HIV protease inhibitors

A pharmaceutical composition comprising:

• (a) an active ingredient that is:
• (i) a compound of the formula:
• wherein:
• Q1 and Q2 are each independently selected from hydrogen and substituted and unsubstituted alkyl and aryl;
• Q3 is selected from mercapto and substituted and unsubstituted alkoxyl, aryloxyl, thioether, amino, alkyl, cycloalkyl, saturated and partially saturated heterocycle, and aryl;
• Q4, Q5, Q6, Q7, and Q8 are each independently selected from hydrogen, hydroxyl, mercapto, nitro, halogen, —O-J, where J is a substituted or unsubstituted hydrolyzable group, said substituted and unsubstituted alkoxyl, aryloxyl, thioether, sulfinyl, sulfonyl, amino, alkyl, cycloalkyl, saturated and partially saturated heterocycle, aryl, and L6C(O)L4, where L6 is a single bond, —O or —N, and further where L4 is alkyl, hydroxyl, alkoxyl or hydrogen;
• and further wherein any one or more of Q4, Q5, Q6, Q7, and Q8 may be a member of a spiro ring, and any two of Q4, Q5, Q6, Q7, and Q8 may together be members of a ring;
• E is carbon or nitrogen;
• Q9 is selected from hydrogen, halogen, hydroxyl, mercapto, and substituted and unsubstituted alkoxyl, aryloxyl, thioether, amino, alkyl, and aryl, where Q9 may form part of a ring, wherein when Q9 is thioether, Q9 is selected from substituted and unsubstituted S-alkyl, S-(C5-C7)-cycloalkyl, S-aryl, and S-heterocycle, and wherein said S-heterocycle is selected from decahydroisoquinolinyl, octahydro-thieno[3,2-c]pyridinyl, piperidinyl, piperazinyl, azepinyl, pyrrolyl, pyrrolidinyl, pyrazolyl, pyrazolidinyl, imidazolyl, isobenzofuranyl, furazanyl, imidazolinyl, imidazolidinyl, pyrazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolidinyl, isoxazolyl, thianthrenyl, triazinyl, isoxazolidinyl, morpholinyl, thiazolyl, thiazolidinyl, isothiazolyl, quinuclidinyl, isothiazolidinyl, indolyl, quinolinyl, chromenyl, xanthenyl, isoquinolinyl, benzimidazolyl, thiadiazolyl, benzopyranyl, benzothiazolyl, benzoazolyl, furyl, tetrahydrofuryl, tetrahydropyranyl, thienyl, benzothienyl, benzo[b]thienyl, naptho[2,3-b]thienyl, thiamorpholinyl, thiamorpholinylsulfoxide, thiamorpholinylsulfone, oxadiazolyl, triazolyl, tetrahydroquinolinyl, tetrahydrisoquinolinyl, phenoxathienyl, indolizinyl, isoindolyl, indazolyl, purinyl, isoquinolyl, quinolyl, phthalazinyl, naphthyridinyl, quinoxyalinyl, quinzolinyl, tetrahydroquinolinyl, cinnolinyl, pteridinyl, carbazolyl, beta-carbolinyl, phenanthridinyl, acridinyl, perimidinyl, phenanthrolinyl, phenazinyl, isothiazolyl, phenothiazinyl, and phenoxazinyl;
• is a monocyclic or polycyclic carbocycle or heterocycle, which is optionally further substituted, and when
• is heterocycle, each heterocyclic ring has one to three heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• and
• is a 6-membered monocyclic heterocycle optionally having one or two additional heteroatoms independently selected from nitrogen, oxygen and sulfur, which is optionally further substituted;
• or
• (ii) a prodrug or pharmaceutically acceptable salt of said compound;
• and
• (b) a pharmaceutically acceptable carrier.

A method of inhibiting HIV protease, comprising administering to a host an effective amount of:

• a compound of the formula:
• wherein:
• Q1 and Q2 are each independently selected from hydrogen and substituted and unsubstituted alkyl and aryl;
• Q3 is selected from mercapto and substituted and unsubstituted alkoxyl, aryloxyl, thioether, amino, alkyl, cycloalkyl, saturated and partially saturated heterocycle, and aryl;
• Q4, Q5, Q6, Q7, and Q8 are each independently selected from hydrogen, hydroxyl, mercapto, nitro, halogen, —O-J, where J is a substituted or unsubstituted hydrolyzable group, and substituted or unsubstituted alkoxyl, aryloxyl, thioether, sulfinyl, sulfonyl, amino, alkyl, cycloalkyl, saturated and partially saturated heterocycle, aryl, and L6C(O)L4, where L6 is a single bond, —O or —N, and further where L4 is alkyl, hydroxyl, alkoxyl or hydrogen;
• and further wherein any one or more of Q4, Q5, Q6, Q7, and Q8 may be a member of a spiro ring, and any two of Q4, Q5, Q6, Q7, and Q8 may together be members of a ring;
• E is carbon or nitrogen;
• Q9 is selected from hydrogen, halogen, hydroxyl, mercapto, and substituted and unsubstituted alkoxyl, aryloxyl, thioether, amino, alkyl, and aryl, where Q9 may form part of a ring, wherein when Q9 is thioether, Q9 is selected from substituted and unsubstituted S-alkyl, S-(C5-C7)-cycloalkyl, S-aryl, and S-heterocycle, and wherein said S-heterocycle is selected from decahydroisoquinolinyl, octahydro-thieno[3,2-c]pyridinyl, piperidinyl, piperazinyl, azepinyl, pyrrolyl, pyrrolidinyl, pyrazolyl, pyrazolidinyl, imidazolyl, isobenzofuranyl, furazanyl, imidazolinyl, imidazolidinyl, pyrazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolidinyl, isoxazolyl, thianthrenyl, triazinyl, isoxazolidinyl, morpholinyl, thiazolyl, thiazolidinyl, isothiazolyl, quinuclidinyl, isothiazolidinyl, indolyl, quinolinyl, chromenyl, xanthenyl, isoquinolinyl, benzimidazolyl, thiadiazolyl, benzopyranyl, benzothiazolyl, benzoazolyl, furyl, tetrahydrofuryl, tetrahydropyranyl, thienyl, benzothienyl, benzo[b]thienyl, naphtho[2,3-b]thienyl, thiamorpholinyl, thiamorpholinylsulfoxide, thiamorpholinylsulfone, oxadiazolyl, triazolyl, tetrahydroquinolinyl, tetrahydrisoquinolinyl, phenoxathienyl, indolizinyl, isoindolyl, indazolyl, purinyl, isoquinolyl, quinolyl, phthalazinyl, naphthyridinyl, quinoxyalinyl, quinzolinyl, tetrahydroquinolinyl, cinnolinyl, pteridinyl, carbazolyl, beta-carbolinyl, phenanthridinyl, acridinyl, perimidinyl, phenanthrolinyl, phenazinyl, isothiazolyl, phenothiazinyl, and phenoxazinyl;
• is a monocyclic or polycyclic carbocycle or heterocycle, which is optionally further substituted, and when
• is heterocycle, each heterocyclic ring has one to three heteroatoms independently selected from nitrogen, oxygen, and sulfur;
• and
• is a 6-membered monocyclic heterocycle optionally having one or two additional heteroatoms independently selected from nitrogen, oxygen and sulfur, which is optionally further substituted;
• or a prodrug or pharmaceutically acceptable salt of said compound.