N3 alkylated benzimidazole derivatives as MEK inhibitors

An amino acid prodrug of a compound of the formula

• and pharmaceutically accepted salts thereof, wherein:
• is an optional bond, provided that one and only one nitrogen of the ring is double-bonded;
• R1, R9 and R10 are independently selected from hydrogen, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, —OR3, —C(O)R3, —C(O)OR3, NR4C(O)OR6, —OC(O)R3, —NR4SO2R6, —SO2NR3R4, —NR4C(O)R3, —C(O)NR3R4, —NR5C(O)NR3R4, —NR5C(NCN)NR3R4, —NR3R4, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, —S(O)j(C1-C6 alkyl), —S(O)j(CR4R5)m-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclalkyl, —O(CR4R5)m-aryl, —NR4(CR4R5)m-aryl, —O(CR4R5)m-heteroaryl, —NR4(CR4R5)m-heteroaryl, —O(CR4R5)m-heterocyclyl or —NR4(CR4R5)m-heterocyclyl, where each alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl and heterocyclyl portion is optionally substituted with one to five groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, —NR4SO2R6, —SO2NR3R4, —C(O)R3, —C(O)OR3, —OC(O)R3, —NR4C(O)OR6, —NR4C(O)R3, —C(O)NR3R4, —NR3R4, —NR5C(O)NR3R4, —NR5C(NCN)NR3R4, —OR3, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl;
• R3 is selected from hydrogen, trifluoromethyl, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl, where each alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl and heterocyclyl portion optionally substituted with one to five groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, phosphate, amino acid residue, polypeptide, hemisuccinate, phosphate esters, dimethylaminoacetate, phosphoryloxymethyloxycarbonyl, phosphonamide, —NR′SO2R″″′, —SO2NR′R″, —C(O)R′, —C(O)OR′, —OC(O)R′, —NR′C(O)OR″″,—NR′C(O)R″, —C(O)NR′R″, —SR′, —S(O)R″″, —SO2R″″, —NR′R″, —NR′C(O)NR″R′″, —NR′C(NCN)NR″R′″, —OR′, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl,
• or R3 and R4 together with the atom to which they are attached form a 4 to 10 membered heteroaryl or heterocyclic ring, each of which is optionally substituted with one to three groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, —NR′SO2R″″, —SO2NR′R″, —C(O)R′, —C(O)OR′, —OC(O)R′, —NR′C(O)OR″″, —NR′C(O)R″, —C(O)NR′R″, —SO2R″″, —NR′R″, —NR′C(O)NR″R′″, —NR′C(NCN)NR″R′″, —OR′, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl;
• R′, R″ and R′″ independently are selected from hydrogen, lower alkyl, lower alkenyl, aryl and arylalkyl;
• R″″ is selected from alkyl, lower alkenyl, aryl and arylalkyl;
• or any two of R′, R″, R′″ or R″″ together with the atom to which they are attached form a 4 to 10 membered heteroaryl or heterocyclic ring, each of which is optionally substituted with one to three groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl;
• R4 and R5 independently represent hydrogen or C1-C6 alkyl, or
• R4 and R5 together with the atom to which they are attached form a 4 to 10 membered carbocyclic, heteroaryl or heterocyclic ring, each of which is optionally substituted with one to three groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, —NR′SO2R″″, —SO2NR′R″, —C(O)R′, —C(O)OR′, —OC(O)R′, —NR′C(O)OR″″, —NR′C(O)R″, —C(O)NR′R″, —SO2R″″, —NR′R″, —NR′C(O)NR″R′″, —NR′C(NCN)NR″R′″, —OR′, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl;
• R6 is selected from trifluoromethyl, C1-C10 alkyl, C3-C10 cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl, where each alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl portion is optionally substituted with one to five groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, —NR′SO2R″″,—SO2NR′R″, —C(O)R′, —C(O)OR′, —OC(O)R′, —NR′C(O)OR″″, —NR′C(O)R″, —C(O)NR′R″, —SO2R″″, —NR′R′, —NR′C(O)NR″R′″, —NR′C(NCN)NR″R′″, —OR′, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl;
• R7 is selected from hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl, where each alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl and heterocyclyl portion is optionally substituted with one to five groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, —NR4SO2R6, —SO2NR3R4, —C(O)R3, —C(O)OR3, —OC(O)R3, —NR4C(O)OR6, —NR4C(O)R3, —C(O)NR3R4, —SO2R6, —NR3R4, —NR5C(O)NR3R4, —NR5C(NCN)NR3R4, —OR3, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl;
• W is selected from heteroaryl, heterocyclyl, —C(O)OR3, —C(O)NR3R4, —C(O)NR4OR3, —C(O)(C3-C10 cycloalkyl), —C(O)(C1-C10 alkyl), —C(O)(aryl), —C(O)(heteroaryl) and —C(O)(heterocyclyl), each of which is optionally substituted with 1-5 groups independently selected from
• —NR3R4, —OR3, —R2, or C1-C10 alkyl, C2-C10 alkenyl, and C2-C10 alkynyl, each of which is optionally substituted with 1 or 2 groups independently selected from —NR3R4 and —OR3;
• R2 is hydrogen, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, —OR3, —C(O)R3, —C(O)OR3, NR4C(O)OR6, —OC(O)R3, —NR4SO2R6, —SO2NR3R4, —NR4C(O)R3, —C(O)NR3R4, —NR5C(O)NR3R4, —NR5C(NCN)NR3R4, —NR3R4, or C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, —S(O)j(C1-C6 alkyl), —S(O)j(CR4R5)m-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclalkyl, —O(CR4R5)m-aryl, —NR4(CR4R5)m-aryl, —O(CR4R5)m-heteroaryl, —NR4(CR4R5)m-heteroaryl, —O(CR4R5)m-heterocyclyl or —NR4(CR4R5)m-heterocyclyl, where each alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl and heterocyclyl portion is optionally substituted with one to five groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, —NR4SO2R6, —SO2NR3R4, —C(O)R3, —C(O)OR3, —OC(O)R3, —NR4C(O)OR6, —NR4C(O)R3, —C(O)NR3R4, —NR3R4, —NR5C(O)NR3R4, —NR5C(NCN)NR3R4, —OR3, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl;
• R8 is selected from hydrogen, —SCF3, —Cl, —Br, —F, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, —OR3, —C(O)R3, —C(O)OR3, —NR4C(O)OR6, —OC(O)R3, —NR4SO2R6, —SO2NR3R4, —NR4C(O)R3, —C(O)NR3R4, —NR5C(O)NR3R4, —NR3R4, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, —S(O)j(C1-C6 alkyl), —S(O)j(CR4C5)m-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, —O(CR4R5)m-aryl, —NR4(CR4R5)m-aryl, —O(CR4R5)m-heteroaryl, —NR4(CR4R5)m-heteroaryl, —O(CR4R5)m-heterocyclyl or —NR4(CR4R5)m-heterocyclyl, where each alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl and heterocyclyl portion is optionally substituted with one to five groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, —NR4SO2R6, —SO2NR3R4, —C(O)R3, —C(O)OR3, —OC(O)R3, —NR4C(O)OR6, —NR4C(O)R3, —C(O)NR3R4, —NR3R4, —NR5C(O)NR3R4, —NR5C(NCN)NR3R4, —OR3, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl;
• m is 0, 1, 2, 3, 4 or 5;
• and
• j is 1 or 2.