174850-08-9Relevant academic research and scientific papers
Transition state analogy of phosphonic acid peptide inhibitors of pepsin
Bartlett, Paul A.,Giangiordano, Mark A.
, p. 3433 - 3438 (2007/10/03)
A series of 11 phosphonate peptide analogs, RO2C-Xaa-Yaa-Phe-{PO2--O}-Phe O-(3-(4-pyridyl)propyl ester), were synthesized and evaluated as inhibitors of the aspartic peptidase pepsin. For the inhibitors with Gly or Ala at the P2 position, the K(i) values correlate with the K(m)/k(cat) values of the corresponding substrates, demonstrating that these analogs mimic the transition state in the way the P2-P4 residues bind. Deviations from the correlation for the other inhibitor/substrate pairs imply a different binding orientation as a result of N-substitution at P2 (Pro), contamination with the more potent diastereomer (D-Ala), or a change in rate-limiting step for turnover (Ile).
Design and synthesis of phosphinic acids that triply inhibit endothelin converting enzyme, angiotensin converting enzyme and neutral endopeptidase 24.11
McKittrick, Brian A.,Stamford, Andrew W.,Weng, Xiaoyu,Ma, Ke,Chackalamannil, Samuel,Czarniecki, Michael,Cleven, Renee M.,Fawzi, Ahmad B.
, p. 1629 - 1634 (2007/10/03)
We have synthesized a series of phosphinic acids as inhibitors of the metalloprotease endothelin converting enzyme (ECE). Potent ECE inhibitors 4g and 4o were identified. These compounds are members of a novel class of ECE inhibitors that are also potent inhibitors of angiotensin converting enzyme and neutral endopeptidase.
DERIVATIVES OF PHOSPHINIC ACID USEFUL AS ENDOTHELIN CONVERTING ENZYME INHIBITORS
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, (2008/06/13)
Phosphinic acid derivatives of the structural formula STR1 or a pharmaceutically acceptable salt thereof, wherein R is H, alkyl or alkanoyloxymethylene;R 1, R 2, R 3 and R. sub.4 are H, alkyl, alkenyl, alkenylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxyalkyl, carboxyalkyl, thioalkyl, alkoxythioalkyl, aminoalkyl, alkylaminoalkyl, cycloalkyl-substituted alkyl or heterocycloalkyl; or R 1 and R 2 form a cycloalkyl ring of 3-8 members and R 3 and R 4 are as defined; or R 3 and R 4 form a cycloalkyl ring of 3-7 members and R 1 and R 2 are as defined; or R 1 and R 2 together, and R 3 and R 4 together, each form a cycloalkyl ring;R 5 is--OR. sub.9 or--NHR 9, wherein R. sub.9 is hydrogen or alkyl;n is 0 or 1;A. sub.1 is p-aminobenzoyl or p-aminobenzenesulfonyl, or A 1 and R 5 together form a radical of an α-aminoacyl derivative; andR. sub.6 is phenylmethoxycarbonyl, arylcarbonyl, heteroarylcarbonyl or--A 2--R. sub.7, wherein A 2 is a divalent α-aminoacyl radical, and R 7 is a substituent on the α-amino atom selected from H, R 8 OCO--, R. sub.8 SO 2--and R 8 NHCO--, wherein R 8 is aryl, arylmethyl or (C. sub.1-C 8)alkyl;are disclosed for use as endothelin converting enzyme inhibitors; also disclosed are a genus of novel compounds wherein R 3 and R 4 form a cycloalkyl ring, and pharmaceutical compositions comprising said novel compounds.
Antibody-catalyzed hydrolysis of an unsubstituted amide
Martin, Mark T.,Angeles, Thelma S.,Sugasawara, Renee,Aman, Nureddin I.,Napper, Andrew D.,Darsley, Michael J.,Sanchez, Rosa I.,Booth, Paul,Titmas, Richard C.
, p. 6508 - 6512 (2007/10/02)
The generation of antibodies capable of catalyzing the unassisted hydrolysis of unactivated amides has been an enduring goal of research in the field. Antidialkylphosphinate 1 monoclonal antibodies were screened for their ability to catalyze the hydrolysi
