Patent NZ-275961-A (NZ)
Title: 5,6-dihydropyrone derivatives and pharmaceutical compositions as anti-viral agents in the treatment of HIV infection
Inventor: ELLSWORTH EDMUND LEE
IPC: C07D405/12
Filed: 1994-10-26
Abstract: Derivatives of 5,6-dihydropyrone and related structures which inhibit the Human Immunodeficiency Virus (HIV) aspartyl protease are described.  The 5,6-dihydropyrone derivatives are useful in the development of therapies for the treatment of bacterial and viral/retroviral infections and diseases, including AIDS.  Synthesis of multifunctional 5,6-dihydropyrone and related structures is also described. The preferred compound is that of formula 1 wherein X is OR5, NHR5, CH2OR5, CO2R6, or SR5, wherein R5 is R6 or COR6 wherein R6 is independently H, a straight chain alkyl group containing 1 to 6 carbon atoms, a branched or cyclic alkyl group containing 3 to 7 carbon atoms, an alkylcycloalkyl group of 5 to 9 carbon atoms, benzyl, phenyl, or a heterocycle; Z is O or S; Y is O or S, C(R6)2, NF, or NR6; R1 and R1' are each independently [CH2]n1-[W1]n2-[Ar]n2-[CH2]n3-[W2]n4-R7; R2 is independently selected from the group of structures from which R1 is selected with the proviso that if W1 is a heteroatom n1 is an integer of from 1 to 4; R3 is independently selected from the group of structures from which R1 is selected with the proviso that if W1 is a heteroatom n1 is an integer of from 1 to 4; R2 and R3 may be taken together to form an unsubstituted or substituted 3-, 4-, 5-, 6-, or 7-membered ring, wherein the substituents are one or more of the R7 groups listed below; R4 is [CH2]n1-[W3]n2-[W4]n4-[Ar]n2-[CH2]n3-[W2]n4-R7; n1, n2, n3, n4, and n5 are independently integers of from 0 to 4, 0 to 1, 0 to 4, 0 to 1, and 0 to 2, respectively; W1, W2 and W4 are independently O, OCONR7S(O)n5, CO, C(=NR7)NR7, CR7=CR7, C.tbd.C, NR7, CS, C=N-R7, C=NOR7, NR7SO2, SO2NR7, C=C(R7) 2, CR7N(R7) 2, CR7OR7, C(R7) 2, NCO2R7, NR7CO2, CO2, NCON(R7) 2, NR7CONR7, NCOR7, NR7CO, or CONR7; W3 is independently selected from the group of structures from which W1 is selected, with the further limitation that if n1 in R4 is zero, that W3 is selected from the group of structures consisting of -CO, -CR7=CR7, -C.tbd.C, -CS, -C=N-R7, -C=NOR7, -CR7N(R7)2, -C=C(R7) 2, -CR7OR7, -C(R7) 2, -CO2, and -CONR7; R7 is independently H, Ar, a straight or branched alkyl or alkenyl group containing from 1 to 6 carbon atoms, or two R7 groups can be taken together to form a ring of 3 to 7 atoms, or a substituted derivative thereof wherein the substituents are one or more of CO2R6, COR6, CON(R6)2, NR6CON(R6)2, NR6COR6, OR6, S(O)n5R6, N(R6)2 , Cl, Br, F, CF3, Ar, OAr, or S(O)n5Ar; Ar is independently phenyl, naphthyl, a 5- or 6-membered heterocycle containing 1 to 4 heteroatoms, a cycloalkyl containing 3 to 6 atoms, a fused ring system containing 8 to10 atoms, or a substituted derivative thereof wherein the substituents are of F, Cl, Br, CN, NO2, (CH2)n6R6, (CH2)n6C(Me)=CH2, (CH2)n6N(R6)2, (CH2)n6NR6CON(R6)2, (CH2)n6NR6COR6, (CH2)n6OR6, (CH2)n6OCOR6, (CH2)n6OCON(R6)2, (CH2)n6 CO2 R6, (CH2)n6 CON(R6)2, (CH2)n6 COR6, CF3, (CH2)n6 S(O)n5R6, OCH2O, or O(CH2)2O; and n6 is independently an integer of from 0 to 3.