Piperidine-based renin inhibitors: Upper chain optimization

被引：22

作者：

Corminboeuf, Olivier ^{[1
]}

Bezencon, Olivier ^{[1
]}

Remen, Lubos ^{[1
]}

Grisostomi, Corinna ^{[1
]}

Richard-Bildstein, Sylvia ^{[1
]}

Bur, Daniel ^{[1
]}

Prade, Lars ^{[1
]}

Strickner, Panja ^{[1
]}

Hess, Patrick ^{[1
]}

Fischli, Walter ^{[1
]}

Steiner, Beat ^{[1
]}

Treiber, Alexander ^{[1
]}

机构：

[1] Actel Pharmaceut Ltd, Drug Discovery Chem & Biochem, CH-4123 Allschwil, Switzerland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 21期

关键词：

Hypertension; Renin angiotensin aldosterone system; Renin inhibitor; Piperidine; ALPHA; BETA-UNSATURATED CARBONYL-COMPOUNDS; BLOOD-PRESSURE; HEART-RATE; RADIOTELEMETRY; REDUCTION; DESIGN; POTENT; RAT;

D O I：

10.1016/j.bmcl.2010.08.087

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The optimization of the 4-position of recently described new 3,4-disubstituted piperidine-based renin inhibitors is reported herein. The synthesis and characterization of compounds leading to the discovery of 11 (ACT-178882, MK-1597), a renin inhibitor with a suitable profile for development is described. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：6291 / 6296

页数：6

共 11 条

[1] Design and Preparation of Potent, Nonpeptidic, Bioavailable Renin Inhibitors [J].

Bezencon, Olivier ;

Bur, Daniel ;

Weller, Thomas ;

Richard-Bildstein, Sylvia ;

Remen, Lubos ;

Sifferlen, Thierry ;

Corminboeuf, Olivier ;

Grisostomi, Corinna ;

Boss, Christoph ;

Prade, Lars ;

Delahaye, Stephane ;

Treiber, Alexander ;

Strickner, Panja ;

Binkert, Christoph ;

Hess, Patrick ;

Steiner, Beat ;

Fischli, Walter .

JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (12) :3689-3702

[2] A NEW METHOD FOR CONTINUOUS CHRONIC MEASUREMENT AND RECORDING OF BLOOD-PRESSURE, HEART-RATE AND ACTIVITY IN THE RAT VIA RADIOTELEMETRY [J].

BROCKWAY, BP ;

MILLS, PA ;

AZAR, SH .

CLINICAL AND EXPERIMENTAL HYPERTENSION PART A-THEORY AND PRACTICE, 1991, 13 (05) :885-895

[3] Design and optimization of new piperidines as renin inhibitors [J].

Corminboeuf, Olivier ;

Bezencon, Olivier ;

Grisostomi, Corinna ;

Remen, Lubos ;

Richard-Bildstein, Sylvia ;

Bur, Daniel ;

Prade, Lars ;

Hess, Patrick ;

Strickner, Panja ;

Fischli, Walter ;

Steiner, Beat ;

Treiber, Alexander .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (21) :6286-6290

[4] LITHIUM AND POTASSIUM TRIALKYLBOROHYDRIDES - REAGENTS FOR DIRECT REDUCTION OF ALPHA,BETA-UNSATURATED CARBONYL-COMPOUNDS TO SYNTHETICALLY VERSATILE ENOLATE ANIONS [J].

FORTUNATO, JM ;

GANEM, B .

JOURNAL OF ORGANIC CHEMISTRY, 1976, 41 (12) :2194-2200

[5] A RADIOTELEMETRY SYSTEM FOR CHRONIC MEASUREMENT OF BLOOD-PRESSURE AND HEART-RATE IN THE UNRESTRAINED RAT VALIDATION OF THE METHOD [J].

GUIOL, C ;

LEDOUSSAL, C ;

SURGE, JM .

JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS, 1992, 28 (02) :99-105

[6] Piperidine-renin inhibitors compounds with improved physicochemical properties [J].

Güller, R ;

Binggeli, A ;

Breu, V ;

Bur, D ;

Fischli, W ;

Hirth, G ;

Jenny, C ;

Kansy, M ;

Montavon, F ;

Müller, M ;

Oefner, C ;

Stadler, H ;

Vieira, E ;

Wilhelm, M ;

Wostl, W ;

Märki, HP .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1999, 9 (10) :1403-1408

[7] Telemetry monitoring of pulmonary arterial pressure in freely moving rats [J].

Hess, P ;

Clozel, M ;

Clozel, JP .

JOURNAL OF APPLIED PHYSIOLOGY, 1996, 81 (02) :1027-1032

[8] A NOVEL SYNTHETIC APPROACH TO STEROIDS VIA INTRAMOLECULAR 1,3-DIPOLAR CYCLOADDITION - A HIGHLY STEREOCONTROLLED SYNTHESIS OF TESTOSTERONE [J].

IHARA, M ;

TOKUNAGA, Y ;

FUKUMOTO, K .

JOURNAL OF ORGANIC CHEMISTRY, 1990, 55 (15) :4497-4498

[9] Conjugate reduction of α,β-unsaturated carbonyl compounds catalyzed by a copper carbene complex [J].

Jurkauskas, V ;

Sadighi, JP ;

Buchwald, SL .

ORGANIC LETTERS, 2003, 5 (14) :2417-2420

[10] 2-carbomethoxy-3-aryl-8-bicyclo[3.2.1]octanes: Potent non-nitrogen inhibitors of monoamine transporters [J].

Meltzer, PC ;

Blundell, P ;

Yong, YF ;

Chen, ZM ;

George, C ;

Gonzalez, MD ;

Madras, BK .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (16) :2982-2991

← 1 2 →