Obesity can be viewed as an energy balance disorder, arising when energy input exceeds energy output, with most of the excess calories converted into triglycerides and stored in the adipose tissue. Medications currently approved for the treatment of obesity attempts to restore energy balance primarily by decreasing energy input by either suppressing appetite or interfering with lipid absorption in the small intestine. Because of the rapid increase in the prevalence of obesity worldwide and the lack of efficacy of current medical therapies, novel pharmacologic therapies for obesity are required.
One potential therapeutic strategy involves inhibiting triglyceride synthesis. Although triglycerides are essential for normal physiology, excess triglyceride accumulation results in obesity and, particularly when it occurs in nonadipose tissues, is associated with insulin resistance. DGAT is an enzyme that catalyzes the last step in triacylglycerol biosynthesis. DGAT catalyzes the coupling of a 1,2-diacylglycerol with a fatty acyl-CoA resulting in Coenzyme A and triacylglycerol. Two enzymes that display DGAT activity have been identified: DGAT1 (acyl coA-diacylglycerol acyl transferase 1, see Cases et al, Proc. Natl. Acad. Sci. 95:13018-13023, 1998) and DGAT2 (acyl coA-diacylglycerol acyl transferase 2, see Cases et al, J. Biol. Chem. 276:38870-38876, 2001). DGAT1 and DGAT2 do not share significant protein sequence homology. Importantly, DGAT1 knockout mice are protected from high fat diet-induced weight gain and insulin resistance (Smith et al, Nature Genetics 25:87-90, 2000). The phenotype of the DGAT1 knockout mice suggest that a DGAT1 inhibitor has utility for the treatment of obesity and obesity-associated complications.
WO2007/126957 discloses a genus of compounds which are disclosed to be inhibitors of DGAT1, and therefore useful in the treatment of a condition or a disorder such as obesity, diabetes and related metabolic disorders. Example 5-23 of said document discloses the compound 2-((1R,4R)-4-(4-(5-(benzo[d]oxazol-2-ylamino)pyridin-2-yl)phenyl)cyclohexyl)acetic acid having the structural formula (I):

No salt forms of this compound where prepared and the free acid exhibited low intrinsic dissolution and low solubility making large scale manufacture and purification difficult.
It is thus important to provide the compound of formula (I) in a salt form and physical form which can be reliably prepared and purified on a large scale, and ideally is stable and does not degrade on storage. The salt form/physical form chosen must also be stable whilst the drug substance is being manufactured as a formulation which is suitable for the intended route of administration chosen. In that respect, it may be necessary to consider physical properties of the salt form in a particular physical form which lead to improved powder handling properties or higher bulk density. In particular, non-hygroscopicity is particularly important in order to obtain good flow characteristics.
The properties of the final product should also be predictable and reliably reproducible. For example, material which is obtained in an inconsistent manner, for example, where the water content differs from batch to batch, must be carefully monitored. This leads to added complications in the handling, manufacture, analysis and formulation of the drug substance.
Whilst one solid state form may exhibit properties which are considered suitable, another form may also have properties which, with the right measures in place, can lead to its successful development into a drug. The decision as to whether a compound is suitable for commercialization thus depends on finding a solid state form of the compound which has the right balance of desirable characteristics.