Table 3.

Paclitaxel & docetaxel C-10 carbamates

Entry	CNDR#	W	X	Y	CLogPa	MPAb	IC50 HEK293 (μM)	MDR-MDCK
								Pappc AB (10-6 cm/s)	Pappc BA (10-6 cm/s)	Efflux Ratiod
1	paclitaxel	Ph	Ac	H	4.7	NA	0.010	0.20	28.5	143
2	10-deac. taxol	Ph	H	H	4.0	+	0.076	0.13	5.17	39
3	TX-67	Ph		H	1.5*	++	4.7	0.08	0.1	1.3
4	CNDR-3	Ph		H	1.3*	+++	8.3	0.09	0.05	0.6
5	CNDR-31	Ph	Ac		2.2*	-	>25	0.07	0.06	0.9
6	CNDR-24	Ph		H	2.0*	++	1.8	0.06	0.05	0.9
7	CNDR-21	Ph		H	2.6*	+++	1	0.05	0.05	1
8	CNDR-30	Ph		H	4.5	++	0.06	<0.62	3.36	>5.4
9	CNDR-14	Ph		H	3.7	+++	1.9	<0.07	0.21	>3
10	AC409	Ph		H	4.1	+++	1	0.09	0.8	8.8
11	CNDR-12	Ph		H	1.6*	+++	2.5	<0.63	<0.63	ND+
12	CNDR-07	Ph		H	1.6*	+++	3.9	<0.06	<0.06	ND+
13	CNDR-04	Ph		H	1.4*	+++	7.4	<0.64	<0.64	ND+
14	CNDR-29	Ph		H	3.9	+	0.7	<0.21	<0.21	ND+
15	CNDR-15	Ph		H	6.5	+	0.024	<0.2	25.3	>127
16	323-N-01	Ph		H	5.1	+++	ND+	0.17	22.6	133
17	docetaxel	tBuO	H	H	3.8	(NA)	0.027	<0.62	15.5	>25
18	CNDR-5	tBuO		H	1.3*	(+++)e	1.7	<0.2	<0.2	ND+

^aCalculated partition coefficient;

^bThe microtubule polymerization assay (MPA) was carried out using the fluorescence based kit (cat. # BK011) produced by Cytoskeleton (Denver, CO). Test compounds were tested at 0.5, 1.5 and 3 μM. Compounds that produced equal or faster polymerization rate than paclitaxel (or docetaxel) at three, two or one concentrations are classified with “+++”,“++” or “+” respectively. Compounds that produced slower polymerization rate than paclitaxel at all three concentrations are classified with “-“;

^cApparent permeability coefficient;²¹

^dEfflux ratio = Papp(B-A)/Papp(A-B) across monolayers of MDR-MDCK;

^eThe microtubule polymerization assay was run in comparison to docetaxel.

^*ClogP corresponding to the negatively charged carboxylate;

⁺Not determined.