Table 5.

Pyrimidine Inhibitors of 15-PGDH

Compound	R/inhibitor	IC50 (nM)	PGE2 increase at		Aq. Solubility (μg/mL)b
			20 nMa	2.5 μMa
44a		2.4	1.8	2.5	0.3
44b	Ph	4.9
(+)-44c		1.0	62.1	3.1	2.2c
44d		3.7	2.2	2.9	71
44e		2.6	1.6	2.1	37
48		93
51		1320

^aFold-increase in PGE2 levels in A549 cell culture media relative to DMSO. Data color-coded to indicate more active (blue), less active (red) or equally active (white) as compound 1.

^bAmorphous solid unless otherwise indicated. Solubility in pH 7 citrate buffer, 0.1 M. pH 7 citrate buffer, 0.1 M.

^cSolubility of racemate.