Synthesis of analogs of (1,4)-3- and 5-imino oxazepane, thiazepane, and diazepane as inhibitors of nitric oxide synthases

K. Shankaran; Karla L. Donnelly; Shrenik K. Shah; Charles G. Caldwell; Ping Chen; William K. Hagmann; Malcolm MacCoss; John L. Humes; Stephen G. Pacholok; Theresa M. Kelly; Stephan K. Grant; Kenny K. Wong

doi:10.1016/j.bmcl.2004.09.019

Synthesis of analogs of (1,4)-3- and 5-imino oxazepane, thiazepane, and diazepane as inhibitors of nitric oxide synthases

K. Shankaran
, Karla L. Donnelly
, Shrenik K. Shah
, Charles G. Caldwell
, Ping Chen
, William K. Hagmann
, Malcolm MacCoss
, John L. Humes
, Stephen G. Pacholok
, Theresa M. Kelly
, Stephan K. Grant
, Kenny K. Wong

Department of Chemistry and Chemical Biology

Merck

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

Abstract

The preparation and SAR of a series of iNOS inhibitors leading to the most potent compound, incorporating a (1,4)-5-imino thiazepane (R = n-Pr) is disclosed. A series of 3- and 5-imino analogs from oxazepane, thiazepane, and diazepane was prepared and evaluated as inhibitors of human nitric oxide synthesis (NOS). The most potent iNOS inhibitor was the thiazepane analog 25 (IC ₅₀ = 0.19 μM).

Original language	English
Pages (from-to)	5907-5911
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	14
Issue number	23
DOIs	https://doi.org/10.1016/j.bmcl.2004.09.019
State	Published - 6 Dec 2004

Keywords

NOS synthase

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10.1016/j.bmcl.2004.09.019

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Shankaran, K., Donnelly, K. L., Shah, S. K., Caldwell, C. G., Chen, P., Hagmann, W. K., MacCoss, M., Humes, J. L., Pacholok, S. G., Kelly, T. M., Grant, S. K., & Wong, K. K. (2004). Synthesis of analogs of (1,4)-3- and 5-imino oxazepane, thiazepane, and diazepane as inhibitors of nitric oxide synthases. Bioorganic and Medicinal Chemistry Letters, 14(23), 5907-5911. https://doi.org/10.1016/j.bmcl.2004.09.019

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title = "Synthesis of analogs of (1,4)-3- and 5-imino oxazepane, thiazepane, and diazepane as inhibitors of nitric oxide synthases",

abstract = "The preparation and SAR of a series of iNOS inhibitors leading to the most potent compound, incorporating a (1,4)-5-imino thiazepane (R = n-Pr) is disclosed. A series of 3- and 5-imino analogs from oxazepane, thiazepane, and diazepane was prepared and evaluated as inhibitors of human nitric oxide synthesis (NOS). The most potent iNOS inhibitor was the thiazepane analog 25 (IC 50 = 0.19 μM).",

keywords = "NOS synthase",

author = "K. Shankaran and Donnelly, \{Karla L.\} and Shah, \{Shrenik K.\} and Caldwell, \{Charles G.\} and Ping Chen and Hagmann, \{William K.\} and Malcolm MacCoss and Humes, \{John L.\} and Pacholok, \{Stephen G.\} and Kelly, \{Theresa M.\} and Grant, \{Stephan K.\} and Wong, \{Kenny K.\}",

year = "2004",

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doi = "10.1016/j.bmcl.2004.09.019",

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Shankaran, K, Donnelly, KL, Shah, SK, Caldwell, CG, Chen, P, Hagmann, WK, MacCoss, M, Humes, JL, Pacholok, SG, Kelly, TM, Grant, SK & Wong, KK 2004, 'Synthesis of analogs of (1,4)-3- and 5-imino oxazepane, thiazepane, and diazepane as inhibitors of nitric oxide synthases', Bioorganic and Medicinal Chemistry Letters, vol. 14, no. 23, pp. 5907-5911. https://doi.org/10.1016/j.bmcl.2004.09.019

TY - JOUR

T1 - Synthesis of analogs of (1,4)-3- and 5-imino oxazepane, thiazepane, and diazepane as inhibitors of nitric oxide synthases

AU - Shankaran, K.

AU - Donnelly, Karla L.

AU - Shah, Shrenik K.

AU - Caldwell, Charles G.

AU - Chen, Ping

AU - Hagmann, William K.

AU - MacCoss, Malcolm

AU - Humes, John L.

AU - Pacholok, Stephen G.

AU - Kelly, Theresa M.

AU - Grant, Stephan K.

AU - Wong, Kenny K.

PY - 2004/12/6

Y1 - 2004/12/6

N2 - The preparation and SAR of a series of iNOS inhibitors leading to the most potent compound, incorporating a (1,4)-5-imino thiazepane (R = n-Pr) is disclosed. A series of 3- and 5-imino analogs from oxazepane, thiazepane, and diazepane was prepared and evaluated as inhibitors of human nitric oxide synthesis (NOS). The most potent iNOS inhibitor was the thiazepane analog 25 (IC 50 = 0.19 μM).

AB - The preparation and SAR of a series of iNOS inhibitors leading to the most potent compound, incorporating a (1,4)-5-imino thiazepane (R = n-Pr) is disclosed. A series of 3- and 5-imino analogs from oxazepane, thiazepane, and diazepane was prepared and evaluated as inhibitors of human nitric oxide synthesis (NOS). The most potent iNOS inhibitor was the thiazepane analog 25 (IC 50 = 0.19 μM).

KW - NOS synthase

UR - https://www.scopus.com/pages/publications/7044269371

UR - https://www.scopus.com/pages/publications/7044269371#tab=citedBy

U2 - 10.1016/j.bmcl.2004.09.019

DO - 10.1016/j.bmcl.2004.09.019

M3 - Article

C2 - 15501067

AN - SCOPUS:7044269371

SN - 0960-894X

VL - 14

SP - 5907

EP - 5911

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 23

ER -

Synthesis of analogs of (1,4)-3- and 5-imino oxazepane, thiazepane, and diazepane as inhibitors of nitric oxide synthases

Abstract

Keywords

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