IE49479B1 - Esters of 2-(6-methoxy-2-naphthyl)-1-propanol - Google Patents

Abstract

Esters of 2-(6-methoxy-2-naphthy])-1-propanol of formula (I> in which R is an alkyl radical of 1 to 20 carbon atoms are described. The compounds exhibit antiinflammatory, antirheumatic, analgesic and antipyretic activity.

Description

This invention relates to esters of a carboxylic acid and a 2-substituted propanol and specifically, propanol substituted by a 6-methoxy-2-naphthyl group of formula (I) in which R is the alkyl residue of a carboxylic acid RCOOH and contains from 1 to 20 carbon atoms.

It has been found that compounds of formula (I) exhibit very outstanding properties, specifically antiin10 flammatory, antirheumatic, analgesic and antipyretic properties comparable to the properties of a known substance, specifically Naproxen, which is the more active enantiomer of the 2-(6-methoxy-2-naphthyl) propionic acid. Yet compared with Naproxen the compounds according to the present invention are less toxic, exhibit an activity which is substantially more pronounced and cause much less noticeable gastric injury. - 49478 The object of the present invention is to provide compounds of formula (I). Another object of the present invention is to provide pharmaceutical compositions having antiinflammatory, antirheumatic, analgesic and antipyretic activity which contain, as the active substance, at least one of the confounds of formula (I): Another object of the present invention, is to provide a process for the preparation of the compounds of formula (I) according to which 2-(6-methoxy-2-natphyl)-ΙΙΟ propanol (II) is reacted with a carboxylic acid of formula R-COOH in which R is as defined hereabove, in the presence of an acid catalyst. According to one embodiment of the invention, the preparation may be carried out from the same substituted alcohol with one active derivative of the same carboxylic acid according to the reaction scheme shown hereinbelow: CH, ch-ch2oh + R-COX· (III) CH,0 (IX) In the above reaction scheme, X is OH or an activating group, for instance a halogen atom or an alkoxycarboniloxy residue, for instance the group CjHgO-CO-O-.

The process according to the present invention is illustrated by the example hereinbelow.

EXAMPLE 1 2-(6-Methoxy-2-naphthyl)-propyl acetate a) 2-(6-Methoxy-2-naphthyl-l-propanol) - 4 In a three-neck flask provided with a mechanical stirrer, a condenser and a funnel, there are placed 300 ml of THF, 53.5 g of 2-(6-Methoxy-2-naphthyl) propionaldehyde and 25 ml of water containing 2.5 g of NaOH.

Under stirring, 2 g of NaBH^ is slowly added keeping the temperature at 40°C. The mixture is stirred for one hour at room temperature and then there is added slowly under stirring and cooling, acetic acid for the purpose of destroying the excess of NaBH^. The greater part of the solvent is evaporated under vacuo, then water is added and the material is extracted three times with ether using a 100 ml portion each time. The ether extract is combined, evaporated under vacuo and the oily residue is crystallized from a mixture 50:50 of petroleum ether and ethyl ether.

The yield is 49.9 g (93.3%); M.P. 82-84°C. b) 2-(6-Methoxy-2-naphthyl) propyl acetate In a three-neck flask provided with mechanical stirrer, condenser and a funnel, there are introduced 500 ml of ethyl ether, 58.9 g (0.725 mole) of pyridine and slowly under agitation 58.8 g (0.725 mole) of acetyl chloride.

The solution is cooled to 0° and then there is introduced slowly through the funnel, 108 g (0.5 mole) of 2-(6-methoxy-2-naphthyl)propyl alcohol, dissolved in 200 ml of ethyl ether. The temperature rises up to about 40°C. Stirring is continued for a period of four hours at room temperature and then the solution is poured into 250 ml of water. The mixture is stirred and the organic phase is separated, washed with 0.1N HCl solution. The organic phase so washed, is dried over anhydrous sodium sulfate. The solvent is evaporated under vacuo and the oily residue is distilled. The pure ester distills at 175 - 178°C at a pressure of 0.01 mm Hg. 48479 - 5 The yield is 102 g (75%).

According to the same procedure described hereinabove, the following substances are prepared: - 2-(6-methoxy-2-naphthyl,propyl propionate; Boiling Point-178-183°C at a pressure of 0.01 mm Hg. - 2-(6-methoxy-2-naphthyl)propyl hexanoate Boiling Point-188-190°C at a pressure of 0.01 Hg.

EXAMPLE 2 Preparation of 2-(6-methoxy-2-naphthyl)propyl enanthate In a three-neck flask provided with stirrer, condenser, and a funnel there are introduced 500 ml of ethyl ether, 58.9 g (0.725 mole) of pyridine and slowly under stirring 107.4 g (0.725 mole) of enanthyl chloride. The solution is cooled to 0°C. Through the funnel, there are introduced 108 g (0.5 mole) of 2-(6-methoxy-2-naphthyl)propyl alcohol dissolved in 200 ml of ethyl ether. The temperature rises to 40°C. Stirring is continued for four hours at room temperature and then the solution is poured into 250 ml of water. The mixture is stirred, the organic phase is separated, washed with 0.1N HCI solution. The organic phase so washed is dried over anhydrous sodium sulfate. The solvent Is distilled under vacuo and the oily residue is distilled. The pure ester boils at 191-193°C at 0.01 mm Hg. The yield is 125.3 g (73.2%).

Ultraviolet light spectrum: a solution of the substance in ethanol (25 mcg/ml) exhibits two maxima: (1) at 260 + 1 - 270 + 1 and (2) at 316 + 1 - 331 + 1.

The substance is insoluble in water, soluble in chloroform, ethanol, acetone, hexane and in addition, in oils. - 6 Application of the same procedure described herein above gives other esters of 2-(6-methoxy-2-naphthyl)propanol as indicated in Table 1 hereinbelow, which also reports the physical properties and analytical values. Ό § Ο Ρμ νο γ4 m «Η Ο Ο ιη ο Ι™| σϊ CO σ> CO ιη co Λ r-1 co νο Γ γ* CO CO 00 co σ» σ\ Η-Ο-Ο'ΉΟ-ΗΟ - 8 49478 TABLE 1 (continued) 2Ο1-2Ο2/Ο.ΟΟ5 79.84 - 79.77 10.48 - 10.44 - 9 The pharmaceutical properties of the compounds according to the present invention, together with toxicological data are reported by way of example with the compound 2-(6-methoxy-2-naphthyl)propyl enanthate referred to hereinafter with the symbol ENA.

Antiinflammatory activity This activity has been evaluated by comparison with Naproxen in equimolar dose. There are utilized male rats of average weight, about 150 g. Two tests, that is one acute and one sub-acute, have been carried out. a) acute test: plantar edema caused by carragenin according to C.A. Winter et al. Proc. Soc. Exp. Biol. Med., Ill, 544 (1962).

The two substances under test are administered through the oral route in an equimolar dose: ENA = 60 mg/ kg, Naproxen = 40 mg/kg, in 1% carboxymethylcellulose (CMC) at 20 ml/kg immediately after the appearance of the edema as a result of the subplantar injection of carragenin in the amount of 1% in the dose of 0.05 ml/paw. The results of this test are reported in Table 2. b) sub-acute test: plantar edema caused by nystation according to E. Arrigoni-Martelli et al. Pharmacology, 5, 215 (1971). The two substances are administered through the oral route in an equimolar dose for two successive days as follows: The first day, ENA = 30 mg/kg, Naproxen = 20 mg/kg in 1% CMC in the amount of 10 ml/kg.

The second day, ENA = 60 mg/kg, Naproxen = 40 mg/ kg in 1% CMC in the amount of 20 mg/kg. Edema has been caused the night preceding the first treatment by the subplantar injection of nystatin in the amount of 300,000 U/ml in the amount of 0.1 ml/paw. The results of this test are reported in Table 3. 48479 Antiinflammatory activity - acute μ Φ «μ <4-1 (0 ¢0 β Φ Ό ω ιμ Ο C ο •μ £» •μ A •μ £3 β (fl μ A co 0 Φ O fi > • •H O 4J IP 3 ϋ V ΓΟ w β « μ ο Λ (0 μ Ρ ο Λ (0 μ Ο £ί □ μ ο β g Η o Φ Cn (0 μ φ Ο ιο μ •μ > Ή +> Ο β CM β 02 Φ μ β O ο rH μ A o Οι nJ -μ d 3 β Φ V β CM φ cr d φ tfl £3 > β •μ (fl •P ϋ Φ tn (ti A OJ A o η (ti β o •μ w V •μ Φ CM •μ 3 +> w ϋ β Φ 0 μ £3 ο • to β ω Ο) 02 > Ο Λ β β •μ Φ Μ Φ Λ r» (ti Η β * β β 4J μ 0) 4J □ ο β β x: β β •μ 0) Ό ο 4J φ Φ μ •μ A β Η 10 μ Φ (Λ +J Ο •μ β Λ τί «μ β μ .μ & -μ β Φ CM β β ο Φ μ 3 β 4J 0 02 α β Ε< W 3 ω υ ^3 φ rn λ u β ω and after 8 hours still exhibits a very considerable activity - 11 P Φ 4J M4 <0 ca a o Λ m n O ω P xs o id 0) O g ω « o 6 Ο V io ft >1 -P •d rd > (0 H Antiinflammatory activity - sub-acute test tw o • •d ω «Ρ & •d a) id 10 A P Q CM •d P 0 O Λ P s • o G 0 •d O r-1 H ffi •P d in Z 0 V tp t» i-1 id W 10 CU φ cn !> (0 β) ♦C P 4J a 0) f—I (0 Λ ϋ W o z & Q (0 fl) P a 0) x o P & Z § n •d P <0 I u - 12 49 479 io P □ Λ Cp H QJ P O g W Φ f> •rl P □ nJ in O O v & •rl (0 P a o si CM -=31 H >1 +1 •rl · rH > ω 10 •rl » 3 2 σ ϋ φ nJ ft Treatment % Inhibition of Edema after to P Λ CM si i—1 >1 P •H · rH > ω nJ •H • 3 •P 2 0* ϋ Φ nJ ft (ϋ σ ν >1 •μ •Η > •Η 4J ϋ <ϋ ω ft C •H (0 QJ •P •rl K to P 0 •H to P P & ft nJ g 2 nJ 4-) 0 ω 2 w u As it is clearly shown by the data, ENA exhibits a therapeut towards a stable previously induced edema which is not only ile to that of Naproxen, but particularly for very prolonged of time is greater and is statistically very significant. >1 A +) nJ to •rl p •ϋ nJ 0 •rl ft •H +) g P u 0 QJ nJ 0 ft - 13 Analgesic activity The analgesic activity has been determined by comparison with Naproxen in an equimolar dose. Two tests are carried out: one in female mice of about 25 g average weight and one in male rats of about 100 g average weight. a) test in the female mouse: contortions due to phenylquinone according to L.C. Hendershot et al, J. Pharm. Exp. Ther., 125, 237 (1959).

The two compounds are administered through the 10 oral route in essentially equimolar doses with respect to each other: ENA 30 mg/kg, naproxen 20 mg/kg in 1% CMC in the dose of 20 ml/kg. The contortions are induced at different intervals after administration of the compounds by endoperitoneal injection of 0.02% phenylquinone in 5% alcohol in the dose of 10 ml/kg.

The results of this test are reported in Table 4. b) test in the male rat: this test is carried out by applying pressure on an inflamed paw according to L. 0, Randall et al, Arch. Int. Pharmacodyn., Ill, 409 (1957).

The two compounds are administered through the oral route in doses which are equimolar with respect to each other: ENA 60 mg/kg, naproxen 40 mg/kg in 1% CMC in the dose of 20 ml/kg immediately after the inducement of the inflammation: sub-planar injection of 10% yeast in the amount of 0.1 ml/paw.

The results of this test are reported in Table 5. Φ ϋ •rt ε X Λ ζρ X ο φ tn rd rt Φ > tO rt Φ X X tO w rt X3 » rt x! ω rt X3 rt o Λ Φ O k* · •rt o X □ v Φ fh >1 X •rt irt > (0 *rt 3 X σ o Φ Φ >1 X •rt • irt > ω (0 •rt a 3 X s CO CP ϋ V£> Φ to CM >1 X •rt a > ω (0 •rt a 3 X sz 0* ϋ Φ fti Ch activity rd X Φ rt tP •rt X XJ O (0 W X d I x (0 φ rt E-i irt (0 □ d •rt » φ X •rt x ω rt 0 •rt td rt X & < Ch to § s to X 0 ω 5Z ω o As the data hereinabove show, ENA exhibits an activity comparable to that of Naproxen in the first few hours, but the activity is maintaine< still high in the sixth hour while. With Naproxen, the activity is substantially reduced. - 15 •rl Φ Cn CP •rl MH υ φ w >1 ta •P ρ •rl • rH > ω 0 Φ •d • 43 O d •P Z O ID O’ 0 in r-l (0 Pi Treatment % Inhibition of pain after: 4J ϋ « ta •d • •d 01 p rH > W ta Ρ 3 (0 •rl • φ β o β +3 ζ cn 0 43 rH σ Ο rH 43 n ID Φ <3 CM β 4J rH β £ 0 «3 Φ β ΜΗ Ρ 43 Φ 43 β >1 43 01 43 to 43 Φ Ρ M •d • Φ •d κ £j rH W Ρ *Η 43 o φ τΗ • Cn β 43 CN r* a •Ρ ζ Φ Φ in ID σ ϋ 01 43 Ρ CO r-1 φ (0 & 4J 43 Φ •d CM Λ β CM •d τΗ Φ 43 Φ ι-Η X Ρ ca 01 Ρ ο Φ Φ •d μ Ο φ ο β 6 > rtj β o •d 6 Ζ Φ 43 43 O cn 4J W ε •d o I** ϋ V > CN 0 Φ CM 43 43 •d 01 β 43 Φ Φ ϋ 43 ϋ Φ Φ rH •d Η Ο ta Μη Ρ μ Ο φ ο •d •d Φ 3 ε > 43 £ 43 0 •Η ο 43 σ Φ 43 o r* < 43 •Η Φ ^3* *s* ζ ϋ V β ca Ρ rH CN W (0 Λ τΗ Φ Cn • ta β to 43 $ •Η Ρ β 0 β Φ 43 β 0 υ 01 Φ 43 •d X ΜΗ γΗ <ϋ 0 •d (3 β 43 Ρ Φ β □ Ο (0 CM ΜΗ CP β •d to Ό Φ •rl Φ 43 •d Ζ 43 01 X CO Μ φ Φ 0 •d β 43 β Ρ >1 p 4J Οι 43 φ •Η r—1 a (3 6 43 ΜΗ Η § (0 «Ρ 0 (0 •Ρ Φ W z ω Ο < >1 Φ 43 ϋ •rl 43 43 43 •d 01 > Ρ •rl τί Φ 43 43 43 Φ ϋ ΜΗ 43 Φ to - 16 Antipyretic activity This activity has been determined by comparison with Naproxen in equimolar doses. Two animal species have been utilized. Male rats of weight about 250 g and female rabbits of about 2.6 kg of weight. a) the test in the rat: pyrexia caused by yeast according to CJ.M. Teotino et al, J. Med. Chem., 6, 248 (1963).

The two compounds are administered through the oral 10 route in doses which are equimolar with respect to each other: ENA 60 mg/kg. Naproxen 40 mg/kg in 1% CMC, in the dose of 10 ml/kg. The fever has been induced the previous night by subcutaneous injection of a 20% yeast suspension in the dose of 10 rol/kg. The results are reported in Table 6. b) the test in the rabbit: pyrexia caused by yeast.

The two compounds are administered in the oral route by equimolar doses: ENA 60 mg/kg, Naproxen 40 mg/kg in 1% CMC in the dose of 10 ml/kg immediately after the first inducement of fever by means of 20% yeast suspension, which is centrifuged, filtered and the filtrate injected endovenously in the dose of 1 ml/kg. This treatemnt to cause fever has been repeated twice at intervals of one hour and 30 minutes. The results are reported in Table 7. 3 H > CO o o ti P • A O O' 3 P * 91 0 co P O Φ ti cu I Eh £ o (Q >1 P 43 ti 0 43 P • & P > co IQ P ,, o CN CN ti P • P 43 $4 x! CO CO 3 P O' Φ « • σ □ DO P P P P φ ti 0( Φ Φ P ti 0 3 Φ ti 43 O P P 0 IQ 43 3 β >1 3 P P IQ P n $4 P >1 h 3 P > co g P Φ o CN M’ ti P • P > 43 CN CN 3 P P > φ • • 01 0 P p CN P P Φ ti 0< φ d P r\ P r-« P ti 05 0 P 43 p β 0 cn ti g 0 p >1 P >4 P 43 P β P 0 3 P P > co P P 3 ti 3 0 o LO ti P • > P *3 43 co Γ* 3 P P ti LO Φ • • σ υ P P 0$ r-l O O φ ti 0( υ ni Φ 1» >1 P P !> P Ο Φ O' ti Μ i> ti Each data is the r-i ti P 0 0 3 3 P to Φ Φ P P g X IQ h p 0 P ti ti P & Φ < & ti g M z ti P 0 E-i M Z co u P to Φ P IQ P +) H r-i ti ti - 18 Antipyretic activity - test in the rabbit m rd tO ε •rl β to M-t Φ σ» to P Φ > to Φ A •P tO tO Ό A ϋ «0 W fi s > · rd in -HO m CN Z •P □ V μ CO d O W to A φ Ό £ fi O (0 CO rd QJ 43 ε P A 0 co X u μ id Φ 10 μ in •id 10 A μ 0 QJ O Qd □ 6 > • 0) fi o co co •H o -P rfi QJ ,, Λ CN 4J (0 •P X μ , • z O V O Φ 10 o o H to 04 to fi μ +J •rl •w A Ud to fi to Z z QJ Q E3 43 Ud o •P O >1 m c 01 4J 0 Ό >1 T-l μ •rl • fi P 3 ι—1 > CQ >1 (0 τ| μ o co rd t0 id • +J > Φ χ: m ID fi fi Z •id *· •id > , • σ1 0 > rd P Φ O o φ to A •rl /0 0 Ψ4 •P fi (0 0 σ» m tO QJ QJ o 43 υ CO P fi •rl id o ω P QJ 0] co in Φ P rd 4J μ Φ Φ O μ •id •id □ 3 r-i i> • >1 43 fi 0 cn *3» •H o A fi £ Ό xj m o •P Ή QJ Φ , z □ V •P 43 •P oi CN O 1—1 w tfl A § •P fi to •P Φ fi to rfi cd fi P O CJ * fi «Ρ QJ CO rd ω X fi (0 fi QJ O •rl +i 0 0 «Ρ μ s fi fi id ω A 6 Φ Φ •P •rl ω (0 Φ β * 0) μ •rl z μ 4J 0 •rl <0 43 10 μ «Ρ A •P Md CO QJ a (0 S 0 μ kt z (0 +J 0 fi fi Eh w 2 CQ o H +> (0 0 43 43 P 43 •P C 43 (0 cn 43 hd P 0) statistically significant (0 C •r4 P O •rl μ Q) Md fi • 49479 - 19 Acute toxicity The acute toxicity of ENA has been determined on two species of animals: mice of both sexes of average weight about 20 g and rats of both sexes of average weight about 200 g.

Pour routes of administration have been used: oral, endoperitonea1, endovenous and subcutaneous. In each instance, the animals were deprived of food the night before the test. There are utilized ten animals, that is five males and five female per each dOse of treatment. The values of DL 50, expressed in ml/kg, are calculated according to the method of probits on the basis of the mortality found within a period of eight days of the treatment.

Hie results are reported in Table 8. They shew the ccnpariscsi of DL 50 of ENA with the DL 50 of Naproxen, which comparison is partly based upon literature data and partly upon original experimental work. - 20 ω « Eh Acute toxicity ; DL 50 in mg/kg o id P (0 ffi z w G Φ X P cu (0 z o 0 m P CU (0 Q Z 00 o sp r- in rd in LO o in *3· rd LO o cs CS LO o 6 6 6 V O d d V * K * rd Γ cn rd o in O ro in O O *-* ro in O Xf r- O o cs rd in rd rd in in ’T o rd rd rd P φ G % Φ 0 rd P (0 cu O o > nJ o o id z o ro r* o ro CS Γ- O 3 o ro LO LO ro CS ιο cs σ 0 co ro LD Λ rd cs io A w P cs ro cs n o o in o o O o Ο Ο o o o o O o Ο ro o o J Z cs o O σι cs ro o ro Q w in rd Λ co ro rd Λ QJ P 3 rd C0 P cu 0 rd (0 P ά > 0 0 id id ω 0 id id oi w φ id Φ ϋ ω Φ 3 P CU 0 <0 ω S ffi σ\ Γ-Ι rd| P X» S' w nJ CU rd (0 P Φ Ή ω £ ο N CO s ffi As shown in the ratios in the last column of the above table, ENA is much less toxic, about 1/2 to 1/5 as compared to Naproxen, keeping also in mind the different molecular weight. 49478 - 21 Toxicity in the fetus This type of toxicity has been investigated in two animals species, rats and rabbits. a) the test in the rat: ten female rats have been treated in the first 20 days of gestation through the oral route with ENA in the dose of 20 ml/kg/day, equal to 13.2 mg/kg of Naproxen. Afterwards, the animals have been sacrificed in order to remove the fetuses and to observe the uterus. The properties which have been observed are: the growth of the mother, the number of live fetuses, the number of dead fetuses, average weight of the litter, number of reabsorptions and malformations.

Results: no toxic symptoms on the gestation and on the fetuses has been observed. b) the test in the rabbit: five female rabbits have been treated in the first 24 days of gestation through the oral route with ENA in the dose of 20 mg/kg/day, equal to 13.2 mg/kg of Naproxen. Afterwards the animals have been sacrificed in order to remove the fetuses and to observe the uterus. The properties which have been observed have been: the growth of the mother, the number of live fetuses, the number of dead fetuses, the average weight of the litter, the number of reabsorptions and malformations .

Results: no toxic symptons have been observed either on the gestation or on the fetuses.

Sub-acute toxicity through the rectal route Six rabbits, that is three male and three female rabbits of average weight about 2 kg have been treated. The daily treatment for a period of ten days consisted of suppositories containing 300 mg of active material which was introduced deep down in the rectal orifice while the - 22 orifice was kept closed for a period of 30 minutes with cocher clamps. This treatment has not shown significant variation of the general state of health, the body weight, hematic crasis, lever function, glycemia, azotemia, gly5 cosuria, proteinuria, ematuria.

Sub-acute toxicity through the oral route (ulcerogenesis) The comparison has been carried out. using an amount of ENA which is equimolar to that dose of Naproxen which is known to be ulcerogenic. Male rats of 150 g about average weight, have been used, being kept partially fasting (only at night) in a total number of five. The daily treatment has been carried out by introducing into the esophagus: ENA in the amount of 150 mg/kg/day, Naproxen 100 mg/kg/day in 1¾ CMC in the dose of 5 mg/kg. A few hours after the fifth administration, one animal died between the treatments with Naproxen and it was decided to sacrifice all the animals to observe them. The results of the observations made during the five-day period and of the death are reported schematically in Table 9. 49478 - 23 Ulcerogenic gastro-enteric effect in £ φ W K H 0 <0 ft 5 s s I 1 rtj *rl 2 £ 0 W < £ +» ti Φ *0 P P Ή P ft co £ •rt P ti > P Φ co Ο O vo >1 <ϋ OOOO CO ’T CM Wf CM CM H Φ «Ρ £ Φ s Φ HP in r-i 0 >1 ti •ri o Λ ti ft 44 (-1 s Ό 44 0 £ P 0 0 43 £ n3 h 44 ti Φ tn b> m U P £ •d •d m Ό tp 44 e 0 £ •d 43 c ti £ tn •rl Λ! tn •d en 0 43 •d φ V It 44 to 2 Λ J £ •P Φ m £ •d Ό O r-l « •d £ •d P Φ ft Φ ti Φ Ό P Φ tp ti CO £ •d o Ή *d Φ Φ tp £ Φ > •d CO Φ tn ι-intestinal ulcer 43 > 0 0 0 P 43 u •d P P 44 Φ Λ! B 4j ti ti 03 0 Φ CQ •rl Φ Λ ιΐ £ ti Ω Ω O hi «3 0 - 24 As it appears from the data hereinabove, the daily dose of Naproxen which has been used is very toxic up to the point of being lethal through the gastro-enteric route, while the equimolar dose of ENA gives no symptoms of intolerability nor symptoms of gastro-entero injury even after five days.

EXAMPLE 3 Capsules of soft gelatin: every capsule contains: 2-(6-methoxy-2-naphthyl)propyl enanthate 350 mg EXAMPLE 4 Suppositories: each suppository contains: 2-(6-methoxy-2-naphthyl)propyl enanthate Miglyol Witepsol E 85 Witepsol W 35 to 300 mg 50 mg 460 mg 2.2 g EXAMPLE 5 Suppositories: each suppository contains: 2-(6-methoxy-2-naphthyl)propyl enanthate 600 mg Miglyol (R.T.M.) 10 mg Witepsol (R.T.M.) E 85 370 mg Witepsol W 35 to 2.3 g EXAMPLE 6 ¾ Cream; 100 g of cream contain: 2- (6-methoxy-2-naphthy1)propy1 enanthate 5 g Cetylstearyl alcohol 5 g - 25 Isopropyl myristate 7 g Oil of Vaseline (R.T.M.) 5 g Spermacetes 7 g Stearic acid 2 g Polysorbitan monolaurate 60 0.5 g Carboxyvinylpolymer with triethanolamine 1 g Benzoic acid 2 g Distilled water 100 g EXAMPLE 7 Phthials of 300 mg: each 2 ml phthial contains: 2-(6-methoxy-2-naphthyl)propyl enanthate 300 mg Lidocain base 10 mg Benzyl Alcohol 50 mg Ethyl oleate (or olive oil Fg) to 3 ml.

This composition of the present invention may be used to relieve a living subject from inflammation, pain, fever in the dose of 300-1200 mg/day.

Claims (5)

1. CLAIM S:1. An ester of 2-(6-methoxy-2-naphthyl)propanol of formula (I) ch 3 o 5 wherein R is an alkyl radical of 1 to 20 carbon atoms.

2. A compound according to claim 1 which is 2-(6-methoxy-2-naphthyl)propyl enanthate.

3. A pharmaceutical ocnpositian having antiin flarretory^antirheumatic, analgesic, and antipyretic activity which comprises 10 as the active ingredient at least one compound according to claim 1.

4. A pharmaceutical composition according to claim 3 wherein the active compound is 2-(6-methoxy-2-naphthyl)propyl enanthate. 15 5. The process for the preparation of an ester of 2-(6-methoxy-2-naphthyl)propanol of formula (I) which consists of reacting 2-(6-methoxy-2-naphthyl)propanol of formula (II) with a compound of formula (III) according to the equation hereinbelow: (I) wherein R is an alkyl radical between 1 and 20 carbon atoms, X is OH or halogen or an alkoxy-carbonyloxy radical and isolating said compound of formula (I) from the

5. Reaction mixture.