This invention relates to the use of cyclopropylamine derivatives for the modulation, notably the inhibition of the activity of Lysine-specific demethylase 1 (LSD1). Suitably, the present invention relates to the use of cyclopropylamines in the treatment of cancer.

This invention relates to the use of cyclopropylamine derivatives for the modulation, notably the inhibition of the activity of Lysine-specific demethylase 1 (LSD1). Suitably, the present invention relates to the use of cyclopropylamines in the treatment of cancer.

The present invention is directed to processes for preparing beta 3 agonists of Formula (I) and Formula (II) and their intermediates. The beta 3 agonists are useful in the treatment of certain disorders, including overactive bladder, urinary incontinence, and urinary urgency.

The present invention is directed to processes for preparing beta 3 agonists of Formula (I) and Formula (II) and their intermediates. The beta 3 agonists are useful in the treatment of certain disorders, including overactive bladder, urinary incontinence, and urinary urgency.

The invention provides for compounds of formula I: wherein Z is absent or (CR.sub.AR.sub.B).sub.nW; each RA and RB is independently (i) H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, haloalkyl, each of which may be optionally substituted; (ii) OH, ORc, NH2, NHR.sub.c, NR.sub.cR.sub.c, SH, S(O).sub.mR.sub.c; or (iii) R.sub.A and R.sub.B together form C(O); W is absent, C(O), C(O)O, C(O)NR.sub.cR.sub.c, O, S(O).sub.m, or NR.sub.cR.sub.c; Y is an optionally substituted heterocyclic, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted aryl, or NR.sub.XR.sub.Y; wherein R.sub.x and R.sub.y are each independently H, alkyl or aryl; X.sup.1 is selected from the group consisting of halogen, methyl, and hydroxyl; X2 is a halogen; each R.sub.c is independently alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, or heteroaralkyl, each of which may be optionally substituted; m is O, 1, or 2; and n is 1, 2, 3, 4, 5, or 6; and pharmaceutically acceptable salts thereof. ##STR00001##

The invention provides for compounds of formula I: wherein Z is absent or (CR.sub.AR.sub.B).sub.nW; each RA and RB is independently (i) H, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, haloalkyl, each of which may be optionally substituted; (ii) OH, ORc, NH2, NHR.sub.c, NR.sub.cR.sub.c, SH, S(O).sub.mR.sub.c; or (iii) R.sub.A and R.sub.B together form C(O); W is absent, C(O), C(O)O, C(O)NR.sub.cR.sub.c, O, S(O).sub.m, or NR.sub.cR.sub.c; Y is an optionally substituted heterocyclic, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted aryl, or NR.sub.XR.sub.Y; wherein R.sub.x and R.sub.y are each independently H, alkyl or aryl; X.sup.1 is selected from the group consisting of halogen, methyl, and hydroxyl; X2 is a halogen; each R.sub.c is independently alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, aralkyl, or heteroaralkyl, each of which may be optionally substituted; m is O, 1, or 2; and n is 1, 2, 3, 4, 5, or 6; and pharmaceutically acceptable salts thereof. ##STR00001##

The present invention is directed to a compound represented by Structural Formula (A):

##STR00001##

or a pharmaceutically acceptable salt thereof. The variables for Structural Formula (A) are defined herein. Also described is a pharmaceutical composition comprising the compound of Structural Formula (A) and its therapeutic use.

The present invention is directed to a compound represented by Structural Formula (A):

##STR00001##

or a pharmaceutically acceptable salt thereof. The variables for Structural Formula (A) are defined herein. Also described is a pharmaceutical composition comprising the compound of Structural Formula (A) and its therapeutic use.

Compositions and methods are disclosed that relate to small molecule lipopeptidomimetic inhibitors of mammalian ghrelin O-acyl transferase (GOAT). Compounds of general Formula (I) and substructures thereof, i.e., Formulae (II), (IIa), (IIa1), (IIa2), (IIb), (IIb1), (IIb2), (IIc) and (III), are shown to exhibit potent inhibition of the octanoylation of ghrelin peptide, where the resulting non-octanoylated (des-acyl) form of ghrelin lacks GHSr ligand activity that is associated with weight gain and insulin resistance. These and related embodiments will find uses for treating subjects known to have, or suspected of being at risk for having, a condition that would benefit from a decreased level of acylated ghrelin peptide, such as type II diabetes, impaired glucose tolerance, insulin resistance, Prader-Willi syndrome (PWS) and obesity.

Compositions and methods are disclosed that relate to small molecule lipopeptidomimetic inhibitors of mammalian ghrelin O-acyl transferase (GOAT). Compounds of general Formula (I) and substructures thereof, i.e., Formulae (II), (IIa), (IIa1), (IIa2), (IIb), (IIb1), (IIb2), (IIc) and (III), are shown to exhibit potent inhibition of the octanoylation of ghrelin peptide, where the resulting non-octanoylated (des-acyl) form of ghrelin lacks GHSr ligand activity that is associated with weight gain and insulin resistance. These and related embodiments will find uses for treating subjects known to have, or suspected of being at risk for having, a condition that would benefit from a decreased level of acylated ghrelin peptide, such as type II diabetes, impaired glucose tolerance, insulin resistance, Prader-Willi syndrome (PWS) and obesity.