5-Propynylpyrimidine nucleoside derivatives: Rationally designed mechanism-based inactivators of thymidylate synthase

T. I. Kalman; Z. Nie; A. Kamat

doi:10.1081/NCN-100002448

5-Propynylpyrimidine nucleoside derivatives: Rationally designed mechanism-based inactivators of thymidylate synthase

T. I. Kalman
, Z. Nie
, A. Kamat

Chemistry

SUNY Buffalo

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

8 Scopus citations

Abstract

A novel series of 5-propynyl-dUMP derivatives, with a variety of leaving groups on the side-chain, was designed as potential mechanism-based inhibitors of thymidylate synthase (TS), and synthesized from 5-iodo-2′-deoxyuridine by Pd(O)-catalyzed coupling, followed by direct phosphorylation with POCl₃. All members of the series inhibited TS competitively with Ki-values of 0.015-18 μM. Analogs with fluorine or imidazole-based leaving groups caused rapid, irreversible inactivation of TS.

Original language	English
Pages (from-to)	869-871
Number of pages	3
Journal	Nucleosides, Nucleotides and Nucleic Acids
Volume	20
Issue number	4-7
DOIs	https://doi.org/10.1081/NCN-100002448
State	Published - 2001

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abstract = "A novel series of 5-propynyl-dUMP derivatives, with a variety of leaving groups on the side-chain, was designed as potential mechanism-based inhibitors of thymidylate synthase (TS), and synthesized from 5-iodo-2′-deoxyuridine by Pd(O)-catalyzed coupling, followed by direct phosphorylation with POCl3. All members of the series inhibited TS competitively with Ki-values of 0.015-18 μM. Analogs with fluorine or imidazole-based leaving groups caused rapid, irreversible inactivation of TS.",

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T1 - 5-Propynylpyrimidine nucleoside derivatives

T2 - Rationally designed mechanism-based inactivators of thymidylate synthase

AU - Kalman, T. I.

AU - Nie, Z.

AU - Kamat, A.

PY - 2001

Y1 - 2001

N2 - A novel series of 5-propynyl-dUMP derivatives, with a variety of leaving groups on the side-chain, was designed as potential mechanism-based inhibitors of thymidylate synthase (TS), and synthesized from 5-iodo-2′-deoxyuridine by Pd(O)-catalyzed coupling, followed by direct phosphorylation with POCl3. All members of the series inhibited TS competitively with Ki-values of 0.015-18 μM. Analogs with fluorine or imidazole-based leaving groups caused rapid, irreversible inactivation of TS.

AB - A novel series of 5-propynyl-dUMP derivatives, with a variety of leaving groups on the side-chain, was designed as potential mechanism-based inhibitors of thymidylate synthase (TS), and synthesized from 5-iodo-2′-deoxyuridine by Pd(O)-catalyzed coupling, followed by direct phosphorylation with POCl3. All members of the series inhibited TS competitively with Ki-values of 0.015-18 μM. Analogs with fluorine or imidazole-based leaving groups caused rapid, irreversible inactivation of TS.

UR - https://www.scopus.com/pages/publications/0034846510

U2 - 10.1081/NCN-100002448

DO - 10.1081/NCN-100002448

M3 - Article

C2 - 11563134

AN - SCOPUS:0034846510

SN - 1525-7770

VL - 20

SP - 869

EP - 871

JO - Nucleosides, Nucleotides and Nucleic Acids

JF - Nucleosides, Nucleotides and Nucleic Acids

IS - 4-7

ER -

5-Propynylpyrimidine nucleoside derivatives: Rationally designed mechanism-based inactivators of thymidylate synthase

Abstract

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