JP2937589B2 - 環状イミノ誘導体、これらの化合物を含む製薬組成物及びそれらの調製方法 - Google Patents
環状イミノ誘導体、これらの化合物を含む製薬組成物及びそれらの調製方法Info
- Publication number
- JP2937589B2 JP2937589B2 JP3313154A JP31315491A JP2937589B2 JP 2937589 B2 JP2937589 B2 JP 2937589B2 JP 3313154 A JP3313154 A JP 3313154A JP 31315491 A JP31315491 A JP 31315491A JP 2937589 B2 JP2937589 B2 JP 2937589B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- substituted
- silica gel
- pyrrolidinone
- value
- 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 title claims abstract description 142
- 238000000034 method Methods 0.000 title claims abstract description 10
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 3
- 238000002360 preparation method Methods 0.000 title abstract description 4
- 150000003839 salts Chemical class 0.000 claims abstract description 33
- -1 phenylsulfenyl Chemical group 0.000 claims description 265
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 87
- 125000000217 alkyl group Chemical group 0.000 claims description 82
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 63
- 125000003545 alkoxy group Chemical group 0.000 claims description 54
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 37
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 35
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 31
- 125000002947 alkylene group Chemical group 0.000 claims description 29
- 125000004432 carbon atom Chemical group C* 0.000 claims description 29
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 27
- 229910052801 chlorine Inorganic materials 0.000 claims description 27
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 25
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 24
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 19
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 19
- 239000000460 chlorine Substances 0.000 claims description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 16
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical group O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 15
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 14
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 14
- 229910052731 fluorine Inorganic materials 0.000 claims description 14
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 13
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- 125000004647 alkyl sulfenyl group Chemical group 0.000 claims description 12
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 12
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 11
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 11
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 10
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 10
- 229910052794 bromium Chemical group 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims description 10
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 9
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 9
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 9
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 8
- 239000011737 fluorine Substances 0.000 claims description 8
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 8
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 5
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 5
- 125000000638 benzylaminocarbonyl group Chemical group C(C1=CC=CC=C1)NC(=O)* 0.000 claims description 5
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 5
- 125000002071 phenylalkoxy group Chemical group 0.000 claims description 5
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 5
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 4
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 4
- 239000004305 biphenyl Substances 0.000 claims description 4
- 235000010290 biphenyl Nutrition 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000006260 ethylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 4
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 230000002785 anti-thrombosis Effects 0.000 claims description 3
- 239000003146 anticoagulant agent Substances 0.000 claims description 3
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 3
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 125000005805 dimethoxy phenyl group Chemical group 0.000 claims description 2
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 7
- 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims 2
- IKZACQMAVUIGPY-HOTGVXAUSA-N fradafiban Chemical compound C1=CC(C(=N)N)=CC=C1C(C=C1)=CC=C1OC[C@H]1NC(=O)[C@H](CC(O)=O)C1 IKZACQMAVUIGPY-HOTGVXAUSA-N 0.000 claims 2
- PGCFXITVMNNKON-ROUUACIJSA-N lefradafiban Chemical compound N1C(=O)[C@H](CC(=O)OC)C[C@H]1COC1=CC=C(C=2C=CC(=CC=2)C(=N)NC(=O)OC)C=C1 PGCFXITVMNNKON-ROUUACIJSA-N 0.000 claims 2
- 125000006678 phenoxycarbonyl group Chemical group 0.000 claims 2
- TTZNALWEAVOYKD-UHFFFAOYSA-N 1-ethenoxy-2-phenylbenzene Chemical group C=COC1=CC=CC=C1C1=CC=CC=C1 TTZNALWEAVOYKD-UHFFFAOYSA-N 0.000 claims 1
- UGTHWNIGSYZNJB-KBPBESRZSA-N 2-[(3s,5s)-5-[[4-(4-carbamimidoyl-3-fluorophenyl)phenoxy]methyl]-2-oxopyrrolidin-3-yl]acetic acid Chemical compound C1=C(F)C(C(=N)N)=CC=C1C(C=C1)=CC=C1OC[C@H]1NC(=O)[C@H](CC(O)=O)C1 UGTHWNIGSYZNJB-KBPBESRZSA-N 0.000 claims 1
- WDUIUOFAFWCIKB-UIOOFZCWSA-N 2-[(3s,5s)-5-[[4-(4-carbamimidoylphenyl)-2,3-dimethylphenoxy]methyl]-2-oxo-1-(3-phenylpropyl)pyrrolidin-3-yl]acetic acid Chemical compound O=C([C@H](CC(O)=O)C[C@H]1COC2=CC=C(C(C)=C2C)C=2C=CC(=CC=2)C(N)=N)N1CCCC1=CC=CC=C1 WDUIUOFAFWCIKB-UIOOFZCWSA-N 0.000 claims 1
- PEUZGDCTOKAEBL-OALUTQOASA-N 2-[(3s,5s)-5-[[4-(4-carbamimidoylphenyl)phenoxy]methyl]-1-[2-(dimethylamino)-2-oxoethyl]-2-oxopyrrolidin-3-yl]acetic acid Chemical compound C1[C@@H](CC(O)=O)C(=O)N(CC(=O)N(C)C)[C@@H]1COC1=CC=C(C=2C=CC(=CC=2)C(N)=N)C=C1 PEUZGDCTOKAEBL-OALUTQOASA-N 0.000 claims 1
- WPYAKRHWSXYNPP-IRXDYDNUSA-N 2-[(3s,5s)-5-[[4-(4-carbamimidoylphenyl)phenoxy]methyl]-1-methyl-2-oxopyrrolidin-3-yl]acetic acid Chemical compound C1[C@@H](CC(O)=O)C(=O)N(C)[C@@H]1COC1=CC=C(C=2C=CC(=CC=2)C(N)=N)C=C1 WPYAKRHWSXYNPP-IRXDYDNUSA-N 0.000 claims 1
- OCPOXFXBJLSWBJ-DQEYMECFSA-N 2-[(3s,5s)-5-[[4-(4-carbamimidoylphenyl)phenoxy]methyl]-2-oxo-1-(3-phenylpropyl)pyrrolidin-3-yl]acetic acid Chemical compound C1=CC(C(=N)N)=CC=C1C(C=C1)=CC=C1OC[C@H]1N(CCCC=2C=CC=CC=2)C(=O)[C@H](CC(O)=O)C1 OCPOXFXBJLSWBJ-DQEYMECFSA-N 0.000 claims 1
- MMILHWWEEAFASW-UNMCSNQZSA-N 2-[(3s,5s)-5-[[4-(4-carbamimidoylphenyl)phenoxy]methyl]-2-oxo-1-phenylpyrrolidin-3-yl]acetic acid Chemical compound C1=CC(C(=N)N)=CC=C1C(C=C1)=CC=C1OC[C@H]1N(C=2C=CC=CC=2)C(=O)[C@H](CC(O)=O)C1 MMILHWWEEAFASW-UNMCSNQZSA-N 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- UHYITUGSXYQQEV-IRXDYDNUSA-N methyl 2-[(3s,5s)-5-[[4-(4-carbamimidoylphenyl)phenoxy]methyl]-2-oxopyrrolidin-3-yl]acetate Chemical compound N1C(=O)[C@H](CC(=O)OC)C[C@H]1COC1=CC=C(C=2C=CC(=CC=2)C(N)=N)C=C1 UHYITUGSXYQQEV-IRXDYDNUSA-N 0.000 claims 1
- 230000002776 aggregation Effects 0.000 abstract description 6
- 238000004220 aggregation Methods 0.000 abstract description 6
- 230000002401 inhibitory effect Effects 0.000 abstract description 5
- 150000007524 organic acids Chemical class 0.000 abstract description 5
- 150000007522 mineralic acids Chemical class 0.000 abstract description 4
- 235000005985 organic acids Nutrition 0.000 abstract description 4
- 230000000144 pharmacologic effect Effects 0.000 abstract description 3
- 230000008569 process Effects 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 576
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 492
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 414
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 310
- 229910002027 silica gel Inorganic materials 0.000 description 309
- 239000000741 silica gel Substances 0.000 description 308
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 207
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 168
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 129
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 125
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 113
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 112
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 103
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 99
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 90
- 239000002904 solvent Substances 0.000 description 88
- 239000000203 mixture Substances 0.000 description 87
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 84
- 229910052757 nitrogen Inorganic materials 0.000 description 81
- 230000008018 melting Effects 0.000 description 77
- 238000002844 melting Methods 0.000 description 77
- 125000004433 nitrogen atom Chemical group N* 0.000 description 72
- 239000000243 solution Substances 0.000 description 64
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 63
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 60
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 57
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 56
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 54
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 49
- 239000002253 acid Substances 0.000 description 45
- 125000003277 amino group Chemical group 0.000 description 44
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 40
- 229960000583 acetic acid Drugs 0.000 description 40
- 239000012362 glacial acetic acid Substances 0.000 description 36
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 33
- 229910052799 carbon Inorganic materials 0.000 description 33
- 238000006243 chemical reaction Methods 0.000 description 33
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 32
- 238000003756 stirring Methods 0.000 description 32
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 30
- 238000001704 evaporation Methods 0.000 description 30
- 150000001721 carbon Chemical group 0.000 description 29
- 230000008020 evaporation Effects 0.000 description 28
- 239000012074 organic phase Substances 0.000 description 28
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 25
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 24
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 24
- 125000001841 imino group Chemical group [H]N=* 0.000 description 24
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 24
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 24
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 22
- 239000003208 petroleum Substances 0.000 description 22
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 22
- 125000003118 aryl group Chemical group 0.000 description 21
- 238000001816 cooling Methods 0.000 description 21
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 21
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 20
- 125000003710 aryl alkyl group Chemical group 0.000 description 20
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 19
- 235000011114 ammonium hydroxide Nutrition 0.000 description 19
- 239000002244 precipitate Substances 0.000 description 19
- 239000011541 reaction mixture Substances 0.000 description 19
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 18
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 18
- 239000002585 base Substances 0.000 description 18
- 239000000706 filtrate Substances 0.000 description 18
- 230000002829 reductive effect Effects 0.000 description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 17
- 229910052717 sulfur Inorganic materials 0.000 description 17
- 125000004430 oxygen atom Chemical group O* 0.000 description 16
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 16
- 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 16
- 238000004587 chromatography analysis Methods 0.000 description 15
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 15
- 125000005842 heteroatom Chemical group 0.000 description 15
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- 125000004434 sulfur atom Chemical group 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
- 239000002168 alkylating agent Substances 0.000 description 13
- 229940100198 alkylating agent Drugs 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
- 239000008346 aqueous phase Substances 0.000 description 12
- 238000009835 boiling Methods 0.000 description 12
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 12
- 239000005457 ice water Substances 0.000 description 12
- 150000003951 lactams Chemical group 0.000 description 12
- 229910052760 oxygen Inorganic materials 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 239000012071 phase Substances 0.000 description 11
- 229910000027 potassium carbonate Inorganic materials 0.000 description 11
- 235000011181 potassium carbonates Nutrition 0.000 description 11
- 230000009467 reduction Effects 0.000 description 11
- 238000006722 reduction reaction Methods 0.000 description 11
- 229910052938 sodium sulfate Inorganic materials 0.000 description 11
- 235000011152 sodium sulphate Nutrition 0.000 description 11
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 10
- 230000010933 acylation Effects 0.000 description 10
- 238000005917 acylation reaction Methods 0.000 description 10
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 10
- 239000012043 crude product Substances 0.000 description 10
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 10
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- WPHGSKGZRAQSGP-UHFFFAOYSA-N methylenecyclohexane Natural products C1CCCC2CC21 WPHGSKGZRAQSGP-UHFFFAOYSA-N 0.000 description 10
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
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- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
- NKAVNKIPGZYOIW-UHFFFAOYSA-N trisodium;copper(1+);tetracyanide Chemical compound [Na+].[Na+].[Na+].[Cu+].N#[C-].N#[C-].N#[C-].N#[C-] NKAVNKIPGZYOIW-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
- 229940019333 vitamin k antagonists Drugs 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- 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
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/273—2-Pyrrolidones 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 other ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/273—2-Pyrrolidones 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 other ring carbon atoms
- C07D207/277—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/572—Five-membered rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Molecular Biology (AREA)
- Hematology (AREA)
- Vascular Medicine (AREA)
- Pulmonology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Hydrogenated Pyridines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyrrole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Detergent Compositions (AREA)
- Indole Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4035961.1 | 1990-11-02 | ||
| DE4035961A DE4035961A1 (de) | 1990-11-02 | 1990-11-02 | Cyclische iminoderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH04264068A JPH04264068A (ja) | 1992-09-18 |
| JP2937589B2 true JP2937589B2 (ja) | 1999-08-23 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3313154A Expired - Lifetime JP2937589B2 (ja) | 1990-11-02 | 1991-11-01 | 環状イミノ誘導体、これらの化合物を含む製薬組成物及びそれらの調製方法 |
Country Status (25)
Families Citing this family (90)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4127404A1 (de) * | 1991-08-19 | 1993-02-25 | Thomae Gmbh Dr K | Cyclische iminoderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| AU646966B2 (en) * | 1991-08-23 | 1994-03-10 | Takeda Chemical Industries Ltd. | 2-piperazinone compounds, their production and use |
| DK0567967T3 (da) * | 1992-04-28 | 1996-11-18 | Thomae Gmbh Dr K | Tritium-mærkede fibrinogen-receptor-antagonister, deres anvendelse og fremgangsmåde til deres fremstilling |
| DE4213919A1 (de) * | 1992-04-28 | 1993-11-04 | Thomae Gmbh Dr K | Cyclische iminoderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| DE4213931A1 (de) * | 1992-04-28 | 1993-11-04 | Thomae Gmbh Dr K | Cyclische iminoderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
| DE4219158A1 (de) * | 1992-06-11 | 1993-12-16 | Thomae Gmbh Dr K | Biphenylderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| DE4241632A1 (de) * | 1992-12-10 | 1994-06-16 | Thomae Gmbh Dr K | Carbonsäurederivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| US5314902A (en) * | 1993-01-27 | 1994-05-24 | Monsanto Company | Urea derivatives useful as platelet aggregation inhibitors |
| ATE195117T1 (de) * | 1993-03-31 | 2000-08-15 | Searle & Co | 1-amdinophenyl-pyrrolidone/piperidinone als blutblättchen-aggregations inhibitoren |
| US6169107B1 (en) | 1993-04-28 | 2001-01-02 | Sumitomo Pharmaceutical Co., Ltd. | Indoloylguanidine derivatives |
| DE4424975A1 (de) * | 1994-07-15 | 1996-01-18 | Thomae Gmbh Dr K | 2-Piperidinone, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| BR9510360A (pt) * | 1994-12-23 | 1997-12-23 | Thomae Gmbh Dr K | Derivados de piperazina medicamentos contendo esses compostos sua aplicação e processo para sua preparação |
| DE69620165T2 (de) * | 1995-04-26 | 2002-10-31 | Takeda Chemical Industries, Ltd. | Piperazinone als inhibitoren von blutplattchenaggregation |
| DE19515500A1 (de) * | 1995-04-27 | 1996-10-31 | Thomae Gmbh Dr K | Substituierte Phenylamidine, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| US5719296A (en) * | 1995-10-30 | 1998-02-17 | Merck & Co., Inc. | Pseudopeptide lactam inhibitors of peptide binding to MHC class II proteins |
| DE19604191A1 (de) * | 1996-02-06 | 1997-08-07 | Hoechst Schering Agrevo Gmbh | 2,4-Diamino-1,3,5-triazine, Verfahren zu deren Herstellung und deren Verwendung als Herbizide und Pflanzenwachstumsregulatoren |
| US5942544A (en) * | 1996-02-22 | 1999-08-24 | Dupont Pharmaceuticals Company | α-branched anilines, toluenes, and analogs thereof as factor Xa inhibitors |
| DE19621483A1 (de) * | 1996-05-29 | 1997-12-04 | Hoechst Ag | Substituierte 2-Naphthoylguanidine, Verfahren zur ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| DE19621482A1 (de) * | 1996-05-29 | 1997-12-04 | Hoechst Ag | Substituierte 1-Naphthoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
| US6057342A (en) * | 1996-08-16 | 2000-05-02 | Dupont Pharmaceutical Co. | Amidinophenyl-pyrrolidines, -pyrrolines, and -isoxazolidines and derivatives thereof |
| JP2000516234A (ja) * | 1996-08-16 | 2000-12-05 | デュポン ファーマシューティカルズ カンパニー | アミジノフェニル―ピロリジン類、アミジノフェニル―ピロリン類、およびアミジノフェニル―イソオキサゾリジン類およびそれらの誘導体 |
| US6740682B2 (en) | 1997-08-29 | 2004-05-25 | Tularik Limited | Meta-benzamidine derivatives as serine protease inhibitors |
| DE69830410T2 (de) * | 1997-08-29 | 2006-01-26 | Tularik Ltd. | Meta-benzamidinderivate als serinprotease-inhibitoren |
| US5962504A (en) | 1997-09-08 | 1999-10-05 | Georgetown University | Substituted 2-pyrrolidinone activators of PKC |
| CA2310330A1 (en) | 1997-11-20 | 1999-06-03 | Teijin Limited | Biphenylamidine derivatives |
| WO1999050249A2 (en) | 1998-04-01 | 1999-10-07 | Du Pont Pharmaceuticals Company | Pyrimidines and triazines as integrin antagonists |
| WO1999052861A1 (de) * | 1998-04-09 | 1999-10-21 | Institut für Diagnostikforschung GmbH an der Freien Universität Berlin | Neue benzylguanidinderivate für die therapie, in-vivo- und in-vitro-diagnostik |
| DE69919149D1 (de) | 1998-04-10 | 2004-09-09 | Japan Tobacco Inc | Amidin-verbindungen |
| US6455571B1 (en) | 1998-04-23 | 2002-09-24 | Abbott Laboratories | Inhibitors of neuraminidases |
| CN1328546A (zh) * | 1998-04-23 | 2001-12-26 | 艾博特公司 | 作为神经氨酸酶抑制剂的吡咯烷 |
| US6518305B1 (en) | 1998-04-23 | 2003-02-11 | Abbott Laboratories | Five-membered carbocyclic and heterocyclic inhibitors of neuraminidases |
| WO2000005234A1 (en) * | 1998-07-22 | 2000-02-03 | Suntory Limited | NF-λB INHIBITORS CONTAINING INDAN DERIVATIVES AS THE ACTIVE INGREDIENT |
| US6284796B1 (en) * | 1998-08-06 | 2001-09-04 | Abbott Laboratories | Ukokinase inhibitors |
| DE19844787A1 (de) * | 1998-09-30 | 2000-04-13 | Boehringer Ingelheim Pharma | Disubstituierte Pyrrolidinone, diese Verbindung enthaltende Arzneimittel und deren Verwendung sowie ihre Herstellung |
| WO2000051609A1 (en) * | 1999-03-02 | 2000-09-08 | Merck & Co., Inc. | 3-alkyl substituted pyrrolidine modulators of chemokine receptor activity |
| US6395897B1 (en) | 1999-03-02 | 2002-05-28 | Boehringer Ingelheim Pharmaceuticals, Inc. | Nitrile compounds useful as reversible inhibitors of #9 cathepsin 5 |
| US6372764B1 (en) | 1999-03-02 | 2002-04-16 | Merck & Co., Inc. | Pyrrolidine modulators of chemokine receptor activity |
| US6362201B1 (en) | 1999-03-02 | 2002-03-26 | Merck & Co., Inc. | 3-cyclopropyl and 3-cyclobutyl pyrrolidine modulators of chemokine receptor activity |
| US6420364B1 (en) | 1999-09-13 | 2002-07-16 | Boehringer Ingelheim Pharmaceuticals, Inc. | Compound useful as reversible inhibitors of cysteine proteases |
| RU2177317C1 (ru) * | 2000-10-24 | 2001-12-27 | Московский научно-исследовательский институт медицинской экологии (МНИИМЭ) | Производные хинолина для коррекции системы гемостаза, фармацевтическая композиция, средство для коррекции гемостаза |
| FR2817257B1 (fr) * | 2000-11-30 | 2009-03-20 | Sanofi Synthelabo | Cyclohexyl(alkyl)-propanolamines, leur preparation et compositions pharmaceutiques en contenant |
| WO2002060894A2 (en) | 2001-01-30 | 2002-08-08 | Bristol-Myers Squibb Company | Sulfonamide lactam inhibitors of factor xa |
| DE10121003A1 (de) * | 2001-04-28 | 2002-12-19 | Aventis Pharma Gmbh | Anthranilsäureamide, Verfahren zur Herstellung, ihrer Verwendung als Medikament sowie sie enthaltende pharmazeutische Zubereitungen |
| GB0114004D0 (en) | 2001-06-08 | 2001-08-01 | Glaxo Group Ltd | Chemical compounds |
| GB0114005D0 (en) | 2001-06-08 | 2001-08-01 | Glaxo Group Ltd | Chemical compounds |
| PT1397130E (pt) * | 2001-06-20 | 2007-11-13 | Wyeth Corp | Derivados ácidos de indole substituído como inibidores de inibidor 1 do activador de plasminogénio (pai-1) |
| TWI224101B (en) * | 2001-06-20 | 2004-11-21 | Wyeth Corp | Substituted naphthyl indole derivatives as inhibitors of plasminogen activator inhibitor type-1 (PAI-1) |
| MXPA05006282A (es) * | 2002-12-10 | 2005-08-19 | Wyeth Corp | Derivados del acido 1h-indol-1-il acetico de 3-alquilo y 3-arilalquilo sustituido como inhibidores del inhibidor-1 de activador de plasminogeno (pai-1). |
| UA80453C2 (en) * | 2002-12-10 | 2007-09-25 | Derivatives of substituted dyhydropyranoindol-3,4-dion as inhibitors of plasminogen activator inhibitor-1 (pai-1) | |
| DE60324183D1 (en) * | 2002-12-10 | 2008-11-27 | Wyeth Corp | Aryl-, aryloxy- und alkyloxysubstituierte 1h-indol-3-yl-glyoxylsäurederivateals inhibitoren des plasminogenaktivatorinhibitors-1 (pai-1) |
| US7078429B2 (en) * | 2002-12-10 | 2006-07-18 | Wyeth | Substituted 3-carbonyl-1H-indol-1-yl acetic acid derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1) |
| WO2004069254A2 (en) * | 2003-02-07 | 2004-08-19 | Boehringer Ingelheim International Gmbh | Use of dipyridamole or mopidamole for treatment and prevention of mmp-9-dependent disorders |
| JP2006524203A (ja) | 2003-04-24 | 2006-10-26 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | トロンビンの過剰形成及び／又はトロンビンレセプターの発現上昇により生じる血栓塞栓性疾病及び疾患の治療及び予防のためのジピリダモール又はモピダモールの使用 |
| DE602004011767T2 (de) * | 2003-05-16 | 2009-02-19 | Merck Sharp & Dohme Ltd., Hoddesdon | Cyclohexylsulfone als gamma-sekretase-inhibitoren |
| US7582773B2 (en) * | 2003-09-25 | 2009-09-01 | Wyeth | Substituted phenyl indoles |
| US7163954B2 (en) * | 2003-09-25 | 2007-01-16 | Wyeth | Substituted naphthyl benzothiophene acids |
| US7268159B2 (en) * | 2003-09-25 | 2007-09-11 | Wyeth | Substituted indoles |
| US7420083B2 (en) * | 2003-09-25 | 2008-09-02 | Wyeth | Substituted aryloximes |
| US7411083B2 (en) | 2003-09-25 | 2008-08-12 | Wyeth | Substituted acetic acid derivatives |
| US7265148B2 (en) * | 2003-09-25 | 2007-09-04 | Wyeth | Substituted pyrrole-indoles |
| US7534894B2 (en) | 2003-09-25 | 2009-05-19 | Wyeth | Biphenyloxy-acids |
| US7446201B2 (en) * | 2003-09-25 | 2008-11-04 | Wyeth | Substituted heteroaryl benzofuran acids |
| US7332521B2 (en) * | 2003-09-25 | 2008-02-19 | Wyeth | Substituted indoles |
| US7141592B2 (en) * | 2003-09-25 | 2006-11-28 | Wyeth | Substituted oxadiazolidinediones |
| US7442805B2 (en) * | 2003-09-25 | 2008-10-28 | Wyeth | Substituted sulfonamide-indoles |
| US7342039B2 (en) * | 2003-09-25 | 2008-03-11 | Wyeth | Substituted indole oximes |
| US7351726B2 (en) * | 2003-09-25 | 2008-04-01 | Wyeth | Substituted oxadiazolidinediones |
| TW200524865A (en) | 2003-10-08 | 2005-08-01 | Nicholas Piramal India Ltd | Fibrinogen receptor antagonists and their use |
| BRPI0507374A (pt) * | 2004-02-02 | 2007-07-10 | Pfizer Prod Inc | moduladores do receptor de histamina-3 |
| EA011097B1 (ru) | 2004-05-07 | 2008-12-30 | Янссен Фармацевтика Н.В. | Производные пирролидин-2-она и пиперидин-2-она, используемые в качестве ингибиторов 11-бета-гидроксистероид-дегидрогеназы |
| BRPI0514572A (pt) * | 2004-08-23 | 2008-06-17 | Wyeth Corp | ácidos de tiazolo-naftila |
| US7754747B2 (en) * | 2004-08-23 | 2010-07-13 | Wyeth Llc | Oxazolo-naphthyl acids |
| MX2007002177A (es) * | 2004-08-23 | 2007-04-02 | Wyeth Corp | Acidos de pirrolo-naftilo como inhibidores de pai-1. |
| EP1796657B1 (en) * | 2004-08-30 | 2009-12-23 | Janssen Pharmaceutica N.V. | N-2 adamantanyl-2-phenoxy-acetamide derivatives as 11-beta hydroxysteroid dehydrogenase inhibitors |
| WO2006024628A1 (en) * | 2004-08-30 | 2006-03-09 | Janssen Pharmaceutica N.V. | Tricyclic lactam derivatives as 11-beta hydroxysteroid dehydrogenase inhibitors |
| DE602005017159D1 (de) | 2004-08-30 | 2009-11-26 | Janssen Pharmaceutica Nv | Oxysteroid-dehydrogenase-inhibitoren |
| WO2006114096A1 (en) * | 2005-04-25 | 2006-11-02 | Danmarks Tekniske Universitet | Pyrrolidinone dipeptide analogs and use thereof as artificial sweeteners |
| MX2008002117A (es) * | 2005-08-17 | 2008-09-26 | Wyeth Corp | Indoles sustituidos y metodos de uso de estos. |
| MX337100B (es) | 2007-10-05 | 2016-02-11 | Acucela Inc | Compuestos alcoxi para el tratamiento de enfermedades. |
| CN101868455B (zh) * | 2007-10-23 | 2013-11-13 | 阿勒根公司 | 治疗性的取代的内酰胺 |
| JP5860398B2 (ja) | 2009-07-02 | 2016-02-16 | アキュセラ インコーポレイテッド | 視覚サイクルモジュレーターの薬理 |
| US20130267699A1 (en) | 2011-06-24 | 2013-10-10 | California Institute Of Technology | Quaternary heteroatom containing compounds |
| US8822679B2 (en) * | 2011-06-24 | 2014-09-02 | California Institute Of Technology | Quaternary heteroatom containing compounds |
| US9518034B2 (en) | 2013-10-14 | 2016-12-13 | California Institute Of Technology | Synthesis of chiral enaminones, their derivatives, and bioactivity studies thereof |
| AU2014352830B2 (en) | 2013-11-21 | 2018-12-13 | Concordia University, Inc. | Substituted (4'-hydroxyphenyl)cycloalkane compounds and uses thereof as selective agonists of the estrogen receptor beta isoform |
| US10421696B2 (en) | 2014-12-18 | 2019-09-24 | California Institute Of Technology | Enantioselective synthesis of α-quaternary mannich adducts by palladium-catalyzed allylic alkylation |
| CN107922373A (zh) | 2015-03-27 | 2018-04-17 | 加利福尼亚技术学院 | 使用低催化剂浓度和稳定的预催化剂的不对称催化脱羧烷基烷基化 |
| US10040784B2 (en) | 2016-03-11 | 2018-08-07 | California Institute Of Technology | Compositions and methods for acylating lactams |
| US10358422B2 (en) | 2017-11-01 | 2019-07-23 | California Institute Of Technology | Methods for enantioselective allylic alkylation of esters, lactones, and lactams with unactivated allylic alcohols |
| US11214568B2 (en) | 2018-10-18 | 2022-01-04 | California Institute Of Technology | Gem-disubstituted pyrrolidines, piperazines, and diazepanes, and compositions and methods of making the same |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4247466A (en) * | 1979-07-05 | 1981-01-27 | American Cyanamid Company | Lactone metabolites of 3-(4-biphenylylcarbonyl)propionic acid |
| EP0194548A3 (de) * | 1985-03-12 | 1988-08-17 | Dr. Karl Thomae GmbH | Neue Sulfonylaminoäthylverbindungen, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| DK117986A (da) * | 1985-03-16 | 1986-09-17 | Wellcome Found | Arylderivater, fremgangsmaader til deres fremstilling og deres anvendelse |
| DE3823299A1 (de) * | 1988-07-07 | 1990-01-11 | Schering Ag | Substituierte phenyl-pyrrolidin-2-one, -oxazolidin-2-one und -imidazolidin-2-one, ihre herstellung sowie verwendung in arzneimitteln |
-
1990
- 1990-11-02 DE DE4035961A patent/DE4035961A1/de not_active Ceased
-
1991
- 1991-10-24 SG SG9601241A patent/SG81852A1/en unknown
- 1991-10-24 DK DK91118148T patent/DK0483667T3/da active
- 1991-10-24 ES ES91118148T patent/ES2113867T3/es not_active Expired - Lifetime
- 1991-10-24 DE DE59108930T patent/DE59108930D1/de not_active Expired - Lifetime
- 1991-10-24 EP EP91118148A patent/EP0483667B1/de not_active Expired - Lifetime
- 1991-10-24 AT AT91118148T patent/ATE163008T1/de not_active IP Right Cessation
- 1991-10-31 PT PT99402A patent/PT99402B/pt not_active IP Right Cessation
- 1991-10-31 FI FI915136A patent/FI107606B/fi not_active IP Right Cessation
- 1991-11-01 NO NO914294A patent/NO174806B/no not_active IP Right Cessation
- 1991-11-01 IL IL9992691A patent/IL99926A/en not_active IP Right Cessation
- 1991-11-01 IE IE382291A patent/IE913822A1/en not_active IP Right Cessation
- 1991-11-01 JP JP3313154A patent/JP2937589B2/ja not_active Expired - Lifetime
- 1991-11-01 HU HU913455A patent/HUT67288A/hu unknown
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- 1991-11-01 RU SU915001905A patent/RU2040519C1/ru active
- 1991-11-02 KR KR1019910019458A patent/KR100223135B1/ko not_active Expired - Lifetime
- 1991-11-04 ZA ZA918734A patent/ZA918734B/xx unknown
- 1991-11-04 NZ NZ240463A patent/NZ240463A/en not_active IP Right Cessation
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1992
- 1992-06-29 MX MX9203677A patent/MX9203677A/es unknown
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1994
- 1994-01-25 BG BG098416A patent/BG62025B2/bg unknown
- 1994-11-23 EE EE9400438A patent/EE03099B1/xx not_active IP Right Cessation
- 1994-12-28 US US08/365,336 patent/US5541343A/en not_active Expired - Lifetime
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1995
- 1995-06-01 US US08/458,096 patent/US5591769A/en not_active Expired - Lifetime
- 1995-06-02 HU HU95P/P00156P patent/HU211563A9/hu unknown
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1997
- 1997-05-06 BR BR1100445-2A patent/BR1100445A/pt active IP Right Grant
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1998
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