- Tetrahydroisoquinoline derivative and application thereof
-
The invention belongs to the technical field of medicines, relates to a 2-{(2s)-1-[(2S)-3-ethanethioate-2-methyl propionyl] pyrrolidine-2-formamido}-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid methyl ester derivative and an application thereof, and in particular relates to a stereomer and a pharmaceutically acceptable salt of the compound. The general structural formula is as shown in the specification. The 2-{(2s)-1-[(2S)-3-ethanethioate-2-methyl propionyl] pyrrolidine-2-formamido}-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid methyl ester compound as well as pharmaceutically acceptable acid and additive salt of the compound can be combined with an existing medicine and can be individually used as an angiotensin-converting enzyme inhibitor to be applied to treatment of hypertension. Compared with the prior art, 6,7,8 side chains of a tetrahydroisoquinoline ring are obviously changed; the inhibition rate of the sample on angiotensin-converting enzyme is significantly improved; and the tetrahydroisoquinoline derivative has good application values and development and application prospects.
- -
-
Paragraph 0033; 0042
(2016/10/27)
-
- ACE inhibitors hypothesis generation for selective design, synthesis and biological evaluation of 3-mercapto-2-methyl-propanoyl-pyrrolidine-3-imine derivatives as antihypertensive agents
-
A series of new 3-mercapto-2-methyl-propanoyl-pyrrolidine derivatives (V, VIa-e) were designed. A new validated ACE inhibitors pharmacophore model (hypothesis) was generated for the first time in this research from the biologically active (frozen) conform
- Ismail, Mohamed A.H.,Nabil Aboul-Enein,Abouzid, Khaled A.M.,Abou El Ella, Dalal A.,Ismail, Nasser S.M.
-
scheme or table
p. 3739 - 3746
(2009/09/30)
-
- Asymmetric induction in the conjugate addition of thioacetic acid to methacrylamides with chiral auxiliaries
-
The conjugate addition of thioacetic acid to methacrylamides with chiral C2-symmetric trans-2,5-disubstituted pyrrolidines afforded the addition products in excellent stereoselectivities (>99% de) and good yields (80-90%). The high selectivity was attributed mainly to the steric effect of the chiral auxiliaries. The cyclic nature of the chiral auxiliaries seemed also important for both the stereoselectivity and the reaction rate. Acidic hydrolysis of the adduct containing (2R,5R)-bis(methoxymethyl)pyrrolidine gave (S)-3-mercapto-2-methylpropanoic acid, a key intermediate for captopril, in 98% ee and 96% yield. The chiral auxiliary was recovered in the demethylated form of N-Boc-(2R,3R)-bis(hydroxymethyl)pyrrolidine in 90% yield.
- Kim, Byung Hyun,Lee, Hee Bong,Hwang, Jae Kwang,Kim, Young Gyu
-
p. 1215 - 1220
(2007/10/03)
-
- Angiotensin-Converting Enzyme Inhibitors. New Orally Active Antihypertensive (Mercaptoalkanoyl)- and glycine Derivatives
-
A variety of N-substituted (mercaptoalkanoyl)- and glycine derivatives was synthesized and their ability in inhibiting the activity of angiotensin-converting enzyme (ACE) was examined in vitro and in vivo.The acylthio derivatives prepared are assumed to act as prodrugs since they are much less active than the corresponding free SH compounds in vitro and can be expected to act in vivo only after conversion to the free sulfhydryl compounds.A number of this compounds are potent ACE inhibitors that lowered blood pressure in Na-deficient, conscious spontaneously hypertensive rats (SHR), a high renin model.One of the most active members of the series was (S)-N-cyclopentyl-N--2-methyl-1-oxopropyl>glycine (REV 3659-(S), pivopril).Structure-activity relationships are discussed.
- Suh, John T.,Skiles, Jerry W.,Williams, Bruce E.,Youssefyeh, Raymond D.,Jones, Howard,et al.
-
-
- HALOGENATED SUBSTITUTED MERCAPTOACYLAMINO ACIDS
-
New halogen substituted mercaptoacylamino acids which have the general formula STR1 and basic salts thereof are useful as hypotensive agents.
- -
-
-