CCR5 antagonists: 3-(pyrrolidin-1-yl)propionic acid analogues with potent anti-HIV activity

被引：17

作者：

Lynch, CL

Hale, JJ

Budhu, RJ

Gentry, AL

Finke, PE

Caldwell, CG

Mills, SG

MacCoss, M

Shen, DM

Chapman, KT

Malkowitz, L

Springer, MS

Gould, SL

DeMartino, JA

Siciliano, SJ

Cascieri, MA

Carella, A

Carver, G

Karen, H

Schleif, WA

Danzeisen, R

Hazuda, D

Kessler, J

Lineberger, J

Miller, M

Emini, E

机构：

[1] Merck Res Labs, Dept Med Chem, Rahway, NJ 07065 USA

[2] Merck Res Labs, Dept Immunol Res, Rahway, NJ 07065 USA

[3] Merck Res Labs, Dept Antiviral Res, W Point, PA 19486 USA

来源：

ORGANIC LETTERS | 2003年 / 5卷 / 14期

关键词：

D O I：

10.1021/ol034707c

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

graphic A novel approach to alpha,alpha-disubstituted-beta-amino acids (beta(2,2)-amino acids) was employed in the synthesis of a series of 3-(pyrrolidin-1-yl)-propionic acids possessing high affinity for the CCR5 receptor and potent anti-HIV activity. The rat pharmacokinetics for these new analogues featured higher bioavailabilities and lower rates of clearance as compared to cyclopentane 1.

引用

页码：2473 / 2475

页数：3

共 50 条

[41] Synthesis, antimycobacterial activity, and acid dissociation constants of polyfunctionalized 3-[2-(pyrrolidin-1-yl)thiazole-5-carbonyl]-2H-chromen-2-one derivatives [J].

Nural, Yahya .

MONATSHEFTE FUR CHEMIE, 2018, 149 (10) :1905-1918

[42] Potent 1,3,4-trisubstituted pyrrolidine CCR5 receptor antagonists: effects of fused heterocycles on antiviral activity and pharmacokinetic properties [J].

Kim, D ;

Wang, LP ;

Hale, JJ ;

Lynch, CL ;

Budhu, RJ ;

MacCross, M ;

Mills, SG ;

Malkowitz, L ;

Gould, SL ;

DeMartino, JA ;

Springer, MS ;

Hazuda, D ;

Miller, M ;

Kessler, J ;

Hrin, RC ;

Carver, G ;

Carella, A ;

Henry, K ;

Lineberger, J ;

Schleif, WA ;

Emini, EA .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (08) :2129-2134

[43] Discovery of a piperidine-4-carboxamide CCR5 antagonist (TAK-220) with highly potent anti-HIV-1 activity [J].

Imamura, S ;

Ichikawa, T ;

Nishikawa, Y ;

Kanzaki, N ;

Takashima, K ;

Niwa, S ;

Iizawa, Y ;

Baba, M ;

Sugihara, Y .

JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (09) :2784-2793

[44] Synthesis and biological evaluation of 5-(piperidrn-1-yl)-3-phenyl-pentylsulfones as CCR5 antagonists for the treatment of HIV-1 infection. [J].

Shankaran, K ;

Donnelly, KF ;

Shah, SK ;

Mills, SG ;

MacCross, M ;

Fink, PE ;

Caldwell, CG ;

Chen, P ;

Oates, B ;

Malkowitz, L ;

Springer, MS ;

DeMartin, J ;

Cascieri, MA ;

Gould, SL ;

Schlief, WA ;

Carella, A ;

Carver, G ;

Holmes, K ;

Emini, EA .

ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2000, 220 :U552-U552

[45] Mitigating hERG Inhibition: Design of Orally Bioavailable CCR5 Antagonists as Potent Inhibitors of R5 HIV-1 Replication [J].

Skerlj, Renato ;

Bridger, Gary ;

Zhou, Yuanxi ;

Bourque, Elyse ;

McEachern, Ernest ;

Danthi, Sanjay ;

Langille, Jonathan ;

Harwig, Curtis ;

Veale, Duane ;

Carpenter, Bryon ;

Ba, Tuya ;

Bey, Michael ;

Baird, Ian ;

Wilson, Trevor ;

Metz, Markus ;

MacFarland, Ron ;

Mosi, Renee ;

Bodart, Veronique ;

Wong, Rebecca ;

Fricker, Simon ;

Huskens, Dana ;

Schols, Dominique .

ACS MEDICINAL CHEMISTRY LETTERS, 2012, 3 (03) :216-221

[46] SYNTHESIS OF NOVEL 6′-SPIROCYCLOPROPYL-5′-NORCARBOCYCLIC ADENOSINE PHOSPHONIC ACID ANALOGUES AS POTENT ANTI-HIV AGENTS [J].

Liu, Lian Jin ;

Kim, Eunae ;

Hong, Joon Hee .

NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS, 2011, 30 (10) :784-797

[47] Highly potent and orally active CCR5 antagonists as anti-HIV-1 agents: Synthesis and biological activities of 1-benzazocine derivatives containing a sulfoxide moiety [J].

Seto, M ;

Aikawa, K ;

Miyamoto, N ;

Aramaki, Y ;

Kanzaki, N ;

Takashima, K ;

Kuze, Y ;

Iizawa, Y ;

Baba, M ;

Shiraishi, M .

JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (06) :2037-2048

[48] Rapamycin causes down-regulation of CCR5 and accumulation of anti-HIV β-chemokines:: An approach to suppress R5 strains of HIV-1 [J].

Heredia, A ;

Amoroso, A ;

Davis, C ;

Le, N ;

Reardon, E ;

Dominique, JK ;

Klingebiel, E ;

Gallo, RC ;

Redfield, RR .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (18) :10411-10416

[49] Design, antiviral and pharmacokinetic profiles of potent 1,3,4-trisubstituted pyrrolidine CCR5 receptor antagonists for the treatment of HIV-1 infection. [J].

Kim, D ;

Wang, LP ;

Hale, JJ ;

Lynch, C ;

Budhu, RJ ;

MacCoss, M ;

Mills, SG ;

Malkowitz, L ;

Gould, SL ;

DeMartino, JA ;

Springer, MS ;

Hazuda, D ;

Kessler, J ;

Danzeisen, R ;

Carella, A ;

Holmes, K ;

Lineberger, J ;

Schleif, WA ;

Emini, EA .

ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2003, 226 :U30-U30

[50] 3-[2-(pyrrolidin-1-yl)ethyl]indoles and 3-[3-(piperidin-1-yl)propyl]indoles: Agonists for the h5-HT1D receptor with high selectivity over the h5-HT1B subtype [J].

Castro, JL ;

Street, LJ ;

Guiblin, AR ;

Jelley, RA ;

Russell, MGN ;

Sternfeld, F ;

Beer, MS ;

Stanton, JA ;

Matassa, VG .

JOURNAL OF MEDICINAL CHEMISTRY, 1997, 40 (22) :3497-3500

← 1 2 3 4 5 →