Discovery and optimization of imidazo[1,2-a]pyridine inhibitors of insulin-like growth factor-1 receptor (IGF-1R)

Kyle A. Emmitte; Brian J. Wilson; Erich W. Baum; Holly K. Emerson; Kevin W. Kuntz; Kristen E. Nailor; James M. Salovich; Stephon C. Smith; Mui Cheung; Roseanne M. Gerding; Kirk L. Stevens; David E. Uehling; Robert A. Mook; Ganesh S. Moorthy; Scott H. Dickerson; Anne M. Hassell; M. Anthony Leesnitzer; Lisa M. Shewchuk; Arthur Groy; Jason L. Rowand; Kelly Anderson; Charity L. Atkins; Jingsong Yang; Peter Sabbatini; Rakesh Kumar

doi:10.1016/j.bmcl.2008.11.058

Discovery and optimization of imidazo[1,2-a]pyridine inhibitors of insulin-like growth factor-1 receptor (IGF-1R)

Kyle A. Emmitte, Brian J. Wilson, Erich W. Baum, Holly K. Emerson, Kevin W. Kuntz, Kristen E. Nailor, James M. Salovich, Stephon C. Smith, Mui Cheung, Roseanne M. Gerding, Kirk L. Stevens, David E. Uehling, Robert A. Mook, Ganesh S. Moorthy, Scott H. Dickerson, Anne M. Hassell, M. Anthony Leesnitzer, Lisa M. Shewchuk, Arthur Groy, Jason L. RowandKelly Anderson, Charity L. Atkins, Jingsong Yang, Peter Sabbatini, Rakesh Kumar

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Abstract

The optimization of imidazo[1,2-a]pyridine inhibitors as potent and selective inhibitors of IGF-1R is presented. Further optimization of oral exposure in mice is also discussed. Detailed selectivity, in vitro activity, and in vivo PK profiles of an optimized compound is also highlighted.

Original language	English
Pages (from-to)	1004-1008
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	19
Issue number	3
DOIs	https://doi.org/10.1016/j.bmcl.2008.11.058
State	Published - 1 Feb 2009

Keywords

Cancer
Imidazo[1,2-a]pyridine
Insulin receptor
Insulin-like growth factor-1 receptor
Kinase inhibitor

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10.1016/j.bmcl.2008.11.058

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Emmitte, K. A., Wilson, B. J., Baum, E. W., Emerson, H. K., Kuntz, K. W., Nailor, K. E., Salovich, J. M., Smith, S. C., Cheung, M., Gerding, R. M., Stevens, K. L., Uehling, D. E., Mook, R. A., Moorthy, G. S., Dickerson, S. H., Hassell, A. M., Anthony Leesnitzer, M., Shewchuk, L. M., Groy, A., ... Kumar, R. (2009). Discovery and optimization of imidazo[1,2-a]pyridine inhibitors of insulin-like growth factor-1 receptor (IGF-1R). Bioorganic and Medicinal Chemistry Letters, 19(3), 1004-1008. https://doi.org/10.1016/j.bmcl.2008.11.058

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title = "Discovery and optimization of imidazo[1,2-a]pyridine inhibitors of insulin-like growth factor-1 receptor (IGF-1R)",

abstract = "The optimization of imidazo[1,2-a]pyridine inhibitors as potent and selective inhibitors of IGF-1R is presented. Further optimization of oral exposure in mice is also discussed. Detailed selectivity, in vitro activity, and in vivo PK profiles of an optimized compound is also highlighted.",

keywords = "Cancer, Imidazo[1,2-a]pyridine, Insulin receptor, Insulin-like growth factor-1 receptor, Kinase inhibitor",

author = "Emmitte, {Kyle A.} and Wilson, {Brian J.} and Baum, {Erich W.} and Emerson, {Holly K.} and Kuntz, {Kevin W.} and Nailor, {Kristen E.} and Salovich, {James M.} and Smith, {Stephon C.} and Mui Cheung and Gerding, {Roseanne M.} and Stevens, {Kirk L.} and Uehling, {David E.} and Mook, {Robert A.} and Moorthy, {Ganesh S.} and Dickerson, {Scott H.} and Hassell, {Anne M.} and {Anthony Leesnitzer}, M. and Shewchuk, {Lisa M.} and Arthur Groy and Rowand, {Jason L.} and Kelly Anderson and Atkins, {Charity L.} and Jingsong Yang and Peter Sabbatini and Rakesh Kumar",

year = "2009",

month = feb,

day = "1",

doi = "10.1016/j.bmcl.2008.11.058",

language = "English",

volume = "19",

pages = "1004--1008",

journal = "Bioorganic and Medicinal Chemistry Letters",

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Emmitte, KA, Wilson, BJ, Baum, EW, Emerson, HK, Kuntz, KW, Nailor, KE, Salovich, JM, Smith, SC, Cheung, M, Gerding, RM, Stevens, KL, Uehling, DE, Mook, RA, Moorthy, GS, Dickerson, SH, Hassell, AM, Anthony Leesnitzer, M, Shewchuk, LM, Groy, A, Rowand, JL, Anderson, K, Atkins, CL, Yang, J, Sabbatini, P & Kumar, R 2009, 'Discovery and optimization of imidazo[1,2-a]pyridine inhibitors of insulin-like growth factor-1 receptor (IGF-1R)', Bioorganic and Medicinal Chemistry Letters, vol. 19, no. 3, pp. 1004-1008. https://doi.org/10.1016/j.bmcl.2008.11.058

TY - JOUR

T1 - Discovery and optimization of imidazo[1,2-a]pyridine inhibitors of insulin-like growth factor-1 receptor (IGF-1R)

AU - Emmitte, Kyle A.

AU - Wilson, Brian J.

AU - Baum, Erich W.

AU - Emerson, Holly K.

AU - Kuntz, Kevin W.

AU - Nailor, Kristen E.

AU - Salovich, James M.

AU - Smith, Stephon C.

AU - Cheung, Mui

AU - Gerding, Roseanne M.

AU - Stevens, Kirk L.

AU - Uehling, David E.

AU - Mook, Robert A.

AU - Moorthy, Ganesh S.

AU - Dickerson, Scott H.

AU - Hassell, Anne M.

AU - Anthony Leesnitzer, M.

AU - Shewchuk, Lisa M.

AU - Groy, Arthur

AU - Rowand, Jason L.

AU - Anderson, Kelly

AU - Atkins, Charity L.

AU - Yang, Jingsong

AU - Sabbatini, Peter

AU - Kumar, Rakesh

PY - 2009/2/1

Y1 - 2009/2/1

N2 - The optimization of imidazo[1,2-a]pyridine inhibitors as potent and selective inhibitors of IGF-1R is presented. Further optimization of oral exposure in mice is also discussed. Detailed selectivity, in vitro activity, and in vivo PK profiles of an optimized compound is also highlighted.

AB - The optimization of imidazo[1,2-a]pyridine inhibitors as potent and selective inhibitors of IGF-1R is presented. Further optimization of oral exposure in mice is also discussed. Detailed selectivity, in vitro activity, and in vivo PK profiles of an optimized compound is also highlighted.

KW - Cancer

KW - Imidazo[1,2-a]pyridine

KW - Insulin receptor

KW - Insulin-like growth factor-1 receptor

KW - Kinase inhibitor

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U2 - 10.1016/j.bmcl.2008.11.058

DO - 10.1016/j.bmcl.2008.11.058

M3 - Article

C2 - 19101143

AN - SCOPUS:58549088976

SN - 0960-894X

VL - 19

SP - 1004

EP - 1008

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 3

ER -

Discovery and optimization of imidazo[1,2-a]pyridine inhibitors of insulin-like growth factor-1 receptor (IGF-1R)

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