US3925411A - Oxotremorine antagonist - Google Patents
Oxotremorine antagonist Download PDFInfo
- Publication number
- US3925411A US3925411A US306829A US30682972A US3925411A US 3925411 A US3925411 A US 3925411A US 306829 A US306829 A US 306829A US 30682972 A US30682972 A US 30682972A US 3925411 A US3925411 A US 3925411A
- Authority
- US
- United States
- Prior art keywords
- oxotremorine
- compound
- antagonist
- pentynyl
- pyrrolidino
- 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
- RSDOPYMFZBJHRL-UHFFFAOYSA-N Oxotremorine Chemical compound O=C1CCCN1CC#CCN1CCCC1 RSDOPYMFZBJHRL-UHFFFAOYSA-N 0.000 title abstract description 26
- 239000005557 antagonist Substances 0.000 title abstract description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 33
- 150000003839 salts Chemical class 0.000 claims abstract description 13
- ZLAHHJCKDNOZMP-UHFFFAOYSA-N 1-(5-pyrrolidin-1-ylpent-3-ynyl)pyrrolidin-2-one Chemical compound O=C1CCCN1CCC#CCN1CCCC1 ZLAHHJCKDNOZMP-UHFFFAOYSA-N 0.000 claims abstract description 4
- 230000005923 long-lasting effect Effects 0.000 abstract description 2
- 230000003512 tremorgenic effect Effects 0.000 abstract 1
- 206010044565 Tremor Diseases 0.000 description 13
- 238000012360 testing method Methods 0.000 description 12
- 230000000144 pharmacologic effect Effects 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical class CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- RGCLLPNLLBQHPF-HJWRWDBZSA-N phosphamidon Chemical compound CCN(CC)C(=O)C(\Cl)=C(/C)OP(=O)(OC)OC RGCLLPNLLBQHPF-HJWRWDBZSA-N 0.000 description 3
- NXAFJDDDPHVQDC-UHFFFAOYSA-N 1-(5-pyrrolidin-1-ylpent-3-ynyl)pyrrolidine-2,5-dione Chemical compound O=C1CCC(=O)N1CCC#CCN1CCCC1 NXAFJDDDPHVQDC-UHFFFAOYSA-N 0.000 description 2
- 208000008238 Muscle Spasticity Diseases 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000008034 disappearance Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 208000018198 spasticity Diseases 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical class OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 229930003347 Atropine Natural products 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical class OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
- 208000006083 Hypokinesia Diseases 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Chemical class [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
- 229960000396 atropine Drugs 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- OFAIGZWCDGNZGT-UHFFFAOYSA-N caramiphen Chemical compound C=1C=CC=CC=1C1(C(=O)OCCN(CC)CC)CCCC1 OFAIGZWCDGNZGT-UHFFFAOYSA-N 0.000 description 1
- 229960004160 caramiphen Drugs 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 229940045803 cuprous chloride Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000003483 hypokinetic effect Effects 0.000 description 1
- 238000013101 initial test Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 239000003509 long acting drug Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 230000001499 parasympathomimetic effect Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000001384 succinic acid Chemical class 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 239000011975 tartaric acid Chemical class 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 230000002747 voluntary effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 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
- C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
- C07D207/27—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/02—Preparation by ring-closure or hydrogenation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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, directly attached to ring carbon atoms
- C07D211/74—Oxygen atoms
- C07D211/76—Oxygen atoms attached in position 2 or 6
Definitions
- the present invention relates to a new compound N-(-pyrrolidino-3-pentynyl)-pyrrolidin-2-one and its therapeutically acceptable salts.
- the compound is represented by the formula:
- oxotremorine N-(4-pyrrolidino-2- butynyl)-pyrrolidin-2-one
- tremors and spasticity have been used to induce tremors and spasticity in several species of laboratory animals. It induces violent generalized tremors, spasticity, hypokinesia and parasympathomimetic effects immediately after injection by intravenous routes and produces both central and peripheral cholinergic reactrons.
- a number of drugs such as atropine and caramiphen l-phenylcyclopentanecarboxylic acid 2-diethylaminoethyl ester
- drugs which will antagonize the oxotremorine-induced tremor.
- These drugs however, have a relatively short pharmacological half-life and must be repeatedly administered in order to obtain a lasting antagonist action. The repeated administration of these drugs is undesirable since they have side effects which affect the peripheral nervous system.
- the compound of the present invention has been found to possess a long pharmacological half-life thereby making it suitable for use as a long-lasting oxotremorine antagonist.
- the compound N-(5-pyrrolidino-3-pentynyl)-pyrrolidin-2-one should preferably be in the free base form.
- the typical therapeutically acceptable salts include, but are not limited to, the salts of the hydrohalides, especially hydrochloric and hydrobromic acid, and the salts of sulfuric acid, phosphoric acid, acetic acid, tartaric acid, citric acid, and succinic acid.
- the salts of hydrochloric and hydrobromic acids are preferred because of their ready availability. Manifestly, many other physiologically acceptable salts will be obvious to those skilled in the art, and all such salts may be employed in the present invention.
- the tremoromimetic effect of oxotremorine has been proposed as a pharmacological model of Parkinson's disease.
- the fact that the compound of the present invention has a long pharmacological half-life in antagonizing the tremoromimetic effect of oxotremorine suggests, therefore, that it might also be useful as a long-acting drug in the treatment of Parkinsons disease.
- Example 14 in Example 14 (as a citrate) and as the ninth compound from the bottom in Table IV of that patent. The following test procedure was used.
- mice Using screening data orally effective doses of the two above-mentioned compounds were chosen. Groups of six female mice weighing 22 to 26 grams were then administered oxotremorine without the test compounds to establish a control group and the median effective dose of oxotremorine needed to produce a spontaneous tremor was determined by the up-anddown" method for small samples described by W. J. Dixon in the Journal of the American S tatislical Association, 60: 967-978 (1965). The tremors in all mice were graded three minutes after intravenous administration of oxotremorine.
- the first animal is treated at an arbitrarily selected level and the presence or absence of tremor response is noted.
- An increased or decreased dosage is then selected for the second animal according to a schedule specified in the Dixon procedure which would tend to produce a change in the tremor response. (For example, if the initial dose produces a tremor, the second animal is treated at a reduced dosage to determine if no tremor will result.)
- the procedure is repeated until all six mice have been tested. If, following the sequence of testing specified by Dixon, all mice of the group showed the same tremor response (all negative or all positive), the group was increased until a change in response was found in two mice.
- the orally effective dose of each of the test com pounds was then administered at varying times before administration of the oxotremorine to succeeding groups of six mice and the increased median effective dose of oxotremorine in the presence of the test compounds was determined in the same manner.
- the compound of the present invention and the compound described in the Dahlbom et al. patent were administered orally.
- the dose of oxotremorine needed to produce tremors which were intermittent and occasional was determined for two dosage levels (i.e., 0.15 mM/kg and 0.05 mM/kg) of the compound of the present invention and one dosage level (i.e., 0.037 mM/kg) of N-(5-pyrrolidino-3-pentynyl) succinimide, the compound described in the Dahlbom et al. patent.
- the acid salt of the compound of the present invention (l mole compound 1.5 moles oxalic acid, mol. wt.
- the Table given below shows the oxotremorine concentration in g/kg necessary to produce tremor in mice after previous administration of N-(5-pyrrolidino- S-pentynyl)pyrrolidin-Z-one.
- the compound of the present invention labelled A in the Table
- N-(S- pyrrolidin-3-pentynyl) succinimidc labelled B in the Table
- the pharmacological half-life of the compound of the claimed invention is 28.4 minutes whereas the half-life of the prior art compound, N-(5- pyrrolidino-3-pentynyl) succinimide, is 12.4 minutes.
- the compound of the present invention achieved its peak effect within l0 minutes after oral administration whereas the Dahlbom et al. compound had its peak effect somewhere between 15 and 30 minutes after oral administration. The disappearance rate cannot be determined by the type of test used herein until after the peak effect has occurred.
- the data suggest that the compound of the present invention is more efficiently absorbed from the gastrointestinal tract than the compound described in the Dahlbom et al. patent.
- the sesquioxalate of the compound of the present invention can be prepared by the following preferred reaction:
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyrrole Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US306829A US3925411A (en) | 1967-11-09 | 1972-11-15 | Oxotremorine antagonist |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB51146/67A GB1245743A (en) | 1967-11-09 | 1967-11-09 | Alkynyl lactams |
| US20390771A | 1971-12-01 | 1971-12-01 | |
| US306829A US3925411A (en) | 1967-11-09 | 1972-11-15 | Oxotremorine antagonist |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| USB306829I5 USB306829I5 (enrdf_load_stackoverflow) | 1975-01-28 |
| US3925411A true US3925411A (en) | 1975-12-09 |
Family
ID=10458832
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US306829A Expired - Lifetime US3925411A (en) | 1967-11-09 | 1972-11-15 | Oxotremorine antagonist |
| US05/473,190 Expired - Lifetime US3959311A (en) | 1967-11-09 | 1974-05-24 | Oxotremorine antagonists |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US05/473,190 Expired - Lifetime US3959311A (en) | 1967-11-09 | 1974-05-24 | Oxotremorine antagonists |
Country Status (9)
| Country | Link |
|---|---|
| US (2) | US3925411A (enrdf_load_stackoverflow) |
| DE (2) | DE1805029A1 (enrdf_load_stackoverflow) |
| DK (1) | DK131935C (enrdf_load_stackoverflow) |
| FI (1) | FI49419C (enrdf_load_stackoverflow) |
| FR (2) | FR1591337A (enrdf_load_stackoverflow) |
| GB (1) | GB1245743A (enrdf_load_stackoverflow) |
| NL (1) | NL6814854A (enrdf_load_stackoverflow) |
| NO (1) | NO127670B (enrdf_load_stackoverflow) |
| SE (1) | SE339225B (enrdf_load_stackoverflow) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4081456A (en) * | 1973-02-28 | 1978-03-28 | Mobil Oil Corporation | Bis-lactam derivatives |
| WO1990001026A1 (en) * | 1988-07-25 | 1990-02-08 | The Upjohn Company | Acetylenic imidazoles having central nervous system activity |
| WO1990004588A1 (en) * | 1988-10-27 | 1990-05-03 | The Upjohn Company | Heterocyclic acetylenic amines having central nervous system activity |
| US5100909A (en) * | 1988-07-25 | 1992-03-31 | The Upjohn Company | Acetylenic imidazoles having central nervous system activity |
| US5157124A (en) * | 1988-10-27 | 1992-10-20 | The Upjohn Company | Heterocyclic acetylenic amines having central nervous system activity |
| US5225567A (en) * | 1988-10-27 | 1993-07-06 | The Upjohn Company | Heterocyclic acetylenic amines having central nervous system activity |
| US5837919A (en) * | 1996-12-05 | 1998-11-17 | The United States Of America As Represented By The Secretary Of The Navy | Portable launcher |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1245743A (en) * | 1967-11-09 | 1971-09-08 | Astra Ab | Alkynyl lactams |
| US4937235A (en) * | 1989-01-23 | 1990-06-26 | American Cyanamid Company | 3- or 4-substituted oxotremorine derivatives |
| IE902294A1 (en) * | 1989-07-06 | 1991-01-16 | Abbott Lab | Alkynyl amines that regulate cholinergic neurotransmission |
| GB201311107D0 (en) * | 2013-06-21 | 2013-08-07 | Univ Edinburgh | Bioorthogonal methods and compounds |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3444185A (en) * | 1964-05-26 | 1969-05-13 | Civile Auguil Soc | Process of preparing 1-(2-oxo 1-pyrrolidino) 4-(1 - pyrrolidino)- but-2-yne and salts thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3354178A (en) * | 1965-04-09 | 1967-11-21 | Sterling Drug Inc | Nu-(4-amino-2-butynyl)-nu-alkylcarboxamides |
| GB1245743A (en) * | 1967-11-09 | 1971-09-08 | Astra Ab | Alkynyl lactams |
| US3856790A (en) * | 1970-01-06 | 1974-12-24 | American Home Prod | Cyclic amides of 1,4-diaminobut-2-yne |
-
1967
- 1967-11-09 GB GB51146/67A patent/GB1245743A/en not_active Expired
-
1968
- 1968-10-17 NL NL6814854A patent/NL6814854A/xx not_active Application Discontinuation
- 1968-10-24 SE SE14426/68A patent/SE339225B/xx unknown
- 1968-10-25 DE DE19681805029 patent/DE1805029A1/de active Pending
- 1968-10-25 NO NO04246/68A patent/NO127670B/no unknown
- 1968-11-06 DE DE19681807218 patent/DE1807218A1/de active Pending
- 1968-11-07 FR FR172979A patent/FR1591337A/fr not_active Expired
- 1968-11-07 FR FR172980A patent/FR8307M/fr not_active Expired
- 1968-11-08 DK DK542668A patent/DK131935C/da active
- 1968-11-08 FI FI683204A patent/FI49419C/fi active
-
1972
- 1972-11-15 US US306829A patent/US3925411A/en not_active Expired - Lifetime
-
1974
- 1974-05-24 US US05/473,190 patent/US3959311A/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3444185A (en) * | 1964-05-26 | 1969-05-13 | Civile Auguil Soc | Process of preparing 1-(2-oxo 1-pyrrolidino) 4-(1 - pyrrolidino)- but-2-yne and salts thereof |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4081456A (en) * | 1973-02-28 | 1978-03-28 | Mobil Oil Corporation | Bis-lactam derivatives |
| WO1990001026A1 (en) * | 1988-07-25 | 1990-02-08 | The Upjohn Company | Acetylenic imidazoles having central nervous system activity |
| US5100909A (en) * | 1988-07-25 | 1992-03-31 | The Upjohn Company | Acetylenic imidazoles having central nervous system activity |
| WO1990004588A1 (en) * | 1988-10-27 | 1990-05-03 | The Upjohn Company | Heterocyclic acetylenic amines having central nervous system activity |
| US5137905A (en) * | 1988-10-27 | 1992-08-11 | The Upjohn Company | Heterocyclic acetylenic amines having central nervous system activity |
| US5157124A (en) * | 1988-10-27 | 1992-10-20 | The Upjohn Company | Heterocyclic acetylenic amines having central nervous system activity |
| US5225567A (en) * | 1988-10-27 | 1993-07-06 | The Upjohn Company | Heterocyclic acetylenic amines having central nervous system activity |
| EP0605393A1 (en) * | 1988-10-27 | 1994-07-06 | The Upjohn Company | Heterocyclic acetylenic amines having central nervous system activity |
| US5837919A (en) * | 1996-12-05 | 1998-11-17 | The United States Of America As Represented By The Secretary Of The Navy | Portable launcher |
Also Published As
| Publication number | Publication date |
|---|---|
| FI49419C (fi) | 1975-06-10 |
| SE339225B (enrdf_load_stackoverflow) | 1971-10-04 |
| DK131935B (da) | 1975-09-29 |
| DE1805029A1 (de) | 1969-06-12 |
| DE1807218A1 (de) | 1969-06-12 |
| NL6814854A (enrdf_load_stackoverflow) | 1969-05-13 |
| FR1591337A (enrdf_load_stackoverflow) | 1970-04-27 |
| DK131935C (da) | 1976-02-23 |
| US3959311A (en) | 1976-05-25 |
| NO127670B (enrdf_load_stackoverflow) | 1973-07-30 |
| FR8307M (enrdf_load_stackoverflow) | 1970-11-23 |
| GB1245743A (en) | 1971-09-08 |
| FI49419B (enrdf_load_stackoverflow) | 1975-02-28 |
| USB306829I5 (enrdf_load_stackoverflow) | 1975-01-28 |
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