Patent GB-1384530-A (GB)
Title: Chromone derivatives
IPC: C07C49/84
Filed: 1971-07-29
Abstract: 1384530 Chromone derivatives FISONS Ltd 10 July 1972 [29 July 1971] 35605/71 Heading C2C Novel compounds of Formula (I)  wherein R<SP>1</SP>, R<SP>2</SP>, R<SP>3</SP>, R<SP>4</SP>, R<SP>5</SP> and R<SP>7</SP> may be the same or different and are H, hydroxy, alkoxy, alkoxy substituted by phenyl, acyl, amino, acylamino, alkenyl, halogen, or alkyl, provided that at least one of R<SP>1</SP>, R<SP>2</SP>, R<SP>3</SP> and R<SP>7</SP> are other than hydrogen and hydroxy, or an adjacent pair of R<SP>1</SP>, R<SP>2</SP>, R<SP>3</SP> and R<SP>7</SP> either represent hydrogen and a 3-(N,N-dialkylamino)acryloyl radical or together represent a chain X is a C 2-10  hydrocarbon chain, optionally substituted by a hydroxy group, and E is a carboxy group or a tetrazole group, or a pharmaceutically acceptable derivative thereof, may be obtained (a) by forming a compound of Formula I in which E is -COOH by cyclizing a compound of Formula II where A<SP>1</SP> and A<SP>2</SP> are the pairs of groups (i) -OH and -COCH 2 COCOR<SP>6</SP>, or (ii)  and H, in which R<SP>6</SP> is an OM group or a group hydrolysable thereto, and M is hydrogen or an alkali metal, (b) by reacting a compound of Formula III or an ester thereof, with a compound IV wherein one of Y and Z represents H or a reactive metal and the other is a C 2-10  hydrocarbon radical containing an anion-forming group or an epoxide group; (c) by hydrolysing a compound of Formula I in which E is a group hydrolysable to a -COOH group; (d) by reacting a compound of Formula I in which E is -CN with an azide in an inert solvent to form a compound in which E is a tetrazole group, (e) by cyclizing a compound of Formula XVI in which L is an alkyl group, or (f) by reacting a compound of Formula XVII with a compound of formula HCONL 2  and where desired or necessary converting the resulting compound of Formula I to a pharmaceutically acceptable derivative thereof. Preparation of the following intermediates is also described: 4 - (5 - bromopentyloxy) - 2- hydroxyacetophenone; 3 - allyl - 4 - (2,3 - epoxy - propoxy) - 2 - hydroxyacetophenone; ethyl 8 - allyl - 7 - hydroxy - 4 - oxo - 4H - 1- benzopyran - 2 - carboxylate; 7 - (5 - bromopentyloxy) - 4 - oxo - 4H - 1 - benzopyran - 2- carboxylic acid ethyl ester; 7-(2,3-epoxypropoxy) - 4 - oxo - 4H - 1 - benzopyran - 2- carboxylic acid ethyl ester; 4-(3-bromopropoxy) - 2 - hydroxy - 3 - propylacetophenone; 3 - (2 - t - butylphenoxy) - 1,2 - epoxypropane; 3 - bromopropyl - 2 - n - butylphenyl ether; 7- bromoheptyl - 2 - n - propylphenyl ether; 1,2- epoxy - 3 - (2 - propylphenoxy)propane; 2- hydroxy - 6 - [2 - hydroxy - 3 - (2 - propylphenoxy)propoxy]acetophenone; 2 - (3 - bromopropoxy)propylbenzene; 2 - hydroxy - 4- or 6 - (3 - [2 - propylphenoxy]propoxy)acetophenone; 2 - ethyl - 3 - (3 - [2 - propylphenoxy]- propoxy)phenol; dimethyl 2 - ethyl - 3 - (3 - [2- propylphenoxy]propoxy)phenoxyfumarate and corresponding free acid; and ethyl 5-(3-[2- {3 - dimethylaminoacryloyl} - 3 - hydroxyphenoxy] - 2 - hydroxypropoxy) - 4 - oxo - 4H- 1-benzopyran-2-carboxylate. Pharmaceutical compositions, useful for treating skin afflictions, hay fever, and asthma, comprise compounds of Formula I in admixture with a pharmaceutically acceptable adjuvant, diluent or carrier, in forms suitable for administration parenterally, by inhalation or topically.