Open chained or fused 1,1′-alkylene-bis-uracil derivatives, useful in skin UV-protection

摘要

The invention provides compounds of formula I; or a salt thereof as described herein. The invention also provides dermatological compositions comprising a compound of formula I or mixtures of one or more compounds of formula I, processes for preparing compounds of formula I, intermediates useful for preparing compounds of formula I and therapeutic methods for protecting skin or DNA from photodamage or repairing photodamaged skin or DNA.;

主权项

1. A compound of formula I: wherein:
each R1 is independently H, (C1-C6)alkyl, (C3-C7)carbocycle or RaC(═O); or the two R1 groups together form a —(C3-C8)alkyl- group, a —(C2-C6)alkyl-Y—(C2-C6)alkyl- group or a —(C1-C6)alkyl-Y′—(C1-C6)alkyl- group;the dashed bonds labeled “a” are absent and the dashed bonds labeled “b” are double bonds; or all the dashed bonds are single bonds;R2 is H, (C1-C6)alkyl or aryl, wherein aryl is optionally substituted with one or more Z1 groups;R3 is H, (C1-C6)alkyl or aryl, wherein aryl is optionally substituted with one or more Z1 groups;R4 is carboxy, (C1-C6)alkoxycarbonyl, —OPO3H2, —ORc, or —NRdRe; and R5 is H;Y is O, S, NH, P, P(═O) or POH;Y′ is Si(Rb)2 or —Si(Rb)2—O—Si(Rb)2—;each Ra is independently (C1-C6)alkyl, (C3-C7)carbocycle or aryl, wherein aryl is optionally substituted with one or more Z1 groups; each Rb is independently (C1-C6)alkyl, (C3-C7)carbocycle or aryl, wherein aryl is optionally substituted with one or more Z1 groups;
Rc is Rf or a C1-C20 saturated or C2-C20 unsaturated carbon chain that is optionally substituted with one or more groups independently selected from oxo (═O), hydroxy, mercapto, (C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy, NRdRe, carboxy, and aryl, wherein aryl is optionally substituted with one or more Z1 groups;Rd is H, (C1-C6)alkyl, or (C1-C6)alkanoyl;Re is H or a C1-C20 saturated or C2-C20 unsaturated carbon chain that is optionally substituted with one or more groups independently selected from oxo (═O), hydroxy, mercapto, (C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, (C1-C6)alkanoyloxy, NRdRe, carboxy, and aryl, wherein aryl is optionally substituted with one or more Z1 groups;each Rf is: each Z1 is independently selected from (C1-C6)alkyl, halogen, —CN, —ORn1, —NRq1Rr1, —NRn1CORp1, —NRn1CO2Rp1, NO2, —C(O)Rn1, —C(O)ORn1 and —C(O)NRq1Rr1, wherein any (C1-C6)alkyl of Z1 is optionally substituted with one or more halogen;each Rn1 is independently selected from H and (C1-C6)alkyl, wherein any (C1-C6)alkyl of Rn1 is optionally substituted with one or more halogen;each Rp1 is independently (C1-C6)alkyl; andRq1 and Rr1 are each independently selected from H and (C1-C6)alkyl or Rq1 and Rr1 together with the nitrogen to which they are attached form a piperidine, pyrrolidine, morpholine, azetidine, thiomorpholine, piperazine or 4-methylpiperazine;or a salt thereof.