SK1052001A3 - Substituted phenylamidines with antithrombotic action - Google Patents

Substituted phenylamidines with antithrombotic action Download PDF

Info

Publication number: SK1052001A3
Authority: SK; Slovakia
Prior art keywords: phenyl; group; salts; ethyl; piperidine
Prior art date: 1998-07-23

Application number

SK105-2001A

Other languages

English (en)

Slovak (sk)

Inventor

Frank Himmelsbach

Brian Guth

Hans Dieter Schubert

Original Assignee

Boehringer Ingelheim Pharma

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.)

1998-07-23

Filing date

1999-07-20

Publication date

2001-08-06

1999-07-20 Application filed by Boehringer Ingelheim Pharma filed Critical Boehringer Ingelheim Pharma

2001-08-06 Publication of SK1052001A3 publication Critical patent/SK1052001A3/sk

Links

230000002785 anti-thrombosis Effects 0.000 title abstract description 4
150000001875 compounds Chemical class 0.000 claims abstract description 41
150000003839 salts Chemical class 0.000 claims abstract description 32
238000000034 method Methods 0.000 claims abstract description 9
150000007522 mineralic acids Chemical class 0.000 claims abstract description 5
150000007524 organic acids Chemical class 0.000 claims abstract description 5
235000005985 organic acids Nutrition 0.000 claims abstract description 5
239000003814 drug Substances 0.000 claims abstract 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 27
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 27
238000002360 preparation method Methods 0.000 claims description 14
-1 4- (ethyl) -1 - [(ethoxycarbonyl) methyl] piperidine Chemical compound 0.000 claims description 8
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
238000004519 manufacturing process Methods 0.000 claims description 8
125000000217 alkyl group Chemical group 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 4
239000000126 substance Substances 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 3
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 2
125000000320 amidine group Chemical group 0.000 claims description 2
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 2
230000008619 cell matrix interaction Effects 0.000 claims description 2
230000006806 disease prevention Effects 0.000 claims description 2
PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 claims 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims 1
125000003545 alkoxy group Chemical group 0.000 claims 1
239000012876 carrier material Substances 0.000 claims 1
125000000753 cycloalkyl group Chemical group 0.000 claims 1
239000000203 mixture Substances 0.000 abstract description 15
230000000144 pharmacologic effect Effects 0.000 abstract description 2
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
239000000741 silica gel Substances 0.000 description 13
229910002027 silica gel Inorganic materials 0.000 description 13
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound 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 10
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
239000013543 active substance Substances 0.000 description 10
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
238000002844 melting Methods 0.000 description 10
230000008018 melting Effects 0.000 description 10
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
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238000001819 mass spectrum Methods 0.000 description 9
229940126062 Compound A Drugs 0.000 description 8
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 8
239000002775 capsule Substances 0.000 description 7
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AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
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QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
239000002253 acid Substances 0.000 description 6
239000003446 ligand Substances 0.000 description 6
239000011541 reaction mixture Substances 0.000 description 6
238000003756 stirring Methods 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
229920002261 Corn starch Polymers 0.000 description 5
238000011088 calibration curve Methods 0.000 description 5
235000019359 magnesium stearate Nutrition 0.000 description 5
230000036470 plasma concentration Effects 0.000 description 5
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
239000000243 solution Substances 0.000 description 5
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 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
239000003146 anticoagulant agent Substances 0.000 description 4
239000008280 blood Substances 0.000 description 4
210000004369 blood Anatomy 0.000 description 4
238000006243 chemical reaction Methods 0.000 description 4
229910052739 hydrogen Inorganic materials 0.000 description 4
239000001257 hydrogen Substances 0.000 description 4
239000004615 ingredient Substances 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 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
150000007513 acids Chemical class 0.000 description 3
150000001408 amides Chemical class 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
239000008120 corn starch Substances 0.000 description 3
QHCPCBHFVWLSPV-UHFFFAOYSA-N cyclohexyl 2-[4-(3-chloro-3-oxopropyl)piperidin-1-yl]acetate Chemical compound C1CC(CCC(=O)Cl)CCN1CC(=O)OC1CCCCC1 QHCPCBHFVWLSPV-UHFFFAOYSA-N 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
229940093915 gynecological organic acid Drugs 0.000 description 3
239000005457 ice water Substances 0.000 description 3
229940098779 methanesulfonic acid Drugs 0.000 description 3
XIQQBZMBLLLRGP-UHFFFAOYSA-N methyl 2-[1-(3-chloro-3-oxopropyl)piperidin-4-yl]acetate;hydrochloride Chemical compound Cl.COC(=O)CC1CCN(CCC(Cl)=O)CC1 XIQQBZMBLLLRGP-UHFFFAOYSA-N 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
239000000843 powder Substances 0.000 description 3
238000000926 separation method Methods 0.000 description 3
239000002904 solvent Substances 0.000 description 3
NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
ABFPKTQEQNICFT-UHFFFAOYSA-M 2-chloro-1-methylpyridin-1-ium;iodide Chemical compound [I-].C[N+]1=CC=CC=C1Cl ABFPKTQEQNICFT-UHFFFAOYSA-M 0.000 description 2
VVLYKQUUEVQXKA-UHFFFAOYSA-N 3-[1-(2-ethoxy-2-oxoethyl)piperidin-4-yl]propanoic acid Chemical compound CCOC(=O)CN1CCC(CCC(O)=O)CC1 VVLYKQUUEVQXKA-UHFFFAOYSA-N 0.000 description 2
NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 2
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QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
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206010027476 Metastases Diseases 0.000 description 2
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
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229910000147 aluminium phosphate Inorganic materials 0.000 description 2
239000005557 antagonist Substances 0.000 description 2
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SEWKVRABQPJHHA-UHFFFAOYSA-N benzyl 3-[1-(2-ethoxy-2-oxoethyl)piperidin-4-yl]propanoate Chemical compound C1CN(CC(=O)OCC)CCC1CCC(=O)OCC1=CC=CC=C1 SEWKVRABQPJHHA-UHFFFAOYSA-N 0.000 description 2
JOYIQOCGSSXZJB-UHFFFAOYSA-N benzyl 3-piperidin-4-ylpropanoate Chemical compound C=1C=CC=CC=1COC(=O)CCC1CCNCC1 JOYIQOCGSSXZJB-UHFFFAOYSA-N 0.000 description 2
230000037396 body weight Effects 0.000 description 2
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125000004432 carbon atom Chemical group C* 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
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238000004587 chromatography analysis Methods 0.000 description 2
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PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
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NPLKZWUGHIMZMQ-UHFFFAOYSA-N hexyl (ne)-n-[amino-(4-nitrophenyl)methylidene]carbamate Chemical compound CCCCCCOC(=O)NC(=N)C1=CC=C([N+]([O-])=O)C=C1 NPLKZWUGHIMZMQ-UHFFFAOYSA-N 0.000 description 2
230000004054 inflammatory process Effects 0.000 description 2
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FLAWEORGRGOOCU-UHFFFAOYSA-N 3-[1-(2-methoxy-2-oxoethyl)piperidin-4-yl]propanoic acid Chemical compound COC(=O)CN1CCC(CCC(O)=O)CC1 FLAWEORGRGOOCU-UHFFFAOYSA-N 0.000 description 1
ARDXKMAETFTYGJ-UHFFFAOYSA-N 3-[1-(2-oxo-2-propan-2-yloxyethyl)piperidin-4-yl]propanoic acid Chemical compound CC(C)OC(=O)CN1CCC(CCC(O)=O)CC1 ARDXKMAETFTYGJ-UHFFFAOYSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
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- 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
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- 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
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/43—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C07C211/44—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having amino groups bound to only one six-membered aromatic ring
- C07C211/49—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having amino groups bound to only one six-membered aromatic ring having at least two amino groups bound to the carbon skeleton
- C07C211/50—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having amino groups bound to only one six-membered aromatic ring having at least two amino groups bound to the carbon skeleton with at least two amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Veterinary Medicine (AREA)
Life Sciences & Earth Sciences (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Diabetes (AREA)
Physical Education & Sports Medicine (AREA)
Hematology (AREA)
Rheumatology (AREA)
Heart & Thoracic Surgery (AREA)
Obesity (AREA)
Oncology (AREA)
Pain & Pain Management (AREA)
Urology & Nephrology (AREA)
Emergency Medicine (AREA)
Endocrinology (AREA)
Vascular Medicine (AREA)
Dermatology (AREA)
Pulmonology (AREA)
Cardiology (AREA)
Orthopedic Medicine & Surgery (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

SK105-2001A 1998-07-23 1999-07-20 Substituted phenylamidines with antithrombotic action SK1052001A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE19833105A DE19833105A1 (de)	1998-07-23	1998-07-23	Substituierte Phenylamidine, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung
PCT/EP1999/005161 WO2000005207A1 (de)	1998-07-23	1999-07-20	Substituierte phenylamidine mit antithrombotischer wirkung

Publications (1)

Publication Number	Publication Date
SK1052001A3 true SK1052001A3 (en)	2001-08-06

Family

ID=7875009

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK105-2001A SK1052001A3 (en)	1998-07-23	1999-07-20	Substituted phenylamidines with antithrombotic action

Country Status (30)

Country	Link
EP (1)	EP1102746B1 (es)
JP (1)	JP3629208B2 (es)
KR (1)	KR20010072046A (es)
CN (1)	CN1310708A (es)
AR (1)	AR019462A1 (es)
AT (1)	ATE240297T1 (es)
AU (1)	AU5285399A (es)
BG (1)	BG105159A (es)
BR (1)	BR9912321A (es)
CA (1)	CA2337413A1 (es)
CO (1)	CO5080745A1 (es)
DE (2)	DE19833105A1 (es)
DK (1)	DK1102746T3 (es)
EA (1)	EA200100106A1 (es)
EE (1)	EE200100048A (es)
ES (1)	ES2199587T3 (es)
HK (1)	HK1038750A1 (es)
HU (1)	HUP0103327A3 (es)
ID (1)	ID27205A (es)
IL (1)	IL140774A0 (es)
NO (1)	NO20010354D0 (es)
PL (1)	PL345624A1 (es)
PT (1)	PT1102746E (es)
SK (1)	SK1052001A3 (es)
TR (1)	TR200100182T2 (es)
TW (1)	TW460461B (es)
UY (1)	UY25621A1 (es)
WO (1)	WO2000005207A1 (es)
YU (1)	YU3701A (es)
ZA (1)	ZA200100363B (es)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE10002510A1 (de)	2000-01-21	2001-07-26	Boehringer Ingelheim Pharma	Substituierte Phenylamidine, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung
US8399678B2 (en) *	2009-11-18	2013-03-19	Boehringer Ingelheim International Gmbh	Process for the manufacture of dabigatran etexilate
EP2522662A1 (en) *	2011-05-11	2012-11-14	Medichem, S.A.	Dabigatran etexilate and related substances, processes and compositions, and use of the substances as reference standards and markers
CN105330568B (zh) *	2015-11-27	2017-05-10	山东省医学科学院药物研究所	一种对氨基苯甲脒盐酸盐的制备方法
CN105732433A (zh) *	2016-04-13	2016-07-06	山东新华制药股份有限公司	达比加群酯中间体缩合物的精制方法

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN1170409A (zh) *	1994-12-01	1998-01-14	富山化学工业株式会社	新的2,3－二氧代哌嗪衍生物及其盐
DE19515500A1 (de) *	1995-04-27	1996-10-31	Thomae Gmbh Dr K	Substituierte Phenylamidine, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung

1998
- 1998-07-23 DE DE19833105A patent/DE19833105A1/de not_active Withdrawn
1999
- 1999-07-19 CO CO99045660A patent/CO5080745A1/es unknown
- 1999-07-20 TR TR2001/00182T patent/TR200100182T2/xx unknown
- 1999-07-20 HU HU0103327A patent/HUP0103327A3/hu unknown
- 1999-07-20 EP EP99938296A patent/EP1102746B1/de not_active Expired - Lifetime
- 1999-07-20 AT AT99938296T patent/ATE240297T1/de not_active IP Right Cessation
- 1999-07-20 DK DK99938296T patent/DK1102746T3/da active
- 1999-07-20 BR BR9912321-5A patent/BR9912321A/pt not_active IP Right Cessation
- 1999-07-20 IL IL14077499A patent/IL140774A0/xx unknown
- 1999-07-20 ES ES99938296T patent/ES2199587T3/es not_active Expired - Lifetime
- 1999-07-20 KR KR1020017001005A patent/KR20010072046A/ko not_active Withdrawn
- 1999-07-20 PT PT99938296T patent/PT1102746E/pt unknown
- 1999-07-20 JP JP2000561164A patent/JP3629208B2/ja not_active Expired - Fee Related
- 1999-07-20 CA CA002337413A patent/CA2337413A1/en not_active Abandoned
- 1999-07-20 CN CN99808971A patent/CN1310708A/zh active Pending
- 1999-07-20 YU YU3701A patent/YU3701A/sh unknown
- 1999-07-20 ID IDW20010171A patent/ID27205A/id unknown
- 1999-07-20 EA EA200100106A patent/EA200100106A1/ru unknown
- 1999-07-20 HK HK02100364.6A patent/HK1038750A1/zh unknown
- 1999-07-20 PL PL99345624A patent/PL345624A1/xx not_active Application Discontinuation
- 1999-07-20 AU AU52853/99A patent/AU5285399A/en not_active Abandoned
- 1999-07-20 WO PCT/EP1999/005161 patent/WO2000005207A1/de not_active Application Discontinuation
- 1999-07-20 SK SK105-2001A patent/SK1052001A3/sk unknown
- 1999-07-20 DE DE59905568T patent/DE59905568D1/de not_active Expired - Fee Related
- 1999-07-20 EE EEP200100048A patent/EE200100048A/xx unknown
- 1999-07-21 TW TW088112395A patent/TW460461B/zh not_active IP Right Cessation
- 1999-07-22 UY UY25621A patent/UY25621A1/es not_active Application Discontinuation
- 1999-07-23 AR ARP990103627A patent/AR019462A1/es not_active Withdrawn
2001
- 2001-01-12 ZA ZA200100363A patent/ZA200100363B/en unknown
- 2001-01-16 BG BG105159A patent/BG105159A/bg active Pending
- 2001-01-22 NO NO20010354A patent/NO20010354D0/no unknown

Also Published As

Publication number	Publication date
HUP0103327A3 (en)	2003-11-28
ATE240297T1 (de)	2003-05-15
AU5285399A (en)	2000-02-14
BR9912321A (pt)	2001-04-24
HUP0103327A2 (hu)	2002-01-28
NO20010354L (no)	2001-01-22
TW460461B (en)	2001-10-21
BG105159A (bg)	2001-07-31
TR200100182T2 (tr)	2001-07-23
ID27205A (id)	2001-03-08
EA200100106A1 (ru)	2001-08-27
PL345624A1 (en)	2002-01-02
CA2337413A1 (en)	2000-02-03
IL140774A0 (en)	2002-02-10
ES2199587T3 (es)	2004-02-16
CO5080745A1 (es)	2001-09-25
JP3629208B2 (ja)	2005-03-16
KR20010072046A (ko)	2001-07-31
ZA200100363B (en)	2001-07-18
EP1102746B1 (de)	2003-05-14
HK1038750A1 (zh)	2002-03-28
UY25621A1 (es)	2001-12-28
YU3701A (sh)	2003-01-31
DE19833105A1 (de)	2000-01-27
PT1102746E (pt)	2003-10-31
NO20010354D0 (no)	2001-01-22
EE200100048A (et)	2002-06-17
AR019462A1 (es)	2002-02-20
DE59905568D1 (de)	2003-06-18
DK1102746T3 (da)	2003-09-08
JP2002521363A (ja)	2002-07-16
CN1310708A (zh)	2001-08-29
WO2000005207A1 (de)	2000-02-03
EP1102746A1 (de)	2001-05-30

Publication	Publication Date	Title
AU668765B2 (en)	1996-05-16	Carboxylic acid derivatives
JP3833116B2 (ja)	2006-10-11	ビフェニル誘導体、その製法及び薬剤としての使用
US5994356A (en)	1999-11-30	Carboxylic acid derivatives, medicaments comprising these compounds, their use and processes for their production
CA2098158A1 (en)	1993-12-12	Biphenyl derivatives, pharmaceutical compositions containing these compounds and processes for preparing them
CZ20022281A3 (cs)	2002-10-16	Substituované piperazinové deriváty jako inhibitory MTP, způsob jejich výroby a pouľití pro výrobu farmaceutického prostředku
SK1052001A3 (en)	2001-08-06	Substituted phenylamidines with antithrombotic action
PL184276B1 (pl)	2002-09-30	Podstawione fenyloamidyny, kompozycje farmaceutyczne zawierające te związki i sposób wytwarzania podstawionych fenyloamidyn
US6242466B1 (en)	2001-06-05	Substituted phenylamidines
US6838460B2 (en)	2005-01-04	Substituted phenylamidines medicaments containing said compounds and method for production thereof
CZ2001285A3 (cs)	2001-05-16	Substituované fenylamidiny s antitrombotickým účinkem
CZ289526B6 (cs)	2002-02-13	(S) nebo (R) Enantiomer piperazinylové sloučeniny a způsob jeho přípravy
MXPA00012835A (es)	2002-05-09	Fenilamidinas sustituidas con accion antitrombotica
CA2244860A1 (en)	1997-10-16	Carboxylic acid derivatives with an aggregation-inhibiting action
HK1009800A (en)	1999-06-11	Substituted phenyl amidines, medicaments containing these compounds and process for producing them