| 主权项 |
1. A compound represented by formula I:or a stereoisomer, a salt, a metabolite, or a deuteride thereof,wherein
1) R1 is selected from the group consisting of
a) hydrogen,b) —P(O)(OH)2,c) —P(O)(O(CH2)1-3OC(O)O(alkyl))2,d) —P(O)(O(CH2)1-3OC(O)(alkyl))2,e) —P(O)(O(CH2)1-3SC(O)(alkyl))2,f) —P(O)(O(CH2)1-3OCH2(aryl))2,g) —P(O)(O(CH2)1-3SCH2(aryl))2,h) —P*(O)(OR1a)(NHCHR1bC(O)OR1c),whereR1a is
i) hydrogen,ii) alkyl,iii) cycloalkyl, oriv) aryl,R1b is
i) hydrogen,ii) C1-6alkyl,iii) cycloalkyl,iv) alkaryl, orv) alk(heteroaryl), andR1c is
i) hydrogenii) alkyl,iii) cycloalkyl, oriv) alkaryl,i) —P*(O)(NH(alkaryl)(O(CH2)1-3SC(O)(alkyl)),j) a 1,3,2-dioxaphosphinane-2-oxide,k) a 4H-benzo[d][1,3,2]dioxaphosphinine-2-oxide,l) —P*(O)(OR1c)˜, when Y is —O˜,m) —P(O)(OH)—O—P(O)(OH)2,n) —P(O)(OH)—O—P(O)(OH)—O—P(O)(OH)2,o) an acyl,p) a C1-6-alkylene-oxy-acyl, andq) a —C(O)—O-alkyl; 2) R2 is selected from the group consisting of
a) hydrogen,b) fluoro,c) azido,d) cyano,e) a C1-6alkyl,f) a vinyl, andg) an ethynyl; 3) R3 is selected from the group consisting of
a) hydrogen,b) methyl, andc) cyano; 4) Y is selected from the group consisting of
a) hydrogen,b) fluoro,c) —OH,d) —O˜, when R1 is —P(O)(OR1c)˜,e) —O(acyl),f) —O(C1-6-alkylene-oxy-acyl),g) —O—C(O)—O-alkyl,h) —NH2,i) —NH(acyl),j) —NH—C(O)—O-alkyl, andk) azido; 5) X is selected from the group consisting of
a) —O—,b) —S—,c) —NH—,d) —CH2—,e) >C═CH2, andf) —NH—C(O)—O-alkyl; 6)is a four- or five-membered ring selected from the group consisting of radicals a-o represented by the following structureswhere * represents the point of attachment to the 2′-carbon and where
a) A is selected from the group consisting of
i) —O—,ii) —S—,iii) —S(O)—,iv) —S(O)2—, andv) —NH—, b) D is selected from the group consisting of
i) —O—,ii) —S— except for rings i and j,iii) —S(O)— except for rings i and j,iv) —S(O)2— except for rings i and j,v) —NH— except for rings i and j,vi) —N—,vii) a methylene except for rings i and j,viii) a methine, andix) a vinylidene except for rings i and j, c) R4, R4′, R5, R5′, R6, R7, R8, R8′, R9, and R9′ are independently selected from the group consisting of
i) hydrogen,ii) halo,iii) C1-6alkyl,iv) hydroxy,v) alkoxy,vi) cycloalkoxy,vii) —O(acyl),viii) —O(C1-6-alkyleneoxyacyl),ix) —O—C(O)—O-alkyl,x) C1-6alkylene-oxy(alkyl),xi) alkenyl,xii) ethynyl,xiii) —NH2,xiv) —NH(alkyl),xv) —NH(cycloalkyl),xvi) heterocyclyl,xvii) aryl, andxviii) heteroaryl; and 7) B is selected from among B2, and B3 represented by the following structures:where for B2,
a) R13 is selected from the group consisting of
i) hydrogen,ii) halo,iii) cyano,iv) —C(O)NH2,v) C1-6alkyl,vi) vinyl, andvii) ethynyl,where for B3 m is 0 or 1, and ---- is a single or double bond
a) when m is 0, ----- is a double-bond and R16 and R17 are independently selected from the group consisting of
i) hydrogen,ii) —NH2,iii) —NH(alkyl),iv) —NH(acyl),iv) —NH—C(O)—O-alkyl,v) -cycloheteroalkyl,vi) —O(alkyl),vii) —O(acyl),viii) —O(C1-6alkyleneoxyacyl),ix) —O—C(O)—O-alkyl, andx) —S(alkyl), or b) when m is 1, ----- is a single-bond
b1) R16 is selected from the group consisting of
i) ═O,ii) ═NH, andiii) ═N(alkyl), andb2) R17 is selected from the group consisting of
i) —NH2,ii) —NH(alkyl),iii) —NH(acyl),iv) —NH—C(O)—O-alkyl, andv) -cycloheteroalkyl, and c) independent of the value of m, each bonding pair, W1----W2, W2----C, C----W4, W4----W3, and W3----W1, contained in the five-membered ring comprises a single or a double bond and
i) W1 is O, S, N, or CR14,ii) W2 is N or CR15,iii) W3 is C or N, andiv) W4 is C or N and where R14 and R15, if present, are independently selected from the group consisting of
i) hydrogen,ii) halo,iii) cyano,iv) —C(O)NH2,iv) C1-6alkyl,vii) vinyl, andviii) ethynyl. |
