GB2096605A - Cycloheptyl nicotinate - Google Patents
Cycloheptyl nicotinate Download PDFInfo
- Publication number
- GB2096605A GB2096605A GB8209164A GB8209164A GB2096605A GB 2096605 A GB2096605 A GB 2096605A GB 8209164 A GB8209164 A GB 8209164A GB 8209164 A GB8209164 A GB 8209164A GB 2096605 A GB2096605 A GB 2096605A
- Authority
- GB
- United Kingdom
- Prior art keywords
- cycloheptyl
- nicotinate
- pharmaceutical
- veterinary
- 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.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
Abstract
A novel nicotinate of the formula <IMAGE> having peripheral vasodilator activity is useful as a rubefacient agent.
Description
SPECIFICATION
A compound having peripheral vasodilator activity useful as rubefacient process for making same and pharmaceutical compositions containing said compound
This invention relates to a compound having peripheral vasodilator activity. More particularly, this invention relates to a nicotine ester having peripheral vasodilator activity, useful as a rubefacient agent.
Use of nicotinic acid esters as rubefacient agents has come into common practice since several years (see Piantanida, Z. Physiol.Chem.) 244,56 (1936), Hartmann, Merz. U.S. Patent 2,498,152(1949) Backer, Br. J. Derm., 81, 60 (1969); Fountain, Br.J. Derm. 81, 202 (1969); Dixon, Henderson, Prescribers's J. 13, 41, 1973).
Said esters of nicotinic acid are generally used at concentrations from 1 % to 5%, in creams and ointments for pain relief in muscular rheumatism, lumbago, fibrositises and the like.
It has now been found that cycloheptyl nicotinate of formula
M.W. = 219.29 has a peripheral vasodilating action and is useful as a rubefacient agent.
The compound of the present invention is suitably prepared by reaction of nicotinyl chloride hydrochloride with cyclopentanol in a suitable anhydrous organic solvent, such as , for example, benzene, toluene, DMF, DMSO, pyridine in the presence of a base which is capable of neutralizing the two molecules of hydrochloric acid which liberate during the condensation reaction.
The following examples serve to better illustrate the present invention.
Example 1
To a solution of 11.42 g (0.1 M) of cycloheptanol in 200 ml of anhydrous benzene 22.2 g (0.22 M) of triethylamine and, then, under vigorous stiring and goor aspiration, .17.8 g (0.1 M) of nicotinyl chloride hydrochloride is added, in small portions, operating so that the temperature does not exceed 35"C.
At the end of the addition, the mixture is refluxed for 1 hour, it is left to cool, the reaction mass is transferred to a separating funnel and washed repeatebly with water to chlorides disappearance, then with a 5% aqueous sodium bicarbonate solution, and after this again with water to neutrality.
The water-washings are discarded, the remaining mixture is dried over anhydrous sodium sulphate and the benzene phase is evaporated to give, almost quantitatively, the cyclo-heptyl nicotinate with a good purity degree.
A very pure product can be obtained by rectifying under reduced pressure the substance, which is in the form of a slightly straw-colored oil, with a boiling point of 170"C/lmm.
Example 2
A vigorously stirred solution of 11.42 (0.1 M) of cycloheptanol in 1 20 ml of anhydrous pure pyridine is admixed with 1 7.8 g (0.1 M) of nicotinyl chloride, operating under aspiration and controlling the addition of the nicotinyl chloride so that the temperature does not exceed 50"C.
At the end of the addition the reaction mass is kept at the same temperature for 2 hours. Then it is cooled and poured into 1 litre of frozen water, under vigorous stirring.
It is allowed to stand some time and then the oily phase which separates is extracted with ethyl ether. The aqueous phase is discarded, the ether phase is separated, the solvent is evaporated and distilled under the same conditions given in Example 1, to yield cycloheptyl nicotinate with similar purity characteristic.
Elemental analysis
C H N 0 Calculated 71.20 7.81 6.39 14.59
Found 71.0 7.83 6.41
PHARMACOLOGICAL ACTIVITY 1. Acute toxicity
It is tested in mouse by aral administration, by means of a gastric probe, of increasing doses of the compound of this invention, after having previously prepared solutions of known concentration. LD50 is found to be greater than 3000 mg/kg.
2. Peripheral vasodilating activity.
The compound of the present invention is tested for peripheral vasodilating activity, by application onto rabbit's ear, and thereafter measuring the intensity and duration of the vasodilation by means of known tests.
The cycloheptyl nicotinate has an effect of equal intensity, but lasting about 50% longer than the one caused by the same amount of cyclohexyl nicotinate used for comparison. A further object of the present invention are the pharmaceutical compositions, which, together with suitable non-toxic, pharmacologically inert carriers, contain the compound of this invention in a sufficient amount to alleviate the symptoms of topic inflammatory conditions.
According to the present invention, the inventive cycloheptyl nicotinate can be administered in the form of a pomade, ointment, paste or cream.
These pharmaceutical forms, as well known, contain, along with the pharmacologically active substance, usual carriers or vehicles, such as, for example, animal or vegetable fats, waxes, parffins, starches, tragacanth gum, cellulose derivatives, polyethylene glycols, silicones, bentonite, silic acid, talc and zinc oxide or mixtures thereof.
Examples of pharmaceutical compositions
A) Normal type pomade
Cycloheptyl nicotinate 1 g Carbowax 2000 209 B) Strong type pomade
Cycloheptyl nicotinate 1 g Carbowax mixture 209
Claims (8)
1. A compound having peripheral vasodilating activity, of formula
2. Cycloheptyl nicotinate for use as a method of treatment by therapy practised on the human or animal body.
3. A process for preparing the compound of formula (I) as defined in claim 1, wherein nictoinyl chloride hydrochloride is reacted with cyclopentanol in a suitable organic solvent in the presence of a base.
4. A process for preparing cycloheptyl nicotinate substantially as hereinbefore described in
Example 1 or Example 2.
5. A pharmaceutical composition for the treatment of topic inflammatory conditions, containing an amount sufficient for alleviating the symptoms of topic inflammatory conditions in humans of compounds of formula (I) as defined in claim 1, together with a suitable non-toxic, pharmacologically inert carrier, useful for preparing -pomades, ointments, pastes or creams.
6. A pharmaceutical or veterinary formulation comprising cycloheptyl nictinate formulated for pharmaceutical or veterinary use.
7. A pharmaceutical or veterinary composition comprising cycloheptyl nicotinate and a pharmaceutically or veterinarily acceptable carrier or excipient.
8. A pharmaceutical or veterinary cream or ointment comprising cycloheptyl nicotinate.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT21199/81A IT1137375B (en) | 1981-04-15 | 1981-04-15 | COMPOUND WITH PERIPHERAL VASODILATOR ACTIVITY USEFUL AS RUBEFACENT, PROCEDURE FOR ITS PREPARATION AND PHARMACEUTICAL COMPOSITIONS BASED ON THAT COMPOUND |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB2096605A true GB2096605A (en) | 1982-10-20 |
Family
ID=11178258
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB8209164A Withdrawn GB2096605A (en) | 1981-04-15 | 1982-03-29 | Cycloheptyl nicotinate |
Country Status (7)
| Country | Link |
|---|---|
| KR (1) | KR830010075A (en) |
| BE (1) | BE892870A (en) |
| DE (1) | DE3213082A1 (en) |
| FR (1) | FR2509301A1 (en) |
| GB (1) | GB2096605A (en) |
| IT (1) | IT1137375B (en) |
| NL (1) | NL8201439A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0182635A1 (en) * | 1984-11-15 | 1986-05-28 | Nitto Denko Corporation | Composition for percutaneous administration |
| US4968685A (en) * | 1986-09-08 | 1990-11-06 | L'oreal | Composition for inducing and stimulating hair growth and retarding its loss, based on nicotinic esters and pyrimidine derivatives |
| US5157036A (en) * | 1986-09-08 | 1992-10-20 | L'oreal | Composition for inducing and stimulating hair growth and retarding its loss, based on nicotinic esters and pyrimidine derivatives |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB620687A (en) * | 1945-05-22 | 1949-03-29 | Winthrop Chem Co Inc | Improvements in or relating to alkyl esters of nicotinic acid |
| FR2003097A1 (en) * | 1968-03-02 | 1969-11-07 | Takeda Chemical Industries Ltd | Cpds. of general formula (I) A=CH or N Spasmolytics and peripheral vasodilators. Dose: 100-200 mg/d. (p.o). Z and X are OH or reactive |
-
1981
- 1981-04-15 IT IT21199/81A patent/IT1137375B/en active
-
1982
- 1982-03-29 GB GB8209164A patent/GB2096605A/en not_active Withdrawn
- 1982-04-03 KR KR1019820001484A patent/KR830010075A/en unknown
- 1982-04-05 NL NL8201439A patent/NL8201439A/en not_active Application Discontinuation
- 1982-04-07 DE DE19823213082 patent/DE3213082A1/en not_active Withdrawn
- 1982-04-15 FR FR8206456A patent/FR2509301A1/en active Pending
- 1982-04-15 BE BE0/207843A patent/BE892870A/en unknown
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0182635A1 (en) * | 1984-11-15 | 1986-05-28 | Nitto Denko Corporation | Composition for percutaneous administration |
| US4968685A (en) * | 1986-09-08 | 1990-11-06 | L'oreal | Composition for inducing and stimulating hair growth and retarding its loss, based on nicotinic esters and pyrimidine derivatives |
| US5157036A (en) * | 1986-09-08 | 1992-10-20 | L'oreal | Composition for inducing and stimulating hair growth and retarding its loss, based on nicotinic esters and pyrimidine derivatives |
Also Published As
| Publication number | Publication date |
|---|---|
| IT8121199A0 (en) | 1981-04-15 |
| BE892870A (en) | 1982-08-02 |
| NL8201439A (en) | 1982-11-01 |
| DE3213082A1 (en) | 1982-11-18 |
| FR2509301A1 (en) | 1983-01-14 |
| KR830010075A (en) | 1983-12-26 |
| IT1137375B (en) | 1986-09-10 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |