The present invention provides an agent for the prophylactic or treatment of diabetes, diabetic complications, insulin resistance syndrome, metabolic syndrome, hyperglycemia, dyslipidemia, atherosclerosis, cardiac failure, cardiomyopathy, myocardial ischemia, brain ischemia, cerebral apoplexy, pulmonary hypertension, hyperlactacidemia, mitochondrial disease, mitochondrial encephalomyopathy or cancer, namely, a PDHK inhibitor and the like. A compound represented by the following formula [I] or a pharmaceutically acceptable salt thereof, or a solvate thereof:

##STR00001##

wherein each symbol is as defined in the specification.

The present invention provides an agent for the prophylactic or treatment of diabetes, diabetic complications, insulin resistance syndrome, metabolic syndrome, hyperglycemia, dyslipidemia, atherosclerosis, cardiac failure, cardiomyopathy, myocardial ischemia, brain ischemia, cerebral apoplexy, pulmonary hypertension, hyperlactacidemia, mitochondrial disease, mitochondrial encephalomyopathy or cancer, namely, a PDHK inhibitor and the like. A compound represented by the following formula [I] or a pharmaceutically acceptable salt thereof, or a solvate thereof:

##STR00001##

wherein each symbol is as defined in the specification.

A method for synthesizing halogenated organic compounds, such as halogenated alkenyl group-containing and halogenated alkyl group-containing compounds having a heteroatom (e.g., O,N.S) coupled to a carbon atom of a halogenated alkenyl or halogenated alkyl group, involves reacting a halogenated olefin such as a chloro-substituted trifluoropropenyl compound with an active hydrogen-containing organic compound such as an alcohol (e.g., an aliphatic monoalcohol, aliphatic polyalcohol, or a phenolic compound), a primary amine, a secondary amine or a thiol.

A method for synthesizing halogenated organic compounds, such as halogenated alkenyl group-containing and halogenated alkyl group-containing compounds having a heteroatom (e.g., O,N.S) coupled to a carbon atom of a halogenated alkenyl or halogenated alkyl group, involves reacting a halogenated olefin such as a chloro-substituted trifluoropropenyl compound with an active hydrogen-containing organic compound such as an alcohol (e.g., an aliphatic monoalcohol, aliphatic polyalcohol, or a phenolic compound), a primary amine, a secondary amine or a thiol.

A method for treating cancer can include administering a therapeutically effective amount of a compound of formula (Ia): ##STR00001##
or pharmaceutically acceptable salts or solvates thereof, wherein R.sup.1a, R.sup.1b, R.sup.1c, R.sup.1d, R.sup.2, and R.sup.3 are as defined, and A----B is selected from CHCH, CHCH(CH.sub.2).sub.pCH.sub.2, or CH.sub.2CH.sub.2(CH.sub.2)pCH.sub.2, and where p is 1 or 2.

A method for treating cancer can include administering a therapeutically effective amount of a compound of formula (Ia): ##STR00001##
or pharmaceutically acceptable salts or solvates thereof, wherein R.sup.1a, R.sup.1b, R.sup.1c, R.sup.1d, R.sup.2, and R.sup.3 are as defined, and A----B is selected from CHCH, CHCH(CH.sub.2).sub.pCH.sub.2, or CH.sub.2CH.sub.2(CH.sub.2)pCH.sub.2, and where p is 1 or 2.

This disclosure relates to modulators of liver receptor homologue 1 (LRH-1) and methods of managing disease and conditions related thereto. In certain embodiments, modulators are derivatives of hexahydropentalene. In certain embodiments, this disclosure relates to methods of treating or preventing cancer, diabetes, or cardiovascular disease by administering an effective amount of a hexahydropentalene derivative disclosed herein.

One aspect of the present invention relates to compounds, compositions and methods for diagnosis and/or treatment of a subject suffering from an amyloidosis-associated pathological condition. In certain embodiments, the imaging and/or therapeutic agents of the instant invention may be administered to a subject for identification and/or treatment of amyloid deposits. A specific imaging method detects amyloid deposits by administering the imaging agent to the subject and detecting the spatial distribution of the agent. Differential accumulation of the agent is indicative of AD or an amyloidosis-associated pathological condition and can be monitored by using a PET or SPECT camera.

One aspect of the present invention relates to compounds, compositions and methods for diagnosis and/or treatment of a subject suffering from an amyloidosis-associated pathological condition. In certain embodiments, the imaging and/or therapeutic agents of the instant invention may be administered to a subject for identification and/or treatment of amyloid deposits. A specific imaging method detects amyloid deposits by administering the imaging agent to the subject and detecting the spatial distribution of the agent. Differential accumulation of the agent is indicative of AD or an amyloidosis-associated pathological condition and can be monitored by using a PET or SPECT camera.

Glucose deprivation is an attractive strategy in cancer research and treatment. Cancer cells upregulate glucose uptake and metabolism for maintaining accelerated growth and proliferation rates. Specifically blocking these processes is likely to provide new insights to the role of glucose transport and metabolism in tumorigenesis, as well as in apoptosis. As solid tumors outgrow the surrounding vasculature, they encounter microenvironments with a limited supply of nutrients leading to a glucose deprived environment in some regions of the tumor. Cancer cells living in the glucose deprived environment undergo changes to prevent glucose deprivation-induced apoptosis. Knowing how cancer cells evade apoptosis induction is also likely to yield valuable information and knowledge of how to overcome the resistance to apoptosis induction in cancer cells. Disclosed herein are novel anticancer compounds that inhibit basal glucose transport, resulting in tumor suppression and new methods for the study of glucose deprivation in animal cancer research.