A novel series of arylsulfonylthiophene-2-carboxamidine inhibitors of the complement component C1s

Nalin L. Subasinghe; Jeremy M. Travins; Farah Ali; Hui Huang; Shelley K. Ballentine; Juan José Marugán; Ehab Khalil; Heather R. Hufnagel; Roger F. Bone; Renee L. Desjarlais; Carl S. Crysler; Nisha Ninan; Maxwell D. Cummings; Christopher J. Molloy; Bruce E. Tomczuk

doi:10.1016/j.bmcl.2006.01.036

A novel series of arylsulfonylthiophene-2-carboxamidine inhibitors of the complement component C1s

Nalin L. Subasinghe, Jeremy M. Travins, Farah Ali, Hui Huang, Shelley K. Ballentine, Juan José Marugán, Ehab Khalil, Heather R. Hufnagel, Roger F. Bone, Renee L. Desjarlais, Carl S. Crysler, Nisha Ninan, Maxwell D. Cummings, Christopher J. Molloy, Bruce E. Tomczuk

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

17 Scopus citations

Abstract

Inhibiting the classical pathway of complement activation by attenuating the proteolytic activity of the serine protease C1s is a potential strategy for the therapeutic intervention in disease states such as hereditary angioedema, ischemia-reperfusion injury, and acute transplant rejection. A series of arylsulfonylthiophene-2-carboxamidine inhibitors of C1s were synthesized and evaluated for C1s inhibitory activity. The most potent compound had a K _i of 10 nM and >1000-fold selectivity over uPA, tPA, FX _a, thrombin, and plasmin.

Original language	English (US)
Pages (from-to)	2200-2204
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	16
Issue number	8
DOIs	https://doi.org/10.1016/j.bmcl.2006.01.036
State	Published - Apr 15 2006
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Keywords

C1s
C1s inhibitor
Classical pathway
Classical pathway inhibitor
Complement
Complement inhibitor

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10.1016/j.bmcl.2006.01.036

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Subasinghe, N. L., Travins, J. M., Ali, F., Huang, H., Ballentine, S. K., Marugán, J. J., Khalil, E., Hufnagel, H. R., Bone, R. F., Desjarlais, R. L., Crysler, C. S., Ninan, N., Cummings, M. D., Molloy, C. J., & Tomczuk, B. E. (2006). A novel series of arylsulfonylthiophene-2-carboxamidine inhibitors of the complement component C1s. Bioorganic and Medicinal Chemistry Letters, 16(8), 2200-2204. https://doi.org/10.1016/j.bmcl.2006.01.036

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abstract = "Inhibiting the classical pathway of complement activation by attenuating the proteolytic activity of the serine protease C1s is a potential strategy for the therapeutic intervention in disease states such as hereditary angioedema, ischemia-reperfusion injury, and acute transplant rejection. A series of arylsulfonylthiophene-2-carboxamidine inhibitors of C1s were synthesized and evaluated for C1s inhibitory activity. The most potent compound had a K i of 10 nM and >1000-fold selectivity over uPA, tPA, FX a, thrombin, and plasmin.",

keywords = "C1s, C1s inhibitor, Classical pathway, Classical pathway inhibitor, Complement, Complement inhibitor",

author = "Subasinghe, {Nalin L.} and Travins, {Jeremy M.} and Farah Ali and Hui Huang and Ballentine, {Shelley K.} and Marug{\'a}n, {Juan Jos{\'e}} and Ehab Khalil and Hufnagel, {Heather R.} and Bone, {Roger F.} and Desjarlais, {Renee L.} and Crysler, {Carl S.} and Nisha Ninan and Cummings, {Maxwell D.} and Molloy, {Christopher J.} and Tomczuk, {Bruce E.}",

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doi = "10.1016/j.bmcl.2006.01.036",

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Subasinghe, NL, Travins, JM, Ali, F, Huang, H, Ballentine, SK, Marugán, JJ, Khalil, E, Hufnagel, HR, Bone, RF, Desjarlais, RL, Crysler, CS, Ninan, N, Cummings, MD, Molloy, CJ & Tomczuk, BE 2006, 'A novel series of arylsulfonylthiophene-2-carboxamidine inhibitors of the complement component C1s', Bioorganic and Medicinal Chemistry Letters, vol. 16, no. 8, pp. 2200-2204. https://doi.org/10.1016/j.bmcl.2006.01.036

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T1 - A novel series of arylsulfonylthiophene-2-carboxamidine inhibitors of the complement component C1s

AU - Subasinghe, Nalin L.

AU - Travins, Jeremy M.

AU - Ali, Farah

AU - Huang, Hui

AU - Ballentine, Shelley K.

AU - Marugán, Juan José

AU - Khalil, Ehab

AU - Hufnagel, Heather R.

AU - Bone, Roger F.

AU - Desjarlais, Renee L.

AU - Crysler, Carl S.

AU - Ninan, Nisha

AU - Cummings, Maxwell D.

AU - Molloy, Christopher J.

AU - Tomczuk, Bruce E.

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N2 - Inhibiting the classical pathway of complement activation by attenuating the proteolytic activity of the serine protease C1s is a potential strategy for the therapeutic intervention in disease states such as hereditary angioedema, ischemia-reperfusion injury, and acute transplant rejection. A series of arylsulfonylthiophene-2-carboxamidine inhibitors of C1s were synthesized and evaluated for C1s inhibitory activity. The most potent compound had a K i of 10 nM and >1000-fold selectivity over uPA, tPA, FX a, thrombin, and plasmin.

AB - Inhibiting the classical pathway of complement activation by attenuating the proteolytic activity of the serine protease C1s is a potential strategy for the therapeutic intervention in disease states such as hereditary angioedema, ischemia-reperfusion injury, and acute transplant rejection. A series of arylsulfonylthiophene-2-carboxamidine inhibitors of C1s were synthesized and evaluated for C1s inhibitory activity. The most potent compound had a K i of 10 nM and >1000-fold selectivity over uPA, tPA, FX a, thrombin, and plasmin.

KW - C1s

KW - C1s inhibitor

KW - Classical pathway

KW - Classical pathway inhibitor

KW - Complement

KW - Complement inhibitor

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A novel series of arylsulfonylthiophene-2-carboxamidine inhibitors of the complement component C1s

Abstract

All Science Journal Classification (ASJC) codes

Keywords

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