Gamma-hydroxy-2-(fluoroalkylaminocarbonyl)-1-piperazinepentanamides and uses thereof

A compound of formula:

• wherein
• R1 is aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
• wherein aryl is phenyl or naphthyl and heteroaryl is (i) a 5- or 6-membered aromatic ring consisting of carbon atoms and from 1 to 3 heteroatoms selected from N, S, and O or (ii) an 8- to 10-membered bicyclic ring system consisting of carbon atoms and from 1 to 3 heteroatoms selected from N, S, and O, wherein at least one of the rings in the bicyclic system is an aromatic ring;
• wherein
• (i) each of the substituents on substituted aryl is independently
• (a) halogen,
• (b) cyano,
• (c) hydroxy,
• (d) C1-C6 alkyl,
• (e) C2-C6 alkenyl,
• (f) C2-C6 alkynyl,
• (g) fluorinated C1-C6 alkyl,
• (h) C1-C6 alkoxy,
• (i) fluorinated C1-C6 alkoxy,
• (j) S—(C1-C6 alkyl),
• (k) heterocycle, or
• (l) heterocycle substituted with one or more substituents independently selected from halogen, cyano, hydroxy, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, S—(C1-C6 alkyl), and NRaRb;
• (ii) each of the substituents on substituted heteroaryl is independently
• (a) halogen,
• (b) cyano,
• (c) hydroxy,
• (d) NRaRb,
• (e) C1-C6 alkyl,
• (f) C2-C6 alkenyl,
• (g) C2-C6 alkynyl,
• (h) fluorinated C1-C6 alkyl,
• (i) C1-C6 alkoxy,
• (j) fluorinated C1-C6 alkoxy,
• (k) S—(C1-C6 alkyl),
• (l) phenyl,
• (m) phenyl substituted with one or more substituents independently selected from halogen, cyano, hydroxy, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, and S—(C1-C6 alkyl),
• (n) heterocycle, or
• (o) heterocycle substituted with one or more substituents independently selected from halogen, cyano, hydroxy, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, S—(C1-C6 alkyl), NRaRb, and a 5- or 6-member heteroaromatic ring consisting of carbon atoms and from 1 to 3 heteroatoms selected from N, O and S;
• wherein heterocycle in (i)(k), (i)(l), (ii)(n), or (ii)(o) is independently a 5- or 6-membered unsaturated monocyclic ring consisting of carbon atoms and from 1 to 3 heteroatoms selected from N, O, and S;
• R2 and R3 are each independently hydrogen or C1-C4 alkyl;
• or R2 and R3 together with the carbon to which they are attached form C3-C6 cycloalkyl;
• R4 is C1-C6 alkyl, C3-C6 cycloalkyl, aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
• wherein aryl is phenyl or naphthyl, and heteroaryl is selected from pyridyl, pyrazinyl, pyrimidinyl, thiophenyl, thiazolyl, pyridofuranyl, pyrimidofuranyl, pyridothienyl, pyridazothienyl, pyridooxazolyl, pyridazooxazolyl, pyrimidooxazolyl, pyridothiazolyl, and pyridazothiazolyl;
• and wherein each of the substituents on substituted aryl is independently halogen, cyano, hydroxy, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, fluorinated C1-C6 alkyl, or C1-C6 alkoxy;
• and each of the substituents on substituted heteroaryl is independently halogen, cyano, hydroxy, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy, or aryl;
• R5 is carbocyclic, substituted carbocyclic, heterocyclic or substituted heterocyclic, wherein carbocyclic is cyclopentyl, indanyl, or tetralin, and heterocyclic is chroman, thiochroman, or dioxoisothiochroman;
• wherein each of the substituents on substituted carbocyclic or substituted heterocyclic is independently halogen, hydroxy, C1-C6 alkyl, fluorinated C1-C6 alkyl, or C1-C6 alkoxy;
• R6 is fluorinated C1-C6 alkyl;
• and
• Ra and Rb are each independently hydrogen or C1-C4 alkyl;
• or Ra and Rb together with the nitrogen to which they are attached form C3-C6 azacycloalkyl;
• or a pharmaceutically acceptable salt thereof.