COMPOUNDS FOR USE IN THE TREATMENT OF ACUTE INTERMITTENT PORPHYRIA

摘要

The invention provides compounds of formula (I), their pharmaceutically acceptable salts and prodrugs thereof for use in preventing, inhibiting or treating a disease caused by a mutation in the gene coding for hydroxymethylbilane synthase, in particular for preventing, inhibiting or treating acute intermittent porphyria: (I) wherein: A is selected from N and CR¹⁰ (wherein R¹⁰ is H, -NO₂, C_1-6 haloalkyl or -C(O)R¹⁷ in which R¹⁷ is H or C_1-6 alkyl); Z is selected from N and CR ⁹ (wherein R⁹ is H, halogen (e.g. F, C1, Br or I) or -OR¹⁶ in which R¹⁶ is H, C_1-6 haloalkyl, or optionally substituted C_1-6 alkyl); L is selected from -CH₂-, -C(O)-, -CH(OH)-, -C(O)-NR'-, and -NR'-C(O)- (wherein R' is H or C_1-3 alkyl, e.g. -CH₃); R ¹ is H; R² is selected from H, halogen (e.g. F, C1, Br or I), -NR¹¹R¹² (wherein R¹¹ and R¹² are independently selected from H and C_1-6 alkyl or, together with the nitrogen atom to which they are attached, form a 5- or 6-membered saturated ring), and -OR13 (wherein R¹³ is H or C_1-6 alkyl); R ³ is selected from H, -CH²OH and -C(O)R ¹⁴ (wherein R¹⁴ is H or C_1-6 alkyl); R ⁴ is selected from H, halogen (e.g. F, C1, Br or I) and -OR¹⁵ (where R¹⁵ is H or C_1-6 alkyl); R ⁵ is selected from H and C_1-6 alkyl; R ⁶ is selected from H, -NO₂ and halogen (e.g. F, Cl, Br or I); R⁷ is H; and R⁸ is selected from H, C_1-6 alkyl, and halogen (e.g. F, C1, Br or I); or wherein: R⁷ and R⁸ together with the intervening ring carbon atoms form an unsaturated ring, preferably an aryl ring.