Modulators of the cholesterol biosynthetic pathway

A method of modulating cholesterol biosynthesis in a mammal by administering to said mammal a composition comprising:

• (a) a compound of formula (I):
• 186
• wherein:
• each Q is a monocyclic, bicyclic or tricyclic ring system wherein in said ring system:
• a. each ring is independently partially unsaturated or fully saturated;
• b. each ring comprises 3 to 7 ring atoms independently selected from C, N, O or S;
• c. no more than 4 ring atoms in Q are selected from N, O or S;
• d. any S is optionally replaced with S(O) or S(O)2;
• e. at least one ring comprises a N ring atom that is substituted with R1;
• and
• f. one to five hydrogen atoms in Q are optionally and independently replaced with halo, —OH, ═O, ═N—OR1, (C1-C6)-straight or branched alkyl, Ar-substituted-(C1-C6)-straight or branched alkyl, (C2-C6)-straight or branched alkenyl or alkynyl, Ar-substituted-(C2-C6)-straight or branched alkenyl or alkynyl, O—(C1-C6)-straight or branched alkyl, O-[(C1-C6)-straight or branched alkyl]-Ar, O—(C2-C6)-straight or branched alkenyl or alkynyl, O-[(C2-C6)-straight or branched alkenyl or alkynyl]-Ar, or O—Ar;
• wherein
• each R1 is independently selected from (C1-C6)-straight or branched alkyl, Ar-substituted-(C1-C6)-straight or branched alkyl, cycloalkyl-substituted-(C1-C6)-straight or branched alkyl, (C2-C6)-straight or branched alkenyl or alkynyl, or Ar-substituted-(C2-C6)-straight or branched alkenyl or alkynyl;
• wherein
• one to two CH2 groups of said alkyl, alkenyl, or alkynyl chains in R1 are optionally and independently replaced with O, S, S(O), S(O)2, C(O) or N(R2), wherein when R1 is bound to nitrogen, the CH2 group of R1 bound directly to said nitrogen cannot be replaced with C(O);
• Ar is selected from phenyl, 1-naphthyl, 2-naphthyl, indenyl, azulenyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyraxolyl, pyrazolinyl pyraolidinyl, isoxazolyl, isothiazolyl, 1,2,3-oxadiazolyl, 1,2,3-triazolyl, 1,3,4-thiadiazolyl, 1,2,4-triazolyl, 1,2,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,2,3-thiadiazolyl, benoxazolyl, pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, pyrazinyl, 1,3,5-triazinyl, 1,3,5-trithianyl, indolizinyl, indolyl, isoindolyl, 3H-indolyl, indolinyl, benzo[b]furanyl, benzo[b]thiophenyl, 1H-indazolyl, benzimidazolyl, benzthiazolyl, purinyl, 4H-quinolizinyl, quinolinyl, 1,2,3,4-tetrahydroisoquinolinyl, isoquinolinyl, 1,2,3,4-tetrahydroquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, or any other chemically feasible monocyclic or bicyclic ring system, wherein each ring consists of 5 to 7 ring atoms and wherein each ring comprises 0 to 3 heteroatoms independently selected from N, O, or S, wherein
• each Ar is optionally and independently substituted with one to three substituents selected from halo, hydroxy, nitro, —SO3H, ═O, trifluoromethyl, trifluoromethoxy, (C1-C6)-straight or branched alkyl, (C1-C6)-straight or branched alkenyl, O-[(C1-C6)-straight or branched alkyl], O-[(C1-C6)-straight or branched alkenyl], O-benzyl, O-phenyl, 1,2-methylenedioxy, —N(R3) (R4), carboxyl, N-(C1-C6-straight or branched alkyl or C2-C6-straight or branched alkenyl) carboxamides, N,N-di-(C1-C6-straight or branched alkyl or C2-C6-straight or branched alkenyl) carboxamides, N-(C1-C6-straight or branched alkyl or C2-C6-straight or branched alkenyl) sulfonamides, or N,N-di-(C1-C6-straight or branched alkyl or C2-C6-straight or branched alkenyl) sulfonamides;
• each of R3 and R4 are independently selected from (C1-C6)-straight or branched alkyl, (C2-C6)-straight or branched alkenyl or alkynyl, hydrogen, phenyl or benzyl;
• or wherein R3 and R4 are taken together with the nitrogen atom to which they are bound to form a 5-7 membered heterocyclic ring;
• R2 is selected from hydrogen, (C1-C6)-straight or branched alkyl, or (C2-C6)-straight or branched alkenyl or alkynyl;
• X is selected from C, N(R2), N, O, S, S(O), or S(O)2
• Y is selected from a bond, —O—, (C1-C6)-straight or branched) alkyl, or (C2-C6)-straight or branched) alkenyl or alkynyl;
• wherein Y is bonded to the depicted ring via a single bond or a double bond;
• and wherein one to two of the CH2 groups of said alkyl, alkenyl, or alkynyl is optionally and independently replaced with O, S, S(O), S(O)2, C(O) or N(R);
• p is 0, 1 or 2;
• each of A and B is independently selected from hydrogen or Ar;
• and
• wherein two carbon ring atoms in the depicted ring structure may be linked to one another via a C1-C4 straight alkyl or a C2-C4 straight alkenyl to create a bicyclic moiety;
• and
• (b) a pharmaceutically acceptable carrier.