CA1263653A - Tetrahydro-benzthiazoles, the preparation thereof and their use as intermediate products or as pharmaceuticals - Google Patents
Tetrahydro-benzthiazoles, the preparation thereof and their use as intermediate products or as pharmaceuticalsInfo
- Publication number
- CA1263653A CA1263653A CA000498237A CA498237A CA1263653A CA 1263653 A CA1263653 A CA 1263653A CA 000498237 A CA000498237 A CA 000498237A CA 498237 A CA498237 A CA 498237A CA 1263653 A CA1263653 A CA 1263653A
- Authority
- CA
- Canada
- Prior art keywords
- group
- carbon atoms
- compound
- represent
- general formula
- 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
Links
- 239000013067 intermediate product Substances 0.000 title abstract description 4
- 238000002360 preparation method Methods 0.000 title description 12
- ALUQMCBDQKDRAK-UHFFFAOYSA-N 2,3,3a,4-tetrahydro-1,3-benzothiazole Chemical class C1C=CC=C2SCNC21 ALUQMCBDQKDRAK-UHFFFAOYSA-N 0.000 title description 2
- 239000003814 drug Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 105
- -1 pyrrolidino, piperidino, hexamethyleneimino Chemical group 0.000 claims abstract description 76
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 57
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 52
- 238000000034 method Methods 0.000 claims abstract description 50
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 41
- 239000002253 acid Substances 0.000 claims abstract description 29
- 150000003839 salts Chemical class 0.000 claims abstract description 29
- 125000002252 acyl group Chemical group 0.000 claims abstract description 22
- 239000000460 chlorine Chemical group 0.000 claims abstract description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 17
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 16
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 16
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 16
- 125000003884 phenylalkyl group Chemical group 0.000 claims abstract description 14
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229910052794 bromium Chemical group 0.000 claims abstract description 9
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 8
- 125000005843 halogen group Chemical group 0.000 claims abstract description 7
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims abstract description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 4
- 239000011737 fluorine Substances 0.000 claims abstract description 4
- 230000008569 process Effects 0.000 claims description 46
- 239000000203 mixture Substances 0.000 claims description 30
- 238000006243 chemical reaction Methods 0.000 claims description 29
- 239000004480 active ingredient Substances 0.000 claims description 19
- 239000002904 solvent Substances 0.000 claims description 19
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 16
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 15
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
- 125000006239 protecting group Chemical group 0.000 claims description 9
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 8
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Substances OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 230000000269 nucleophilic effect Effects 0.000 claims description 8
- 230000009467 reduction Effects 0.000 claims description 8
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 229910052987 metal hydride Inorganic materials 0.000 claims description 6
- 150000004681 metal hydrides Chemical class 0.000 claims description 6
- 125000004888 n-propyl amino group Chemical group [H]N(*)C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 125000006325 2-propenyl amino group Chemical group [H]C([H])=C([H])C([H])([H])N([H])* 0.000 claims description 5
- LMBFUMXVHAJSNJ-UHFFFAOYSA-N 4-(dimethylamino)cyclohexan-1-one Chemical compound CN(C)C1CCC(=O)CC1 LMBFUMXVHAJSNJ-UHFFFAOYSA-N 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- 230000037396 body weight Effects 0.000 claims description 5
- 150000001728 carbonyl compounds Chemical class 0.000 claims description 5
- 239000012279 sodium borohydride Substances 0.000 claims description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 5
- 239000000829 suppository Substances 0.000 claims description 5
- DRRYZHHKWSHHFT-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine Chemical compound C1C(N)CCC2=C1SC(N)=N2 DRRYZHHKWSHHFT-UHFFFAOYSA-N 0.000 claims description 4
- YNLWAJULBSGGFC-UHFFFAOYSA-N 6-n,6-n-dimethyl-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine Chemical compound C1C(N(C)C)CCC2=C1SC(N)=N2 YNLWAJULBSGGFC-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 230000010933 acylation Effects 0.000 claims description 4
- 238000005917 acylation reaction Methods 0.000 claims description 4
- 238000003776 cleavage reaction Methods 0.000 claims description 4
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 4
- 150000007522 mineralic acids Chemical class 0.000 claims description 4
- 150000007524 organic acids Chemical class 0.000 claims description 4
- 230000007017 scission Effects 0.000 claims description 4
- 239000001117 sulphuric acid Substances 0.000 claims description 4
- JGSJAYTWMVKMPF-UHFFFAOYSA-N 2-(2-amino-4,5,6,7-tetrahydro-1,3-benzothiazol-6-yl)isoindole-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(N=C(S2)N)=C2C1 JGSJAYTWMVKMPF-UHFFFAOYSA-N 0.000 claims description 3
- PWUJQPNLEZZILN-UHFFFAOYSA-N 2-(4-oxocyclohexyl)isoindole-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)CC1 PWUJQPNLEZZILN-UHFFFAOYSA-N 0.000 claims description 3
- 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 3
- 125000006512 3,4-dichlorobenzyl group Chemical group [H]C1=C(Cl)C(Cl)=C([H])C(=C1[H])C([H])([H])* 0.000 claims description 3
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 3
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 3
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 3
- 239000003708 ampul Substances 0.000 claims description 3
- 125000004803 chlorobenzyl group Chemical group 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 230000007062 hydrolysis Effects 0.000 claims description 3
- 238000006460 hydrolysis reaction Methods 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 claims description 3
- 239000000725 suspension Substances 0.000 claims description 3
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 2
- FASDKYOPVNHBLU-UHFFFAOYSA-N N6-Propyl-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine Chemical compound C1C(NCCC)CCC2=C1SC(N)=N2 FASDKYOPVNHBLU-UHFFFAOYSA-N 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 150000001450 anions Chemical class 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- GJLUFTKZCBBYMV-UHFFFAOYSA-N carbamimidoylsulfanyl carbamimidothioate Chemical compound NC(=N)SSC(N)=N GJLUFTKZCBBYMV-UHFFFAOYSA-N 0.000 claims description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical group OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 claims description 2
- 239000011975 tartaric acid Substances 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims 19
- 229910052739 hydrogen Inorganic materials 0.000 claims 19
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 6
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 5
- 238000004519 manufacturing process Methods 0.000 claims 5
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims 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 claims 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims 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 claims 1
- PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 claims 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 239000002552 dosage form Substances 0.000 claims 1
- 239000012467 final product Substances 0.000 claims 1
- 239000001530 fumaric acid Substances 0.000 claims 1
- 239000004310 lactic acid Substances 0.000 claims 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims 1
- 239000011976 maleic acid Substances 0.000 claims 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims 1
- 239000000047 product Substances 0.000 claims 1
- 150000003254 radicals Chemical class 0.000 claims 1
- 239000001384 succinic acid Substances 0.000 claims 1
- 239000003826 tablet Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 22
- 230000000144 pharmacologic effect Effects 0.000 abstract description 4
- 210000003169 central nervous system Anatomy 0.000 abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 42
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 36
- 239000000243 solution Substances 0.000 description 31
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 22
- 235000002639 sodium chloride Nutrition 0.000 description 19
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- 239000000126 substance Substances 0.000 description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
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- 241001465754 Metazoa Species 0.000 description 13
- 229960001701 chloroform Drugs 0.000 description 13
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- 239000013543 active substance Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
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- 208000018737 Parkinson disease Diseases 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 229940073584 methylene chloride Drugs 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
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- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 6
- 238000009835 boiling Methods 0.000 description 6
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- IMLXLGZJLAOKJN-UHFFFAOYSA-N 4-aminocyclohexan-1-ol Chemical compound NC1CCC(O)CC1 IMLXLGZJLAOKJN-UHFFFAOYSA-N 0.000 description 5
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- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
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- 150000002500 ions Chemical class 0.000 description 4
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- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
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- 102000015554 Dopamine receptor Human genes 0.000 description 3
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- 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
- 208000027089 Parkinsonian disease Diseases 0.000 description 3
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- FLFDADQYQLFDEJ-UHFFFAOYSA-N O.Cl.Cl.C(C)NC1CC2=C(N=C(S2)NCCC2=CC=CC=C2)CC1.C(C)NC1CC2=C(N=C(S2)NCCC2=CC=CC=C2)CC1.Cl.Cl Chemical compound O.Cl.Cl.C(C)NC1CC2=C(N=C(S2)NCCC2=CC=CC=C2)CC1.C(C)NC1CC2=C(N=C(S2)NCCC2=CC=CC=C2)CC1.Cl.Cl FLFDADQYQLFDEJ-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
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- QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 1
- 206010071390 Resting tremor Diseases 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- UCTLHLZWKJIXJI-LXIBVNSESA-N [(3s,8r,9s,10r,13s,14s)-17-chloro-16-formyl-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15-decahydro-1h-cyclopenta[a]phenanthren-3-yl] acetate Chemical compound C([C@@H]12)C[C@]3(C)C(Cl)=C(C=O)C[C@H]3[C@@H]1CC=C1[C@]2(C)CC[C@H](OC(=O)C)C1 UCTLHLZWKJIXJI-LXIBVNSESA-N 0.000 description 1
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- HFEHLDPGIKPNKL-UHFFFAOYSA-N allyl iodide Chemical compound ICC=C HFEHLDPGIKPNKL-UHFFFAOYSA-N 0.000 description 1
- HTKFORQRBXIQHD-UHFFFAOYSA-N allylthiourea Chemical compound NC(=S)NCC=C HTKFORQRBXIQHD-UHFFFAOYSA-N 0.000 description 1
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- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
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- 210000004369 blood Anatomy 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- 229960000846 camphor Drugs 0.000 description 1
- 229930008380 camphor Natural products 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
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- 239000011248 coating agent Substances 0.000 description 1
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- 210000001653 corpus striatum Anatomy 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- 230000034994 death Effects 0.000 description 1
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- 238000006114 decarboxylation reaction Methods 0.000 description 1
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- 239000012024 dehydrating agents Substances 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 229940117389 dichlorobenzene Drugs 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 150000002238 fumaric acids Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- QMNWXHSYPXQFSK-UHFFFAOYSA-N hydron;6-n-propyl-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine;dichloride Chemical compound Cl.Cl.C1C(NCCC)CCC2=C1SC(N)=N2 QMNWXHSYPXQFSK-UHFFFAOYSA-N 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
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- 238000007918 intramuscular administration Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 150000002689 maleic acids Chemical class 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical compound COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-UHFFFAOYSA-N 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- QXKCTWPNUINDQK-UHFFFAOYSA-N n-(2-amino-4,5,6,7-tetrahydro-1,3-benzothiazol-6-yl)acetamide Chemical compound C1C(NC(=O)C)CCC2=C1SC(N)=N2 QXKCTWPNUINDQK-UHFFFAOYSA-N 0.000 description 1
- KHGYHNYVZMYHPI-UHFFFAOYSA-N n-[2-(benzylamino)-4,5,6,7-tetrahydro-1,3-benzothiazol-6-yl]acetamide Chemical compound S1C=2CC(NC(=O)C)CCC=2N=C1NCC1=CC=CC=C1 KHGYHNYVZMYHPI-UHFFFAOYSA-N 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000002581 neurotoxin Substances 0.000 description 1
- 231100000618 neurotoxin Toxicity 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 150000007530 organic bases Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007119 pathological manifestation Effects 0.000 description 1
- 125000003395 phenylethylamino group Chemical group [H]N(*)C([H])([H])C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- LGRFSURHDFAFJT-UHFFFAOYSA-N phthalic anhydride Chemical compound C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 1
- 229960003147 reserpine Drugs 0.000 description 1
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229960003339 sodium phosphate Drugs 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 210000003523 substantia nigra Anatomy 0.000 description 1
- 150000003444 succinic acids Chemical class 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
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- 230000001052 transient effect Effects 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles 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 in position 2
- C07D277/82—Nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Steroid Compounds (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Cereal-Derived Products (AREA)
- Bakery Products And Manufacturing Methods Therefor (AREA)
- Professional, Industrial, Or Sporting Protective Garments (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19843447075 DE3447075A1 (de) | 1984-12-22 | 1984-12-22 | Tetrahydro-benzthiazole, deren herstellung und deren verwendung als zwischenprodukte oder als arzneimittel |
| DEP3447075.1 | 1984-12-22 | ||
| DE19853508947 DE3508947A1 (de) | 1985-03-13 | 1985-03-13 | Mittel zur behandlung des parkinsonismus bzw. der parkinsonschen-erkrankung |
| DEP3508947.4 | 1985-03-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1263653A true CA1263653A (en) | 1989-12-05 |
Family
ID=25827684
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000498237A Expired CA1263653A (en) | 1984-12-22 | 1985-12-20 | Tetrahydro-benzthiazoles, the preparation thereof and their use as intermediate products or as pharmaceuticals |
Country Status (25)
| Country | Link |
|---|---|
| US (3) | US4731374A (https=) |
| EP (1) | EP0186087B1 (https=) |
| KR (1) | KR930009791B1 (https=) |
| AT (1) | ATE45735T1 (https=) |
| AU (1) | AU583874B2 (https=) |
| BG (1) | BG62023B2 (https=) |
| CA (1) | CA1263653A (https=) |
| CS (1) | CS409991A3 (https=) |
| DE (1) | DE3572485D1 (https=) |
| DK (1) | DK168862B1 (https=) |
| ES (5) | ES8702787A1 (https=) |
| FI (1) | FI81787C (https=) |
| GR (1) | GR853126B (https=) |
| HK (1) | HK78692A (https=) |
| HU (1) | HU193618B (https=) |
| IE (1) | IE58863B1 (https=) |
| IL (1) | IL77415A (https=) |
| LU (1) | LU90208I2 (https=) |
| MX (1) | MX9202792A (https=) |
| NL (1) | NL980002I2 (https=) |
| NO (1) | NO165070C (https=) |
| NZ (1) | NZ214661A (https=) |
| PH (1) | PH24533A (https=) |
| PT (1) | PT81735B (https=) |
| SG (1) | SG82492G (https=) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7695734B2 (en) | 2004-08-13 | 2010-04-13 | Boehringer Ingelheim International Gmbh | Extended release tablet formulation containing pramipexole or a pharmaceutically acceptable salt thereof |
| US8399016B2 (en) | 2002-07-25 | 2013-03-19 | Boehringer Ingelheim International Gmbh | Sustained-release tablet composition of pramipexole |
| US8715728B2 (en) | 2004-08-13 | 2014-05-06 | Boehringer Ingelheim International Gmbh | Extended release pellet formulation containing pramipexole or a pharmaceutically acceptable salt thereof |
Families Citing this family (119)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3620813A1 (de) * | 1986-06-21 | 1987-12-23 | Boehringer Ingelheim Kg | Neue tetrahydro-benzothiazole, ihre herstellung und verwendung |
| US4826860A (en) * | 1987-03-16 | 1989-05-02 | Warner-Lambert Company | Substituted 2-aminobenzothiazoles and derivatives useful as cerebrovascular agents |
| US4988699A (en) * | 1989-03-14 | 1991-01-29 | Warner-Lambert Company | Substituted tetrahydrobenzothiazoles as dopaminergic agents |
| DE3923689A1 (de) * | 1989-07-18 | 1991-01-24 | Boehringer Ingelheim Kg | Neue verwendung von tetrahydrobenzthiazolderivaten als arzneistoffe |
| DE3930282A1 (de) * | 1989-09-11 | 1991-03-21 | Boehringer Ingelheim Kg | Verwendung von dopamin-autorezeptor-agonisten bei der behandlung von drogenabhaengigkeit |
| DE3937271A1 (de) * | 1989-11-09 | 1991-05-16 | Boehringer Ingelheim Kg | Transdermale applikation von 2-amino-6-n-propylamino-4,5,6,7-tetrahydrobenzothiazol |
| FR2674853B1 (fr) * | 1991-04-03 | 1995-01-20 | Synthelabo | Derives de piperidinylguanidine, leur preparation et leur application en therapeutique. |
| DE4241013A1 (de) * | 1992-12-05 | 1994-06-09 | Boehringer Ingelheim Kg | Verwendung von 2-Amino-6-n-propyl-amino-4,5,6,7-tetrahydrobenzothiazol als Arzneimittel mit antidepressiver Wirkung |
| US6156777A (en) * | 1994-12-15 | 2000-12-05 | Pharmacia & Upjohn Company | Use of pramipexole as a neuroprotective agent |
| US5650420A (en) * | 1994-12-15 | 1997-07-22 | Pharmacia & Upjohn Company | Pramipexole as a neuroprotective agent |
| DE19507752A1 (de) * | 1995-03-06 | 1996-09-12 | Bayer Ag | Verfahren zur Herstellung von substituierten Cyclohexanonen |
| DE19536916A1 (de) * | 1995-10-04 | 1997-04-10 | Boehringer Ingelheim Kg | Inhalative Applikation von 2-Amino-6n-propyl-amino-4,5,6,7-tetrahydrobenzothiazol, insbesondere seines (-)-Enantiomeren, sowie deren pharmakologisch verträgliche Säureadditionssalze |
| ES2205227T3 (es) * | 1996-05-31 | 2004-05-01 | PHARMACIA & UPJOHN COMPANY | Aminas ciclicas aril-sustituidas como ligandos selectivos de dopamina d3'. |
| US6001861A (en) | 1998-01-16 | 1999-12-14 | Pharmacia & Upjohn Company | Use of pramipexole in the treatment of restless legs syndrome |
| DE19701619B4 (de) * | 1997-01-17 | 2007-10-11 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verwendung von Pramipexol zur Behandlung des restless legs syndroms |
| AU760439B2 (en) * | 1998-05-15 | 2003-05-15 | Pharmacia & Upjohn Company | Cabergoline and pramipexole: new uses and combinations |
| SE9802360D0 (sv) * | 1998-07-01 | 1998-07-01 | Wikstroem Hakan Vilhelm | New 2-aminothiazol-fused 2-aminoindans and 2-aminotetralins ((basic)-N-substituted and (basic)-N,N-disubstituted derivatives of 2,6-diamino-thiazolo(4,5-f)indan and 2,7-di-amino-thiazolo(4,5-g)tetralin |
| DE19830201A1 (de) * | 1998-07-07 | 2000-01-13 | Boehringer Ingelheim Pharma | Mittel mit antidepressiver Wirkung |
| US6232326B1 (en) | 1998-07-14 | 2001-05-15 | Jodi A. Nelson | Treatment for schizophrenia and other dopamine system dysfunctions |
| PE20011074A1 (es) | 2000-02-23 | 2001-10-04 | Upjohn Co | Uso de pramipexol en el tratamiento de trastornos de adiccion |
| AU7887501A (en) * | 2000-07-06 | 2002-01-21 | Us Gov Health & Human Serv | Tetrahydrobenzothiazole analogues as neuroprotective agents |
| US6277875B1 (en) * | 2000-07-17 | 2001-08-21 | Andrew J. Holman | Use of dopamine D2/D3 receptor agonists to treat fibromyalgia |
| US20030114410A1 (en) | 2000-08-08 | 2003-06-19 | Technion Research And Development Foundation Ltd. | Pharmaceutical compositions and methods useful for modulating angiogenesis and inhibiting metastasis and tumor fibrosis |
| DE10041478A1 (de) * | 2000-08-24 | 2002-03-14 | Sanol Arznei Schwarz Gmbh | Neue pharmazeutische Zusammensetzung |
| ES2187249B1 (es) | 2000-09-18 | 2004-09-16 | Synthon Bv | Procedimiento para la preparacion de 2-amino-6-(alquil)amino-4,5,6,7-tetrahidrobenzotiazoles. |
| US20020165246A1 (en) * | 2001-03-05 | 2002-11-07 | Andrew Holman | Administration of sleep restorative agents |
| DE10137453A1 (de) * | 2001-08-02 | 2003-02-20 | Boehringer Ingelheim Pharma | Pramlpexol als Antikonvulsivum |
| DE10138275A1 (de) * | 2001-08-10 | 2003-02-27 | Boehringer Ingelheim Pharma | Verbindungen zur Beseitigung der Anhedonie |
| ES2432527T3 (es) * | 2001-12-11 | 2013-12-04 | University Of Virginia Patent Foundation | Uso de pramipexol para tratar la esclerosis lateral amiotrófica |
| US20060281797A1 (en) * | 2001-12-11 | 2006-12-14 | University Of Virginia Patent Foundation | Neurorestoration with R(+) Pramipexole |
| US20030166696A1 (en) * | 2002-01-24 | 2003-09-04 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Pramipexole for the treatment of HIV dementia |
| EP2316468A1 (en) | 2002-02-22 | 2011-05-04 | Shire LLC | Delivery system and methods for protecting and administering dextroamphetamine |
| US20070196481A1 (en) * | 2002-07-25 | 2007-08-23 | Amidon Gregory E | Sustained-release tablet composition |
| PA8578501A1 (es) * | 2002-07-25 | 2005-02-04 | Pharmacia Corp | Forma de dosificacion una vez al dia de pramipexol |
| GB0221513D0 (en) * | 2002-09-17 | 2002-10-23 | Generics Uk Ltd | Novel compounds and processes |
| GB2394951A (en) * | 2002-11-04 | 2004-05-12 | Cipla Ltd | One pot synthesis of 2,6-diamino-4,5,6,7-tetrahydro-benzothiazole |
| US7365086B2 (en) * | 2003-07-25 | 2008-04-29 | Synthon Ip Inc. | Pramipexole acid addition salts |
| DE102004006808A1 (de) * | 2004-02-11 | 2005-09-01 | Grünenthal GmbH | Substituierte 4,5,6,7-Tetrahydro-benzothiazol-2-ylamin-Verbindungen |
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1985
- 1985-12-16 DE DE8585116016T patent/DE3572485D1/de not_active Expired
- 1985-12-16 EP EP85116016A patent/EP0186087B1/de not_active Expired
- 1985-12-16 AT AT85116016T patent/ATE45735T1/de active
- 1985-12-18 DK DK590285A patent/DK168862B1/da not_active IP Right Cessation
- 1985-12-19 US US06/810,947 patent/US4731374A/en not_active Expired - Lifetime
- 1985-12-20 CA CA000498237A patent/CA1263653A/en not_active Expired
- 1985-12-20 PH PH33232A patent/PH24533A/en unknown
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- 1985-12-20 FI FI855102A patent/FI81787C/fi not_active IP Right Cessation
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- 1985-12-20 IE IE327085A patent/IE58863B1/en not_active IP Right Cessation
- 1985-12-20 PT PT81735A patent/PT81735B/pt unknown
- 1985-12-20 NO NO855195A patent/NO165070C/no not_active IP Right Cessation
- 1985-12-20 ES ES550235A patent/ES8702787A1/es not_active Expired
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- 1985-12-20 IL IL77415A patent/IL77415A/xx not_active IP Right Cessation
- 1985-12-20 HU HU854935A patent/HU193618B/hu unknown
- 1985-12-21 KR KR1019850009688A patent/KR930009791B1/ko not_active Expired - Lifetime
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1986
- 1986-07-03 ES ES556874D patent/ES8707514B9/es not_active Expired - Lifetime
- 1986-07-03 ES ES556875A patent/ES8707515A1/es not_active Expired
- 1986-07-03 ES ES556873A patent/ES8707513A1/es not_active Expired
- 1986-07-03 ES ES556874A patent/ES8707514A1/es not_active Expired
-
1987
- 1987-11-23 US US07/124,197 patent/US4843086A/en not_active Expired - Lifetime
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1988
- 1988-10-12 US US07/256,671 patent/US4886812A/en not_active Expired - Lifetime
-
1991
- 1991-12-27 CS CS914099A patent/CS409991A3/cs unknown
-
1992
- 1992-06-11 MX MX9202792A patent/MX9202792A/es unknown
- 1992-08-18 SG SG824/92A patent/SG82492G/en unknown
- 1992-10-15 HK HK786/92A patent/HK78692A/xx not_active IP Right Cessation
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1994
- 1994-01-24 BG BG098405A patent/BG62023B2/bg unknown
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- 1998-01-09 NL NL980002C patent/NL980002I2/nl unknown
- 1998-01-30 LU LU90208C patent/LU90208I2/fr unknown
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| US8399016B2 (en) | 2002-07-25 | 2013-03-19 | Boehringer Ingelheim International Gmbh | Sustained-release tablet composition of pramipexole |
| US7695734B2 (en) | 2004-08-13 | 2010-04-13 | Boehringer Ingelheim International Gmbh | Extended release tablet formulation containing pramipexole or a pharmaceutically acceptable salt thereof |
| US8377977B2 (en) | 2004-08-13 | 2013-02-19 | Boehringer Ingelheim International Gmbh | Extended release tablet formulation containing pramipexole or a pharmaceutically acceptable salt thereof |
| US8715728B2 (en) | 2004-08-13 | 2014-05-06 | Boehringer Ingelheim International Gmbh | Extended release pellet formulation containing pramipexole or a pharmaceutically acceptable salt thereof |
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