Quinazolines useful as modulators of voltage gated ion channels

A compound of formula IA or formula IB:

• or a pharmaceutically acceptable salt or derivative thereof, wherein:
• z is 0-3;
• RYZ is C1-C6 aliphatic group, optionally substituted with W4 independent occurrences of —R14, wherein W4 is 0-3;
• wherein up to two methylene units in RYZ are optionally replaced with —NR—, —O—, —COO, —OCO—, —NRCO—, —CONR—, —SO2NR—, or —NRSO2—;
• x and y, each, is independently 0-4;
• W is halo, —ORXY, —CHF2, or —CF3;
• RXY is hydrogen or a group selected from:
• wherein:
• each of wA, wB, wC, and wD is independently 0 or 1;
• each M is independently selected from hydrogen, Li, Na, K, Mg, Ca, Ba, —N(R7)4, —C1-C12-alkyl, C2-C12-alkenyl, or —R6;
• wherein 1 to 4-CH2 radicals of the alkyl or alkenyl group, other than the —CH2 that is bound to Z, is optionally replaced by a heteroatom group selected from O, S, S(O), S(O2), or N(R7);
• and wherein any hydrogen in said alkyl, alkenyl or R6 is optionally replaced with a substituent selected from oxo, —OR7, —R7, —N(R7)2, —N(R7)3, —R7OH, —CN, —CO2R7, —C(O)—N(R7)2, S(O)2—N(R7)2, N(R7)—C(O)—R7, C(O)R7, —S(O)n—R7, OCF3, —S(O)n—R6, —N(R7)—S(O)2(R7), halo, —CF3, or —NO2;
• n is 0-2;
• M′ is H, —C1-C12-alkyl, —C2-C12-alkenyl, or —R6;
• wherein 1 to 4-CH2 radicals of the alkyl or alkenyl group is optionally replaced by a heteroatom group selected from O, S, S(O), S(O2), or N(R7);
• and wherein any hydrogen in said alkyl, alkenyl or R6 is optionally replaced with a substituent selected from oxo, —OR7, —R7, —N(R7)2, —N(R7)3, —R7OH, —CN, —CO2R7, —C(O)—N(R7)2, —S(O)2—N(R7)2, —N(R7)—C(O)—R7, —C(O)R7, —S(O)n—R7, —OCF3, —S(O)n—R6, —N(R7)—S(O)2(R7), halo, —CF3, or —NO2;
• Z is —CH2—, —O—, —S—, —N(R7)2—;
• or,
• when M is absent, then Z is hydrogen, ═O, or ═S;
• Y is P or S, wherein when Y is S, then Z is not S;
• X is O or S;
• each R7 is independently selected from hydrogen, or C1-C4 aliphatic, optionally substituted with up to two Q1;
• each Q1 is independently selected from a 3-7 membered saturated, partially saturated or unsaturated carbocyclic ring system;
• or a 5-7 membered saturated, partially saturated or unsaturated heterocyclic ring containing one or more heteroatom or heteroatom group selected from O, N, NH, S, SO, or SO2;
• wherein Q1 is optionally substituted with up to three substituents selected from oxo, —OH, —O(C1-C4 aliphatic), —C1-C4 aliphatic, —NH2, —NH(C1-C4 aliphatic), —N(C1-C4 aliphatic)2, —N(C1-C4 aliphatic)-C(O)—C1-C4 aliphatic, —(C1-C4 aliphatic)-OH, —CN, —CO2H, —CO2(C1-C4 aliphatic), —C(O)—NH2, —C(O)—NH(C1-C4 aliphatic), —C(O)—N(C1-C4 aliphatic)2, halo or —CF3;
• R6 is a 5-6 membered saturated, partially saturated or unsaturated carbocyclic or heterocyclic ring system, or an 8-10 membered saturated, partially saturated or unsaturated bicyclic ring system;
• wherein any of said heterocyclic ring systems contains one or more heteroatoms selected from O, N, S, S(O)n or N(R7);
• and wherein any of said ring systems optionally contains 1 to 4 substituents independently selected from —OH, —C1-C4 alkyl, —O—C1-C4 alkyl or —O—C(O)—C1-C4 alkyl;
• R9 is C(R7)2, O or N(R7);
• each occurrence of R14, R3, R4, and R5 is independently Q-Rx;
• wherein Q is a bond or is a C1-C6 alkylidene chain wherein up to two non-adjacent methylene units of Q are optionally and independently replaced by —NR—, —S—, —O—, —CS—, —CO2—, —OCO—, —CO—, —COCO—, —CONR—, —NRCO—, —NRCO2—, —SO2NR—, —NRSO2—, —CONRNR—, —NRCONR—, —OCONR—, —NRNR—, —NRSO2NR—, —SO—, —SO2—, —PO—, —PO2—, —OP(O)(OR)—, or —POR—;
• and each occurrence of Rx is independently selected from —R′, halogen, ═NR′, —NO2, —CN, —OR′, —SR′, —N(R′)2, —NR′COR′, —NR′CON(R′)2, —NR′CO2R′, —COR′, —CO2R′, —OCOR′, —CON(R′)2, —OCON(R′)2, —SOR′, —SO2R′, —SO2N(R′)2, —NR′SO2R′, —NR′SO2N(R′)2, —COCOR′, —COCH2COR′, —OP(O)(OR′)2, —P(O)(OR′)2, —OP(O)2OR′, —P(O)2OR′, —PO(R′)2, or —OPO(R′)2;
• and
• each occurrence of R is independently hydrogen or C1-C6 aliphatic group having up to three substituents;
• and each occurrence of R′ is independently hydrogen, a C1-C6 aliphatic group, a 3-8-membered saturated, partially unsaturated, or fully unsaturated monocyclic ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-12 membered saturated, partially unsaturated, or fully unsaturated bicyclic ring system having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur wherein R′ has up to four substituents, or R and R′, two occurrences of R, or two occurrences of R′, are taken together with the atom(s) to which they are bound to form a 3-12 membered saturated, partially unsaturated, or fully unsaturated monocyclic or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
• provided that the following compounds are excluded:
• carbamic acid, [(3R)-1-[2-(2-hydroxyphenyl)-7-methyl-4-quinazolinyl]-3-pyrrolidinyl]-, phenylmethyl ester;
• carbamic acid, [(3R)-1-[2-(2-hydroxyphenyl)-7-methyl-4-quinazolinyl]-3-pyrrolidinyl]-, phenylmethyl ester, monohydrochloride;
• carbamic acid, [(3S)-1-[2-(2-hydroxyphenyl)-7-methyl-4-quinazolinyl]-3-pyrrolidinyl]-, 1,1-dimethylethyl ester;
• carbamic acid, [(3R)-1-[2-(2-hydroxyphenyl)-7-methyl-4-quinazolinyl]-3-pyrrolidinyl]-, 1,1-dimethylethyl ester;
• carbamic acid, [(3R)-1-[6-fluoro-2-(2-hydroxyphenyl)-4-quinazolinyl]-3-pyrrolidinyl]-, 1,1-dimethylethyl ester;
• carbamic acid, [(3R)-1-[2-(2-fluoro-6-hydroxyphenyl)-7-methyl-4-quinazolinyl]-3-pyrrolidinyl]-, 1,1-dimethylethyl ester;
• carbamic acid, [(3R)-1-[2-(2-hydroxyphenyl)-7-methyl-4-quinazolinyl]-3-pyrrolidinyl]-, 3-pyridinylmethyl ester, trifluoroacetate (salt);
• carbamic acid, [(3R)-1-[2-(2-hydroxyphenyl)-7-methyl-4-quinazolinyl]-3-pyrrolidinyl]-, 4-pyridinylmethyl ester, trifluoroacetate (salt);
• carbamic acid, [(3R)-1-[2-(2-hydroxyphenyl)-7-methyl-4-quinazolinyl]-3-pyrrolidinyl]-, 1,3-benzodioxol-4-ylmethyl ester, trifluoroacetate (salt);
• carbamic acid, [(3R)-1-[6-fluoro-2-(2-hydroxyphenyl)-4-quinazolinyl]-3-pyrrolidinyl]-, (tetrahydro-2H-pyran-2-yl)methyl ester, trifluoroacetate (salt);
• and
• carbamic acid, [(3R)-1-[2-(2-hydroxyphenyl)-7-methyl-4-quinazolinyl]-3-pyrrolidinyl]-, (tetrahydro-2H-pyran-2-yl)methyl ester.