Patent GB-1410597-A (GB)
Title: Benzopyrans and thiapyrans
IPC: C07D311/24
Filed: 1971-11-30
Abstract: 1410597 4-Spiro-2<SP>1</SP>-(1<SP>1</SP>,3<SP>1</SP>-dithiolane or -dithiane)-4H-1-benzo-pyrano or -thiapyrans FISONSLtd 16 Nov 1972 [30 Nov 1971] 55435/71 Heading C2C Novel 4-spiro-2<SP>1</SP>-(1<SP>1</SP>,3<SP>1</SP>-dithiolane or -dithiane) 4H-1-benzo-pyrans or -thiapyrans of the general formula wherein R is -COOH, -CN or tetrazolyl, W is O or S, n is 2 or 3 and each of Rx, Ry, Rz and Rw is hydrogen, halogen, alkyl, hydroxy, alkenyl, phenyl, alkenyloxy, phenylalkyl, phenylalkoxy, alkanoyloxy or alkoxy (optionally substituted by alkoxy, hydroxy or a 5 or 6 membered heterocyclic ring containing C and O), or one of Rx, Ry, Rz and Rw is a group of formula or wherein X is a hydrocarbon chain, optionally substituted by hydroxy and each of Rv, Rs and Rt is as Rx, Ry, Rz and Rw above, apart from a group (i) or (ii), or one or more adjacent pairs of Rx, Ry, Rz and Rw may be -W-CR=CHCO- or a chain of formula and the remainder of Rx, Ry, Rz and Rw are as defined above, and pharmaceutically acceptable salts or, when R is -COOH, esters and amides thereof are prepared (a) by reacting a 4-oxo-4H- 1-benzo-pyran or -thiapyran of the general formula with a compound of the general formula HS(CH 2 ) n SH; (b) by selectively hydrolysing a compound of the general formula wherein R<SP>1</SP> is a group hydrolysable to R; or (c) when the product has the general formula wherein one of Ra, Rb, Rc and Rd is a group (i) or (ii) above and the remainder are each hydrogen, halogen, alkyl, hydroxy, alkenyl, phenyl, alkenyloxy, phenylalkyl, phenylalkoxy, alkanoyloxy or alkoxy (optionally substituted by alkoxy, hydroxy or a 5 or 6 membered heterocyclic ring containing C and O, by reacting a compound of the general formula wherein one of Re, Rf, Rg and Rh is -OM (M is hydrogen or a reactive metal) or one of Re, Rf, Rg and Rh is -OX<SP>1</SP>Y, in which X<SP>1</SP>Y is such that, on reaction with -OM, it leaves an X residue and Y is an anion-forming group or, together with X<SP>1</SP>, forms an epoxide group, and the remainder of Re, Rf, Rg and Rh are as the remainder of Ra, Rb, Rc and Rd above, with a compound of the general formula or wherein when one of Re, Rf, Rg and Rh is -OM, one of Ri, Rj, Rk and Rl is -OX<SP>1</SP>Y and when one of Be, Rf, Rg and Rh is -OX<SP>1</SP>Y, one of Ri, Rj, Rk and Rl is -OM, and the remainder of Ri, Rj, Rk and Rl are as the remainder of Ra, Rb, Rc and Rd above; and optionally converting the product to a pharmaceutically acceptable salt or, where R is -COOH, ester or amide thereof. 4-Oxo-4H-l-benzo-pyrans and -thiapyrans of the second general formula above and pharmaceutically acceptable salts and, when R is -COOH, esters and amides thereof are prepared by oxidatively hydrolysing a compound of the first or fourth general formula above and optionally converting the product to a pharmaceutically acceptable salt or, where R is -COOH, ester or amide thereof. Pharmaceutical compositions, which inhibit the release and/or action of pharmacological mediators which result from the in vivo combination of certain types of antibody and specific antigen, comprise, as active ingredient, a 4- spiro-2<SP>1</SP>-(1<SP>1</SP>,3<SP>1</SP>-dithiolane or -dithiane)-4H-1- benzo-pyran or -thiapyran of the first general formula above or a pharmaceutically acceptable salt or, when R is -COOH, ester or amide thereof, in admixture with a pharmaceutically acceptable diluent, adjuvant or carrier.