Convenient Syntheses of Sulfinic Ester Derivatives

Furukawa, Mitsuru; Okawara, Tadashi; Noguchi, Yoshihide; Nishikawa, Masumi

doi:10.1055/s-1978-24773

Cited by 25 publications

(5 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Non-peptide orally active Ang II blocking agents that selectively block the AT1-type receptors were developed [40,41].…”

Section: -1988mentioning

confidence: 99%

“…Classic information on the RAS was accumulated over long period of time, from 1898, when Tigerstedt and Bergman [14] discovered renin until the discovery of the ACE inhibitors and Ang-receptor blockers [39][40][41]. The discovery of renin, as a hypertensive factor in extracts of rabbit kidney, was appreciated many years later when it was shown that it had an important role in the experimental models of hypertension ( Table 1).…”

Section: Formation Metabolism and Actions Of Angiotensinsmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacological, Immunological, and Gene Targeting of the Renin-Angiotensin System for Treatment of Cardiovascular Disease

Igić¹,

Behnia²

2007

CPD

View full text Add to dashboard Cite

Effective blood pressure control with a large arsenal of conventional antihypertensive drugs, such as diuretics, beta-adrenergic blockers, and calcium channel blockers, significantly reduce the morbidity and mortality associated with cardiovascular disease. However, blood pressure control with these drugs does not reduce cardiovascular disease risks to the levels in normotensive persons. Only two drug classes that inhibit or antagonize portions of the renin-angiotensin system (RAS), angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor type-1 (AT(1) receptor) blockers, have protective and beneficial effects unrelated to the degree of blood pressure reduction. These drugs may prevent the blood pressure related functional and structural abnormalities of the cardiovascular system and reduce the end organ-damage. The first part of this review presents the components of the RAS, biological actions of angiotensin peptides, and the functions of the enzymes that generate and metabolize angiotensins, including the likely effect of manipulating them. Special attention is devoted to renin, ACE, ACE2, chymase, and neprilysin. The second part of this review presents the rationale for targeting the RAS, based on clinical studies of the ACE inhibitors and AT(1) receptor blockers. Finally, we present the investigational agents acting on the RAS that have a potential for clinical usage, and give the perspective of pharmacological, immunological and gene targeting of the RAS for treatment of cardiovascular disease.

show abstract

“…Non-peptide orally active Ang II blocking agents that selectively block the AT1-type receptors were developed [40,41].…”

Section: -1988mentioning

confidence: 99%

Section: Formation Metabolism and Actions Of Angiotensinsmentioning

confidence: 99%

Pharmacological, Immunological, and Gene Targeting of the Renin-Angiotensin System for Treatment of Cardiovascular Disease

Igić¹,

Behnia²

2007

CPD

View full text Add to dashboard Cite

show abstract

“…0022-2623/95/1838-3759$09.00/0 addition, exhibited partial agonist effects in vivo and poor bioavailability.18 '19 This peptide, however, has served to demonstrate the usefulness of Ang II blockade and hence established several research programs directed toward the discovery of nonpeptide Ang II antagonists. [20][21][22][23][24][25] The first orally active, nonpeptide Ang II receptor antagonist, DuP 753 (Cozaar), has recently been marketed for the clinical treatment of hypertension. 26 We have previously described aspects of our research programs relating to both ATi27 and AT228 specific ligands and now describe a novel series of potent ATi ligands.…”

Section: Introductionmentioning

confidence: 99%

Derivatives of 5-[[1-4(4-carboxybenzyl)imidazolyl]methylidene]hydantoins as orally active angiotensin II receptor antagonists

Jj¹,

Klutchko²,

Jm³

et al. 1995

J. Med. Chem.

View full text Add to dashboard Cite

A series of 5-[[1-(4'-carboxybenzyl)imidazolyl]methylidene]hydantoins have been prepared and evaluated as in vitro and in vivo angiotensin II (Ang II) antagonists. Variation of substituents on the hydantoin ring leads to potent and selective Ang II antagonists with nanomolar IC50 values at the AT1 receptor and negligible affinity for the AT2 receptor. Preferred substituents include an n-butyl at R1 and an alkyl or heteroarylmethyl substituent at R2. The selection of the R2 substituent was guided in part by the calculation of its log P since a significant correlation was observed between CLOGP and AT1 binding affinity. The biphenyl tetrazole pharmacophore, common to a number of AT1 antagonists, could be replaced by, for example, a 4-carbomethoxyphenyl substituent resulting in potent Ang II antagonists both in vitro and in vivo. A representative compound of this series is 57, which reduced the mean arterial blood pressure of renal hypertensive rats by 40% at 30 mg/kg po and by 25% at 10 mg/kg po. In addition this compound was efficacious in the salt-deplete normotensive monkey model maximally decreasing blood pressure 27% at 10 mg/kg po. In summary, these compounds belong to a novel class of Ang II antagonists that lack the biphenyl tetrazole moiety yet display appreciable and long lasting oral activity.

show abstract

“…The combined ether layers were passed through a short column of silica gel. Evaporation of the eluant gave the required 2-aldehyde (9) (330 mg, 83%), m.p. 153-156 "C (lit.,' 153-156 "C).…”

Section: -A1 (9)mentioning

confidence: 99%