The invention is directed to the treatment of tauopathic neurodegenerative conditions and the underlying processes thereof. Based on the discovery that Rhes acts as a negative regulator of normal tau clearance, the compositions and methods of the invention may be applied to inhibit Rhes and reduce pathogenic tau aggregation. Rhes may be disrupted by disrupting RAS2D gene expression or reducing the abundance of Rhes protein in neurons. Additionally, post-translational modifications of Rhes may be targeted, including the disruption of Rhes farnesylation by the administration of farnesyltransferase inhibitors.

The invention is directed to the treatment of tauopathic neurodegenerative conditions and the underlying processes thereof. Based on the discovery that Rhes acts as a negative regulator of normal tau clearance, the compositions and methods of the invention may be applied to inhibit Rhes and reduce pathogenic tau aggregation. Rhes may be disrupted by disrupting RAS2D gene expression or reducing the abundance of Rhes protein in neurons. Additionally, post-translational modifications of Rhes may be targeted, including the disruption of Rhes farnesylation by the administration of farnesyltransferase inhibitors.

The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof:
X-A-Y-L-R(I)
which inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function of the HBV life cycle of the hepatitis B virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HBV infection. The invention also relates to methods of treating an HBV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof:
X-A-Y-L-R(I)
which inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function of the HBV life cycle of the hepatitis B virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HBV infection. The invention also relates to methods of treating an HBV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Biologically active cannabidiol analogs comprising a compound of the formula

##STR00001##

wherein one of R.sub.1 or R.sub.2 or both is/are the residue of a moiety formed by the reaction of an amino group of the amino acid ester of R.sub.1 or R.sub.2 or both with a dicarboxylic acid or a dicarboxylic acid derivative and the other R.sub.1 or R.sub.2 (in the case of the mono) is the residue of a dicarboxylic acid or dicarboxylic acid derivative or Hydrogen (H), (i.e. underivatized), and salts thereof. These CBD analogs are be useful in pain management in oncology and other clinical settings in which neuropathy is presented. Furthermore, these CBD-analogs are useful in blocking the addictive properties of opiates.

Biologically active cannabidiol analogs comprising a compound of the formula

##STR00001##

wherein one of R.sub.1 or R.sub.2 or both is/are the residue of a moiety formed by the reaction of an amino group of the amino acid ester of R.sub.1 or R.sub.2 or both with a dicarboxylic acid or a dicarboxylic acid derivative and the other R.sub.1 or R.sub.2 (in the case of the mono) is the residue of a dicarboxylic acid or dicarboxylic acid derivative or Hydrogen (H), (i.e. underivatized), and salts thereof. These CBD analogs are be useful in pain management in oncology and other clinical settings in which neuropathy is presented. Furthermore, these CBD-analogs are useful in blocking the addictive properties of opiates.

Systems, techniques and methods for estimating the metabolic state or flux, e.g., the body energy state (BES) of a patient, are disclosed. The BES provides a deep insight into the nutritional needs of the patient, thus allowing for a sort of exquisite glycemic control with regard to the patient. The invention discloses systems and methods for estimating fractional gluconeogenesis. The invention also discloses systems and methods for estimating and targeting patient blood lactate concentration, both as a target itself and as an intermediate step to estimating and targeting patient fractional gluconeogenesis glucose production. Nutritional support methods and formulations are also disclosed. The invention is suitable for any sort of patient, including those who are injured, such as with traumatic brain injury, ill, or have other conditions that stress the metabolic system.

Systems, techniques and methods for estimating the metabolic state or flux, e.g., the body energy state (BES) of a patient, are disclosed. The BES provides a deep insight into the nutritional needs of the patient, thus allowing for a sort of exquisite glycemic control with regard to the patient. The invention discloses systems and methods for estimating fractional gluconeogenesis. The invention also discloses systems and methods for estimating and targeting patient blood lactate concentration, both as a target itself and as an intermediate step to estimating and targeting patient fractional gluconeogenesis glucose production. Nutritional support methods and formulations are also disclosed. The invention is suitable for any sort of patient, including those who are injured, such as with traumatic brain injury, ill, or have other conditions that stress the metabolic system.

A compound represented by Formula [3] or a salt thereof and a method of making the same,

##STR00001## in the formula, L.sup.3 represents a group represented by Formula [2c]

##STR00002##

wherein R.sup.3c, R.sup.4c, R.sup.5c, and R.sup.6c are the same as or different from each other and represent a hydrogen atom or a C.sub.1-6 alkyl group; p.sup.3 represents an integer of 1 to 3; q.sup.3 represents an integer of 0 to 3; and r.sup.3 represents an integer of 1 to 6; A.sup.1 represents any one of the groups represented by Formulae [4] to [9],

##STR00003## wherein * represents a binding position; and R.sup.7 represents a carboxyl-protecting group; and m represents an integer of 1 to 3.

A compound represented by Formula [3] or a salt thereof and a method of making the same,

##STR00001## in the formula, L.sup.3 represents a group represented by Formula [2c]

##STR00002##

wherein R.sup.3c, R.sup.4c, R.sup.5c, and R.sup.6c are the same as or different from each other and represent a hydrogen atom or a C.sub.1-6 alkyl group; p.sup.3 represents an integer of 1 to 3; q.sup.3 represents an integer of 0 to 3; and r.sup.3 represents an integer of 1 to 6; A.sup.1 represents any one of the groups represented by Formulae [4] to [9],

##STR00003## wherein * represents a binding position; and R.sup.7 represents a carboxyl-protecting group; and m represents an integer of 1 to 3.