US3746743A - 2 - (ethylpropylamine)ethyl-alpha,alpha-diphenyl-glycollate and the hydrochloride thereof - Google Patents
2 - (ethylpropylamine)ethyl-alpha,alpha-diphenyl-glycollate and the hydrochloride thereof Download PDFInfo
- Publication number
- US3746743A US3746743A US00187558A US3746743DA US3746743A US 3746743 A US3746743 A US 3746743A US 00187558 A US00187558 A US 00187558A US 3746743D A US3746743D A US 3746743DA US 3746743 A US3746743 A US 3746743A
- Authority
- US
- United States
- Prior art keywords
- compounds
- formula
- new
- alpha
- hydrochloride
- 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
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 title description 12
- XCVNDBIXFPGMIW-UHFFFAOYSA-N n-ethylpropan-1-amine Chemical compound CCCNCC XCVNDBIXFPGMIW-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 abstract description 54
- 208000027089 Parkinsonian disease Diseases 0.000 abstract description 11
- 206010034010 Parkinsonism Diseases 0.000 abstract description 11
- 239000002253 acid Substances 0.000 abstract description 4
- 150000002168 ethanoic acid esters Chemical class 0.000 abstract description 4
- 150000001414 amino alcohols Chemical class 0.000 abstract description 3
- 231100000252 nontoxic Toxicity 0.000 abstract description 3
- 230000003000 nontoxic effect Effects 0.000 abstract description 3
- 238000002638 palliative care Methods 0.000 abstract description 3
- 150000003839 salts Chemical class 0.000 abstract description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract 2
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical group [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 abstract 1
- 241000699670 Mus sp. Species 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 230000000694 effects Effects 0.000 description 11
- 125000000217 alkyl group Chemical group 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
- -1 alkaline earth metal alkoxide Chemical class 0.000 description 8
- 230000000648 anti-parkinson Effects 0.000 description 7
- 239000000939 antiparkinson agent Substances 0.000 description 7
- 206010044565 Tremor Diseases 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 230000002911 mydriatic effect Effects 0.000 description 5
- 230000003594 anti-tremorine Effects 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- JSUAJTLKVREZHV-UHFFFAOYSA-N 1-[4-(1-pyrrolidinyl)but-2-ynyl]pyrrolidine Chemical compound C1CCCN1CC#CCN1CCCC1 JSUAJTLKVREZHV-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 206010010904 Convulsion Diseases 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 208000006550 Mydriasis Diseases 0.000 description 3
- RSDOPYMFZBJHRL-UHFFFAOYSA-N Oxotremorine Chemical compound O=C1CCCN1CC#CCN1CCCC1 RSDOPYMFZBJHRL-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 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 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- SLYZAVUTVSKACM-UHFFFAOYSA-N 3-[ethyl(propyl)amino]propan-1-ol Chemical compound CCCN(CC)CCCO SLYZAVUTVSKACM-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 125000004663 dialkyl amino group Chemical group 0.000 description 2
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 2
- 239000000284 extract Substances 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
- 239000007788 liquid Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- PSUBDZSVEGLUQA-UHFFFAOYSA-N 1-(2-methylbutylamino)ethanol Chemical compound C(C)C(CNC(C)O)C PSUBDZSVEGLUQA-UHFFFAOYSA-N 0.000 description 1
- IVQOFBKHQCTVQV-UHFFFAOYSA-N 2-hydroxy-2,2-diphenylacetic acid 2-(diethylamino)ethyl ester Chemical compound C=1C=CC=CC=1C(O)(C(=O)OCCN(CC)CC)C1=CC=CC=C1 IVQOFBKHQCTVQV-UHFFFAOYSA-N 0.000 description 1
- 229930003347 Atropine Natural products 0.000 description 1
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-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
- 231100000111 LD50 Toxicity 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- HWHLPVGTWGOCJO-UHFFFAOYSA-N Trihexyphenidyl Chemical compound C1CCCCC1C(C=1C=CC=CC=1)(O)CCN1CCCCC1 HWHLPVGTWGOCJO-UHFFFAOYSA-N 0.000 description 1
- 206010047513 Vision blurred Diseases 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000001004 anti-acetylcholinic effect Effects 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 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
- 239000002585 base Substances 0.000 description 1
- 229960001498 benactyzine Drugs 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004914 dipropylamino group Chemical group C(CC)N(CCC)* 0.000 description 1
- 230000009429 distress Effects 0.000 description 1
- 206010013781 dry mouth Diseases 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 231100000161 signs of toxicity Toxicity 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- 229960001032 trihexyphenidyl Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
Definitions
- R and R are difierent lower alkyl groups of 1 to 6 carbon atoms
- X is divalent alkylene of 2 or 3 carbon atoms
- the present invention relates to new basic esters useful for the palliative treatment of Parkinsonism and the present application is a continuation of application Ser. No. 732,517, filed May 28, 1968, now abandoned, which is a continuation-in-part of application Ser. No. 390,173, filed Aug. 17, 1964, now abandoned.
- the new anti-Parkinson compounds of the present invention have the formula:
- R and R are different lower alkyl groups of 1 to 6 carbon atoms
- X is divalent alkylene of 2 or 3 carbon atoms
- the dosage and route of administration of the new anti-Parkinson compounds are in general the same as with known anti-Parkinson compounds. It is well recognized, however, that the dosage of active drug used for the treatment of Parkinsonism varies considerably from patient to patient and depending upon the severity of the condition existing in each patient as well as the length of time during which the patient has been affected with Parkinsonism. It is thus not possible to make a general rule with respect to amount and frequency of dosage as the physician or clinician must use his own best judgment.
- the reaction is preferably but not necessarily carried out int he presence of a catalyst which is an alkali or alkaline earth metal alkoxide. Sodium methoxide is a particularly good catalyst.
- the reaction is preferably carried out by heating the reactants II and III in a solvent such as light petroleum or n-heptane and the catalyst may be and usually is dissolved in a suitable solvent such as a sodium alkoxide which is present in excess of the corresponding alkanol.
- the substituted acetic acid esters of Formula II which are used as the starting materials for the new compounds I, are prepared according to methods known per se.
- Tests for pharmacological activity have been carried out on two of the compounds of the present invention together with comparative tests on compounds of similar structure.
- the compounds tested were the hydrochlorides R and R are identical Me 0(CH ),N
- mice Initially, the toxicities of compounds I to VI were determined in mice. Groups of 5 mice were each injected subcutaneously with solutions of compounds I, II, IV, V and VI and intravenously with a solution of compound III, and they were observed for toxic symptoms over a period of 24 hours. The number of animals that died in each group was noted and the LD (the median lethal dose), in mg./ kg. body weight, was calculated. The results were as follows:
- the anti-tremorine activity of compounds I to VI was determined by dosing groups of 5 mice subcutaneously with a solution of each compound. After 30 minutes the mice were challenged with 40 mg./ kg. of tremorine administered intraperitoneally and the mice were assessed after a further 30 minutes for tremor. The degree of inhibition of tremor due to the tremorine was used to calculate the ED (medium efiective dose), and the results were as The mydriatic activity of compounds I and VI in mice was determined by dosing groups of 5 mice subcutaneous- 1y with a solution of each compound. After 20 minutes the eyes of the mice were inspected under a binocular microscope and the degree of mydriasis was measured in orbitary units by using a scale in one eyepiece. The results were used to determine the ED and were as follows:
- mice The effect of compounds I and VI on the central nervous system was determined by measuring their inhibiting action in preventing convulsions due to the application of a maximal electroshock (MES) to the brain of mice.
- MES maximal electroshock
- Groups of 10 mice were injected subcutaneously with solutions of the compounds, then subjected to an MES one hour later.
- the mice used had been preselected for their ability to exhibit maximum seizure before the active compound was administered.
- the ED values for compounds I and II were 6.8 and 50 mg./kg. respectively, whereas compounds III to VI showed no inhibition of the MES.
- Atropine is not used in the regular treatment of Parkinsonism as the side elfects are such that it would cause undue distress and hospitalization of the patient if used in therapeutic doses for the treatment of this condition.
- EXAMPLE 1 A methanolic solution of sodium methoxide (from sodium (0.2 g.) and dry methanol (3 ml.) was added dropwise during minutes to a boiling solution of methyl u,a-diphenylglycollate (11 g.) and Z-ethylpropylaminoethanol (6 g.) in light petroleum (150 ml., B.P. 80-100") and the methanol that separated was removed by using a Dean and Starke apparatus. At the end of 5 hours no further separation of methanol occurred and the reaction mixture after being washed with water (3X 20 ml.) was extracted with 1 N hydrochloric acid (3X ml.).
- EXAMPLE 2 Preparation of 2-(ethylpropylamino)ethyl a-cyclohexyl-a-phenylglycollate hydrochloride
- a methanolic solution of sodium methoxide [from sodium (0.2 g.) in dry methanol (3 ml.)] was added dropwise during 20 minutes to a boiling solution of methyl a-cyclohexyl-u-phenylglycollate (16 g.) and 2-ethylpropylaminoethanol (12.7 g.) in light petroleum (500 ml., B.P. -100").
- Esters of the following formula were prepared similarly (Ph, Me, Et, Pr and Bu stand for phenyl, methyl, ethyl, propyl and butyl, respectively):
- the parent alcohol 3-(ethylpropylamino)propan-l-ol was obtained as follows:
- Ethyl acrylate was added dropwise with stirring to an excess of n-propylamine (600 g.) containing water (10 ml.) and allowed to stand at room temperature for 4 hours. After removal of excess of propylamine, the residual oil was dissolved in ether, dried (MgSO the solvent removed by evaporation and the liquid distilled under reduced pressure to give ethyl fi-n-propylaminopropionate (136 g., 86%) as a colorless liquid, B.P. 78 C./9 mm., n 1.4258.
- R and R cannot be identical and it is of critical significance that they be difierent lower alkyl groups as exemplified by the foregoing examples. It is only when R and R are dilferent lower alkyl groups that the full benefit and utility of the new compounds is realized for the treatment of Parkinsonism.
- Compounds are known of similar constitution to the compounds of this invention but where the dialkylamino moiety has two like alkyl groups such as diethylamino or dipropylamino. Such compounds do not have anti-Parkinson utility, but on the contrary, may have utility as mere tranquilizers.
- the lower alkyl groups of the dialkylamino moiety of the new compounds of this invention have different lower alkyl groups and an important aspect of the present invention resides in the discovery that these alkyl groups must be diiferent, because it they are not different, the resulting compounds have properties and usefulness for purposes other than the treatment of Parkinsonism.
- the efiective dose of the new compounds of the present invention is below that which causes mydriasis whereas such is not true of substances hereintofore used in the treatment of Parkinsonism and wherein some effectiveness can be attained only by the use of such large dosages as to cause adverse unpleasant and even serious side effects such as blurred vision, dry mouth and symptoms of mydriasis.
Landscapes
- Health & Medical Sciences (AREA)
- Emergency Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB33248/63A GB1007845A (en) | 1963-08-22 | 1963-08-22 | Basic glycollic acid esters |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3746743A true US3746743A (en) | 1973-07-17 |
Family
ID=10350453
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US00187558A Expired - Lifetime US3746743A (en) | 1963-08-22 | 1971-10-07 | 2 - (ethylpropylamine)ethyl-alpha,alpha-diphenyl-glycollate and the hydrochloride thereof |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US3746743A (nl) |
| AT (1) | AT246731B (nl) |
| BE (1) | BE651753A (nl) |
| BR (1) | BR6461501D0 (nl) |
| CH (1) | CH434293A (nl) |
| DE (1) | DE1244798B (nl) |
| DK (1) | DK108730C (nl) |
| ES (1) | ES303275A1 (nl) |
| FR (1) | FR3611M (nl) |
| GB (1) | GB1007845A (nl) |
| NL (1) | NL147132B (nl) |
| SE (1) | SE319778B (nl) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4212886A (en) * | 1978-11-01 | 1980-07-15 | Survival Technology, Inc. | Stabilized benactyzine hydrochloride |
| US20080058350A1 (en) * | 2006-08-28 | 2008-03-06 | Forest Laboratories Holdings Limited | Imidazopyridine and imidazopyrimidine derivatives |
| US10504496B1 (en) | 2019-04-23 | 2019-12-10 | Sensoplex, Inc. | Music tempo adjustment apparatus and method based on gait analysis |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2046659A1 (nl) * | 1970-01-28 | 1972-03-23 |
-
1963
- 1963-08-22 GB GB33248/63A patent/GB1007845A/en not_active Expired
-
1964
- 1964-08-06 BR BR161501/64A patent/BR6461501D0/pt unknown
- 1964-08-13 BE BE651753D patent/BE651753A/xx unknown
- 1964-08-18 ES ES0303275A patent/ES303275A1/es not_active Expired
- 1964-08-19 CH CH1082764A patent/CH434293A/de unknown
- 1964-08-20 SE SE10056/64A patent/SE319778B/xx unknown
- 1964-08-20 AT AT719364A patent/AT246731B/de active
- 1964-08-21 DE DEB78218A patent/DE1244798B/de active Pending
- 1964-08-21 DK DK413764AA patent/DK108730C/da active
- 1964-08-21 NL NL646409696A patent/NL147132B/nl unknown
- 1964-08-21 FR FR985841A patent/FR3611M/fr not_active Expired
-
1971
- 1971-10-07 US US00187558A patent/US3746743A/en not_active Expired - Lifetime
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4212886A (en) * | 1978-11-01 | 1980-07-15 | Survival Technology, Inc. | Stabilized benactyzine hydrochloride |
| US20080058350A1 (en) * | 2006-08-28 | 2008-03-06 | Forest Laboratories Holdings Limited | Imidazopyridine and imidazopyrimidine derivatives |
| US7563797B2 (en) | 2006-08-28 | 2009-07-21 | Forest Laboratories Holding Limited | Substituted imidazo(1,2-A)pyrimidines and imidazo(1,2-A) pyridines as cannabinoid receptor ligands |
| US10504496B1 (en) | 2019-04-23 | 2019-12-10 | Sensoplex, Inc. | Music tempo adjustment apparatus and method based on gait analysis |
Also Published As
| Publication number | Publication date |
|---|---|
| NL6409696A (nl) | 1965-02-23 |
| DK108730C (da) | 1968-02-05 |
| NL147132B (nl) | 1975-09-15 |
| DE1244798B (de) | 1967-07-20 |
| GB1007845A (en) | 1965-10-22 |
| SE319778B (nl) | 1970-01-26 |
| AT246731B (de) | 1966-05-10 |
| BR6461501D0 (pt) | 1973-08-07 |
| BE651753A (nl) | 1964-12-01 |
| FR3611M (fr) | 1965-10-11 |
| ES303275A1 (es) | 1965-02-16 |
| CH434293A (de) | 1967-04-30 |
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