NO312894B1 - Heterocykelderivater som inhiberer faktor Xa, farmasöytisk formulering og fremgangsmåte for fremstilling derav - Google Patents
Heterocykelderivater som inhiberer faktor Xa, farmasöytisk formulering og fremgangsmåte for fremstilling derav Download PDFInfo
- Publication number
- NO312894B1 NO312894B1 NO19992230A NO992230A NO312894B1 NO 312894 B1 NO312894 B1 NO 312894B1 NO 19992230 A NO19992230 A NO 19992230A NO 992230 A NO992230 A NO 992230A NO 312894 B1 NO312894 B1 NO 312894B1
- Authority
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- Norway
- Prior art keywords
- formula
- ppm
- compound
- group
- piperazine
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 34
- 108010074860 Factor Xa Proteins 0.000 title claims description 18
- 238000002360 preparation method Methods 0.000 title claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 5
- 230000008569 process Effects 0.000 title claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 title description 9
- 150000001875 compounds Chemical class 0.000 claims description 91
- 238000006243 chemical reaction Methods 0.000 claims description 19
- 239000002253 acid Substances 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 11
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 10
- -1 1,4-piperazinediyl Chemical group 0.000 claims description 9
- 230000002401 inhibitory effect Effects 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 238000007363 ring formation reaction Methods 0.000 claims description 5
- 238000005859 coupling reaction Methods 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000000524 functional group Chemical group 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- PSTBXECIKAJFMC-UHFFFAOYSA-N [4-(6-chloronaphthalen-2-yl)sulfonylpiperazin-1-yl]-(4-pyridin-4-ylphenyl)methanone Chemical compound C1=CC2=CC(Cl)=CC=C2C=C1S(=O)(=O)N(CC1)CCN1C(=O)C(C=C1)=CC=C1C1=CC=NC=C1 PSTBXECIKAJFMC-UHFFFAOYSA-N 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- SGUBDMZIXCTGGS-UHFFFAOYSA-N [4-(6-bromonaphthalen-2-yl)sulfonylpiperazin-1-yl]-(4-pyrimidin-4-ylphenyl)methanone Chemical group C1=CC2=CC(Br)=CC=C2C=C1S(=O)(=O)N(CC1)CCN1C(=O)C(C=C1)=CC=C1C1=CC=NC=N1 SGUBDMZIXCTGGS-UHFFFAOYSA-N 0.000 claims description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
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- 235000019341 magnesium sulphate Nutrition 0.000 description 6
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- UMTQOAOMAZQBTA-UHFFFAOYSA-N 1-(6-bromonaphthalen-2-yl)sulfonylpiperazine;hydrochloride Chemical compound Cl.C1=CC2=CC(Br)=CC=C2C=C1S(=O)(=O)N1CCNCC1 UMTQOAOMAZQBTA-UHFFFAOYSA-N 0.000 description 3
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- 229950003499 fibrin Drugs 0.000 description 1
- 239000003527 fibrinolytic agent Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229940087051 fragmin Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000002682 general surgery Methods 0.000 description 1
- 210000003709 heart valve Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000011540 hip replacement Methods 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 230000000055 hyoplipidemic effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000012623 in vivo measurement Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 1
- 201000010849 intracranial embolism Diseases 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000008263 liquid aerosol Substances 0.000 description 1
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- UYVXZUTYZGILQG-UHFFFAOYSA-N methoxyboronic acid Chemical compound COB(O)O UYVXZUTYZGILQG-UHFFFAOYSA-N 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- KGVQAANSYPONFM-UHFFFAOYSA-N methyl 2-[4-(6-bromonaphthalen-2-yl)sulfonylpiperazine-1-carbonyl]-5-pyridin-4-ylbenzoate Chemical compound C=1C=C(C(=O)N2CCN(CC2)S(=O)(=O)C=2C=C3C=CC(Br)=CC3=CC=2)C(C(=O)OC)=CC=1C1=CC=NC=C1 KGVQAANSYPONFM-UHFFFAOYSA-N 0.000 description 1
- HEROHJCPUUNJDV-UHFFFAOYSA-N methyl 4-(6-chloronaphthalen-2-yl)sulfonylpiperazine-2-carboxylate;hydrochloride Chemical compound Cl.C1CNC(C(=O)OC)CN1S(=O)(=O)C1=CC=C(C=C(Cl)C=C2)C2=C1 HEROHJCPUUNJDV-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- CUQOHAYJWVTKDE-UHFFFAOYSA-N potassium;butan-1-olate Chemical compound [K+].CCCC[O-] CUQOHAYJWVTKDE-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 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
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical compound [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 1
- 229910000080 stannane Inorganic materials 0.000 description 1
- 229960005202 streptokinase Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- VAGPACMEEDNFDA-UHFFFAOYSA-N tert-butyl 4-(2-methyl-4-pyridin-3-ylbenzoyl)piperazine-1-carboxylate Chemical compound CC1=CC(C=2C=NC=CC=2)=CC=C1C(=O)N1CCN(C(=O)OC(C)(C)C)CC1 VAGPACMEEDNFDA-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 229960003766 thrombin (human) Drugs 0.000 description 1
- 229960000103 thrombolytic agent Drugs 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 239000002396 thromboxane receptor blocking agent Substances 0.000 description 1
- 239000003768 thromboxane synthase inhibitor Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229960000187 tissue plasminogen activator Drugs 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 229940038773 trisodium citrate Drugs 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000003966 vascular damage Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 210000001631 vena cava inferior Anatomy 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/73—Unsubstituted amino or imino radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—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
- C07D213/56—Amides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/61—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/84—Nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/89—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/08—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/26—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB9623283.0A GB9623283D0 (en) | 1996-11-08 | 1996-11-08 | Heterocyclic derivatives |
GBGB9715893.5A GB9715893D0 (en) | 1997-07-29 | 1997-07-29 | Heterocyclic derivatives |
PCT/GB1997/003033 WO1998021188A1 (en) | 1996-11-08 | 1997-11-04 | HETEROCYCLE DERIVATIVES WHICH INHIBIT FACTOR Xa |
Publications (3)
Publication Number | Publication Date |
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NO992230D0 NO992230D0 (no) | 1999-05-07 |
NO992230L NO992230L (no) | 1999-05-07 |
NO312894B1 true NO312894B1 (no) | 2002-07-15 |
Family
ID=26310361
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO19992230A NO312894B1 (no) | 1996-11-08 | 1999-05-07 | Heterocykelderivater som inhiberer faktor Xa, farmasöytisk formulering og fremgangsmåte for fremstilling derav |
Country Status (28)
Country | Link |
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US (2) | US6300330B1 (sk) |
EP (2) | EP1358909A1 (sk) |
JP (1) | JP2001504113A (sk) |
KR (1) | KR20000053128A (sk) |
CN (1) | CN1220682C (sk) |
AT (1) | ATE258167T1 (sk) |
AU (1) | AU731929B2 (sk) |
BG (1) | BG64258B1 (sk) |
BR (1) | BR9712672A (sk) |
CA (1) | CA2266890A1 (sk) |
CZ (1) | CZ296342B6 (sk) |
DE (1) | DE69727308T2 (sk) |
DK (1) | DK0937048T3 (sk) |
ES (1) | ES2213208T3 (sk) |
HU (1) | HUP0001098A3 (sk) |
IL (1) | IL129706A (sk) |
MY (1) | MY124122A (sk) |
NO (1) | NO312894B1 (sk) |
NZ (1) | NZ334710A (sk) |
PL (1) | PL189703B1 (sk) |
PT (1) | PT937048E (sk) |
RU (2) | RU2213732C2 (sk) |
SK (1) | SK284665B6 (sk) |
TR (1) | TR199901006T2 (sk) |
TW (1) | TW458968B (sk) |
UA (1) | UA56197C2 (sk) |
WO (1) | WO1998021188A1 (sk) |
YU (1) | YU20999A (sk) |
Families Citing this family (43)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL115420A0 (en) | 1994-09-26 | 1995-12-31 | Zeneca Ltd | Aminoheterocyclic derivatives |
EP0880501A1 (en) | 1996-02-02 | 1998-12-02 | Zeneca Limited | Heterocyclic compounds useful as pharmaceutical agents |
UA56197C2 (uk) | 1996-11-08 | 2003-05-15 | Зенека Лімітед | Гетероциклічні похідні |
EP0966462B1 (en) | 1997-02-13 | 2003-06-11 | AstraZeneca AB | Heterocyclic compounds useful as oxido-squalene cyclase inhibitors |
WO1998035956A1 (en) | 1997-02-13 | 1998-08-20 | Zeneca Limited | Heterocyclic compounds useful as oxido-squalene cyclase inhibitors |
EP0986551B1 (en) | 1997-05-30 | 2006-08-02 | Takeda Pharmaceutical Company Limited | Sulfonamide derivatives, their production and use |
GB9715895D0 (en) | 1997-07-29 | 1997-10-01 | Zeneca Ltd | Heterocyclic compounds |
GB9715894D0 (en) * | 1997-07-29 | 1997-10-01 | Zeneca Ltd | Heterocyclic derivatives |
JP4256065B2 (ja) * | 1997-09-30 | 2009-04-22 | 第一三共株式会社 | スルホニル誘導体 |
KR20010034442A (ko) | 1998-01-27 | 2001-04-25 | 아벤티스 파마슈티칼즈 프로덕츠 인코포레이티드 | 치환된 옥소아자헤테로사이클릴 인자 Xa 억제제 |
US6403595B1 (en) | 1998-02-05 | 2002-06-11 | Takeda Chemical Industries, Ltd. | Sulfonamide derivatives, processes for producing the same and utilization thereof |
GB9809350D0 (en) * | 1998-05-02 | 1998-07-01 | Zeneca Ltd | Novel salt |
GB9809349D0 (en) * | 1998-05-02 | 1998-07-01 | Zeneca Ltd | Heterocyclic derivatives |
EP1082321B1 (en) * | 1998-05-02 | 2004-11-17 | AstraZeneca AB | Heterocyclic derivatives which inhibit factor xa |
WO2000009480A1 (fr) * | 1998-08-11 | 2000-02-24 | Daiichi Pharmaceutical Co., Ltd. | Nouveaux derives sulfonyle |
CA2348740A1 (en) | 1998-12-23 | 2000-07-06 | Ruth R. Wexler | Thrombin or factor xa inhibitors |
GB9902989D0 (en) | 1999-02-11 | 1999-03-31 | Zeneca Ltd | Heterocyclic derivatives |
TW200404789A (en) | 1999-03-15 | 2004-04-01 | Axys Pharm Inc | Novel compounds and compositions as protease inhibitors |
GB9914342D0 (en) * | 1999-06-19 | 1999-08-18 | Zeneca Ltd | Compound |
EP1188755B1 (en) | 1999-06-22 | 2006-05-03 | Takeda Pharmaceutical Company Limited | Acylhydrazine derivatives, process for preparing the same and use thereof |
GB9917344D0 (en) * | 1999-07-24 | 1999-09-22 | Zeneca Ltd | Novel salt |
EE200200045A (et) * | 1999-07-28 | 2003-06-16 | Aventis Pharmaceuticals Products Inc. | Asendatud oksoasaheterotsüklüülühendid, farmatseutiline kompositsioon ja vaheühendid |
TWI290136B (en) | 2000-04-05 | 2007-11-21 | Daiichi Seiyaku Co | Ethylenediamine derivatives |
GB0012448D0 (en) | 2000-05-24 | 2000-07-12 | Astrazeneca Ab | New process |
EP1322643A1 (en) * | 2000-09-29 | 2003-07-02 | Millennium Pharmaceuticals, Inc. | Piperazin-2-one amides as inhibitors of factor xa |
CA2426009C (en) | 2000-11-02 | 2008-10-07 | F. Hoffmann-La Roche Ag | Cholesterol lowering benzo[b]thiophenes and benzo[d]isothiazoles |
MXPA03005601A (es) | 2000-12-22 | 2004-12-02 | Axys Pharm Inc | Nuevos compuestos y composiciones como inhibidores de catepsina. |
US7030116B2 (en) | 2000-12-22 | 2006-04-18 | Aventis Pharmaceuticals Inc. | Compounds and compositions as cathepsin inhibitors |
US7365205B2 (en) | 2001-06-20 | 2008-04-29 | Daiichi Sankyo Company, Limited | Diamine derivatives |
EP1430068A1 (en) | 2001-09-17 | 2004-06-23 | Ortho-Mcneil Pharmaceutical, Inc. | 6-o-carbamate-11,12-lacto-ketolide antimicrobials |
RU2004117877A (ru) | 2001-11-14 | 2006-01-10 | Авентис Фармасьютикалз Инк. (Us) | Олигопептиды и композиции, содержащие их, в качестве ингибиторов катепсина s |
NZ533282A (en) | 2001-12-05 | 2006-09-29 | Ortho Mcneil Pharm Inc | 6-O-Acyl ketolide derivatives of erythromycine useful as antibacterials |
AU2003265398A1 (en) * | 2002-08-09 | 2004-02-25 | Transtech Pharma, Inc. | Aryl and heteroaryl compounds and methods to modulate coagulation |
EP2982668A3 (en) | 2002-12-03 | 2016-04-13 | Pharmacyclics LLC | 2-(2-hydroxybiphenyl-3-yl)-1h-benzoimidazole-5-carboxamidine derivatives as factor viia inhibitors for the treatment of thromboembolic disorders |
MXPA05006989A (es) * | 2002-12-25 | 2005-09-22 | Daiichi Seiyaku Co | Derivados de diamina. |
US7208601B2 (en) * | 2003-08-08 | 2007-04-24 | Mjalli Adnan M M | Aryl and heteroaryl compounds, compositions, and methods of use |
WO2005014532A1 (en) * | 2003-08-08 | 2005-02-17 | Transtech Pharma, Inc. | Aryl and heteroaryl compounds, compositions and methods of use |
CN101128428A (zh) * | 2005-02-24 | 2008-02-20 | 詹森药业有限公司 | 作为钾离子通道打开剂的新的吡啶衍生物 |
WO2007008145A1 (en) * | 2005-07-08 | 2007-01-18 | Astrazeneca Ab | Heterocyclic sulfonamide derivatives as inhibitors of factor xa |
JP4987324B2 (ja) * | 2006-03-03 | 2012-07-25 | エヌ・イーケムキャット株式会社 | 炭素−炭素結合の生成方法 |
GB0813142D0 (en) | 2008-07-17 | 2008-08-27 | Glaxo Group Ltd | Novel compounds |
LT3993876T (lt) | 2019-07-01 | 2024-11-11 | Tonix Pharma Limited | Antikūnai prieš cd154 ir jų panaudojimas |
EP4274587A1 (en) | 2021-01-06 | 2023-11-15 | Tonix Pharma Limited | Methods of inducing immune tolerance with modified anti-cd154 antibodies |
Family Cites Families (57)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AT340933B (de) | 1973-08-20 | 1978-01-10 | Thomae Gmbh Dr K | Verfahren zur herstellung neuer pyrimidinderivate und ihrer saureadditionssalze |
US4167567A (en) | 1978-05-05 | 1979-09-11 | The Upjohn Company | Antihypertensive 4-aminoquinolines |
US4231938A (en) | 1979-06-15 | 1980-11-04 | Merck & Co., Inc. | Hypocholesteremic fermentation products and process of preparation |
SE8203887D0 (sv) | 1982-06-23 | 1982-06-23 | Kabivitrum Ab | Nya trombininhiberande foreningar |
DE3246932A1 (de) | 1982-12-16 | 1984-06-20 | Schering AG, 1000 Berlin und 4709 Bergkamen | Substituierte 5h-pyrimido(5,4-b)indole |
FR2557570B1 (fr) | 1984-01-04 | 1986-04-18 | Adir | Nouveaux derives de la quinoleine, leur procede de preparation et les compositions pharmaceutiques les renfermant |
US4840963A (en) | 1984-03-14 | 1989-06-20 | Merck & Co., Inc. | 2-Sulfamoyl-1H-indole derivatives for the treatment of elevated intraocular pressure |
GB8601160D0 (en) | 1986-01-17 | 1986-02-19 | Fujisawa Pharmaceutical Co | Heterocyclic compounds |
GB8603120D0 (en) | 1986-02-07 | 1986-03-12 | Pfizer Ltd | Anti-dysrhythmia agents |
GB8609630D0 (en) | 1986-04-19 | 1986-05-21 | Pfizer Ltd | Anti-arrhythmia agents |
GB8710494D0 (en) | 1987-05-02 | 1987-06-03 | Pfizer Ltd | Antiarrhythmic agents |
JPH0696575B2 (ja) | 1987-09-17 | 1994-11-30 | 三菱化成株式会社 | 4−アミノピリジン誘導体及びその酸付加塩 |
US4871721A (en) | 1988-01-11 | 1989-10-03 | E. R. Squibb & Sons, Inc. | Phosphorus-containing squalene synthetase inhibitors |
GB8817315D0 (en) | 1988-07-20 | 1988-08-24 | Pfizer Ltd | Triazole antifungal agents |
GB8819307D0 (en) | 1988-08-13 | 1988-09-14 | Pfizer Ltd | Antiarrhythmic agents |
DE3905364A1 (de) | 1989-02-22 | 1990-08-23 | Hoechst Ag | Substituierte pyrimidin-derivate, verfahren zu ihrer herstellung und ihre verwendung als tool |
IL94805A (en) * | 1989-06-28 | 1994-04-12 | Ciba Geigy Ag | Certain translocated carboxylic acids (a) Arylsulfonamide - and pyridyl - or imidazolil (), process for their preparation and pharmaceutical preparations containing them |
IE64358B1 (en) | 1989-07-18 | 1995-07-26 | Ici Plc | Diaryl ether heterocycles |
US5032604A (en) | 1989-12-08 | 1991-07-16 | Merck & Co., Inc. | Class III antiarrhythmic agents |
DE3943225A1 (de) | 1989-12-23 | 1991-06-27 | Schering Ag | Neue ss-carboline, verfahren zu deren herstellung und deren verwendung in arzneimitteln |
JPH05503300A (ja) | 1990-11-15 | 1993-06-03 | ペンタファルム アクチェンゲゼルシャフト | メタ置換フェニルアラニン誘導体 |
DE4036552C1 (sk) | 1990-11-16 | 1992-02-06 | Boehringer Mannheim Gmbh, 6800 Mannheim, De | |
EP0495750A3 (en) | 1991-01-14 | 1992-09-16 | Ciba-Geigy Ag | Heterocyclic hydroxylamine |
IT1245712B (it) | 1991-04-09 | 1994-10-14 | Boehringer Mannheim Italia | Ammine eterocicliche utili terapia dell'asma e dell'infiammazione delle vie aeree |
FR2676054B1 (fr) | 1991-05-03 | 1993-09-03 | Sanofi Elf | Nouveaux composes n-alkylenepiperidino et leurs enantiomeres, procede pour leur preparation et compositions pharmaceutiques les contenant. |
EP0589985A1 (en) | 1991-06-21 | 1994-04-06 | Boehringer Mannheim Italia S.P.A. | 2-amino-4-aryl-thiazoles with antiasthmatic and anti-inflammatory activities on the respiratory tract |
EP0604529A1 (en) | 1991-09-19 | 1994-07-06 | Smithkline Beecham Corporation | Pyridine compounds for treating leukotriene-related diseases |
PH31294A (en) | 1992-02-13 | 1998-07-06 | Thomae Gmbh Dr K | Benzimidazolyl derivatives, pharmaceutical compositions containing these compounds and process for preparing them. |
HU211995B (en) | 1992-06-30 | 1996-01-29 | Gyogyszerkutato Intezet | Process to prepare novel benzoyl amino acid derivs. and pharmaceutical compns. contg.them |
US5371091A (en) | 1992-08-31 | 1994-12-06 | Bristol-Myers Squibb Company | Heteroaromatic amine thrombin inhibitors |
FR2697252B1 (fr) | 1992-10-28 | 1994-12-09 | Fournier Ind & Sante | Dérivés de 1,2,3,5,6,7,8,8a-octahydro-5,5,8a-triméthyl-(8abeta)-6-isoquinolineamine, leur procédé de préparation et leur utilisation en thérapeutique. |
DE4243858A1 (de) | 1992-12-23 | 1994-06-30 | Thomae Gmbh Dr K | Aminosäurederivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
US5332822A (en) | 1992-12-24 | 1994-07-26 | Bristol-Myers Squibb Company | Heteroaromatic and thioheteroaromatic substituted sulfonamide thrombin inhibitors |
US5364865A (en) | 1992-12-30 | 1994-11-15 | Sterling Winthrop Inc. | Phenoxy- and phenoxyalkyl-piperidines as antiviral agents |
DE4302485A1 (de) | 1993-01-29 | 1994-08-04 | Merck Patent Gmbh | Piperazinderivate |
CZ245994A3 (en) | 1993-02-10 | 1995-10-18 | Pentapharm Ag | Piperazides of substituted phenylalanine derivatives as thrombin inhibitors |
DE4306506A1 (de) | 1993-03-03 | 1994-09-08 | Boehringer Mannheim Gmbh | Neue 4-Alkylaminopyridine - Verfahren zu ihrer Herstellung sowie diese Verbindungen enthaltende Arzneimittel |
TW257757B (sk) | 1993-03-03 | 1995-09-21 | Boehringer Mannheim Gmbh | |
DE4306873A1 (de) | 1993-03-05 | 1994-09-08 | Boehringer Mannheim Gmbh | Neue 4-Aminopyridine-Verfahren zu ihrer Herstellung sowie diese Verbindungen enthaltende Arzneimittel |
AU692439B2 (en) | 1993-03-29 | 1998-06-11 | Zeneca Limited | Heterocyclic compounds as platelet aggregation inhibitors |
PT825184E (pt) | 1993-03-29 | 2001-11-30 | Astrazeneca Ab | Derivados heterociclicos como inibidores de agregacao de plaquetas |
US5681954A (en) | 1993-05-14 | 1997-10-28 | Daiichi Pharmaceutical Co., Ltd. | Piperazine derivatives |
WO1996005189A1 (de) | 1994-08-09 | 1996-02-22 | Pentapharm Ag | Neue inhibitoren vom benzamidintyp |
IL115420A0 (en) * | 1994-09-26 | 1995-12-31 | Zeneca Ltd | Aminoheterocyclic derivatives |
EP0801650A4 (en) | 1994-12-22 | 1998-05-06 | Smithkline Beecham Corp | FIBRINOGEN RECEPTOR ANTAGONISTS |
JPH10511359A (ja) | 1994-12-22 | 1998-11-04 | スミスクライン・ビーチャム・コーポレイション | フィブリノゲン受容体拮抗物質 |
IL117149A0 (en) | 1995-02-23 | 1996-06-18 | Schering Corp | Muscarinic antagonists |
IL117580A0 (en) | 1995-03-29 | 1996-07-23 | Merck & Co Inc | Inhibitors of farnesyl-protein transferase and pharmaceutical compositions containing them |
US5856326A (en) | 1995-03-29 | 1999-01-05 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
IT1282797B1 (it) | 1995-04-21 | 1998-03-31 | Colla Paolo | Pirril-(indolil)-aril-sulfoni e relativo processo di produzione ed impiego nella terapia delle infezioni da virus dell'aids |
GB9516709D0 (en) | 1995-08-15 | 1995-10-18 | Zeneca Ltd | Medicament |
EP0880501A1 (en) | 1996-02-02 | 1998-12-02 | Zeneca Limited | Heterocyclic compounds useful as pharmaceutical agents |
GB9602166D0 (en) * | 1996-02-02 | 1996-04-03 | Zeneca Ltd | Aminoheterocyclic derivatives |
GB9602294D0 (en) | 1996-02-05 | 1996-04-03 | Zeneca Ltd | Heterocyclic compounds |
PT892780E (pt) * | 1996-02-22 | 2003-02-28 | Bristol Myers Squibb Pharma Co | Analogos de m-amidino fenilo como inibidores do factor xa |
TR199900303T2 (xx) | 1996-08-14 | 1999-06-21 | Zeneca Limited | �kame edilmi� pirimidin t�revleri ve bunlar�n farmas�tik kullan�m�. |
UA56197C2 (uk) | 1996-11-08 | 2003-05-15 | Зенека Лімітед | Гетероциклічні похідні |
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- 1997-11-04 TR TR1999/01006T patent/TR199901006T2/xx unknown
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- 1997-11-04 WO PCT/GB1997/003033 patent/WO1998021188A1/en active IP Right Grant
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- 1997-11-04 BR BR9712672-1A patent/BR9712672A/pt not_active Application Discontinuation
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