Potent and selective proline derived dipeptidyl peptidase IV inhibitors

被引：49

作者：

Edmondson, SD

Mastracchio, A

Beconi, M

Colwell, LF

Habulihaz, B

He, HB

Kumar, SJ

Leiting, B

Lyons, KA

Mao, A

Marsilio, F

Patel, RA

Wu, JK

Zhu, L

Thornberry, NA

Weber, AE

Parmee, ER

机构：

[1] Merck & Co Inc, Dept Med Chem, Rahway, NJ 07065 USA

[2] Merck & Co Inc, Dept Drug Metab, Rahway, NJ 07065 USA

[3] Merck & Co Inc, Dept Metab Disorders, Rahway, NJ 07065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 20期

关键词：

dipeptidyl peptidase IV; selective; proline amide; thiazolidine; type; 2; diabetes;

D O I：

10.1016/j.bmcl.2004.07.056

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In-house screening of the Merck sample collection identified proline derived homophenylalanine 3 as a DPP-IV inhibitor with modest potency (DPP-IV IC50 = 1.9 muM). Optimization of 3 led to compound 37, which is among the most potent and selective DPP-IV inhibitors discovered to date. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：5151 / 5155

页数：5

共 19 条

[1] Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes
Ahrén, B
Landin-Olsson, M
Jansson, PA
Svensson, M
Holmes, D
Schweizer, A
[J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2004, 89 (05) : 2078 - 2084
[2] 2-cyanopyrrolidides as potent, stable inhibitors of dipeptidyl peptidase IV
Ashworth, DM
Atrash, B
Baker, GR
Baxter, AJ
Jenkins, PD
Jones, DM
Szelke, M
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1996, 6 (10) : 1163 - 1166
[3] Dipeptidyl peptidase IV inhibitors as new therapeutic agents for the treatment of Type 2 diabetes
Augustyns, K
Van der Veken, P
Senten, K
Haemers, A
[J]. EXPERT OPINION ON THERAPEUTIC PATENTS, 2003, 13 (04) : 499 - 510
[4] Substituted piperazines as novel dipeptidyl peptidase IV inhibitors
Brockunier, LL
He, JF
Colwell, LF
Habulihaz, B
He, HB
Leiting, B
Lyons, KA
Marsilio, F
Patel, RA
Teffera, Y
Wu, JK
Thornberry, NA
Ann, AE
Parmee, ER
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (18) : 4763 - 4766
[5] Therapeutic potential of dipeptidyl peptidase IV inhibitors for the treatment of type 2 diabetes
Drucker, DJ
[J]. EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2003, 12 (01) : 87 - 100
[6] Glucagon-like peptide-1 receptor is involved in learning and neuroprotection
During, MJ
Cao, L
Zuzga, DS
Francis, JS
Fitzsimons, HL
Jiao, XY
Bland, RJ
Klugmann, M
Banks, WA
Drucker, DJ
Haile, CN
[J]. NATURE MEDICINE, 2003, 9 (09) : 1173 - 1179
[7] Optimization of a tertiary alcohol series of phosphodiesterase-4 (PDE4) inhibitors:: Structure-activity relationship related to PDE4 inhibition and human ether-a-go-go related gene potassium channel binding affinity
Friesen, RW
Ducharme, Y
Ball, RG
Blouin, M
Boulet, L
Côté, B
Frenette, R
Girard, M
Guay, D
Huang, Z
Jones, TR
Laliberté, F
Lynch, JJ
Mancini, J
Martins, E
Masson, P
Muise, E
Pon, DJ
Siegl, PKS
Styhler, A
Tsou, NN
Turner, MJ
Young, RN
Girard, Y
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (12) : 2413 - 2426
[8] Lankas G, 2004, DIABETES, V53, pA2
[9] ON THE PREPARATION OF BETA-AMINO ACIDS FROM ALPHA-AMINO-ACIDS USING THE ARNDT-EISTERT REACTION - SCOPE, LIMITATIONS AND STEREOSELECTIVITY. APPLICATION TO CARBOHYDRATE PEPTIDATION - STEREOSELECTIVE ALPHA-ALKYLATIONS OF SOME BETA-AMINO ACIDS
PODLECH, J
SEEBACH, D
[J]. LIEBIGS ANNALEN, 1995, (07): : 1217 - 1228
[10] Dipeptidyl peptidase IV inhibitor treatment stimulates β-cell survival and islet neogenesis in streptozotocin-induced diabetic rats
Pospisilik, JA
Martin, J
Doty, T
Ehses, JA
Pamir, N
Lynn, FC
Piteau, S
Demuth, HU
McIntosh, CHS
Pederson, RA
[J]. DIABETES, 2003, 52 (03) : 741 - 750

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