Spiro Compounds. Группа авторов

that a carbonyl to oxetane switch can be a viable approach to mitigate epimerization at adjacent stereocenters.

Table 2.2 Physicochemical and biochemical properties of selected oxetanes, and their carbonylated and gem‐dimethyl counterparts.

      Source: Based on Wuitschik et al. [55].

Solubility (μg ml−1)	4000	1400	220	4100	730	40	n.d.	24 000	290
Lipophilicity logD (logP)	1.2 (1.6)	1.0 (2.0)	2.3 (4.4)	−0.1 (−0.1)	0.7 (1.5)	1.4 (3.7)	n.d.	0.5 (1.2)	0.8 (3.1)
hCLint (min−1 mg−1 μl)	120	6	23	100	2	10	n.d.	3	0
mCLint (min−1 mg−1 μl)	88	22	31	580	27	39	n.d.	7	16
pK a amine	7.5	8.3	9.5	6.1	8.1	9.7	n.d.	8.0	9.6

Figure 2.6 (a) Spiro‐oxetane as a morpholine bioisostere.

      Sources: Based on Carreira and Fessard [48]; Burkhard et al. [56];

      (b) comparison of exit vectors in the piperidine motif and its spiro counterpart; (c) spirocyclic oxetane based on mimics of morpholine.

Table 2.3 Comparison of the properties of spirocyclic oxetanes with their morpholine parent.

      Source: Adapted from Carreira Wuitschik et al. [55].

Solubility (μg ml−1)	730	8000	24 000
Lipophilicity logD (logP)	0.7 (1.5)	1.5 (1.6)	0.5 (1.2)
hCLint (min−1 mg−1 μl)	2	9	3
mCLint (min−1 mg−1 μl)	27	8	7
pK a amine	8.1	7.0	8.0 Скачать книгу В начало < 13 14 15 16 17 18 19 20 21 22 > В конец