ACS Medicinal Chemistry Letters
Page 8 of 8
Hypoxia-Inducible Factor Prolyl Hydroxylase 1-3 (HIF PHD1-3)
for the Treatment of Anemia. J. Med. Chem. 2016, 59, 11039–
11049.
Abbreviations: EPO, erythropoietin; rhEPO,
recombinant human erythropoietin; HIF, hypoxia
inducible factor; PHD, prolyl hydroxylase; RBC, red
blood cell; Hb, hemoglobin; CKD, chronic kidney
disease; CIA, chemotherapy induced anemia; ACD,
anemia of chronic disease; PAP, pulmonary arterial
pressure; OATP, organic anion transporting
polypeptide; PSA, polar surface area; Papp, apparent
permeability; MDCK, Madin Darby canine kidney;
PO, oral; QD, once a day; MED, minimum effective
dose; PXR, Pregnane X receptor.
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(17) The HIF-PHD inhibitors, including FG-2216, that have reached
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(29) Also see: Cai, J.; Crespo, A.; Du, X.; Dubois, B. G.; Guiadeen, D.;
Kothandaraman, S.; Liu, P.; Liu, R.; Quan, W.; Sinz, C.; Wang, L.
Oxazinoquinolinecarboxamidoacetic acid derivatives as inhibitors
of HIF prolyl hydroxylase and their preparation, WO 2016045127,
2016.
(30) Dieckmann, W. Ber. Dtsch. Chem. Ges. 1894, 27, 102–103.
(31) For synthesis of 27, also see: Cai, J.; Colandrea, V.; Crespo, A.;
Debenham, J.; Du, X.; Guiadeen, D.; Liu, P.; Liu, R.; Madsen-
Duggan, C. B.; McCoy, J. G.; Quan, W.; Sinz, C.; Wang, L.
Quinolinecarboxamidoacetic acids and related compounds as
inhibitors of HIF prolyl hydroxylase and their preparation, WO
2016045125, 2016.
(32) For synthesis of 28, also see: Cai, J.; Crespo, A.; Du, X.; Dubois,
B. G.; Liu, P.; Liu, R.; Quan, W.; Sinz, C.; Wang, L.
Tetrahydrofuropyridineecarboxamidoacetic acid derivatives as
inhibitors of HIF prolyl hydroxylase and their preparation, WO
2016045128, 2016.
(33) Pregnane X receptor (PXR) is a nuclear receptor known to regulate
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