Derivatives of the potent angiotensin converting enzyme inhibitor 5(S)-benzamido-4-oxo-6-phenylhexanoyl-L-proline: effect of changes at postions 2 and 5 of the hexanoic acid portion

Abstract

Several derivatives of the potent angiotensin converting enzyme inhibitor 5(S)-benzamido-4-oxo-6-phenylhexanoyl-L-proline (1) were synthesized and tested for converting enzyme inhibition activity and blood pressure lowering effects in rats. One compound, 5(S)-benzamido-2(R)-methyl-4-oxo-6-phenylhexanoyl-L-proline (2a), had and I50 against angiotensin converting enzyme of 1.0 x 10(-9) M and is the most potent inhibitor prepared thus far in this class of compounds. Testing of 2a orally at 30 mg/kg for inhibition of the angiotensin I induced blood pressure increase in conscious normotensive rats gave 100% inhibition that required 143 min before the angiotensin I blood pressure response returned to 70% of the pretreatment control response. In the conscious renal hypertensive rat, 2a given orally at a dose of 3 mg/kg caused a lowering of blood pressure that reached its maximum of 40 mmHg 8 h following drug administration.

Secondary Retinal Ganglion Cell Death and the Neuroprotective Effects of the Calcium Channel Blocker Lomerizine

“…3). 55,56 There is no significant secondary cell death with caspase-3 expression in dorsal retina at either time point (Fig. 3).…”

Silanediols: A New Class of Potent Protease Inhibitors

“…[23] The measured IC 50 values are listed in Table 1 together with the reported values for 6 a and 6 b. [24] Notably for both 6 and 7, introduction of the methyl group (R) in the position a to the amide carbonyl group increases the enzyme inhibition by a factor of 3 ± 4. The more potent inhibitors 6 b and 7 b differ by a factor of 14.…”

Computergestützte Syntheseplanung: Das Ende vom Anfang

“…Das dritte Beispiel ist die Synthese von racemischem Juvabion, ein aus Abies lasiocarpa isoliertes Analogon eines Insektenjuvenilhormons (Abbildung c). Der von Syntaurus gefundene Syntheseweg beginnt mit der Umwandlung eines kommerziell erhältlichen, verzweigten ungesättigten Alkohols in das Bromid mit Br 2 /PPh 3 (Schritt a), das danach in ein Grignard‐Reagens überführt wird . Dessen Umsetzung mit einem Nitril (Schritt b) liefert das für die abschließende Diels‐Alder‐Reaktion benötigte Dienophil (Schritt d; zu weiteren Details siehe Hintergrundinformationen, Abschnitt S17).…”