 (en) * | 2000-12-13 | 2001-01-24 | Lilly Co Eli | Compounds |
-
2002
- 2002-06-05 TW TW091112134A patent/TWI257389B/zh not_active IP Right Cessation
- 2002-06-06 AU AU2002348501A patent/AU2002348501A1/en not_active Abandoned
- 2002-06-06 US US10/477,192 patent/US20040162295A1/en not_active Abandoned
- 2002-06-06 AT AT02778933T patent/ATE305452T1/de not_active IP Right Cessation
- 2002-06-06 DE DE60206376T patent/DE60206376T2/de not_active Expired - Fee Related
- 2002-06-06 WO PCT/US2002/016569 patent/WO2002100847A2/en not_active Ceased
- 2002-06-06 ES ES02778933T patent/ES2248618T3/es not_active Expired - Lifetime
- 2002-06-06 JP JP2003503615A patent/JP2004534062A/ja active Pending
- 2002-06-06 EP EP02778933A patent/EP1397348B1/en not_active Expired - Lifetime
- 2002-06-10 MY MYPI20022155A patent/MY137876A/en unknown
- 2002-06-10 PE PE2002000496A patent/PE20030198A1/es not_active Application Discontinuation
- 2002-06-11 AR ARP020102199A patent/AR036048A1/es unknown
- 2002-06-11 SV SV2002001085A patent/SV2003001085A/es not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EP1397348A2 (en) | 2004-03-17 |
| PE20030198A1 (es) | 2003-03-12 |
| SV2003001085A (es) | 2003-03-18 |
| ATE305452T1 (de) | 2005-10-15 |
| WO2002100847A3 (en) | 2003-08-21 |
| MY137876A (en) | 2009-03-31 |
| EP1397348B1 (en) | 2005-09-28 |
| US20040162295A1 (en) | 2004-08-19 |
| DE60206376D1 (de) | 2006-02-09 |
| DE60206376T2 (de) | 2006-06-22 |
| AU2002348501A1 (en) | 2002-12-23 |
| JP2004534062A (ja) | 2004-11-11 |
| ES2248618T3 (es) | 2006-03-16 |
| WO2002100847A2 (en) | 2002-12-19 |
| AR036048A1 (es) | 2004-08-04 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Annulment or lapse of patent due to non-payment of fees |