186808-53-7Relevant academic research and scientific papers
Synthesis and Structure-Activity Relationships of 5,6,7,8-Tetrahydro-4H-thieno[3,2-b]azepine Derivatives: Novel Arginine Vasopressin Antagonists
Cho, Hidetsura,Murakami, Kengo,Nakanishi, Hiroyuki,Fujisawa, Akitaka,Isoshima, Hirotaka,Niwa, Misako,Hayakawa, Kazuhide,Hase, Yasunori,Uchida, Itsuo,Watanabe, Hidenori,Wakitani, Korekiyo,Aisaka, Kazuo
, p. 101 - 109 (2007/10/03)
A variety of novel heterocyclic compounds having thienoazepine, pyrroloazepine, furoazepine, and thienodiazepine skeletons were synthesized, most of which exhibited potent antagonism of [3H]-AVP specific binding in assays using rat liver (V1), rat kidney (V2), human platelet plasma membranes, and recombinant human CHO cells (V2), as well as antagonizing AVP-induced hypertension in rats (V1, intravenous) and showing a diuretic effect in rats (V2, oral). By detailed studies of the structure-activity relationships of these compounds, the thienoazepine derivative 1 was found to be a very potent combined V1 and V2 antagonist. After further pharmacological and toxicological evaluation as well as physical properties, the hydrochloride 2 (JTV-605) of compound 1 was selected for clinical studies as a potent AVP antagonist with a long duration of action.
Synthesis of novel 5,6,7,8-tetrahydro-4H-thieno[2,3-b][1,4]-diazepine derivatives
Cho, Hidetsura,Murakami, Kengo,Fujisawa, Akitaka,Niwa, Misako,Nakanishi, Hiroyuki,Uchida, Itsuo
, p. 1555 - 1566 (2007/10/03)
Unsubstituted 5,6,7,8-tetrahydro-4H-thieno[2,3-b][1,4]diazepine (1) and 4H-thieno[2,3-b][1,4]diazepine-5,7(6H,8H)-dione (2) were newly synthesized. Benzoylation of 1 regioselectively afforded thienodiazepine (13) substituted with a benzoyl group at position 4. Alternatively, novel synthetic procedures were devised to yield thienodiazepine (22) substituted with an alkyl group or compound (14) with an aralkyl group at position 8. Thus, the ingenious introduction of functional groups at the N-4 or 8 position of a thienodiazepine skeleton was achieved and then a variety of 5,6,7,8-tetrahydro-4H-thieno[2,3-b][1,4]diazepines (5)-(9), and (27), some of which exhibited potent arginine vasopressin antagonistic activity, were obtained using the key intermediates (1), (13), (14), and (22).
