Roussel Uclaf

About: Roussel Uclaf is a based out in . It is known for research contribution in the topics: Alkyl & Alkoxy group. The organization has 1888 authors who have published 2338 publications receiving 36508 citations.

Structure-activity relationships of a new family of steroidal aromatase inhibitors. 1. Synthesis and evaluation of a series of analogs related to 19-[(methylthio)methyl]androstenedione (RU54115).

Abstract: During the course of a study aimed at the search for new potent aromatase inhibitors, several new androstenedione analogs were synthesized and evaluated. This study led to the discovery of 19-[(methylthio)methyl]androsta-4,9(11)-diene-3,17-dione (7; RU54115) already described by our laboratory. The object of the present series of papers is to disclose the result of the structure−activity relationship studies that gave rise to this compound. This first part deals mainly with the substitution in the 19-position of the steroid nucleus. Several parameters were varied, the length of the chain and its rigidity and branching, as well as the nature of the heteroatom itself and its substitution. The interaction of these new compounds with human placental aromatase in competition with the substrate androstenedione was studied by difference visible spectroscopy. The in vivo aromatase-inhibiting activities were evaluated by measuring the estradiol lowering after oral administration of the compounds to PMSG-primed fem...

Pharmacokinetics of intrapleural recombinant interleukin-2 in immunotherapy for malignant pleural effusion.

Abstract: Background. The authors measured pharmacokinetic parameters before, during, and after immunotherapy by continuous intrapleural infusion of recombinant interleukin-2 (rIL-2) and correlated the resulting data with clinical effects in nine patients with malignant pleural effusion. Methods. The underlying disease was malignant mesothelioma in five patients and adenocarcinoma in four patients. Continuous intrapleural infusion of rIL-2 was performed for 5 days at 21 × 106 IU/m2/day. Maximum tolerated dose previously was determined to be 24 × 106 IU/m2/day in a Phase I study. Peak levels, the areas under the concentration curve (AUC), and drug half-lives were measured in pleural fluid and plasma samples collected at 0 (baseline), 12, 24, 48, 72, 96, and 120 hours during infusion and at 2, 6, 8, 32, 44, 56, 80, and 120 hours after the end of infusion. Results. High and prolonged intracavitary drug levels were achieved in all but two patients, with a statistically significant correlation between peak values and AUC. Four patients achieved objective responses according to World Health Organization criteria. Neither of the patients with undetectable rIL-2 levels had response to therapy. Serum rIL-2 levels were low regardless intrapleural levels. Mean AUC was lower in the plasma than in the pleural fluid. Conclusions. This study demonstrates that continuous intrapleural infusion of rIL-2 is an active method of treatment for malignant pleural effusion. The low serum levels associated with this method greatly improve tolerance. The results also indicate that the concentration and duration of intrapleural rIL-2 levels may depend on the extent of pleural invasion. Additional study is needed to confirm this finding.

Novel 6-amino-7-hydroxy-4,5,6,7-tetrahydro-imidazo[4,5,1-j-k][1]-benzazepin-2-(1H)-one

Abstract: Novel 6-amino-7-hydroxy-4,5,6,7-tetrahydro-imidazo[4,5,l-j-k][1]-benzazepin-2-(1H)-one derivatives of the formula ##STR1## wherein R is selected from the group consisting of hydrogen, alkyl of 1 to 8 carbon atoms optionally substituted with a hydroxyl, aryl and aryloxy of 6 to 10 carbon atoms, cycloalkyl of 3 to 7 carbon atoms optionally interrupted with a heteroatom optionally substituted with alkyl of 1 to 4 carbon atoms and the wavy lines indicates that the 7-OH and 6-amino have the trans configuration and their non-toxic, pharmaceutically acceptable acid addition salts having remarkable anti-hypertensive and hypotensive activity and vasodilatatory activity and their preparation.