3(2H)pyridazinone, process for its preparation and anti-allergic agent containing it

Claim 2

A 3(2H)pyridazinone of the formula: wherein R 1 is hydrogen or C 1 -C 5 alkyl; R 2 is hydrogen, C 1 -C 8 alkyl, chlorine or bromine; A is -NR 3 - (wherein R 3 is hydrogen or C 1 -C 4 alkyl) or -O-; X is -(C H 2 ) n -(wherein n is an integer of 1 to 4), -CH(OR 4 )- (wherein R 4 is hydrogen or C 1 -C 4 alkyl), -CO- or a single bond; when X is -(CH 2 ) n - (wherein n is as defined above) or a single bond, B is -0-, -S-, -NH-, -OSO 2 -, or -OCO- or a single bond, when X is -CH(OR 4 )- (wherein R 4 is as defined above), B is -O-, -S-, -NH- or -OSO 2 -, and when X is -CO-, B is -0- or -S-; and each of Y 1 , Y 2 and Y 3 which may be the same or different, is hydrogen, C 1 -C 8 alkyl, C 2 -C 8 alkenyl, halogen, -OR 5 (wherein R 5 is hydrogen or C l -C 4 alkyl), -C0 2 R 6 (wherein R 6 is hydrogen or C1-C 4 alkyl), -CH=CHCO 2 R 7 (wherein R 7 is hydrogen or C 1 -C 4 alkyl), -CN, -OON(R 8 )(R 9 ) (wherein each of R8 and R 9 which may be the same or different, is hydrogen or Cl-C4 alkyl), -COR 10 [wherein R 10 is hydrogen, C 1 -C 5 alkyl or - (wherein m is an integer of

Claim 3

The pyridazinone according to Claim 1, wherein R 1 is hydrogen or C 1 -C 4 alkyl; R 2 is C 1 -C 6 alkyl, chlorine or bromine; A is -NR 3 - (wherein R 3 is hydrogen or methyl) or -0-; X is -(CH 2 ) n - (wherein n is an integer of 1 to 3, -CH(OR 4 )- (wherein R 4 is hydrogen or C 1 -C 4 alkyl) or -CO-; when X is -(CH 2 ) n - (wherein n is as defined above), -CH(OR 4 )- (wherein R 4 is as defined above) or -CO-, B is -0- or -S-; Y 1 is hydrogen; and each of Y 2 and Y 3 which may be the same or different, is hydrogen, C 1 -C 8 alkyl, C 3 -C 5 alkenyl, halogen, -OR 5 (wherein R 5 is hydrogen or C 1 -C 4 alkyl), -CO 2 R 6 (wherein R 6 is hydrogen or C 1 -C 4 alkyl), -CONH 2 , -COR 10 [wherein R 10 is hydrogen, C 1 -C 5 alkyl or (wherein R 11 is hydrogen or methyl, m is 0 or 1, and R 12 is hydrogen or methyl)].

Claim 4

The pyridazinone according to Claim 1, wherein R 1 is hydrogen or C 1 -C 4 alkyl; R 2 is C 1 -C 6 alkyl, chlorine or bormine; A is -NH- or -0-; X is -CH 2 -, -CH(OR 4 )- (wherein R 4 is hydrogen or methyl) or -CO-; B is -0-; Y 1 is hydrogen; and each of Y 2 and Y 3 which may be the same or different, is C 1 -C 6 alkyl, C 3 -C 5 alkenyl, halogen, -OR 5 (wherein R 5 is hydrogen, methyl or ethyl), -CO 2 R 6 (wherein R 6 is hydrogen, methyl or ethyl), -CN, -CONH 2 , -CHO, -CH=CHCO 2 H or -COR 7 (wherein R 7 is hydrogen or C 1 -C 5 alkyl).

Claim 5

The pyridazinone according to Claim 1, wherein R 1 is hydrogen, ethyl or i-propyl; R 2 is C l -C 4 alkyl, chlorine or bormine; A is -NH- or -0-; X is -CH 2 -, -CH(OR 4 )-(wherein R 4 is hydrogen or methyl); B is -O-; Y 1 is hydrogen; and each of Y 2 and Y 3 which may be the same or different, C 2 -C 5 alkyl, allyl, -OR 5 (wherein R 5 is hydrogen, methyl or ethyl), -CO 2 R 4 (wherein R 4 is hydrogen, methyl or ethyl), -CN, -CONH 2 or -CHO.

Claim 6

The pyridazinone according to Claim 1, which is 4-cholor-5-[3-(2-n-propyl-4-methoxycarbonylphenoxy)propylamino]-2-ethyl-3(2H)pyridazinone, 4-chloro-5-[3-(2-n-propyl-4-methoxycarbonylphenoxy)propylamino]-2-i-propyl-3(2H)pyridazinone, 4-chloro-5-[3-(2-n-propyl-4-carboxy- phenoxy)propylaminol-2-i-propyl-3-(2H)pyridazinone, 4-chloro-5-[3-(2-n-propyl-4-carbamoylphenoxy)propylamino]-2-i-propyl-3-(2H)pyridazinone, 4-chloro-5-[3-(2-n-propyl-4-ethoxyearbonylphenoxy)propylaminol-2-i-propyl-3(2H) pyridazinone, 4-n-propyl-5-[3-(2-n-propyl-4-methoxy- carbonylphenoxy)propylaminol-2-ethyl-3(2H)pyridazinone, 4-chloro-5-[3-(2-allyl-4-cyanophenoxy)propylamino]-2-i-propyl-3(2H)pyridazinone, 4-chloro-5-[3-(2-allyl-4-cyano- phenoxy)propylamino]-2-ethyl-3(2H)pyridazinone, 4-chloro-5-[3-(2-ethyl-4-formylphenoxy)propylamino]-2-i-propyl-3(2H)pyridazinone, 4-chloro-5-[3-(2-ethyl-4-cyanophenoxy)propylaminol-2-i-propyl-3(2H)pyridazinone, 4-chloro-5-[3-(2-ethyl-4-methoxycarbonylphenoxy)-propylaminol-2-i-propyl-3(2H)pyridazinone, 4-chloro-5-[3-(2-n-propyl-4-methoxyphenoxy)propylamino]-2-i-propyl-3(2H)pyridazinone, 4-chloro-5-[3-(2-ethyl-4-methoxyphenoxy)propylamino]-2-ethyl-3(2H)pyridazinone, 4-chloro-5-[3-(2-ethyl-4-methoxyphenoxy)propylamino]-2-i-propyl-3(2H)pyridazinone, 4-chloro-5-[3-(2-n-propyl-4-hydroxyphenoxy)propylamino]-2-ethyl-3(2H)pyridazinone, 4-chloro-5-[3-(2-n-propyl-4-hydroxyphenoxy)propylamino]-2-i-propyl-3(2H)pyridazinone, 4-chloro-5-[3-(2-n-butyl-4-methoxycarbonylphenoxy) propylamino]-2-ethyl-3(2H)pyridazinone, 4-chloro-5-[3-(2-n-butyl-4-carboxyphenoxy)propylamino]-2-I-propyl-3(2H) pyridazinone, 4-chloro-5-[3-(2-n-butyl-4-carboxyphenoxy) propylamino]-2-ethyl-3-(2H)pyridazinone, 4-chloro-5-[3-(2-n-butyl-4-carbamoylphenoxy)propylamino]-2-i-propyl-3(2H)pyridazinone, 4-chloro-5-[3-(2-n-butyl-4-carbamoylphenoxy)propylamino]-2-ethyl-3(2H)pyridazinone, 4-bromo-5-[3-(2-n-propyl-4-cyanophenoxy)propylamino]-2-ethyl-3(2H)pyridazinone, 4-bromo-5-[3-(2-allyl-4-cyano- phenoxy)propylamino]-2-ethyl-3(2H)pyridazinone, 4-bromo-5-[3-(2-n-propyl-4-methoxycarbonylphenoxy) propylamino]-2-ethyl-3(2H)pyridazinone, 4-bromo-5-[3-(2-n-propyl-4-carbamoylphenoxy)propylamino]-2-i-propyl-3(2H) pyridazinone, 4-bromo-5-[3-(2-allyl-4-cyanophenoxy) propylamino]-2-i-propyl-3(2H)pyridazinone, 4-bromo-5-[3-(2-n-propyl-4-methoxycarbonylphenoxy)propylamino]-2-i-propyl-3(2H)pyridazinone, 4-bromo-5-[3-(2-n-propyl-4-carboxyphenoxy)propylamino]-2-i-propyl-3(2H)pyridazinone, 4-bromo-5-[3-(2-n-butyl-4-methoxycarbonylphenoxy) propylamino]-2-i-propyl-3(2H)pyridazinone, 4-bromo-5-[3-(2-n-butyl-4-carboxyphenoxy)propylamino]-2-i-propy-3-(2H) pyridazinone, 4-bromo-5-[3-(2-n-propyl-4-methoxyphenoxy) propylamino]-2-ethyl-3(2H)pyridazinone, 4-bromo-5-[3-(2-ethyl-4-methoxyphenoxy)propylamino]-2-ethyl-3(2H) pyridazinone, 4-chloro-5-[3-(2-n-propyl-4-methoxy- carbonylphenoxy)propoxy]-2-ethyl-3(2H)pyridazinone, 4-chloro-5-[3-(2-n-propyl-4-cyanophenoxy)propoxy]-2-ethyl-3(2H)pyridazinone, 4-n-butyl-5-[3-(2-n-propyl-4-methoxy- carbonylphenoxy)propylamino]-3(2H))pyridazinone, 4-chloro-5-[2-methoxy-3-(2-n-propyl-4-cyanophenoxy) propylamino]-2-i-propyl-3(2H)pyridazinone, or 4-chloro-5-[2-hydroxy-3-(2-n-propyl-4-cyanophenoxy)propylaminol-2-i-propyl-3(2H)pyridazinone.

Claim 7

A process for producing a 3(2H)pyridazinone of the formula: wherein R 1 is hydrogen or C 1 -C 5 alkyl; R 2 is hydrogen, C 1 -C 8 alkyl, chlorine or bromine; A is -NR 3 - (wherein R 3 is hydrogen or C 1 -C 4 alkyl) or -0-; X is -(CH 2 ) n -(wherein n is an integer of 1 to 4), -CH(OR 4 )- (wherein R 4 is hydrogen or C l -C 4 alkyl) or a single bond; B is -0-, -S- or -NH-; and each of Y 1 , Y 2 and Y 3 which may be the same or different, is hydrogen, C l -C 8 alkyl, C 2 -C 8 alkenyl, halogen, -OR 5 (wherein R 5 is hydrogen or C 1 -C 4 alkyl), -CO 2 R 6 (wherein R 6 is hydrogen or C l -C 4 alkyl), -CH=CHCO 2 R 7 (wherein R 7 is hydrogen or C 1 -C 4 alkyl), -CN, -CON(R 8 )(R 9 ) (wherein each of R 8 and R 9 which may be the same or different, is hydrogen or C 1 -C 4 alkyl), -COR 10 [wherein R 10 is hydrogen, C 1 -C 5 alkyl or (wherein m is an integer of 0 to 3, R 11 is hydrogen or C 1 -C 3 alkyl, and R 12 is hydrogen or C 1 -C 4 alkyl)], or two of Y 1 , Y 2 and Y 3 together form (wherein R 13 is hydrogen or C 1 -C 4 alkyl), which comprises reacting a compound of the formula: wherein R 1 and R 2 are as defined above, and Z is chlorine or bromine, with a compound of the formula: wherein A and X are as defined above, in the presence of a dehydrohalogenating agent to obtain a compound of the formula: wherein R 1 , R 2 , A and X are as defined above, then reacting the compound of the formula IV with p-toluenesulfonyl chloride, methanesulfonyl chloride or a halogenating agent in the presence of a dehydrohalogenating agent to obtain a compound of the formula: - wherein R 1 , R 2 , A and X are as defined above, and T is chlorine, bromine or iodine, and reacting the compound of the formula V with a compound of the formula VI: wherein B, Y l' Y 2 and Y 3 are as defined above.

Claim 8

A process for producing a 3(2H)pyridazinone of the formula: wherein R 1 is hydrogen or C 1 -C 5 alkyl; R 2 is hydrogen, C 1 -C 8 alkyl, chlorine or bromine; A is -NR 3 - (wherein R 3 is hydrogen or C 1 -C 4 alkyl) or -0-; X is -(CH 2 ) n -(wherein n is an integer of 1 to 4), -CH(OR 4 )- (wherein R 4 is hydrogen or C l -C 4 alkyl) or a single bond; B is -0-, -S- or -NH-; and each of Y 1 , Y 2 and Y 3 which may be the same or different, is hydrogen, C l -C 8 alkyl, C 2 -C 8 alkenyl, halogen, -OR 5 (wherein R 5 is hydrogen or C 1 -C 4 alkyl), -CO 2 R 6 (wherein R 6 is hydrogen or C l -C 4 alkyl), -CH=CHCO 2 R 7 (wherein R 7 is hydrogen or C 1 -C 4 alkyl), -CN, -CON(R 8 )(R 9 ) (wherein each of R 8 and R 9 which may be the same or different, is hydrogen or C 1 -C 4 alkyl), -COR 10 [wherein R 10 is hydrogen, C 1 -C 5 alkyl or (wherein m is an integer of 0 to 3, R 11 is hydrogen or C 1 -C 3 alkyl, and R 12 is hydrogen or C 1 -C 4 alkyl)], or two of Y 1 , Y 2 and Y 3 together form (wherein R 13 is hydrogen or C 1 -C 4 alkyl), which comprises reacting a compound of the formula: wherein R 1 and R 2 are as defined above, and Z is chlorine or bromine, with a compound of the formula: wherein A and X are as defined above, in the presence of a dehydrohalogenating agent to obtain a compound of the formula: wherein R 1 , R 2 , A and X are as defined above, then reacting the compound of the formula IV with p-toluenesulfonyl chloride, methanesulfonyl chloride or a halogenating agent in the presence of a dehydrohalogenating agent to obtain a compound of the formula: - wherein R 1 , R 2 , A and X are as defined above, and T is chlorine, bromine or iodine, and reacting the compound of the formula V with a compound of the formula VI: wherein B, Y l' Y 2 and Y 3 are as defined above.

Claim 9

An anti-allergic agent comprising an effective amount of a 3(2H)pyridazinone of the formula I as defined in Claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

Claim 10

A method of reducing the incidence or severity of allergy induced in a subject by SRS-A, which comprises administering to said subject an amount effective to reduce the incidence or severity of the allergy of a 3(2H)pyridazinone as defined in Claim 1 or a pharmaceutically acceptable salt thereof.