6(A-(AMIDINO-AND IMIDOYLAMINO-ALKANOYLAMINO)-ARACYLAMINO)-PENICILLANIC ACIDS

摘要

1418656 Penicillins PFIZER Inc 27 Dec 1972 [2 Aug 1972] 59711/72 Heading C2C Novel penicillins having the Formula (I) or (II) and salts thereof, wherein Ar is phenyl, 4- hydroxyphenyl or 2- or 3-thienyl; A is 1,4- phenylene, C 1 -C 3 alkylene or C 2 -C 3 alkylidene; R 1 and R 2 are each hydrogen, C 1 -C 3 alkyl; naphthyl, thienyl, pyrryl, pyridyl, furyl, phenyl, benzyl, or substituted phenyl or benzyl wherein the substituent is Cl, Br, F, CH 3 , CH 3 O, CF 3 , 3,4-dichloro or 3,5-dichloro; or R 1 and R 2 together are C 2 -C 6 alkylene; and R 2 and R 3 together can be C 2 -C 4 alkylene, and R 2 and R 4 together can be C 3 -C 5 alkylene; are prepared by reacting an appropriate α-amino arylacetamido-penicillin or a salt thereof with a compound of formula wherein R is X is OH or Cl, and R 1 , R 2 , R 3 and R 4 are as defined above, in the presence of a condensing agent or acid binding agent respectively. The penicillins (I) and (II) have antibiotic activity, and may be made up into antibacterially active pharmaceutical compositions with conventional pharmaceutical diluents or carriers. The following starting materials and intermediates are also prepared: 3-amidinopropionic acid hydrochloride is produced by reacting methanol, methyl-3-cyanopropionate and HCl to give methyl #-carbomethoxypropionamidate hydrochloride which is treated with ammonia to give #-carbomethoxypropionamidine hydrochloride, the latter then being hydrolysed with 12N hydrochloric acid. By analogous procedure, many other compounds of formula where R 1 , R 2 , R 3 and A are as defined above, are prepared. N,N1 - Diethylamidinoacetic acid hydrochloride is prepared via N-ethyl-carboethoxyacetamide, methyl N - ethyl - carboethoxyacetamide and N,N1 - diethyl - carboethoxyacetamidine hydrochloride. Other analogues wherein R 1 , R 2 , R 3 and A are as before are similarly produced. Other compounds produced are 3-(2-imidazolinyl)propionic acid hydrochloride, 3-amidinopropionyl chloride hydrochloride, ethyl isobutyrimidate hydrochloride, isobutyrimidoylaminoacetic acid hydrochloride and the corresponding free base; N - (N1 - methylacetimidoyl)aminoacetic hydrochloride, 2 - (N - n - propyl - N - carboxymethyl)amino - 1 - aza - cyclohept - 2 - ene hydrochloride, N - carboxymethylimidazoline hydrochloride, N - carbobenzyloxymethyl - imidazoline; formimidoylaminoacetyl chloride hydrochloride; and benzimidoylaminoacetyl chloride hydrochloride.