Table 3.

ADME-related physicochemical parameters, pharmacokinetic properties, and metabolic reactions predicted for benzothiazole 12.

PHYSICOCHEMICAL
logPa	pKab	Swc	DiffCd	MolVole	MDCKf	Peffg	Skinh	Corneai	BBBj	logBBk
4.23	3.73	4.79	8.29	266	5.45	4.90	1.25	1.48	High	0.15
PHARMACOKINETIC
Hum_fupl	RBPm	Vdn	ECCSo	CL_Metbp	CL_Renalq	CL_Uptaker
1.06%	0.12	0.31	Class 2	Yes (99%)	No (95%)	No (99%)
METABOLISM
Phase 1. Oxidations	CYP1A2	CYP2A6	CYP2B6	CYP2C8	CYP2C9	CYP2C19	CYP2D6	CYP2E1	CYP3A4
Substratet	Yes	Yes	Yes	Yes	No	No	Yes	No	Yes
Confidenceu	88%	60%	55%	79%	81%	98%	82%	97%	83%
Kmv	23.02	-	-	-	-	-	63.02	-	55.73
Vmaxw	7.10	-	-	-	-	-	3.48	-	0.41
CLintx	16.04	-	-	-	-	-	0.44	-	0.82
Phase 2. Glucuronidationy	UGT1A1	UGT1A3	UGT1A4	UGT1A6	UGT1A8	UGT1A9	UGT1A10	UGT2B7	UGT2B15
Substratet	Yes	No	No	No	Yes	Yes	No	No	No
Confidenceu	90%	51%	72%	75%	87%	88%	86%	56%	98%

^alogP: octanol-water partition coefficient (lipophilicity)

^bpKa: dissociation constant using submodels to predict protic ionization microconstants for all identified ionizable groups in a molecule.

^cSw (mg/mL×10⁻⁴): native water solubility.

^dDiffC (cm²/s×10⁶): molecular diffusion coefficient in water

^eMolVol (cm³/mol): molal volume at the normal boiling point

^fMDCK (cm²/s×10⁵): apparent MDCK COS permeability

^gPeff (cm²/s×10⁴): human effective jejunal permeability

^hSkin (cm²/s×10⁵): permeability through human skin

ⁱCornea (cm²/s×10⁵): permeability through rabbit cornea

^jBBB: qualitative likelihood (High/Low) of crossing the blood-brain barrier (98% confidence)

^klogBB: logarithm of the brain/blood partition coefficient.

^lHum_fup: percent unbound to blood plasma proteins in human.

^mRBP: blood-to-plasma concentration ratio in human.

ⁿV_d (L/kg): volume of distribution in humans at steady state.

^oECCS Class: Extended Clearance Classification System (ECCS) assignment

^pCL_Metab: predicts whether or not metabolism will be critical to clearance

^qCL_Renal: predicts whether or not renal elimination will be critical to clearance.

^rCL_Uptake: predicts whether or not hepatic uptake will be critical to clearance.

^sMost common chemical reaction of Phase 1 of metabolism (oxidation) by Cytochromes P450 (CYP) enzymes

^tSubstrate: substrate classification models (yes/no) for human CYPxxx or UGTxxx

^uConfidence of predictions

^vKm (μM): estimated Michaelis-Menten Km constant for predicted sites of metabolism by human CYPxxx

^wVmax: [nmol/min/nmol enzyme]: estimated Michaelis-Menten V_max constant for predicted sites of metabolism by CYPxxx

^xCLint (μL/min/mg human liver microsomes (HLM) protein): estimated intrinsic clearance for predicted sites of metabolism by CYPxxx

^yMost common chemical reaction of Phase 2 of metabolism (glucuronidation) by uridine 5′-diphospho-glucuronosyltransferase (UGT)