3(2H)pyridazinone, and anti-allergic agent containing it

Claim 2

A 3(2H)pyridazinone of the formula: ##STR119## wherein R 1 is hydrogen or C 1 -C 5 alkyl; R 2 is hydrogen, C 1 -C 8 alkyl, chlorine or bromine; R 3 is hydrogen or C 1 - C 4 alkyl; X is --(CH 2 ) n --, wherein n is an integer of 1 to 4, --CH(OH 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 singel bond, B is --O--, --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--, is --O-- or --S--; and each or 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 1 -C 4 alkyl, --CO 2 R 6 , wherein R 6 is hydrogen or C 1 -C 4 alkyl, --CH═CHCO 2 R 7 , wherein R 7 is hydrogen or C 1 -C 4 alkyl, ##STR120## wherein each of R 8 an 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 ##STR121## with m being an integer of 0 to 3, R 11 being hydrogen or C 1 -C 3 alkyl, and R 12 being hydrogen or C 1 -C 4 alkyl, or any two, of Y 1 , Y 2 and Y 3 together forming ##STR122## wherein R 13 is hydrogen or C 1 -C 4 alkyl, provided that when R 3 is hydrogen and both X and B are single bonds, Y 1 , Y 2 and Y 3 are not simultaneously hydrogen, and a pharmaceutically acceptable salt thereof.

Claim 3

The pyridazinone according to claim 1, wherein R 2 is C 1 -C 8 alkyl, chlorine or bromine; when X is --(CH 2 ) n --, wherein n is an integer of 1 to 4 or a single bond, B is --O--, --S--, --OCO-- or a single bond; and when X is --CH(OR 4 ), wherein R 4 is hydrogen or C 1 -C 4 alkyl, or --CO--, B is --O-- 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 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 1 -C 4 alkyl, --CH═CHCO 2 R 7 , wherein R 7 is hydrogen or C 1 -C 4 alkyl, ##STR123## --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 ##STR124## wherein m is an integer of 1 to 3, R 11 is hydrogen or C 1 -C 3 alkyl, and R 12 is hydrogen or C 1 -C 4 alkyl.

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 bromine; R 3 is hydrogen or methyl; 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 --O-- 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.sub. 1 -C 4 alkyl, ##STR125## wherein R 10 is hydrogen, C 1 -C 5 alkyl or ##STR126## wherein R 11 is hydrogen or methyl, m is 0 to 1, and R 12 is hydrogen or methyl.

Claim 5

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; R 3 is hydrogen; X is --CH 2 --, --CH(OR 4 )--, wherein R 4 is hydrogen or methyl or --CO--; B is --O--; 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, ##STR127## wherein R 7 is hydrogen or C 1 -C 5 alkyl.

Claim 6

The pyridazinone according to claim 1, wherein R 1 is hydrogen, ethyl or i-propyl; R 2 is C 1 -C 4 straight chain alkyl, chlorine or bromine; R 3 is hydrogen; 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, is C 2 -C 5 alkyl, alkyl, --OR 5 , wherein R 5 is hydrogen or methyl, --CO 2 R 6 , wherein R 6 is hydrogen or methyl, --CN, --CONH 2 or --CHO.

Claim 7

The pyridazinone according to claim 1, which is 4-chloro-5-[3-(2-n-propyl-4-ethoxycarbonylphenoxy)propylamino-2-i-propyl-3(2H) pyridazinone, 4-n-propyl-5-[3-(2-n-propyl-4-methoxycarbonylphenoxy)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)propylamino-2-i-propyl-3(2H)pyridazinone, 4-chloro-5-[3-(2-ethyl-4-methoxycarbonylphenoxy)propylamino] -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-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, methoxy-carbonylphenoxy)propyl-2-ethyl-3(2H)pyridazinone, 4-chloro-5-[3-(2-n-propyl-4-cyanopyhenoxy)propoxy]-2-ethyl-3(2H)pyridazinone, 4-n-butyl-5-[3-(2-n-propyl-4-methoxycarbonylphenoxy)propylamino]-3(2H)pyridazinone, 4-chloro-5-[2-methoxy-3-(2-n-propyl-4-cyanophenoxy)proyylamino]-2-i-propyl-3(2H)pyridazinone, or 4-chloro-5-[2-hydroxy-3-(2-n-propyl-4-cynophenoxy)propylamino]-2-i-propyl-3(2H)pyridazinone.

Claim 8

The pyridazinone according to claim 1, which is 4-chloro-5-[3-(2-n-propyl-4-methoxycarbonylphenoxy)propylamino]-2-ethyl-3-(2H)pyridazinone.

Claim 9

The pyridazinone according to claim 1, which is 4-chloro-5-[3-(2-n-propyl-4-methoxycarbonylphenoxy)propylamino]-2-i-propyl-3(2H)pyridazinone.

Claim 10

The pyridazinone according to claim 1, which is 4-chloro-5-[3-(2-n-propyl-4-carboxyphenoxy)propylamino]-2-i-propyl-3-(2H)pyridazinone.

Claim 11

The pyridazinone according to claim 1, which is 4-chloro-5-[3-(2-n propyl-4-carbamoylphenoxy)propylamino]-2-i-propyl-3-(2H)pyridazinone.

Claim 12

The pyrdazinone according to claim 1, which is 4-chloro-5-[3-(2-allyl-4-cyanophenoxy)propylamino]-2-i-propyl-3(2H)pyridazinone.

Claim 13

The pyridazinone according to claim 1, which is 4-chloro-5-[3-(2-allyl-4-cyanophenoxy)propylamino]-2-ethyl-3(2H)pyridazinone.

Claim 14

The pyridazinone according to claim 1, which is 4-chloro-5-[3-(2-n-butyl-4-methoxycarbonylphenoxy)propylamino]-2-ethyl-3(2H)pyridazinone.

Claim 15

The pyridazinone according to claim 1, which is 4-chloro-5-[3-(2-n-butyl-4-carboxyphenoxy)propylamino]-2-i-propyl-3(2H)pyridazinone.

Claim 16

The pyridazinone according to claim 1, which is 4-chloro-5-[3-(2-n-butyl-4-carboxyphenoxy)propylamino]-2-ethyl-3-(2H)pyridazinone.

Claim 17

The pyridazinone according to claim 1, which is 4-chloro-5-[3-2-n-butyl-4-carbamoylphenoxy)propylamino]-2-i-propyl-3(2H)pyridazinone.

Claim 18

The pyridazinone according to claim 1, which is 4-chloro-5-[3-2-n-butyl-4-carbamoylphenoxy)propylamino]-2ethyl-3(2H)pyridazinone.

Claim 19

The pyridazinone according to claim 1, which is 4-bromo-5-[3-(2-n-propyl-4-cyanophenoxy)propylamino]-2-ethyl-3(2H)pyridazinone.

Claim 20

The pyridazinone according to claim 1, which is 4-bromo-5-[3-(2-allyl-4-cyanophenoxy)propylamino]-2-2-ethyl--3(2H)pyridazinone.

Claim 21

The pyridazinone according to claim 1, which is 4-bromo-5-[3-(2-n-propyl-4-methoxycarbonylphenoxy)propylamino]-2-ethyl-3(2H)pyridazinone.

Claim 22

The pyridazinone according to claim 1, which is 4-bromo-5-[3-(2-n-propyl-4-carbamoylphenoxy)propylamino]-2-i-propyl-3(2H)pyidazinone.

Claim 23

The pyridazinone according to claim 1, which is 4-bromo-5-[3-(2-allyl-4-cyanophenoxy)propylamino]-2-i-propyl-3(2H)pyridazinone.

Claim 24

The pyridazinone according to claim 1, which is 4-bromo-5-[3-(2-n-propyl-4-methoxycarbonylphenoxy)propylamino]-2-i-propyl-3(2H)pyridazinone.

Claim 25

The pyridazinone according to claim 1, which is 4-bromo-5-[3-(2-n-propyl-4-carboxyphenoxy)propylamino]-2-i-propyl-3(2H)pyridazinone.

Claim 26

The pyridazinone according to claim 1, which is 4-bromo-5-[3-(2-n-butyl-4-methoxycarbonylphenoxy)propylamino]-2-i-propyl-3(2H)pyridazinone.

Claim 27

The pyridazinone according to claim 1, which is 4-bromo-5-[3-(2-n-butyl-4-carboxyphenoxy)propylamino]-2-i-propyl-3-(2H)pyridazinone.

Claim 28

An anti-allergic agent, comprising: a pharmaceutically effective amount of a 3(2H)pyridazinone of formula 1 in claim 1 or a pharmaceutically acceptable salt thereof in combination with a pharmaceutically acceptable carrier.

Claim 29

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 of the 3 (2H)pyridazinone as defined in claim 1 which is effective in reducing the incidence or severity of said allergy or a pharmaceutically acceptable salt thereof to a subject suffering from said allergy.

Claim 30

The method of claim 28, wherein the 3(2H)pyridazinone compound is of formula (I) wherein R 1 is hydrogen, ethyl or i-propyl; R 2 is C 1 -C 4 straight chain alkyl, chlorine or bromine; R 3 is hydrogen; 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, is C 2 -C 5 alkyl, allyl, --OR 5 , wherein R 5 is hydrogen or methyl, --COR 6 , wherein R 6 is hydrogen or methyl, --CN, --CONH 2 or --CHO.