Table 1.

Potency and Selectivity of 3,5-dichloro-4-alkoxy RARα agonists.

		Subtype-specific transactivationa
		Relative EC50b
Compd	RO	RARα	RARβ	β/α ratioc	RARγ	γ/α ratioc	cLogPf
4	AGN195183	11	1564	141	9836	867	7.2
5	EtO	24	1917	79	>3,00,000	>12,500	4.4
12	PrO	15	139	9.5	1196	82	4.9
13	BuO	84	717	8.5	1477	18	4.6
14	iPrO	7d	1417	205	823	119	4.7
16	tBuO	7	2927	426	6250	909	5.1
15		10	342	33	4703	452	5.3
26	–	30	355	12	>1,08,000	>3600	4.4
60	H	92d	642	7	5000	55	4.2
61	MeO	30	9525	318	5850	195	3.9
	ATRA	1.0(1.51 nM)e	1.0(0.52 nM) e		1.0(0.22 nM) e

^aTransactivation assays for the RAR alpha, beta and gamma receptors were performed using each of the mouse RAR ligand binding domains, Subtype-specific activity is expressed in terms of relative EC₅₀ which is the concentration of retinoid required to produce 50% of the maximal observed response, normalised relative to that of ATRA.

^bMean EC₅₀ for each compound divided by the mean EC₅₀ of ATRA. Values were obtained from three separate experiments. Errors in these assays are approximately 20% of the mean values.

^cThe relative EC₅₀ ratios of α to β and α to γ.

^dCompound behaves as a partial agonist relative to the amplitude of the normalizing ATRA output.

^eMean of ATRA EC₅₀ (nM).

^fcLog P values were calculated in ChemDraw.