Imidazolyl derivatives

A compound of the formula (II),

• 3867
• the racemic-diastereomeric mixtures and optical isomers of said compound of formula (II), the pharmaceutically-acceptable salts or prodrugs thereof or a pharmaceutically acceptable salt of said prodrug, wherein
• — represents an optional bond;
• R1 is H, —(CH2)m—C(O)—(CH2)m-Z1, —(CH2)m-Z1, —(CH2)m—O-Z1 or —(C0-C6)alkyl-C(O)—NH—(CH2)m-Z3;
• Z1 is an optionally substituted moiety selected from the group consisting of (C1-C12)alkyl, benzo[b]thiophene, phenyl, naphthyl, benzo[b]furanyl, thiophene, isoxazolyl, indolyl,
• 3868
• R2 is H or (C1-C6)alkyl;
• or R1 and R2 are taken together with the nitrogen atoms to which they are attached to form a compound of formula (IIa), (IIb) or (IIc),
• 3869
• R3 is —(CH2)m-E-(CH2)m-Z2;
• E is O, S, —C(O)—, —C(O)—O—, —NH—C(O)—O—, —N(C1-C6)alkyl-C(O)—O— or a bond;
• Z2 is H, (C1-C12)alkyl, amino, (C1-C12)alkylamino, N,N-di-(C1-C12)alkylamino, (C1-C12)alkylguanidino, or an optionally substituted moiety selected from the group consisting of phenyl, indolyl, imidazolyl, thiophene, benzothiophene, pyridinyl and naphthyl;
• R4 is H or —(CH2)m-A1;
• A1 is —C(═Y)—N(X1X2), —C(═Y)—X2, —C(═NH)—X2 or X2;
• Y is O or S;
• X1 is H, (C1-C12)alkyl, —(CH2)m—NH—(C1-C6)alkyl, —(CH2)m—N-di-(C1-C6)alkyl or —(CH2)m-aryl;
• X2 is —(CH2)m—Y1—X3 or optionally substituted (C1-C12)alkyl;
• Y1 is O, S, NH, C═O, (C2-C12)alkenyl having one or more double bonds, —NH—CO—, —CO—NH—, —NH—CO—O—(CH2)m—, —C═C—, SO2 or a bond;
• X3 is H, an optionally substituted moiety selected from the group consisting of (C1-C12)alkyl, (C3-C8)cycloalkyl, (C1-C12)alkoxy, aryloxy, (C1-C12)alkylamino, N,N-di-(C1-C12)alkylamino, —CH-di-(C1-C12)alkoxy, pyrrolidinyl, pyridinyl, thiophene, imidazolyl, piperidinyl, piperazinyl, benzothiazolyl, furanyl, indolyl, morpholino, benzo[b]furanyl, quinolinyl, isoquinolinyl, —(CH2)m-phenyl, naphthyl, fluorenyl, phthalamidyl, pyrimidinyl,
• 3870
• 3871
• or X1 and X2 are taken together with the nitrogen to which they are attached to form an optionally substituted moiety selected from the group consisting of thiazolyl,
• 3872
• Y2 is CH—X4, N—X4, —C(X4X4), O or S;
• X4 for each occurrence is independently H or —(CH2)m—Y3—X5;
• Y3 is —C(O)—, —C(O)O— or a bond;
• X5 is hydroxy, (C1-C12)alkyl, amino, (C1-C12)alkylamino, N,N-di-(C1-C12)alkylamino, or an optionally substituted moiety selected from the group consisting of aryl, aryl(C1-C4)alkyl, furanyl, pyridinyl, indolyl, piperidinyl, —CH(phenyl)2,
• 3873
• R5 is (C1-C12)alkyl, (C0-C6)alkyl-C(O)—O-Z5, (C0-C6)alkyl-C(O)—NH—(CH2)m-Z3 or optionally substituted aryl:
• Z3 for each occurrence is independently amino, (C1-C12)alkylamino, amino(C1-C12)alkyl, (C5-C7)cycloalkylamino, amino(C5-C7)cycloalkyl, N—(C1-C12)alkylamino, N,N-di-(C1-C12)alkylamino, —NH—C(O)—O—(CH2)m-phenyl, —NH—C(O)—O—(CH2)m—(C1-C6)alkyl, —CH(phenyl)2, (C5-C7)cycloalkyl,
• 3874
• or an optionally substituted moiety selected from the group consisting of imidazolyl, pyridinyl, morpholino, piperidinyl, piperazinyl, pyrazolidinyl, furanyl, phenyl, indolyl and thiophene, provided that when m is 0 in the formula for R5 then Z3 is not —NH—C(O)—(CH2)m-phenyl or —NH—C(O)—(CH2)m—(C1-C6)alkyl;
• R6 is H or (C1-C6)alkyl;
• R7 is (C1-C12)alkyl or —(CH2)m-Z4;
• Z4 is an optionally substituted moiety selected from the group consisting of phenyl, naphthyl, indolyl, thiophene, benzo[b]furan, benzo[b]thiophene, isooxazolyl,
• 3875
• Z5 H, (C1-C12)alkyl, or —(CH2)m-aryl;
• wherein an optionally substituted moiety is optionally substituted by one or more substituents, each independently selected from the group consisting of Cl, F, Br, I, CF3, CN, N3, NO2, OH, SO2NH2, —OCF3, (C1-C12)alkoxy, —(CH2)m-phenyl-(X6)n, —S-phenyl-(X6n, —S—(C1-C12)alkyl, —O—(CH2)m-phenyl-(X6)n, —(CH2)m—C(O)—O—(C1-C6)alkyl, —(CH2)m—C(O)—(C1-C6)alkyl, —O—(CH2)m—NH2, —O—(CH2)m—NH—(C1-C6)alkyl, —O—(CH2)m—N-di-((C1-C8)alkyl), —(C0-C12)alkyl-(X6), and —(CH2)m-phenyl-X7;
• X6 for each occurrence is independently selected from the group consisting of hydrogen, Cl, F, Br, I, NO2, N3, CN, OH, —CF3, —OCF3, (C1-C12)alkyl, (C1-C12)alkoxy, —(CH2)m—NH2, —(CH2)m—NH—(C1-C6)alkyl, —(CH2)m—N-di-((C1-C6)alkyl) and —(CH2)m-phenyl;
• X7 is —NH—C(═NH·HI)—X8, wherein X8 is thiophene, (C1-C6)alkyl or phenyl;
• m for each occurrence is independently 0 or an integer from 1 to 6;
• and
• n for each occurrence is independently an integer from 1 to 5;
• provided that:
• (a) when R5 is (C1-C12)alkyl, or —C(O)—O-Z5 and Z5 is (C1-C12)alkyl or optionally substituted aryl;
• R6 is H or (C1-C6)alkyl;
• R7 is (C1-C12)alkyl or Z4 and Z4 is thiophene or optionally substituted phenyl, then R3 is not —C(O)—O—(CH2)m-Z where m is 0 and Z is H or (C1-C12)alkyl or where m is 1 to 6 and Z is H;
• (b) when R5 is (C1-C12)alkyl or optionally substituted phenyl;
• R6 is H or (C1-C6)alkyl;
• R7 is (C1-C12)alkyl and R3 is —O—(CH2)-Z2, then Z2 is not an optionally substituted moiety selected from the group consisting of phenyl, indolyl, imidazolyl, thiophene, benzothiophene, pyridinyl, and naphthyl;
• and
• (c) when R5 is H or (C1-C12)alkyl;
• R6 is (C1-C6)alkyl;
• R7 is (C1-C12)alkyl;
• and R3 is —O-Z2 or —S-Z2, then Z2 is not an optionally substituted moiety selected from the group consisting of phenyl, naphthyl, thiophene, benzothienyl and indolyl.