Phenoxypropoxybiguanides, prodrugs of DHFR-inhibiting diaminotriazine antimalarials

N. P. Jensen, Arba L Ager, R. A. Bliss, C. J. Canfield, B. M. Kotecka, K. H. Rieckmann, J. Terpinski, D. P. Jacobus

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

A total of 34 analogues of the biguanide PS-15 (5s), a prodrug of the diaminotriazine WR-99210 (8s), have been prepared. Several of them, such as 5b (PS-33) and 5m (PS-26), maintain or exceed the in vivo activity of PS-15 while not requiring the use of highly regulated starting materials. The putative diaminotriazine metabolites of these new analogues (compounds 8) have also been prepared and shown to maintain the activity against resistant P. falciparum strains. The structure-activity relationships of biguanides 5 and putative metabolites 8 are discussed.

Original languageEnglish (US)
Pages (from-to)3925-3931
Number of pages7
JournalJournal of Medicinal Chemistry
Volume44
Issue number23
DOIs
StatePublished - Nov 8 2001

Fingerprint

Biguanides
Prodrugs
Antimalarials
Metabolites
Structure-Activity Relationship
PS 15
BRL 6231

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Jensen, N. P., Ager, A. L., Bliss, R. A., Canfield, C. J., Kotecka, B. M., Rieckmann, K. H., ... Jacobus, D. P. (2001). Phenoxypropoxybiguanides, prodrugs of DHFR-inhibiting diaminotriazine antimalarials. Journal of Medicinal Chemistry, 44(23), 3925-3931. https://doi.org/10.1021/jm010089z

Phenoxypropoxybiguanides, prodrugs of DHFR-inhibiting diaminotriazine antimalarials. / Jensen, N. P.; Ager, Arba L; Bliss, R. A.; Canfield, C. J.; Kotecka, B. M.; Rieckmann, K. H.; Terpinski, J.; Jacobus, D. P.

In: Journal of Medicinal Chemistry, Vol. 44, No. 23, 08.11.2001, p. 3925-3931.

Research output: Contribution to journalArticle

Jensen, NP, Ager, AL, Bliss, RA, Canfield, CJ, Kotecka, BM, Rieckmann, KH, Terpinski, J & Jacobus, DP 2001, 'Phenoxypropoxybiguanides, prodrugs of DHFR-inhibiting diaminotriazine antimalarials', Journal of Medicinal Chemistry, vol. 44, no. 23, pp. 3925-3931. https://doi.org/10.1021/jm010089z
Jensen NP, Ager AL, Bliss RA, Canfield CJ, Kotecka BM, Rieckmann KH et al. Phenoxypropoxybiguanides, prodrugs of DHFR-inhibiting diaminotriazine antimalarials. Journal of Medicinal Chemistry. 2001 Nov 8;44(23):3925-3931. https://doi.org/10.1021/jm010089z
Jensen, N. P. ; Ager, Arba L ; Bliss, R. A. ; Canfield, C. J. ; Kotecka, B. M. ; Rieckmann, K. H. ; Terpinski, J. ; Jacobus, D. P. / Phenoxypropoxybiguanides, prodrugs of DHFR-inhibiting diaminotriazine antimalarials. In: Journal of Medicinal Chemistry. 2001 ; Vol. 44, No. 23. pp. 3925-3931.
@article{6d6f5363c0fd4a8f83b27df2f443ef34,
title = "Phenoxypropoxybiguanides, prodrugs of DHFR-inhibiting diaminotriazine antimalarials",
abstract = "A total of 34 analogues of the biguanide PS-15 (5s), a prodrug of the diaminotriazine WR-99210 (8s), have been prepared. Several of them, such as 5b (PS-33) and 5m (PS-26), maintain or exceed the in vivo activity of PS-15 while not requiring the use of highly regulated starting materials. The putative diaminotriazine metabolites of these new analogues (compounds 8) have also been prepared and shown to maintain the activity against resistant P. falciparum strains. The structure-activity relationships of biguanides 5 and putative metabolites 8 are discussed.",
author = "Jensen, {N. P.} and Ager, {Arba L} and Bliss, {R. A.} and Canfield, {C. J.} and Kotecka, {B. M.} and Rieckmann, {K. H.} and J. Terpinski and Jacobus, {D. P.}",
year = "2001",
month = "11",
day = "8",
doi = "10.1021/jm010089z",
language = "English (US)",
volume = "44",
pages = "3925--3931",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "23",

}

TY - JOUR

T1 - Phenoxypropoxybiguanides, prodrugs of DHFR-inhibiting diaminotriazine antimalarials

AU - Jensen, N. P.

AU - Ager, Arba L

AU - Bliss, R. A.

AU - Canfield, C. J.

AU - Kotecka, B. M.

AU - Rieckmann, K. H.

AU - Terpinski, J.

AU - Jacobus, D. P.

PY - 2001/11/8

Y1 - 2001/11/8

N2 - A total of 34 analogues of the biguanide PS-15 (5s), a prodrug of the diaminotriazine WR-99210 (8s), have been prepared. Several of them, such as 5b (PS-33) and 5m (PS-26), maintain or exceed the in vivo activity of PS-15 while not requiring the use of highly regulated starting materials. The putative diaminotriazine metabolites of these new analogues (compounds 8) have also been prepared and shown to maintain the activity against resistant P. falciparum strains. The structure-activity relationships of biguanides 5 and putative metabolites 8 are discussed.

AB - A total of 34 analogues of the biguanide PS-15 (5s), a prodrug of the diaminotriazine WR-99210 (8s), have been prepared. Several of them, such as 5b (PS-33) and 5m (PS-26), maintain or exceed the in vivo activity of PS-15 while not requiring the use of highly regulated starting materials. The putative diaminotriazine metabolites of these new analogues (compounds 8) have also been prepared and shown to maintain the activity against resistant P. falciparum strains. The structure-activity relationships of biguanides 5 and putative metabolites 8 are discussed.

UR - http://www.scopus.com/inward/record.url?scp=0035829466&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035829466&partnerID=8YFLogxK

U2 - 10.1021/jm010089z

DO - 10.1021/jm010089z

M3 - Article

C2 - 11689078

AN - SCOPUS:0035829466

VL - 44

SP - 3925

EP - 3931

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 23

ER -