The design and synthesis of thrombin inhibitors: Analogues of MD805 containing non-polar surrogates for arginine at the P1 position

被引：10

作者：

Baettig, U ^{[1
]}

Brown, L ^{[1
]}

Brundish, D ^{[1
]}

Dell, C ^{[1
]}

Furzer, A ^{[1
]}

Garman, S ^{[1
]}

Janus, D ^{[1
]}

Kane, PD ^{[1
]}

Smith, G ^{[1
]}

Walker, CV ^{[1
]}

Cockcroft, XL ^{[1
]}

Ambler, J ^{[1
]}

Mitchelson, A ^{[1
]}

Talbot, MD ^{[1
]}

Tweed, M ^{[1
]}

Wills, N ^{[1
]}

机构：

[1] Novartis Horsham Res Ctr, Horsham RH12 4AB, W Sussex, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2000年 / 10卷 / 14期

关键词：

D O I：

10.1016/S0960-894X(00)00282-1

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of monocyclic and bicyclic amino acids have been synthesised and incorporated into thrombin inhibitors based on CGH728, an analogue of the Mitsubishi compound MD805. Benzthiazolylalanine (Bta) was found to be a good non-polar substitute for arginine at the P1 position, yielding compounds with low nanomolar potency and good selectivity for thrombin. (C) 2000 Elsevier Science Ltd. All rights reserved.

引用

页码：1563 / 1566

页数：4

共 25 条

[1] Design and synthesis of thrombin inhibitors: Analogues of MD-805 with reduced stereogenicity and improved potency
Brundish, D
Bull, A
Donovan, V
Fullerton, JD
Garman, SM
Hayler, JF
Janus, D
Kane, PD
McDonnell, M
Smith, GP
Wakeford, R
Walker, CV
Howarth, G
Hoyle, W
Allen, MC
Ambler, J
Butler, K
Talbot, MD
JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (22) : 4584 - 4603
[2] Design and synthesis of a series of potent and orally bioavailable noncovalent thrombin inhibitors that utilize nonbasic groups in the P1 position
Tucker, TJ
Brady, SF
Lumma, WC
Lewis, SD
Gardell, SJ
Naylor-Olsen, AM
Yan, YW
Sisko, JT
Stauffer, KJ
Lucas, BJ
Lynch, JJ
Cook, JJ
Stranieri, MT
Holahan, MA
Lyle, EA
Baskin, EP
Chen, IW
Dancheck, KB
Krueger, JA
Cooper, CM
Vacca, JP
JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (17) : 3210 - 3219
[3] The design and synthesis of a series of potent and orally bioavailable non-covalent thrombin inhibitors that utilize non-basic groups in the P1 position.
Tucker, TJ
Brady, SF
Lumma, WC
Lewis, SD
Gardell, SJ
Naylor-Olsen, AM
Yan, YW
Sisko, JT
Stauffer, KJ
Lucas, BJ
Lynch, JJ
Cook, JJ
Stranieri, MT
Holahan, MA
Lyle, EA
Baskin, EP
Chen, IW
Dancheck, KB
Krueger, JA
Cooper, CM
Vacca, JP
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 1998, 216 : U207 - U207
[4] Non-covalent thrombin inhibitors featuring P3-heterocycles with P1-bicyclic arginine surrogates
Cui, JRJ
Araldi, GL
Reiner, JE
Reddy, KM
Kemp, SJ
Ho, JZ
Siev, DV
Mamedova, L
Gibson, TS
Gaudette, JA
Minami, NK
Anderson, SM
Bradbury, AE
Nolan, TG
Semple, JE
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (20) : 2925 - 2930
[5] Non-covalent thrombin inhibitors featuring P3-heterocycles with P1-monocyclic arginine surrogates
Reiner, JE
Siev, DV
Araldi, GL
Cui, JRJ
Ho, JZ
Reddy, KM
Mamedova, L
Vu, PH
Lee, KSS
Minami, NK
Gibson, TS
Anderson, SM
Bradbury, AE
Nolan, TG
Semple, JE
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (08) : 1203 - 1208
[6] Non-covalent thrombin inhibitors featuring P3-heterocycles with P1-monocyclic arginine surrogates.
Semple, JE
Reiner, JE
Cui, JRJ
Siev, DV
Araldi, GL
Ho, JZ
Vu, PH
Lee, KSS
Minami, NK
Gibson, TS
Givson, TS
Anderson, SM
Bradbury, AE
Nolan, TG
Dixon, SA
Ma, MG
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2001, 222 : U679 - U679
[7] Potent non-covalent thrombin inhibitors featuring P3-heterocycles with P1-aminobenzisoxazole arginine surrogates.
Semple, JE
Araldi, GL
Cui, JRJ
Kemp, S
Komandla, M
Siev, DV
Mamedova, L
Reiner, JE
Gibson, TS
Gaudette, JA
Minami, N
Lawrence, CM
Anderson, SM
Bradbury, AE
Nolan, TG
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2002, 224 : U57 - U57
[8] Novel non-covalent azaphenylalanine thrombin inhibitors with an amino-methyl or amino group at the P1 position
Obreza, A
Stegnar, M
Urleb, U
PHARMAZIE, 2004, 59 (09): : 659 - 667
[9] Design, synthesis, and biological evaluation of pyrazinones containing novel P1 needles as inhibitors of TF/VIIa
Trujillo, John I.
Huang, Horng-Chih
Neumann, William L.
Mahoney, Matthew W.
Long, Scott
Huang, Wei
Garland, Danny J.
Kusturin, Carrie
Abbas, Zaheer
South, Michael S.
Reitz, David B.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (16) : 4568 - 4574
[10] Novel inhibitors of HIV protease: Design, synthesis and biological evaluation of picomolar inhibitors containing cyclic P1/P2 scaffolds
Spaltenstein, A
Almond, MR
Bock, WJ
Cleary, DG
Furfine, ES
Hazen, RJ
Kazmierski, WM
Salituro, FG
Tung, RD
Wright, LL
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2000, 10 (11) : 1159 - 1162

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