Abstract: This invention relates to substituted benzo[1,2-b:5,4-b′]dipyran-4-amines which are modulators, agonists or antagonists, of the CCR5 receptor. In addition, this invention relates to the treatment and prevention of disease states mediated by CCR5, including, but not limited to, asthma and a topic disorders (for example, a topic dermatitis and allergies), rheumatoid arthritis, sarcoidosis and other fibrotic diseases, atherosclerosis, psoriasis, autoimmune diseases such as multiple sclerosis, and inflammatory bowel disease, all in mammals, by the use of substituted benzo[1,2-b:5,4-b′]dipyran-4-amines which are CCR5 receptor antagonists. Furthermore, since CD8+T cells have been implicated in COPD, CCR5 may play a role in their recruitment and therefore antagonists to CCR5 could provide potential therpeutic in the treatment of COPD. Also, since CCR5 is a co-receptor for the entry of HIV into cells, selective receptor modulators may be useful in the treatment of HIV infection.

Abstract: Compounds of the formula (I) and pharmaceutically acceptable salts thereof: ##STR1## wherein: X is oxygen or sulphur;R.sub.1 is a C.sub.1-6 alkoxy or C.sub.1-6 alkylthio group;R.sub.2 and R.sub.3 are the same or different and are hydrogen, halogen, CF.sub.3, C.sub.1-7 acyl, C.sub.1-7 acylamino or amino, aminocarbonyl or aminosulphonyl optionally substituted by one or two C.sub.1-6 alkyl groups, C.sub.1-6 alkylsulphonyl, C.sub.1-6 alkylsulphinyl, C.sub.1-6 alkoxy, C.sub.1-6 alkylthio, hydroxy or nitro or R.sub.1 and R.sub.2 taken together are methylenedioxy or ethylenedioxy in which case R.sub.3 is any one of the groups given for R.sub.2 and R.sub.3 above;R.sub.4 is C.sub.1-7 alkyl or a group --(CH.sub.2).sub.s R.sub.5 where s is 0 to 2 and R.sub.5 is a C.sub.3-8 cycloalkyl group, or a group --(CH.sub.2).sub.t R.sub.6 where t is 1 or 2 and R.sub.6 is a phenyl group optionally substituted by one or two substituents selected from C.sub.1-6 alkyl, C.sub.

Abstract: Compounds of the formula (III) and pharmaceutically acceptable salts thereof: ##STR1## wherein: R.sub.1 is a C.sub.1-6 alkoxy or C.sub.1-6 alkylthio group;R.sub.2 and R.sub.3 are the same or different and are hydrogen, halogen, CF.sub.3, C.sub.1-7 acyl, C.sub.1-7 acylamino or amino, aminocarbonyl or aminosulphonyl optionally substituted by one or two C.sub.1-6 alkyl groups, C.sub.1-6 alkylsulphonyl, C.sub.1-6 alkylsulphinyl, C.sub.1-6 alkoxy, C.sub.1-6 alkylthio, hydroxy or nitro or R.sub.1 and R.sub.2 taken together are methylenedioxy or ethylenedioxy in which case R.sub.3 is any one of the groups given for R.sub.2 and R.sub.3 above;R.sub.4 is C.sub.1-7 alkyl or a group --(CH.sub.2).sub.s R.sub.6 where s is 0 to 2 and R.sub.6 is a C.sub.3-8 cycloalkyl group, or a group --(CH.sub.2).sub.t R.sub.7 where t is 1 or 2 and R.sub.7 is a phenyl group optionally substituted by one or two substituents selected from C.sub.1-6 alkyl, C.sub.