Patent GB-1389827-A (GB)
Title: Tetrazolyl benzopyrans
IPC: A61P11/00
Filed: 1971-07-23
Abstract: 1389827 Tetrazolyl benzopyrans FISONS Ltd 10 July 1972 [23 July 1971 (2) 2 Nov 1971] 34574/71 34575/71 and 50816/71 Heading C2C Novel compounds of the Formula I in which one or more adjacent pairs of P, Q, R 1  and T may represent a chain or one of P, Q, R and T may represent a group of Formula V in which X is a carbon-carbon bond, a single linking atom or a substituted or unsubstituted carbocyclic or heterocyclic ring or a straight or branched, saturated or unsaturated, substituted or unsubstituted hydrocarbon chain which chain may be interrupted by one or more carbocyclic or heterocyclic rings, oxygen atoms, sulphur atoms, nitrogen atoms SO or SO 2 , >NH or substituted >NH groups, Pa, Qa, Ta and the remainder of P, Q, R and T are the same or different and each is hydrogen; lower alkyl; lower alkyl carrying a halo; hydroxy; lower alkoxy; acetoxy; carboxy; amino; lower alkylamino; lower di-alkylamino; or a hydroxylamino substituent group; unsaturated lower alkyl; phenyl lower alkyl; halophenyl lower alkyl; lower alkyphenyl lower alkyl; phenyl; naphthyl; phenyl and naphthyl carrying a halo, lower alkyl, nitro carboxy or hydroxy substituent group; pyridyl; furyl; pyrrolyl; cycloalkyl containing from 4-6 carbon atoms; cycloalkyl containing from 4-6 carbon atoms and carrying a hydroxyl, lower alkoxy or carboxy substituent group; nitrile; nitro; nitroso; hydroxy; lower alkoxy; lower alkoxy carrying a hydroxy, lower alkoxy, carboxy, halo, amino, lower alkylamino, or di-lower alkylamino substituent group; lower alkenyloxy or lower alkynyloxy; benzyloxy; phenyloxy; naphthyloxy; pyridyloxy; cyclohexyloxy; cyclopentyloxy; epoxy lower alkoxy; amino; lower alkylamino; lower dialkylamino; cycloalkylamino containing from 4 to 6 carbon atoms; phenylamino; naphthylamino; diphenylamino; halo -lower-alkylamino; lower alkenylamino; amino lower alkylamino; hydroxy amino; lower acyl amino; ureyl; thioureyl; guanidino; thiol; lower alkyl thiol; phenyl thiol; sulphonic acid; halogen, or one or more of the remainder of P, Q, R and T may be a group OY wherein Y is lower alkyl group substituted by lower alkyl or phenyl-lower alkyl in which one or more of the CH 2  groups has been replaced by oxygen, sulphur or carbonyl, which alkyl or phenyllower alkyl may carry one or more hydroxyl or carboxyl substituent groups; or an adjacent pair of P, Q, R and T (together with the adjacent carbon atoms in the benzene ring) together form a benzene ring, or a chain -(CH 2 ) 3 - -O(CH 2 ) 3 -, -O(CH 2 ) 2 -, -C(CH 3 )=CH-CO-O-, -O(CH 2 ) 2 O-, -CH 2 -CH(CH 3 )-O-, -CH = CH-O-, -CH = C(CH 3 )-O-, -OCH 2 O-, -NH-C(R<SP>4</SP>R<SP>5</SP>)-CH 2 -O-, -NR<SP>5</SP>CH = CH-O- or NR<SP>4</SP>CH = CH-NR<SP>4</SP>- (wherein R<SP>4</SP> is hydrogen or lower alkyl or lower alkoxy and R<SP>5</SP> is hydrogen, or R<SP>4</SP> and R<SP>5</SP> together form a = O group), or a pharmaceutically acceptable derivative thereof, which comprises reacting a compound of Formual II in which P<SP>1</SP>, Q<SP>1</SP>, R<SP>1</SP> and T<SP>1</SP> have the same significances as P, Q, R and T above, save that one or more adjacent pairs of P<SP>1</SP>, Q<SP>1</SP>, R<SP>1</SP> and T<SP>1</SP> may represent a chain -COCH=C(E)-O-, or that one of P<SP>1</SP>, Q<SP>1</SP>, R<SP>1</SP> and T<SP>1</SP> may represent a group of Formula VI, in which Pa, Qa, Ta and X are as above and E denotes -CN or -CN 4 H, with an azide in a solvent which is inert under the reaction conditions, and where desired converting the compound of Formula I to a pharmaceutically acceptable derivative, e.g. a salt. Intermediates of Formula II may be obtained by dehydrating a compound of Formula III in which P<SP>2</SP> ,  Q<SP>2</SP> ,  R<SP>2</SP> and T<SP>2</SP> can be the same as P, Q, R and T save that one or more adjacent pairs can be -COCH= C(G)-O-, or one of P, Q, R and T can represent (VIII) in which G is -CN 4 H, -CONH 2  or -CN. The amides of Formula III can be made in known manner for corresponding carboxylic acid esters, e.g. by reaction of the ester with NH 3  in an alkanol solvent at 0‹ to 120‹ C. Pharmaceutical compositions, useful for treatment of allergic or intrinsic asthma, hay fever, urticarea and other conditions in which antigen-antibody reactions are responsible, comprise compounding Formula I above together with a pharmaceutical diluent, preferably in forms suitable for administration by inhalation or aesophageally.