- N-formyl hydroxylamine containing compounds useful as ACE inhibitors and/or NEP inhibitors
-
N-formyl hydroxylamines are provided which have the structure wherein R is H, alkyl, alkenyl, aryl-(CH2)p—, heteroaryl-(CH2)p— or cycloheteroalkyl-(CH2)p— R1is H or COR2where R2is alkyl, aryl-(CH2)p—, cycloheteroalkyl-(CH2)p—, heteroaryl-(CH2)p—, alkoxy or cycloalkyl-(CH2)p—, p is 0 to 8, and A is a dipeptide derived from an amino acid or is a conformationally restricted dipeptide mimic. The above compounds are useful in treating hypertension congestive heart failure, renal failure, and hepatic cirrhosis.
- -
-
Page column 32
(2010/02/08)
-
- Process development in the synthesis of the ACE intermediate MDL 28,726
-
MDL 28,726 is a key intermediate in the synthesis of the ACE inhibitors MDL 27,210A and MDL 100,240. An efficient nine-step synthesis of this tricyclic acid, which has three chiral centers, was developed beginning with 3,4-dihydro-2H-pyran. A key step in the synthesis features an enzyme-catalyzed resolution of the lithium salt of the W-trifluoroacetamide of (A,5)-6-hydroxynorleucine. All of the steps were optimized and completed in reactor equipment using environmentally acceptable processes. Process development of this route is described.
- Horgan, Stephen W.,Burkhouse, David W.,Cregge, Robert J.
-
p. 241 - 247
(2013/09/08)
-
- A novel three-step hydroxy-deamination sequence: Conversion of lysine to 6-hydroxynorleucine derivatives
-
Oxidation of carbamates with catalytic RuO4, generated from RuO2 and NaBrO3, provides the corresponding acyl carbamates, which can be reduced with NaBH4 to provide alcohols. Application of this methodology to L-lysine provides (S)-6-hydroxynorleucine derivatives.
- Nevill Jr., C. Richard,Angell, Paul T.
-
p. 5671 - 5674
(2007/10/03)
-