Synthesis and blood pressure lowering activity of 3-(substituted-amino)-1,2,4-benzothiadiazine 1-oxide derivatives

Abstract

A series of (substituted amino)-1,2,4-benzothiadiazine 1-oxides has been synthesized and most members of the series have been shown to have blood pressure lowering effects in normotensive rabbits and in spontaneously hypertensive rats. The most active member of the series was 3-[4-(2-furoyl)-1-piperazinyl]-6,7-dimethoxy-1-methyl-1H-1,2,4-benzothiadiazine 1-oxide hydrochloride. This compound in animal tests was equipotent to the known antihypertensive Prazosin.

Rhodium‐Catalyzed ortho‐Amidations in the Preparation of Thiadiazine 1‐Oxides

“…Those preparative investigations were the basis for numerous bioactivity studies that revealed interesting properties of thiadiazine 1‐oxide derivatives 1 useful for medical applications . For example, NSC 287474 ( 2 ) was found to be a potential reverse transcriptase inhibitor for the protection of lymphocytes against HIV, and in animal tests thiadiazine 1‐oxide 3 revealed equipotent blood‐pressure‐lowering activity as the commercial antihypertensive drug Prazosin (Scheme ) …”

Efficient Kinetic Resolution of Sulfur‐Stereogenic Sulfoximines by Exploiting CpXRhIII‐Catalyzed C−H Functionalization

“…[5a, 6] Due to these benefits,a ni ncreasing number of sulfoximine-containing bioactive compounds have been disclosed and have entered clinical trials ( Figure 1). For example,k inase inhibitors like roniciclib (A), [6b] ceralasertib (B), [3e] or PfizersP YK2 inhibitor C [7] bear an acyclicc hiral sulfoximine moiety.E li Lillysp razosine analogue D, [8] the kinase inhibitor Gç 4962 (E), [9] and the reverse transcriptase inhibitor NSC 287474 (F)a re representative examples for cyclic benzannulated sulfoximines. [10] Thec hirality of the sulfoximine group has proven important, with each enantiomer of the stereogenic sulfur atom having different properties.…”

Efficient Kinetic Resolution of Sulfur‐Stereogenic Sulfoximines by Exploiting CpXRhIII‐Catalyzed C−H Functionalization

“…For example, kinase inhibitors like roniciclib ( A ), ceralasertib ( B ), or Pfizer's PYK2 inhibitor C bear an acyclic chiral sulfoximine moiety. Eli Lilly's prazosine analogue D , the kinase inhibitor Gö 4962 ( E ), and the reverse transcriptase inhibitor NSC 287474 ( F ) are representative examples for cyclic benzannulated sulfoximines . The chirality of the sulfoximine group has proven important, with each enantiomer of the stereogenic sulfur atom having different properties .…”