Identification of a new class of potent bace-1 inhibitors through scaffold hopping

Due to the constant growth in the number of patients affected with Alzheimer disease (AD), the need of effective drugs able to stop the neuronal degeneration is increasing. Considering the therapeutic necessity of new molecules, we focused our attention in designing new BACE-1 inhibitors with good pharmacokinetic and pharmacodynamics properties, able to cross the bloodbrain barrier. Using a scaffold hopping approach, we moved from a known BACE-1 ligand with good activity but poor values of MW and tPSA to a new aminothiazole scaffold with improved properties. Further optimization, aimed to improve pharmacokinetic properties as well as metabolic stability, led to the synthesis of an aminothiadiazole scaffold library of compounds that have been tested to assess their ability to inhibit BACE-1 activity

Endometriosis and ovarian cancer

In 556 patients undergoing surgery for ovarian cancers the frequency of endometriosis ranged from 3.6% to 5.6% in serous, mucinous, and miscellaneous neoplasms versus 26.3%, 21.1%, and 22.2%, respectively, in endometrioid, clear cell, and mixed subtypes; the differences were statistically significant (chi 2 heterogeneity 50.0, p < 0.001) and consistent in strata of age, parity, menopausal status, and disease stage

Serum Anti-Müllerian Hormone Concentrations Are Elevated in Oligomenorrheic Girls without Evidence of Hyperandrogenism

Context: Serum anti-Müllerian hormone (AMH) levels are significantly elevated in adolescents with polycystic ovary syndrome (PCOS) compared to normal controls. Whether adolescents with oligomenorrhea have elevated AMH levels is unknown

Generation and characterization of androgen receptor knockout (ARKO) mice: An in vivo model for the study of androgen functions in selective tissues

By using a cre-lox conditional knockout strategy, we report here the generation of androgen receptor knockout (ARKO) mice. Phenotype analysis shows that ARKO male mice have a female-like appearance and body weight. Their testes are 80% smaller and serum testosterone concentrations are lower than in wild-type (wt) mice. Spermatogenesis is arrested at pachytene spermatocytes. The number and size of adipocytes are also different between the wt and ARKO mice. Cancellous bone volumes of ARKO male mice are reduced compared with wt littermates. In addition, we found the average number of pups per litter in homologous and heterozygous ARKO female mice is lower than in wt female mice, suggesting potential defects in female fertility and/or ovulation. The cre-lox ARKO mouse provides a much-needed in vivo animal model to study androgen functions in the selective androgen target tissues in female or male mice