Pfizer Corporation

Migenix, Inc.

Michael K Ahlijanian

Frank S Menniti

Mark Allen Sanner

Patricia A Seymour

Chris John Helal

Lit-Fui Lau

Christoper B Cooper

Soumitra S Ghosh

Yazhong Pei

Xiao-Qing Tang

Spiros Liras

Anabella Villalobos

John D McNeish

Annabella Villalobos

The invention provides compounds of formula 1 wherein R, R, R, and Rare as defined, and their pharmaceutically acceptable salts. Compounds of formula 1 are indicated to have activity inhibiting cdk5, cdk2, and GSK-3. Pharmaceutical compositions and methods comprising compounds of formula 1 for treating and preventing diseases and conditions comprising abnormal cell growth, such as cancer, and neurodegenerative diseases and conditions and those affected by dopamine neurotransmission. Also described are pharmaceutical compositions and methods comprising compounds of formula 1 for treating male fertility and sperm motility; diabetes mellitus; impaired glucose tolerance; metabolic syndrome or syndrome X; polycystic ovary syndrome; adipogenesis and obesity; myogenesis and frailty, for example age-related decline in physical performance; acute sarcopenia, for example muscle atrophy and/or cachexia associated with burns, bed rest, limb immobilization, or major thoracic, abdominal, and/or orthopedic surgery; sepsis; hair loss, hair thinning, and balding; and immunodeficiency.

Imidazole derivatives

Compounds which have utility in the treatment of conditions associated with altered mitochondrial function. The compounds have the following structure (I):including stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein R, R, R, R, Rand Rare as defined herein. Pharmaceutical compositions containing a compound of structure (I), as well as methods relating to the use thereof, are also disclosed.

Ligands of adenine nucleotide translocase (ANT) and compositions and methods related thereto

The invention provides transgenic, non-human animals and transgenic non-human mammalian cells harboring a transgene encoding a p25 (activator of the protein kinase cdk 5) polypeptide. The two neuropathological lesions associated with Alzheimer's disease (AD) are amyloid plaques and neurofibrillary tangles (NFTs), composed predominantly of amyloid &bgr; peptides and hyperphosphorylated tau, respectvely. While animal models for plaque formation exist, there is no animal model that recapitulates the formation of NFTs. This invention provides transgenic mice that overexpress human p25, an activator of cdk5, resulting in tau that is hyperphosphorylated at AD-relevant epitopes. Deposition of tau is detected in the amygdala, thalamus and cortex. Increased phosphorylated neurofilament, silver-positive neurons and neuronal death are also observed in these regions. We conclude that the overexpression of p25, an activator of cdk5, is sufficient to produce hyperphosphorylation of tau and neuronal death. The p25 transgenic mouse represents the first model for tau pathology in AD.

Transgenic mice expressing human p25

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Mystic, CT, United States of America

Michael K Ahlijanian