Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are agonists of G-protein coupled receptor 40 (GPR40) and may be useful in the treatment, prevention and suppression of diseases mediated by the G-protein-coupled receptor 40. The compounds of the present invention may be useful in the treatment of Type 2 diabetes mellitus, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia. ##STR00001##

Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are agonists of G-protein coupled receptor 40 (GPR40) and may be useful in the treatment, prevention and suppression of diseases mediated by the G-protein-coupled receptor 40. The compounds of the present invention may be useful in the treatment of Type 2 diabetes mellitus, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia. ##STR00001##

Provided herein are compounds, pharmaceutical compositions including such compounds, and methods of using such compounds to treat diseases or disorders associated with MDM2 activity.

Provided herein are compounds, pharmaceutical compositions including such compounds, and methods of using such compounds to treat diseases or disorders associated with MDM2 activity.

Compositions and methods for inhibits the binding of GTP to oncogenic mutant KRas are disclosed. These compositions may be used in method to treat a subject with cancer. In particular, the compositions may be used to treat cancers involving overactive Ras signaling.

The present invention includes compounds, compositions comprising the same, and methods using the compounds and/or compositions therein, for modulating skin pigmentation in a mammalian subject. In certain embodiments, the compounds of the invention treat or prevent skin disorders or diseases associated with hyperpigmentation in the subject. In other embodiments, the compounds of the invention act as antagonist to the non-canonical sex steroid hormone receptor GPRE1 and do not bind to a canonical nuclear estrogen receptor (ER). In yet other embodiments, the compounds of the invention comprise acts as agonists to the non-canonical sex steroid hormone receptor PAQR7 and do not bind to a canonical nuclear progesterone receptor (PR).

The present invention includes compounds, compositions comprising the same, and methods using the compounds and/or compositions therein, for modulating skin pigmentation in a mammalian subject. In certain embodiments, the compounds of the invention treat or prevent skin disorders or diseases associated with hyperpigmentation in the subject. In other embodiments, the compounds of the invention act as antagonist to the non-canonical sex steroid hormone receptor GPRE1 and do not bind to a canonical nuclear estrogen receptor (ER). In yet other embodiments, the compounds of the invention comprise acts as agonists to the non-canonical sex steroid hormone receptor PAQR7 and do not bind to a canonical nuclear progesterone receptor (PR).

Provided is a compound of formula (I) or a pharmaceutically acceptable salt thereof, in which R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, X.sup.1, X.sup.2, and n are described herein. Also provided is a method of treating an estrogen-mediated disease requiring inhibition of estrogen receptor alpha (ER-alpha), such as cancer, in a subject or inhibiting ER-alpha in a cell with the compound of formula (I) or a pharmaceutically acceptable salt thereof.

##STR00001##

The invention is based on the use of ipidacrine to treat potency disorders and can be used in clinics for treating potency disorders related to the reduced production of reproductive gland hormones, disorders caused by chronic, including physical, stress, and also associated with spontaneously reduced sexual function, including anorgasmia or delayed ejaculation, and other sexual activity disorders not limiting the scope of the invention.

The invention is based on the use of ipidacrine to treat potency disorders and can be used in clinics for treating potency disorders related to the reduced production of reproductive gland hormones, disorders caused by chronic, including physical, stress, and also associated with spontaneously reduced sexual function, including anorgasmia or delayed ejaculation, and other sexual activity disorders not limiting the scope of the invention.