A series of new sympathomimetic amines containing an 8-hydroxycarbostyril moiety was synthesized. These compounds probably exist as resonance hybrids having two acidic hydrogen atoms in locations approximating to those of the hydroxyl groups of catechol-containing adrenergic agents. In an in vitro test, many of these compounds showed potent activity for relaxation of guinea pig tracheal smooth muscle. One of the compounds was 24 000 times more potent than isoproterenol. Their actions on cardiac muscle were also examined in vitro by measuring increase in the beating rate of the right atria of guinea pigs. Several of the compounds appeared to be beta-selective. Some of the compounds seem suitable for use as bronchodilators. The structure-activity relationships of these compounds were discussed in comparison with those of catecholamines.

Background:The emergence of molecular-targeted agents (MTAs) has altered the treatment landscape of hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2−) advanced breast cancer (ABC)/metastatic breast cancer (MBC). Various guidelines recommend molecular-targeted therapy as first-line treatment for HR+/HER2− ABC/MBC. However, subsequent treatment following progressive disease after MTA therapy remains undetermined. This study evaluated the suitability of different types of MTAs for such patients. Methods:In this retrospective study, electronic health records of 56 patients with HR+/HER2− ABC/MBC receiving treatment with palbociclib, abemaciclib, or everolimus in our institution between April 2014 and June 2021 were analyzed.Results: Overall, 39, 14, and 35 regimens with palbociclib, abemaciclib, and everolimus, respectively, were used. A total of 3 and 53 patients were pre-and postmenopausal, respectively. MTAs were included in the 1 st -11 th lines of treatment. The time to failure (TTF) was significantly different among the three MTAs. In contrast, the TTF was not significantly different between the patients with 50 regimens including CDK4/6 inhibitors with/without prior mTOR inhibitor use and those with 35 regimens including mTOR inhibitors with/without prior CDK4/6 inhibitor use. Conclusions:The sequential use of different classes of MTA did not affect the TTF of another MTA. Therefore, mTOR inhibitor + exemestane is a favorable treatment option administered after CDK4/6 inhibitor + hormone therapy. The CDK4/6 inhibitor + hormone therapy is also suitable for patients previously treated with mTOR inhibitor + exemestane.Despite the retrospective and single-center study design, these findings provide useful information for treatment selection in clinical practice.

Abstract8‐Hydroxy‐carbostyrile (I) werden mit den α‐Halogen‐carbonsäurehalogeniden (II) in 5‐Stellung zu (III) substituiert, und anschließend wird das Halogenatom gegen Amine (IV) zu den Aminoketonen (V) ausgetauscht.

The patient was a 74-year-old male. (History) The patient had been experiencing left papillary hematogenous secretion for approximately 3 years. He had been neglecting it for some time, but when he began to notice persistent secretion, he came to our clinic.(Present condition) On physical examination, no mass was palpable, and only bloody nipple discharge was observed. Mammary ultrasonography showed a hypoechoic mass of approximately 8 mm in size in the left nipple. A needle biopsy was performed, a diagnosis of invasive ductal carcinoma was made, and a thoracic muscle-sparing mastectomy and sentinel lymph node biopsy were performed. Histopathological findings showed a diagnosis of invasive ductal carcinoma: tubule-forming type, pT1aN0M0 stage I, ER (+), PgR (+), HER2 score 1, and ki67 30%.(Discussion) Male breast cancer accounts for approximately 1% of all breast cancers. The initial presentation is often palpable as a painless mass. Noninvasive ductal carcinoma is common, although bloody papillary discharge may be present, and invasive ductal carcinoma may be advanced. We report this case because it was treated early and the patient had a good course.