Abstract:
The present invention provides novel 19-hydroxy-19-methyl-13,14-dihydro-PG 2  compounds, methods for their preparation and pharmacological use for the induction of prostaglandin-like effect.

Description:
DESCRIPTION 
     Cross Reference to Related Applications 
     The present application is a division of Ser. No. 025,878, filed 2 Apr. 1979 now abandoned. 
    
    
     BACKGROUND OF THE INVENTION 
     The present invention relates to novel prostaglandin analogs. Particularly, these compounds are analogs of the prostaglandins wherein the C-19 position is substituted by hydroxy, i.e., 19-hydroxy-19-methyl-PG compounds. Most particularly, the present invention relates to novel 19-hydroxy-19-methyl-13,14-dihydro-PG 2  compounds, a disclosure of the preparation and use of which is incorporated here by reference from U.S. Ser. No. 025,899, filed 2 Apr. 1979 now U.S. Pat. No. 4,228,104. 
     PRIOR ART 
     Prostaglandin analogs exhibiting hydroxylation in the 19-position are known in the art. See, for example, U.S. Pat. No. 4,127,612, Sih, J. C., Prostaglandins 13:831 (1977) and U.S. Pat. Nos. 3,657,316, 3,878,046, and 3,922,297. See also the additional references cited in U.S. Ser. No. 025,878. 
    
    
     SUMMARY OF THE INVENTION 
     The present invention particularly provides: a compound of the formula ##STR1## wherein D is (1) cis-CH═CH--CH 2  --(CH 2 ) g  --CH 2  --, or 
     (2) cis-CH═CH--CH 2  --(CH 2 ) g  --CF 2  --, 
     wherein g is zero, one, two, or three; 
     wherein Q is α-OH:β-R 5  or α-R 5  :β-OH, wherein R 5  is hydrogen or methyl; 
     wherein R 6  is 
     (a) hydrogen, 
     (b) alkyl of one to 12 carbon atoms, inclusive, 
     (c) cycloalkyl of 3 to 10 carbon atoms, inclusive, 
     (d) aralkyl of 7 to 12 carbon atoms, inclusive, 
     (e) phenyl, 
     (f) phenyl substituted with one, 2, or 3 chloro or alkyl groups of one to 3 carbon atoms, inclusive, 
     (g) --(p--Ph)--CO--CH 3 , 
     (h) --(p--Ph)--NH--CO--(p--Ph)--NH--CO--CH 3 , 
     (i) --(p--Ph)--NH--CO--(p--Ph), 
     (j) --(p--Ph)--NH--CO--CH 3 , 
     (k) --(p--Ph)--NH--CO--NH 2 , 
     (l) --(p--Ph)--CH═N--NH--CO--NH 2 , 
     (m) β-naphthyl, 
     (n) --CH 2  --CO--R 28 , 
     wherein (p--Ph) is para-phenyl or inter-para-phenylene, 
     wherein R 28  is phenyl, p-bromophenyl, p-biphenylyl, p-nitrophenyl, p-benzamidophenyl, or 2-naphthyl, or 
     (o) a pharmacologically acceptable cation; 
     wherein R 2  is hydrogen, hydroxyl, or hydroxymethyl; 
     wherein R 3  and R 4  are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R 3  and R 4  is fluoro only when the other is hydrogen or fluoro; 
     wherein W is oxo, methylene, α-OH:β-H, or α-H:β-OH; and 
     wherein X is --CH 2  CH 2  --. 
     With regard to the divalent the substituents described above (e.g., Q) these divalent radicals are defined as α-R i  :β-R j , wherein R i  represents the substituent of the divalent moiety in the alpha configuration with respect to the ring and R j  represents the substituent of the divalent moiety in the beta configuration with respect to the plane of the ring. Accordingly, when Q is defined as a-OH:β-R 5 , the hydroxy of the Q moiety is in the alpha configuration, i.e., as in the natural prostaglandin, and the R 5  substituent is in the beta configuration. 
     Specific embodiments of the present invention include: 
     19-hydroxy-19-methyl-13,14-dihydro-PGF 2  α. 
     The compounds of the present invention are particularly useful for inducing prostaglandin-like biological effects, as is described in U.S. Ser. No. 025,878. Uses of compounds in accordance with the present invention include, therefore, anti-asthmatic indications.