Patent Publication Number: US-3968145-A

Title: Methyl 2(1 chloronaphth-2-yloxy)propionate

Description:
CROSS REFERENCE TO RELATED APPLICATION 
     This application is a continuation-in-part of copending application Ser. No. 297,832, filed Oct. 16, 1972 now abandoned 
    
    
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     This invention relates to 2-(1-chloro-2-yloxy) propionic acid and its derivative compounds having physiological activity having uses as antipyretic, antiphlogistic and analgesic properties in pharmaceutically useful compositions. 
     2. Prior Art 
     U.S. Pat. No. 3,740,437 discloses that naphthyloxyacetic acids are useful as anti-inflammatory, analgesic and antipyretic agents. There are no propionic acid esters of the formula I disclosed therein, nor is there a specific teaching of the superiority of such esters in terms of analgesic or antipyretic activity, or antiphlogistic activity. 
     SUMMARY OF THE INVENTION 
     According to the present invention the pharmaceutically useful compositions are prepared from compounds of the formula ##SPC1## 
     In which R 2  represents a hydroxy group, an alkoxy group containing from 1 to 4 carbon atoms, an aralkoxy group, an oxypropylsulfonic acid group and salts thereof, a primary amino, mono-(C 1-4 )-alkylamino or di-(C 1-4 )-alkylamino group, or a hydroxyamino group. These compounds are useful as antiphlogistic, analgesic or antipyretic agents. 
    
    
     Examples of preferred compounds are those wherein R 2  is either a methoxy, ethoxy, n-propoxy, n-butoxy or benzyloxy group. 
     Particularly preferred pharmaceutical compositions are prepared using compounds of formula I by virtue of the good antiphlogistic, analgesic or antipyretic activities of said compounds which include the following: 
     (1) methyl 2-(1-chloronaphth-2-yloxy)propionate (R 2  =CH 3  O) (b.p. 155°-137°C/0.4 mm.Hg); 
     (2) ethyl 2-(1-chloronaphth-2-yloxy)propionate (R 2  =C 2  H 5  O) (b.p. 162°-164°C/0.4 mm.Hg.); 
     (3) n-propyl 2-(chloronaphth-2-yloxy)propionate (R 2  =n--C 3  H 7  O) (b.p. 168°-170°C/0.4 mm.Hg.); 
     (4) n-butyl 2-(1-chloronaphth-2-yloxy)propionate (R 2  =n--C 4  H 9  O) (b.p. 178°-180°C/0.3 mm.Hg.); 
     (5) sodium 3-[1-(1-chloronoaphth-2-yloxy)-ethylcarbonyloxy] propyl sulfonate (R 2  =O(CH 2 ) 3  SO 3  Na) (m.p. 187°-189°C, decomposition); 
     (6) benzyl 2-(1-chloronaphth-2-yloxy)propionate (R 2  =C 6  H 5  CH 2  O) (b.p. 168°-170°C/0.4 mm.Hg.); 
     (7) 2-(1-chloronaphth-2-yloxy)propionamide, (R 2  =NH 2 ) (m.p. 179°-181°C); 
     (8) 2-(1-chloronaphth-2-yloxy)propionylhydroxamic acid, (R 2  =NHOH) (m.p. 155°-156°C). 
     compounds of formula I show interesting physiological activities and they are useful in therapy, in particular as antiphlogistic, analgesic and antipyretic agents. 
     Antiphlogistic activity of various compounds of formula I were tested on carrageen-induced planter oedemas in the rat according to the method of A. C. Winter, E. A. Risely, (see G. W. Nuss, Proc. Soc. Exp. Biol. Med., 111, 544, 1962) and analgesic activity of the same compounds was estimated using phenylquinone in the mouse according to the method of E. Sigmund et al as modified by N. Pisanti, G. Volterra, (see Boll. Chim. Farm., 107, 769, 1968). In general the compounds were administered orally. They were compared with aminophenazone. 
     
                       TABLE                                                       
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Compound       Antiphlogistic                                             
                             Analgesic                                    
               Activity      Activity (°)                          
______________________________________                                    
Aminophenazone 1             1                                            
  2-(1-chloronaph-2-                                                      
               2.56          2.20                                         
  yloxy) propionic                                                        
  acid                                                                    
1              5.12          2.19                                         
2              3.59          2.19                                         
3              3.88          1.01                                         
4              3.50          1.06                                         
5 (°°)                                                      
               2.69 (°°)                                    
                             1.13 (°°)                      
6              4.36          1.01                                         
7              0.87          1.28                                         
8              3.21          1.10                                         
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 (°) The analgesic activities of formula I reported in the table   
 lasted 1-2 hours longer than that of aminophenazone.                     
 (°°) Administered subcutaneously.                          
 
    
     The present invention further provides pharmaceutical compositions comprising at least one compound of formula I in association with a pharmaceutical carrier or excipient. 
     The pharmaceutical compositions may be presented in a form suitable, for example, for oral or parenteral administration. Examples of suitable forms of administration include, tablets, coated tablets, capsules, lozenges, dispersible powders, syrups and elixers. Preferably the compositions are presented in dosage unit form. 
     Compounds of formula I (as hereinbefore defined) are in general new, and per se form a feature of the present invention.