N-(hidroksietil)butandiamida atvasinajumi ka renina inhibitori

• Main Authors: MARC-ANDRE POUPART, TEDDY HALMOS, GRACE LORENA JUNG, BRUNO SIMONEAU, PAUL CATES ANDERSON
• Format: Patent
• Language: Latvian
• Published: 20.12.1995
• Edition: 6
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

Disclosed herein are compounds of the formula: A-N(R )C(O)CH2CHR C(O)-B wherein A is an oxygen-bearing radical selected from the group consisting of: (a) HO-CH(R )CH2 wherein R is, for example, hydrogen, lower alkyl, lower cycloalkyl, phenyl or an unsubstituted five- or six-membered heterocyclic ring containing one or two heteroatoms selected from the group of N, O or S; (b) HO-CH2CH(R ) wherein R is, for example, lower alkyl or phenyl(lower)alkyl; and (c) HO-CR (R )CH2 wherein each of R and R is lower alkyl; or R and R together with the carbon atom to which they are attached form a 1,1-(lower cycloalkanediyl), 1,1-(4-hydroxycyclohexanediyl) or 1,1-(4-oxocyclohexanediyl); (d) (lower alkoxy)CR<5A)<R )CH2 wherein each of R and R is lower alkyl; or R and R together with the carbon atom to which they are attached form a 1,1-(lower cycloalkanediyl); and (e) (lower alkyl)C(O)CH2; R is, for example, benzyl, alkyl, a substituted alkyl such as cyclohexylmethyl, or R R NC(O)CH2 wherein R and R are alkyl such as methyl or ethyl; R is, for example, alkyl, cycloalkylmethyl, 1H-imidazol-4-ylmethyl, 4-thiazolylmethyl or (2-amino-4-thiazolyl)methyl; and B is a renin substrate transition state mimic, for example, [1(S)-(cyclohexylmethyl)-2(R),3(S)-dihydroxy-5-methylhexyl]amino. The compounds inhibit renin activity and are indicated for the treatment of hypertension and congestive heart failure.