IE56043B1 - 1,7-dihydro-pyrrolo(3,4-e)(1,4)diazepin-2(3h)-one derivatives,a process for preparing them and their use as anticonvulsant and antianxiety agents - Google Patents

1,7-dihydro-pyrrolo(3,4-e)(1,4)diazepin-2(3h)-one derivatives,a process for preparing them and their use as anticonvulsant and antianxiety agents

Info

Publication number: IE56043B1
Authority: IE; Ireland
Prior art keywords: hydrogen; compound; formula; methyl; group
Prior art date: 1982-09-08

Application number

IE2098/83A

Other languages

English (en)

Other versions

IE832098L (en

Original Assignee

Lepetit Spa

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1982-09-08

Filing date

1983-09-07

Publication date

1991-03-27

1983-09-07 Application filed by Lepetit Spa filed Critical Lepetit Spa

1984-03-08 Publication of IE832098L publication Critical patent/IE832098L/en

1991-03-27 Publication of IE56043B1 publication Critical patent/IE56043B1/en

Links

239000001961 anticonvulsive agent Substances 0.000 title claims abstract description 10
239000002249 anxiolytic agent Substances 0.000 title claims abstract description 8
238000004519 manufacturing process Methods 0.000 title claims abstract description 5
230000001773 anti-convulsant effect Effects 0.000 title abstract description 9
229960003965 antiepileptics Drugs 0.000 title abstract description 9
NCCPPLQKOSIGFQ-UHFFFAOYSA-N 3,7-dihydro-1h-pyrrolo[3,4-e][1,4]diazepin-2-one Chemical class N1C(=O)CN=CC2=CNC=C21 NCCPPLQKOSIGFQ-UHFFFAOYSA-N 0.000 title abstract 2
150000001875 compounds Chemical class 0.000 claims abstract description 97
239000001257 hydrogen Substances 0.000 claims abstract description 40
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 40
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 27
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 19
125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 17
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 16
125000001246 bromo group Chemical group Br* 0.000 claims abstract description 13
125000000217 alkyl group Chemical group 0.000 claims abstract description 8
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 7
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
125000001153 fluoro group Chemical group F* 0.000 claims abstract description 6
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 3
150000002431 hydrogen Chemical class 0.000 claims description 27
238000000034 method Methods 0.000 claims description 27
-1 -1-methylpropyl Chemical group 0.000 claims description 22
238000006243 chemical reaction Methods 0.000 claims description 20
125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 11
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
239000002253 acid Substances 0.000 claims description 9
150000003839 salts Chemical class 0.000 claims description 9
125000003545 alkoxy group Chemical group 0.000 claims description 6
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
239000004480 active ingredient Substances 0.000 claims description 5
230000031709 bromination Effects 0.000 claims description 5
238000005893 bromination reaction Methods 0.000 claims description 5
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 5
238000006396 nitration reaction Methods 0.000 claims description 5
230000000049 anti-anxiety effect Effects 0.000 claims description 4
125000004432 carbon atom Chemical group C* 0.000 claims description 4
238000005660 chlorination reaction Methods 0.000 claims description 4
229910052736 halogen Inorganic materials 0.000 claims description 4
150000002367 halogens Chemical class 0.000 claims description 4
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
150000008064 anhydrides Chemical class 0.000 claims description 3
150000007522 mineralic acids Chemical class 0.000 claims description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
150000001266 acyl halides Chemical class 0.000 claims description 2
125000005236 alkanoylamino group Chemical group 0.000 claims description 2
125000003282 alkyl amino group Chemical group 0.000 claims description 2
238000005576 amination reaction Methods 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
230000032050 esterification Effects 0.000 claims description 2
238000005886 esterification reaction Methods 0.000 claims description 2
125000005843 halogen group Chemical group 0.000 claims description 2
229940125681 anticonvulsant agent Drugs 0.000 claims 1
230000001131 transforming effect Effects 0.000 claims 1
125000004435 hydrogen atom Chemical class [H]* 0.000 abstract description 4
125000003342 alkenyl group Chemical group 0.000 abstract description 2
ZDJJKOOESFJHGL-UHFFFAOYSA-N pyrrolo[3,2-c]diazepine Chemical class N1=CC=CC2=NC=CC2=N1 ZDJJKOOESFJHGL-UHFFFAOYSA-N 0.000 abstract description 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 2
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 44
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 38
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
239000000243 solution Substances 0.000 description 21
239000011541 reaction mixture Substances 0.000 description 19
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
238000003756 stirring Methods 0.000 description 11
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
238000001914 filtration Methods 0.000 description 9
239000000543 intermediate Substances 0.000 description 9
239000002904 solvent Substances 0.000 description 9
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
239000000203 mixture Substances 0.000 description 8
241000700159 Rattus Species 0.000 description 7
239000000725 suspension Substances 0.000 description 7
241001465754 Metazoa Species 0.000 description 6
150000001204 N-oxides Chemical class 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
VXIVSQZSERGHQP-UHFFFAOYSA-N chloroacetamide Chemical class NC(=O)CCl VXIVSQZSERGHQP-UHFFFAOYSA-N 0.000 description 6
230000000875 corresponding effect Effects 0.000 description 6
238000002474 experimental method Methods 0.000 description 6
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
239000007858 starting material Substances 0.000 description 6
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
230000000949 anxiolytic effect Effects 0.000 description 5
239000003960 organic solvent Substances 0.000 description 5
239000000047 product Substances 0.000 description 5
238000012360 testing method Methods 0.000 description 5
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
229920002472 Starch Polymers 0.000 description 4
239000002585 base Substances 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
230000000694 effects Effects 0.000 description 4
PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical class NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
238000002360 preparation method Methods 0.000 description 4
239000011780 sodium chloride Substances 0.000 description 4
235000019698 starch Nutrition 0.000 description 4
238000005406 washing Methods 0.000 description 4
FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 3
GXQVAUDUEWLDNA-UHFFFAOYSA-N 2-(hydroxyamino)acetamide Chemical compound NC(=O)CNO GXQVAUDUEWLDNA-UHFFFAOYSA-N 0.000 description 3
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 3
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
229940049706 benzodiazepine Drugs 0.000 description 3
150000001557 benzodiazepines Chemical class 0.000 description 3
239000012320 chlorinating reagent Substances 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
238000000354 decomposition reaction Methods 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
235000013305 food Nutrition 0.000 description 3
239000008101 lactose Substances 0.000 description 3
229960005152 pentetrazol Drugs 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
238000003825 pressing Methods 0.000 description 3
239000012264 purified product Substances 0.000 description 3
102000005962 receptors Human genes 0.000 description 3
108020003175 receptors Proteins 0.000 description 3
238000010992 reflux Methods 0.000 description 3
239000008107 starch Substances 0.000 description 3
239000000126 substance Substances 0.000 description 3
CVBUKMMMRLOKQR-UHFFFAOYSA-N 1-phenylbutane-1,3-dione Chemical compound CC(=O)CC(=O)C1=CC=CC=C1 CVBUKMMMRLOKQR-UHFFFAOYSA-N 0.000 description 2
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical class CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 2
125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 2
229910002012 Aerosil® Inorganic materials 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
239000000370 acceptor Substances 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
238000005917 acylation reaction Methods 0.000 description 2
239000003513 alkali Substances 0.000 description 2
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
238000009835 boiling Methods 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
239000003610 charcoal Substances 0.000 description 2
239000007810 chemical reaction solvent Substances 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
239000003179 convulsant agent Substances 0.000 description 2
238000001816 cooling Methods 0.000 description 2
VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
229940079593 drug Drugs 0.000 description 2
239000003814 drug Substances 0.000 description 2
239000000284 extract Substances 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
229960003692 gamma aminobutyric acid Drugs 0.000 description 2
BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 2
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
229910000041 hydrogen chloride Inorganic materials 0.000 description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
235000019359 magnesium stearate Nutrition 0.000 description 2
230000000802 nitrating effect Effects 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
125000001477 organic nitrogen group Chemical group 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
239000002994 raw material Substances 0.000 description 2
238000011084 recovery Methods 0.000 description 2
238000010898 silica gel chromatography Methods 0.000 description 2
239000007787 solid Substances 0.000 description 2
229940014800 succinic anhydride Drugs 0.000 description 2
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
238000003828 vacuum filtration Methods 0.000 description 2
HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 description 1
APPNFPAQYIBGLU-UHFFFAOYSA-N (4-amino-2-methyl-1h-pyrrol-3-yl)-phenylmethanone Chemical compound N1C=C(N)C(C(=O)C=2C=CC=CC=2)=C1C APPNFPAQYIBGLU-UHFFFAOYSA-N 0.000 description 1
HMQRNCNGYBSYSK-UHFFFAOYSA-N (4-amino-2-methyl-1h-pyrrol-3-yl)-phenylmethanone;hydrochloride Chemical compound Cl.N1C=C(N)C(C(=O)C=2C=CC=CC=2)=C1C HMQRNCNGYBSYSK-UHFFFAOYSA-N 0.000 description 1
LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical class N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 description 1
CYPYOGOPKDBEFY-UHFFFAOYSA-N 1-(2-chlorophenyl)butane-1,3-dione Chemical compound CC(=O)CC(=O)C1=CC=CC=C1Cl CYPYOGOPKDBEFY-UHFFFAOYSA-N 0.000 description 1
YXGUIKKVTBDGRO-UHFFFAOYSA-N 1h-diazepine;hydrochloride Chemical compound Cl.N1C=CC=CC=N1 YXGUIKKVTBDGRO-UHFFFAOYSA-N 0.000 description 1
JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 1
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239000007832 Na2SO4 Substances 0.000 description 1
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235000021355 Stearic acid Nutrition 0.000 description 1
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239000003929 acidic solution Substances 0.000 description 1
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125000002252 acyl group Chemical group 0.000 description 1
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150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
229910001516 alkali metal iodide Inorganic materials 0.000 description 1
238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
150000003973 alkyl amines Chemical class 0.000 description 1
230000002152 alkylating effect Effects 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
DFNYGALUNNFWKJ-UHFFFAOYSA-N aminoacetonitrile Chemical compound NCC#N DFNYGALUNNFWKJ-UHFFFAOYSA-N 0.000 description 1
MXMOTZIXVICDSD-UHFFFAOYSA-N anisoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1 MXMOTZIXVICDSD-UHFFFAOYSA-N 0.000 description 1
RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 1
150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
238000003556 assay Methods 0.000 description 1
WXBLLCUINBKULX-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1 WXBLLCUINBKULX-UHFFFAOYSA-N 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
238000004166 bioassay Methods 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
DVECBJCOGJRVPX-UHFFFAOYSA-N butyryl chloride Chemical compound CCCC(Cl)=O DVECBJCOGJRVPX-UHFFFAOYSA-N 0.000 description 1
239000002775 capsule Substances 0.000 description 1
239000007963 capsule composition Substances 0.000 description 1
QGJOPFRUJISHPQ-NJFSPNSNSA-N carbon disulfide-14c Chemical compound S=[14C]=S QGJOPFRUJISHPQ-NJFSPNSNSA-N 0.000 description 1
150000004649 carbonic acid derivatives Chemical class 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
230000002596 correlated effect Effects 0.000 description 1
RVOJTCZRIKWHDX-UHFFFAOYSA-N cyclohexanecarbonyl chloride Chemical compound ClC(=O)C1CCCCC1 RVOJTCZRIKWHDX-UHFFFAOYSA-N 0.000 description 1
125000006639 cyclohexyl carbonyl group Chemical group 0.000 description 1
IPIVAXLHTVNRBS-UHFFFAOYSA-N decanoyl chloride Chemical compound CCCCCCCCCC(Cl)=O IPIVAXLHTVNRBS-UHFFFAOYSA-N 0.000 description 1
150000008050 dialkyl sulfates Chemical class 0.000 description 1
229960003529 diazepam Drugs 0.000 description 1
150000001991 dicarboxylic acids Chemical class 0.000 description 1
238000007865 diluting Methods 0.000 description 1
OMBRFUXPXNIUCZ-UHFFFAOYSA-N dioxidonitrogen(1+) Chemical class O=[N+]=O OMBRFUXPXNIUCZ-UHFFFAOYSA-N 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
MAFQLJCYFMKEJJ-UHFFFAOYSA-N ethyl 4-aminobutanoate Chemical compound CCOC(=O)CCCN MAFQLJCYFMKEJJ-UHFFFAOYSA-N 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
VANNPISTIUFMLH-UHFFFAOYSA-N glutaric anhydride Chemical compound O=C1CCCC(=O)O1 VANNPISTIUFMLH-UHFFFAOYSA-N 0.000 description 1
BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical class NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 description 1
239000008187 granular material Substances 0.000 description 1
230000002140 halogenating effect Effects 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
239000012433 hydrogen halide Substances 0.000 description 1
229910000039 hydrogen halide Inorganic materials 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
239000007788 liquid Substances 0.000 description 1
231100000053 low toxicity Toxicity 0.000 description 1
QXUAFCKBYYPTPQ-ZWKAXHIPSA-L magnesium (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-[(2R,3S,4R,5R)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxane-3,4,5-triol octadecanoate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O QXUAFCKBYYPTPQ-ZWKAXHIPSA-L 0.000 description 1
FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 1
229910000000 metal hydroxide Inorganic materials 0.000 description 1
150000004692 metal hydroxides Chemical class 0.000 description 1
KFOPKOFKGJJEBW-ZSSYTAEJSA-N methyl 2-[(1s,7r,8s,9s,10r,13r,14s,17r)-1,7-dihydroxy-10,13-dimethyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl]acetate Chemical compound C([C@H]1O)C2=CC(=O)C[C@H](O)[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](CC(=O)OC)[C@@]1(C)CC2 KFOPKOFKGJJEBW-ZSSYTAEJSA-N 0.000 description 1
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
OOMMAGWBUSBHMG-UHFFFAOYSA-N n-(4-benzoyl-5-methyl-1h-pyrrol-3-yl)-2-chloroacetamide Chemical compound N1C=C(NC(=O)CCl)C(C(=O)C=2C=CC=CC=2)=C1C OOMMAGWBUSBHMG-UHFFFAOYSA-N 0.000 description 1
AMLJWLYRONUCKO-UHFFFAOYSA-N n-(6-amino-5-iodopyridin-2-yl)acetamide Chemical compound CC(=O)NC1=CC=C(I)C(N)=N1 AMLJWLYRONUCKO-UHFFFAOYSA-N 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
ONTGMLYFJLDCPR-UHFFFAOYSA-M nitronium;trifluoromethanesulfonate Chemical compound O=[N+]=O.[O-]S(=O)(=O)C(F)(F)F ONTGMLYFJLDCPR-UHFFFAOYSA-M 0.000 description 1
IOVCWXUNBOPUCH-UHFFFAOYSA-O nitrosooxidanium Chemical compound [OH2+]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-O 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
239000003921 oil Substances 0.000 description 1
235000019198 oils Nutrition 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
229920001515 polyalkylene glycol Polymers 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
239000000843 powder Substances 0.000 description 1
230000001376 precipitating effect Effects 0.000 description 1
238000000746 purification Methods 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
239000000376 reactant Substances 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
230000008707 rearrangement Effects 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
230000035939 shock Effects 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
229960001866 silicon dioxide Drugs 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017550 sodium carbonate Nutrition 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
230000009870 specific binding Effects 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
235000011044 succinic acid Nutrition 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000007916 tablet composition Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
- 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
- A61P25/20—Hypnotics; Sedatives
- 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
- C07D207/30—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 two double bonds between ring members or between ring members and non-ring members
- C07D207/34—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 two double bonds between ring members or between ring members and non-ring members 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

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Neurosurgery (AREA)
Life Sciences & Earth Sciences (AREA)
Neurology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Biomedical Technology (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Anesthesiology (AREA)
Pain & Pain Management (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

IE2098/83A 1982-09-08 1983-09-07 1,7-dihydro-pyrrolo(3,4-e)(1,4)diazepin-2(3h)-one derivatives,a process for preparing them and their use as anticonvulsant and antianxiety agents IE56043B1 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GB8225582		1982-09-08

Publications (2)

Publication Number	Publication Date
IE832098L IE832098L (en)	1984-03-08
IE56043B1 true IE56043B1 (en)	1991-03-27

Family

ID=10532762

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IE2098/83A IE56043B1 (en)	1982-09-08	1983-09-07	1,7-dihydro-pyrrolo(3,4-e)(1,4)diazepin-2(3h)-one derivatives,a process for preparing them and their use as anticonvulsant and antianxiety agents

Country Status (14)

Country	Link
US (1)	US4508730A (2)
EP (1)	EP0102602B1 (2)
JP (1)	JPS5965093A (2)
KR (1)	KR910000417B1 (2)
AT (1)	ATE51230T1 (2)
AU (1)	AU566404B2 (2)
CA (1)	CA1199633A (2)
DE (1)	DE3381355D1 (2)
DK (1)	DK161077C (2)
ES (2)	ES8503000A1 (2)
GR (1)	GR79626B (2)
IE (1)	IE56043B1 (2)
IL (1)	IL69473A (2)
ZA (1)	ZA835899B (2)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS60208488A (ja) *	1984-04-03	1985-10-21	Nippon Mining Co Ltd	スラグからの有価金属の回収法
US20160009725A1 (en)	2013-02-22	2016-01-14	Bayer Pharma Aktiengesellschaft	Pyrrolo- and pyrazolo-triazolodiazepines as bet-protein inhibitors for treating hyperproliferative diseases
EP2958923A1 (de)	2013-02-22	2015-12-30	Bayer Pharma Aktiengesellschaft	4-substituierte pyrrolo- und pyrazolo-diazepine

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3553210A (en) *	1968-12-16	1971-01-05	Parke Davis & Co	3-methyl-8-phenylpyrazolo(4,3-e)(1,4)diazepin-5(1h)-one, 7-oxide compounds
US3553207A (en) *	1968-12-16	1971-01-05	Parke Davis & Co	Phenylpyrazolodiazepinone compounds
GB1433103A (en) *	1974-03-20	1976-04-22	Lepetit Spa	Pharmacologically active pyrrolodiazepines
GR76455B (2) *	1981-06-04	1984-08-10	Lepetit Spa
IT1167788B (it) *	1981-06-08	1987-05-13	Lepetit Spa	Derivati pirrolo-diazepinici

1983
- 1983-08-09 US US06/521,774 patent/US4508730A/en not_active Expired - Fee Related
- 1983-08-11 ZA ZA835899A patent/ZA835899B/xx unknown
- 1983-08-11 AU AU17900/83A patent/AU566404B2/en not_active Ceased
- 1983-08-12 IL IL69473A patent/IL69473A/xx unknown
- 1983-08-27 DE DE8383108446T patent/DE3381355D1/de not_active Expired - Lifetime
- 1983-08-27 EP EP83108446A patent/EP0102602B1/en not_active Expired - Lifetime
- 1983-08-27 AT AT83108446T patent/ATE51230T1/de not_active IP Right Cessation
- 1983-08-29 GR GR72324A patent/GR79626B/el unknown
- 1983-08-30 DK DK394483A patent/DK161077C/da active
- 1983-09-07 JP JP58163392A patent/JPS5965093A/ja active Granted
- 1983-09-07 ES ES525442A patent/ES8503000A1/es not_active Expired
- 1983-09-07 CA CA000436167A patent/CA1199633A/en not_active Expired
- 1983-09-07 IE IE2098/83A patent/IE56043B1/en not_active IP Right Cessation
- 1983-09-08 KR KR1019830004230A patent/KR910000417B1/ko not_active Expired
1984
- 1984-05-14 ES ES532487A patent/ES8507551A1/es not_active Expired

Also Published As

Publication number	Publication date
DK394483D0 (da)	1983-08-30
ES525442A0 (es)	1985-02-01
ZA835899B (en)	1984-07-25
AU1790083A (en)	1984-03-15
DK161077C (da)	1991-11-18
EP0102602A1 (en)	1984-03-14
EP0102602B1 (en)	1990-03-21
ES532487A0 (es)	1985-09-01
DK394483A (da)	1984-03-09
DE3381355D1 (de)	1990-04-26
CA1199633A (en)	1986-01-21
ES8507551A1 (es)	1985-09-01
ATE51230T1 (de)	1990-04-15
AU566404B2 (en)	1987-10-22
JPH0447672B2 (2)	1992-08-04
IE832098L (en)	1984-03-08
JPS5965093A (ja)	1984-04-13
US4508730A (en)	1985-04-02
IL69473A (en)	1985-12-31
GR79626B (2)	1984-10-31
DK161077B (da)	1991-05-27
KR840006248A (ko)	1984-11-22
ES8503000A1 (es)	1985-02-01
KR910000417B1 (ko)	1991-01-25
IL69473A0 (en)	1983-11-30

Legal Events

Date	Code	Title	Description
1994-01-12	MM4A	Patent lapsed

Publication	Publication Date	Title
Michael et al.	2001	Reformatsky reactions with N-arylpyrrolidine-2-thiones: synthesis of tricyclic analogues of quinolone antibacterial agents
EP0492485B1 (en)	1997-11-19	N-Acyl-2,3-benzodiazepine derivatives, pharmaceutical compositions containing them and process for preparing same
CA1248532A (en)	1989-01-10	Pyrazolo¬3,4-b\|pyridine derivatives and process for producing them
JPS63174988A (ja)	1988-07-19	ヘテロアリール３‐オキソ‐プロバンニトリル誘導体及びその製造方法
FI95795B (fi)	1995-12-15	Menetelmä terapeuttisesti käyttökelpoisten aminohappoantagonistien valmistamiseksi
JP4456765B2 (ja)	2010-04-28	ピリダジン−３−オン誘導体及びこれを含有する医薬
UA57088C2 (uk)	2003-06-16	Похідні 4-оксо-3,5-дигідро-4н-піридазино-[4,5-b]індол-1-ацетаміду, лікувальний засіб та фармацевтична композиція
AU2241400A (en)	2000-10-12	Novel thiazolobenzoimidazole derivative
CZ200471A3 (cs)	2004-11-10	Způsob purifikace N-[3-(3-kyanopyrazol[1,5-a]pyrimidin-7-yl)fenyl]-N-ethylacetamidu (zaleplon) a krystalické formy zaleplonu připravitelné tímto způsobem
JPH03505204A (ja)	1991-11-14	３環式３―オキソ―プロパンニトリル誘導体およびその調製方法
DE69629341T2 (de)	2004-06-09	Pyrrolocarbazolderivate
JPH0433791B2 (2)	1992-06-04
IE56043B1 (en)	1991-03-27	1,7-dihydro-pyrrolo(3,4-e)(1,4)diazepin-2(3h)-one derivatives,a process for preparing them and their use as anticonvulsant and antianxiety agents
US4112112A (en)	1978-09-05	Pyrrolo[2,1-b] [3]benzazepines useful for producing a skeletal muscle relaxing or tranquilizing effect
SU1301830A1 (ru)	1987-04-07	Производные 5,6-дигидро-11 @ -дибензо @ , @ -азепин-6-она,обладающие противосудорожной активностью
EP0066762B1 (en)	1985-11-21	1,7-dihydro-pyrrolo(3,4-e)(1,4)diazepin-2(1h)-one derivatives
US4022766A (en)	1977-05-10	Pharmacologically active pyrrolodiazepines
US6268498B1 (en)	2001-07-31	Process for the preparation of granisetron
IE59173B1 (en)	1994-01-26	Imidazo[1,2-a]quinoline derivatives, their preparation and their application in therapy
Mamouni et al.	1997	Intramolecular amidoalkylation cyclizations in synthesis of novel pyrrolo (or isoindolo) thieno [2] benzazepines
NZ328432A (en)	1997-12-19	Tricyclic bis-imide derivatives and medicaments
CS242858B2 (en)	1986-05-15	Method of octahydro-1h-pyrrolo(2,3-g)-isoquinolines production
AU662730B2 (en)	1995-09-14	Neuroprotectant agents
KR880001659B1 (ko)	1988-09-05	1,7-디하이드로-피롤로[3,4-e][1,4]디아제핀-2-(1H)-온 유도체 및 이의 중간체의 제조방법
IL95021A (en)	1994-06-24	7-Carboxy-pyrrolo [2,1-b] thiazole-3-acetic acid derivatives, their preparation and pharmaceutical compositions containing them