US3124595A - Endo-pemhydro-x - Google Patents
Endo-pemhydro-x Download PDFInfo
- Publication number
- US3124595A US3124595A US3124595DA US3124595A US 3124595 A US3124595 A US 3124595A US 3124595D A US3124595D A US 3124595DA US 3124595 A US3124595 A US 3124595A
- Authority
- US
- United States
- Prior art keywords
- endo
- pemhydro
- perhydro
- acid addition
- tangible embodiments
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 claims description 8
- 239000002253 acid Substances 0.000 description 8
- 238000007792 addition Methods 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- UMGDCJDMYOKAJW-UHFFFAOYSA-N Thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 4
- 125000002947 alkylene group Chemical group 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 230000003000 nontoxic Effects 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- MNDIARAMWBIKFW-UHFFFAOYSA-N 1-Bromohexane Chemical compound CCCCCCBr MNDIARAMWBIKFW-UHFFFAOYSA-N 0.000 description 2
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K 2qpq Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- VBSDAMAWZZSZMY-UHFFFAOYSA-N 36170-23-7 Chemical compound C12CNCC2C2CCC1C2 VBSDAMAWZZSZMY-UHFFFAOYSA-N 0.000 description 2
- VCQSDDNVOLQOOR-UHFFFAOYSA-N C12=CNC=C2C2=CC=C1C2 Chemical class C12=CNC=C2C2=CC=C1C2 VCQSDDNVOLQOOR-UHFFFAOYSA-N 0.000 description 2
- UHNBWKCSAOQKIY-UHFFFAOYSA-N CHEMBL2041550 Chemical compound Cl.C12CNCC2C2CCC1C2 UHNBWKCSAOQKIY-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N Methyl iodide Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000002220 antihypertensive agent Substances 0.000 description 2
- 150000007656 barbituric acids Chemical class 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-M chloride;hydrochloride Chemical compound Cl.[Cl-] IXCSERBJSXMMFS-UHFFFAOYSA-M 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000005712 crystallization Effects 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229940093499 ethyl acetate Drugs 0.000 description 2
- 235000019439 ethyl acetate Nutrition 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N iso-propanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 239000003589 local anesthetic agent Substances 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-L maleate(2-) Chemical compound [O-]C(=O)\C=C/C([O-])=O VZCYOOQTPOCHFL-UPHRSURJSA-L 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
- 239000008024 pharmaceutical diluent Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propanol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 230000003595 spectral Effects 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000002194 synthesizing Effects 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/58—[b]- or [c]-condensed
- C07D209/72—4,7-Endo-alkylene-iso-indoles
Definitions
- the tangible embodiments of this invention possess the inherent general physical characteristics of being, in the form of their acid addition salts, white crystalline solids. Spectral data reveal no unsaturation except as present in the NH portion of peudothiouronium radical. The aforementioned physical characteristics, taken together with the nature of the starting materials and the mode of synthesis, positively confirm the structure of the compounds sought to be patented.
- tangible embodiments of this invention possess the inherent applied use characteristics of having pharmacological activity as anti-hypertensive agents, local anesthetic agents and as agents for prolonging the effects of pharmacologically active barbituric acid derivatives as determined by recognized and accepted pharmacological test procedures.
- N-haloalkyl-endo-perhydro 4,7 methanoisoindoles are prepared according to the method described in my application entitled N-(Haloalkyl)-Endo-Perhydro- 4,7-Methanoisoindoles, Serial No. 213,050 filed July 27, 1962.
- A is lower alkylene and X is a halogen.
- the tangible embodiments of this invention can, if desired, be converted into their non-toxic pharmaceutically acceptable acid addition or quaternary ammonium salts by conventional procedures.
- Typical acid addition salts include the hydrochloride, hydrobromide, citrate, maleate, sulfate, nitrate and the like.
- Typical quaternary ammonium salts are those formed with such alkyl halides as methyl iodide, n-hexyl bromide and the like. Such salts are the full equivalents of the free bases and are included within the scope of this invention.
- tangible embodiments of this invention may be combined with conventional pharmaceutical diluents and carriers to form such dosage forms as tablets, capsules, solutions, suspensions, suppositories and the like.
Description
United States Patent 3,124,595 N (PSEUDOTHIGURQNHUM LQWER ALKYL)- ENDO-PERHYDRG-dfl-MET OHSOENDGUE James W. Bolger, Canoga Park, Caliih, assignor to or Laboratories, linc., Northridge, Calif., a corporation of Deiaware No Drawing. Filed July 27, 1962, Ser. No. 213,031
2 Claims. (Cl. 26tl319) radical.
The tangible embodiments of this invention possess the inherent general physical characteristics of being, in the form of their acid addition salts, white crystalline solids. Spectral data reveal no unsaturation except as present in the NH portion of peudothiouronium radical. The aforementioned physical characteristics, taken together with the nature of the starting materials and the mode of synthesis, positively confirm the structure of the compounds sought to be patented.
The tangible embodiments of this invention possess the inherent applied use characteristics of having pharmacological activity as anti-hypertensive agents, local anesthetic agents and as agents for prolonging the effects of pharmacologically active barbituric acid derivatives as determined by recognized and accepted pharmacological test procedures.
The manner and process of making and using the invention will now be generally described so as to enable a person skilled in the art of chemistry to make and use the same as follows:
The starting materials for the compounds of this invention, N-haloalkyl-endo-perhydro 4,7 methanoisoindoles, are prepared according to the method described in my application entitled N-(Haloalkyl)-Endo-Perhydro- 4,7-Methanoisoindoles, Serial No. 213,050 filed July 27, 1962. i
The preparation of the tangible embodiments of this invention is illustrated as follows:
where A is lower alkylene and X is a halogen.
3,124,595 Patented Mar. 10, 1964 The reaction depicted hereinabove is carried out by treating the starting material with thiourea in the presence of an inert solvent such as ethanol or propanol at reflux temperature.
The tangible embodiments of this invention can, if desired, be converted into their non-toxic pharmaceutically acceptable acid addition or quaternary ammonium salts by conventional procedures. Typical acid addition salts include the hydrochloride, hydrobromide, citrate, maleate, sulfate, nitrate and the like. Typical quaternary ammonium salts are those formed with such alkyl halides as methyl iodide, n-hexyl bromide and the like. Such salts are the full equivalents of the free bases and are included within the scope of this invention.
The tangible embodiments of this invention, either as the free base or in the form of a non-toxic pharmaceutically acceptable acid addition or quaternary ammonium salt, may be combined with conventional pharmaceutical diluents and carriers to form such dosage forms as tablets, capsules, solutions, suspensions, suppositories and the like.
The best mode contemplated by the inventor for carrying out this invention will now be set forth as follows:
EXAMPLE N (2 '-Pseud0thiouronium-Ethyl -End0-Perhya'r0- 4,7-Methan0is0ind0le Chloride Hydrochloride N (2 chloroethyl) endo perhydro 4,7 methanoisoindole hydrochloride (5 g., 0. 0212 mole) is mixed with thiourea (1.61 g., 0.0212 mole). Isopropanol (30 m1.) is added and the mixture is refluxed for three hours. Upon cooling the solution white crystals are obtained. Ethylacetate is added to complete crystallization. The crude product obtained in recrystallized from ethanol/ ether (anhydrous). Yield 5.6 g. of white crystals, MP. 245 C.
Analysis.-Calculated for C H N Cl S: C, 46.15%; H, 742%; C1, 22.71%. Found: C, 46.07%; H, 7.23%; Cl, 22.62%.
The subject matter which the applicant regards as his invention is particularly pointed out and distinctly claimed as follows:
1. A compound of the formula where A is lower alkylene.
2. N (2' pseudothiouronium ethyl) endo perhydro-4,7-methanoisoindole.
No references cited.
Claims (1)
1. A COMPOUND OF THE FORMULA
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3124595A true US3124595A (en) | 1964-03-10 |
Family
ID=3454003
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US3124595D Expired - Lifetime US3124595A (en) | Endo-pemhydro-x |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US3124595A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3268554A (en) * | 1964-12-17 | 1966-08-23 | Rexall Drug Chemical | Substituted endo-perhydro-4, 7-methanoisoindoles and intermediates therein |
-
0
- US US3124595D patent/US3124595A/en not_active Expired - Lifetime
Non-Patent Citations (1)
| Title |
|---|
| None * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3268554A (en) * | 1964-12-17 | 1966-08-23 | Rexall Drug Chemical | Substituted endo-perhydro-4, 7-methanoisoindoles and intermediates therein |
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