The present invention relates to small molecule compounds and their use as HDAC inhibitors and in the treatment of various diseases, such as cancer. The present invention further relates to methods of synthesizing the compounds and methods of treatment. H-L(HA), H is a head group selected from (head group 1), (head group 2), (head group 3), (head group 4), (head group 5) and (head group 6).

##STR00001##

The present invention relates to processes for the preparation of (R)-1-(5-chloro-[1,1-biphenyl]-2-yl)-2,2,2-trifluoroethanol, 1-(5-chloro-[1,1-biphenyl]-2-yl)-2,2,2-trifluoroethanone, and intermediates thereof, which are useful in the preparation of inhibitors of TPH1 for the treatment of, for example, gastrointestinal, cardiovascular, pulmonary, inflammatory, metabolic, low bone mass diseases, serotonin syndrome, and cancer.

Compounds of formula I are provided: ##STR00001##
R.sub.1 is an alkoxy or O(CH.sub.2).sub.pX, p is an integer from 2 to 3 and X is OH, NH.sub.2, or CO.sub.2H, m is an integer from 0 to 5, n is an integer from 0 to 5, each R.sub.2 is independently selected from hydrogen, alkenyl, hydroxyalkyl, alkoxymethyl, heterocyclyl, hetereocyclylmethyl, amino, amido, hydroxamido, any of which may be optionally substituted with one or more of acyl, alkyl, alkoxy, hydroxyalkyl, or halogen, each R.sub.3 is independently selected from hydrogen, halogen, alkyl, alkenyl, carboxy, hydroxymethyl, amido, and at least one of R.sub.2 and R.sub.3 is not hydrogen.

Compounds of formula I are provided: ##STR00001##
R.sub.1 is an alkoxy or O(CH.sub.2).sub.pX, p is an integer from 2 to 3 and X is OH, NH.sub.2, or CO.sub.2H, m is an integer from 0 to 5, n is an integer from 0 to 5, each R.sub.2 is independently selected from hydrogen, alkenyl, hydroxyalkyl, alkoxymethyl, heterocyclyl, hetereocyclylmethyl, amino, amido, hydroxamido, any of which may be optionally substituted with one or more of acyl, alkyl, alkoxy, hydroxyalkyl, or halogen, each R.sub.3 is independently selected from hydrogen, halogen, alkyl, alkenyl, carboxy, hydroxymethyl, amido, and at least one of R.sub.2 and R.sub.3 is not hydrogen.

The invention relates to 18-20 member bi-polycyclic compounds, methods of making these compounds, and methods of using them in treating hyperproliferative disorders (e.g., cancer) and non-malignant tumors; promoting muscle formation; inhibiting muscle degeneration or the loss of muscle mass or muscle function; and myofibers ex vivo.

The invention relates to 18-20 member bi-polycyclic compounds, methods of making these compounds, and methods of using them in treating hyperproliferative disorders (e.g., cancer) and non-malignant tumors; promoting muscle formation; inhibiting muscle degeneration or the loss of muscle mass or muscle function; and myofibers ex vivo.

The present invention relates to processes for the preparation of (R)-1-(5-chloro-[1,1-biphenyl]-2-yl)-2,2,2-trifluoroethanol, 1-(5-chloro-[1,1-biphenyl]-2-yl)-2,2,2-trifluoroethanone, and intermediates thereof, which are useful in the preparation of inhibitors of TPH1 for the treatment of, for example, gastrointestinal, cardiovascular, pulmonary, inflammatory, metabolic, low bone mass diseases, serotonin syndrome, and cancer.

The present invention relates to processes for the preparation of (R)-1-(5-chloro-[1,1-biphenyl]-2-yl)-2,2,2-trifluoroethanol, 1-(5-chloro-[1,1-biphenyl]-2-yl)-2,2,2-trifluoroethanone, and intermediates thereof, which are useful in the preparation of inhibitors of TPH1 for the treatment of, for example, gastrointestinal, cardiovascular, pulmonary, inflammatory, metabolic, low bone mass diseases, serotonin syndrome, and cancer.

This invention provides a compound having the structure:

##STR00001## wherein R.sub.1 is H, halogen, NR.sub.5R.sub.6, NR.sub.5C(0)-R.sub.6, NHC(O)OR.sub.7, OR.sub.7, NO.sub.2, CN, SR.sub.7, SO.sub.2R.sub.7, CO.sub.2R.sub.7, CF.sub.3, SOR.sub.7, POR.sub.7, C(S)R.sub.7, C(O)NR.sub.5R.sub.6, CH.sub.2C(O)NR.sub.5R.sub.6, C(NR.sub.5)R.sub.6, P(O)(OR.sub.5)(OR.sub.6), P(OR.sub.5)(OR.sub.6), C(S)R.sub.7, C.sub.1-5 alkyl, C.sub.2-5 alkenyl, C.sub.2-5 alkynyl, aryl, heteroaryl, or heterocyclyl, wherein R.sub.5, R.sub.6, and R.sub.7 and are each, independently, H, C.sub.1-5 alkyl, C.sub.2-5 alkenyl, C.sub.2-5 alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; m is an integer from 0 to 2; R.sub.2 and R.sub.3 are each, independently, H, halogen, NH.sub.2, CX.sub.3, C(O)OR.sub.8, C(O)R.sub.8, C(O)NR.sub.9R.sub.10, C.sub.1-10 alkyl, C.sub.2-10 alkenyl, C.sub.2-10 alkynyl, heteroalkyl, aryl, heteroaryl, or heterocyclyl; wherein X is Cl, Br, or F; R.sub.8, R.sub.9 and R.sub.10 are each, independently, H, C.sub.1-5 alkyl, C.sub.2-5 alkenyl, C.sub.2-5 alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; Q is Ar.sub.1Z or ZAr.sub.1Z, wherein Ar.sub.1 is aryl or heteroaryl; and each occurrence of Z is independently present or absent, and when present is O, S, CH.sub.2, C(O), NH, NHNH, NHC(O), C(O)NH, NHC(O)CH.sub.2NH, NHC(O)CH.sub.2C(O), N(OH), CH.sub.2CH.sub.2 or NHC(O)CHCH; and R.sub.4 is alkyl, OR.sub.11 or NHOR.sub.11, wherein R.sub.11 is H, C.sub.1-10 alkyl, C.sub.2-10 alkenyl, C.sub.2-10 alkynyl, aryl, heteroaryl, or heterocyclyl, and when Q is Ar.sub.1Z, Z is absent, Ar.sub.1 is phenyl, R.sub.2 and R.sub.3 are H, n=1, and R.sub.4 is NHOH, then R.sub.1 is other than carbazole, tetrahydro--carboline, tetrahydro--carboline, C(O)NR.sub.5R.sub.6 and NR.sub.5C(0)-R.sub.6, wherein one of R.sub.5 or R.sub.6 is quinline and the other of R.sub.5 or R.sub.6 is H;
or a pharmaceutically acceptable salt thereof.

This invention provides a compound having the structure:

##STR00001## wherein R.sub.1 is H, halogen, NR.sub.5R.sub.6, NR.sub.5C(0)-R.sub.6, NHC(O)OR.sub.7, OR.sub.7, NO.sub.2, CN, SR.sub.7, SO.sub.2R.sub.7, CO.sub.2R.sub.7, CF.sub.3, SOR.sub.7, POR.sub.7, C(S)R.sub.7, C(O)NR.sub.5R.sub.6, CH.sub.2C(O)NR.sub.5R.sub.6, C(NR.sub.5)R.sub.6, P(O)(OR.sub.5)(OR.sub.6), P(OR.sub.5)(OR.sub.6), C(S)R.sub.7, C.sub.1-5 alkyl, C.sub.2-5 alkenyl, C.sub.2-5 alkynyl, aryl, heteroaryl, or heterocyclyl, wherein R.sub.5, R.sub.6, and R.sub.7 and are each, independently, H, C.sub.1-5 alkyl, C.sub.2-5 alkenyl, C.sub.2-5 alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; m is an integer from 0 to 2; R.sub.2 and R.sub.3 are each, independently, H, halogen, NH.sub.2, CX.sub.3, C(O)OR.sub.8, C(O)R.sub.8, C(O)NR.sub.9R.sub.10, C.sub.1-10 alkyl, C.sub.2-10 alkenyl, C.sub.2-10 alkynyl, heteroalkyl, aryl, heteroaryl, or heterocyclyl; wherein X is Cl, Br, or F; R.sub.8, R.sub.9 and R.sub.10 are each, independently, H, C.sub.1-5 alkyl, C.sub.2-5 alkenyl, C.sub.2-5 alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; Q is Ar.sub.1Z or ZAr.sub.1Z, wherein Ar.sub.1 is aryl or heteroaryl; and each occurrence of Z is independently present or absent, and when present is O, S, CH.sub.2, C(O), NH, NHNH, NHC(O), C(O)NH, NHC(O)CH.sub.2NH, NHC(O)CH.sub.2C(O), N(OH), CH.sub.2CH.sub.2 or NHC(O)CHCH; and R.sub.4 is alkyl, OR.sub.11 or NHOR.sub.11, wherein R.sub.11 is H, C.sub.1-10 alkyl, C.sub.2-10 alkenyl, C.sub.2-10 alkynyl, aryl, heteroaryl, or heterocyclyl, and when Q is Ar.sub.1Z, Z is absent, Ar.sub.1 is phenyl, R.sub.2 and R.sub.3 are H, n=1, and R.sub.4 is NHOH, then R.sub.1 is other than carbazole, tetrahydro--carboline, tetrahydro--carboline, C(O)NR.sub.5R.sub.6 and NR.sub.5C(0)-R.sub.6, wherein one of R.sub.5 or R.sub.6 is quinline and the other of R.sub.5 or R.sub.6 is H;
or a pharmaceutically acceptable salt thereof.