ES2240775T3 - Isoindoles sustituidos y su uso. - Google Patents
Isoindoles sustituidos y su uso.Info
- Publication number
- ES2240775T3 ES2240775T3 ES02751145T ES02751145T ES2240775T3 ES 2240775 T3 ES2240775 T3 ES 2240775T3 ES 02751145 T ES02751145 T ES 02751145T ES 02751145 T ES02751145 T ES 02751145T ES 2240775 T3 ES2240775 T3 ES 2240775T3
- Authority
- ES
- Spain
- Prior art keywords
- uelm
- substituted
- compounds
- formula
- hydroxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 claims abstract description 105
- -1 hydroxy , carbamoyl Chemical group 0.000 claims abstract description 86
- 239000001257 hydrogen Substances 0.000 claims abstract description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 35
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 30
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 19
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 17
- 150000002367 halogens Chemical class 0.000 claims abstract description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 16
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 12
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 10
- 150000004677 hydrates Chemical class 0.000 claims abstract description 9
- 239000012453 solvate Substances 0.000 claims abstract description 9
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims abstract description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 8
- 125000005241 heteroarylamino group Chemical group 0.000 claims abstract description 7
- 125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims abstract description 7
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims abstract description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 5
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims abstract description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 95
- 239000000460 chlorine Chemical group 0.000 claims description 27
- 238000006243 chemical reaction Methods 0.000 claims description 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
- 238000002360 preparation method Methods 0.000 claims description 17
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 14
- 201000010099 disease Diseases 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 230000002265 prevention Effects 0.000 claims description 12
- 230000008569 process Effects 0.000 claims description 12
- 229940079593 drug Drugs 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 108010074860 Factor Xa Proteins 0.000 claims description 10
- 230000023555 blood coagulation Effects 0.000 claims description 10
- 150000001412 amines Chemical class 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 210000004369 blood Anatomy 0.000 claims description 7
- 239000008280 blood Substances 0.000 claims description 7
- 125000001589 carboacyl group Chemical group 0.000 claims description 7
- 230000015271 coagulation Effects 0.000 claims description 7
- 238000005345 coagulation Methods 0.000 claims description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 5
- 206010047249 Venous thrombosis Diseases 0.000 claims description 5
- 150000001298 alcohols Chemical class 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical group OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 claims description 5
- ZENKESXKWBIZCV-UHFFFAOYSA-N 2,2,4,4-tetrafluoro-1,3-benzodioxin-6-amine Chemical group O1C(F)(F)OC(F)(F)C2=CC(N)=CC=C21 ZENKESXKWBIZCV-UHFFFAOYSA-N 0.000 claims description 4
- 206010002383 Angina Pectoris Diseases 0.000 claims description 4
- 206010002388 Angina unstable Diseases 0.000 claims description 4
- 206010051055 Deep vein thrombosis Diseases 0.000 claims description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- 208000010378 Pulmonary Embolism Diseases 0.000 claims description 4
- 206010038563 Reocclusion Diseases 0.000 claims description 4
- 208000007814 Unstable Angina Diseases 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 4
- 238000002399 angioplasty Methods 0.000 claims description 4
- 238000001212 derivatisation Methods 0.000 claims description 4
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 238000000338 in vitro Methods 0.000 claims description 4
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims description 4
- 230000000302 ischemic effect Effects 0.000 claims description 4
- 208000010125 myocardial infarction Diseases 0.000 claims description 4
- 208000037803 restenosis Diseases 0.000 claims description 4
- 230000009424 thromboembolic effect Effects 0.000 claims description 4
- 230000001052 transient effect Effects 0.000 claims description 4
- 208000031104 Arterial Occlusive disease Diseases 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 230000002093 peripheral effect Effects 0.000 claims description 3
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- 208000024827 Alzheimer disease Diseases 0.000 claims description 2
- 201000001320 Atherosclerosis Diseases 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims description 2
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
- 239000013543 active substance Substances 0.000 claims description 2
- 206010003246 arthritis Diseases 0.000 claims description 2
- 239000012472 biological sample Substances 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims 1
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 abstract description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 abstract 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 2
- 125000000041 C6-C10 aryl group Chemical group 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 140
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 49
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 48
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 40
- 239000000203 mixture Substances 0.000 description 40
- 238000004128 high performance liquid chromatography Methods 0.000 description 35
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- 239000000243 solution Substances 0.000 description 28
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 26
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 22
- 238000012360 testing method Methods 0.000 description 22
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 20
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 20
- 239000000047 product Substances 0.000 description 19
- 239000002904 solvent Substances 0.000 description 19
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- 125000004432 carbon atom Chemical group C* 0.000 description 16
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
- 235000019341 magnesium sulphate Nutrition 0.000 description 15
- 239000000126 substance Substances 0.000 description 15
- 239000002253 acid Substances 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- 239000012074 organic phase Substances 0.000 description 13
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 12
- 208000007536 Thrombosis Diseases 0.000 description 12
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- 125000001424 substituent group Chemical group 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- 239000003480 eluent Substances 0.000 description 10
- 238000010898 silica gel chromatography Methods 0.000 description 10
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
- 108090000190 Thrombin Proteins 0.000 description 9
- 208000001435 Thromboembolism Diseases 0.000 description 9
- 229910052799 carbon Inorganic materials 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- 241000700159 Rattus Species 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 8
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 8
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 8
- 229960004072 thrombin Drugs 0.000 description 8
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 7
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 7
- 239000008346 aqueous phase Substances 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 7
- 229960002897 heparin Drugs 0.000 description 7
- 229920000669 heparin Polymers 0.000 description 7
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- 239000012279 sodium borohydride Substances 0.000 description 7
- 229910000033 sodium borohydride Inorganic materials 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 6
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 6
- QKQLMNATBNLYIT-UHFFFAOYSA-N 5-chloro-n-(1,3-dioxoisoindol-4-yl)thiophene-2-carboxamide Chemical compound S1C(Cl)=CC=C1C(=O)NC1=CC=CC2=C1C(=O)NC2=O QKQLMNATBNLYIT-UHFFFAOYSA-N 0.000 description 6
- LYBLACXLYAUVJI-UHFFFAOYSA-N 5-chloro-n-[1,3-dioxo-2-(2-piperidin-4-ylethyl)isoindol-4-yl]thiophene-2-carboxamide Chemical compound S1C(Cl)=CC=C1C(=O)NC1=CC=CC2=C1C(=O)N(CCC1CCNCC1)C2=O LYBLACXLYAUVJI-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
- 229960000583 acetic acid Drugs 0.000 description 6
- 125000003277 amino group Chemical group 0.000 description 6
- 239000003146 anticoagulant agent Substances 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 235000019253 formic acid Nutrition 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- 230000002792 vascular Effects 0.000 description 6
- JTVUXFVAAGYSSR-UHFFFAOYSA-N 5-chloro-n-(1,3-dioxo-2-benzofuran-4-yl)thiophene-2-carboxamide Chemical compound S1C(Cl)=CC=C1C(=O)NC1=CC=CC2=C1C(=O)OC2=O JTVUXFVAAGYSSR-UHFFFAOYSA-N 0.000 description 5
- 108010088842 Fibrinolysin Proteins 0.000 description 5
- 208000032843 Hemorrhage Diseases 0.000 description 5
- 108090000631 Trypsin Proteins 0.000 description 5
- 102000004142 Trypsin Human genes 0.000 description 5
- 229940127219 anticoagulant drug Drugs 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 229940012957 plasmin Drugs 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 229960001322 trypsin Drugs 0.000 description 5
- 239000012588 trypsin Substances 0.000 description 5
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical group C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 239000004698 Polyethylene Substances 0.000 description 4
- 108010022999 Serine Proteases Proteins 0.000 description 4
- 102000012479 Serine Proteases Human genes 0.000 description 4
- 230000008033 biological extinction Effects 0.000 description 4
- 230000017531 blood circulation Effects 0.000 description 4
- 210000001715 carotid artery Anatomy 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
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- 229960005080 warfarin Drugs 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- QYEFBJRXKKSABU-UHFFFAOYSA-N xylazine hydrochloride Chemical compound Cl.CC1=CC=CC(C)=C1NC1=NCCCS1 QYEFBJRXKKSABU-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 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
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or 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
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Psychiatry (AREA)
- Immunology (AREA)
- Cardiology (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10137163A DE10137163A1 (de) | 2001-07-30 | 2001-07-30 | Substituierte Isoindole und ihre Verwendung |
| DE10137163 | 2001-07-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2240775T3 true ES2240775T3 (es) | 2005-10-16 |
Family
ID=7693643
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES02751145T Expired - Lifetime ES2240775T3 (es) | 2001-07-30 | 2002-07-17 | Isoindoles sustituidos y su uso. |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US7189738B2 (enExample) |
| EP (1) | EP1414817B1 (enExample) |
| JP (1) | JP2005506970A (enExample) |
| CA (1) | CA2455772A1 (enExample) |
| DE (2) | DE10137163A1 (enExample) |
| ES (1) | ES2240775T3 (enExample) |
| WO (1) | WO2003011858A1 (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10134482A1 (de) * | 2001-07-16 | 2003-01-30 | Bayer Ag | Substituierte Isoindole und ihre Verwendung |
| US7361672B2 (en) * | 2004-12-23 | 2008-04-22 | Hoffmann-La Roche Inc. | Heteroarylacetamide inhibitors of factor Xa |
| CA2627426A1 (en) * | 2005-11-11 | 2007-05-18 | Markus Boehringer | Carbocyclic fused cyclic amines as inhibitors of the coagulation factor xa |
| TW200806625A (en) * | 2006-05-26 | 2008-02-01 | Astrazeneca Ab | Therapeutic compounds |
| DE102006025317A1 (de) * | 2006-05-31 | 2007-12-06 | Bayer Healthcare Aktiengesellschaft | Isoindolin-1-on-,Isoindolin-3-on und Isoindolin-1,3-dion-Derivate und ihre Verwendung |
| DE102006025318A1 (de) * | 2006-05-31 | 2007-12-06 | Bayer Healthcare Ag | Dihydro-pyrrolopyridin-, Dihydro-pyrrolopyridazin- und Dihydro-pyrrolopyrimidin-Derivate und ihre Verwendung |
| HUP0600810A3 (en) * | 2006-10-27 | 2008-09-29 | Richter Gedeon Nyrt | New sulfonamide derivatives as bradykinin antagonists, process and intermediates for their preparation and pharmaceutical compositions containing them |
| EA030373B1 (ru) * | 2014-04-23 | 2018-07-31 | Такеда Фармасьютикал Компани Лимитед | Изоиндолин-1-оновые производные в качестве положительных аллостерических модуляторов холинергического мускаринового m1 рецептора для лечения болезни альцгеймера |
| CN105061404B (zh) * | 2015-07-21 | 2017-07-11 | 广东炜林纳新材料科技股份有限公司 | 一种亚酰胺类聚丙烯β晶型成核剂及其制备方法 |
| US10513515B2 (en) | 2017-08-25 | 2019-12-24 | Biotheryx, Inc. | Ether compounds and uses thereof |
| EP3830093A1 (en) | 2018-07-27 | 2021-06-09 | Biotheryx, Inc. | Bifunctional compounds as cdk modulators |
| US11897930B2 (en) | 2020-04-28 | 2024-02-13 | Anwita Biosciences, Inc. | Interleukin-2 polypeptides and fusion proteins thereof, and their pharmaceutical compositions and therapeutic applications |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU8270898A (en) * | 1997-06-26 | 1999-01-19 | Eli Lilly And Company | Antithrombotic agents |
| GB9715894D0 (en) | 1997-07-29 | 1997-10-01 | Zeneca Ltd | Heterocyclic derivatives |
| US6140351A (en) * | 1997-12-19 | 2000-10-31 | Berlex Laboratories, Inc. | Ortho-anthranilamide derivatives as anti-coagulants |
| IL137517A0 (en) | 1998-01-27 | 2001-07-24 | Aventis Pharm Prod Inc | Substituted oxoazaheterocyclyl factor xa inhibitors |
| US6534651B2 (en) | 2000-04-06 | 2003-03-18 | Inotek Pharmaceuticals Corp. | 7-Substituted isoindolinone inhibitors of inflammation and reperfusion injury and methods of use thereof |
| NZ526003A (en) | 2000-10-20 | 2005-09-30 | Biocryst Pharm Inc | Biaryl compounds as serine protease inhibitors |
| US20030045552A1 (en) * | 2000-12-27 | 2003-03-06 | Robarge Michael J. | Isoindole-imide compounds, compositions, and uses thereof |
-
2001
- 2001-07-30 DE DE10137163A patent/DE10137163A1/de not_active Withdrawn
-
2002
- 2002-07-17 DE DE50202730T patent/DE50202730D1/de not_active Expired - Fee Related
- 2002-07-17 JP JP2003517050A patent/JP2005506970A/ja active Pending
- 2002-07-17 CA CA002455772A patent/CA2455772A1/en not_active Abandoned
- 2002-07-17 EP EP02751145A patent/EP1414817B1/de not_active Expired - Lifetime
- 2002-07-17 WO PCT/EP2002/007957 patent/WO2003011858A1/de not_active Ceased
- 2002-07-17 ES ES02751145T patent/ES2240775T3/es not_active Expired - Lifetime
- 2002-07-17 US US10/485,412 patent/US7189738B2/en not_active Expired - Fee Related
-
2007
- 2007-03-12 US US11/717,414 patent/US7482472B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US7189738B2 (en) | 2007-03-13 |
| JP2005506970A (ja) | 2005-03-10 |
| EP1414817A1 (de) | 2004-05-06 |
| DE50202730D1 (de) | 2005-05-12 |
| DE10137163A1 (de) | 2003-02-13 |
| US20080039446A1 (en) | 2008-02-14 |
| US20040215019A1 (en) | 2004-10-28 |
| WO2003011858A1 (de) | 2003-02-13 |
| EP1414817B1 (de) | 2005-04-06 |
| CA2455772A1 (en) | 2003-02-13 |
| US7482472B2 (en) | 2009-01-27 |
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