The stiffness and tensile properties were very much affected due to the bulk cyclohexyl substitution at the 3 position.
This binding pose could be due to the introduction of bulk (para-substituted methoxyphenyl groups) at the N4-position of the triazole ring.
We report herein our progress made towards identifying a potent, selective bombesin receptor subtype-3 (BRS-3) agonist related to the previously described MK-77251 Chobanian et al. (2012) that would prevent atropisomerization through the increase of steric bulk at the C-2 position.
In addition, it was established that substitution at the 2 position of the cyclohexyl skeleton and, more importantly, an increase in steric bulk at that point, led to a drastic reduction of side product formation (i.e., methyl- and methylenecyclopentane).
21,23-Dithiaporphyrins (2 10) were designed and prepared as analogues of 5,20-diphenyl-10,15-bis(4-carboxylatomethoxy phenyl-21,23-dithiaporphyrin (1) to examine the impact of steric bulk at the 5- and 20-meso positions as well as the impact of symmetry.
This idea is supported by the observation that additional steric bulk at the adjacent position (Kcv 62) mitigates the impact of the T→S change at the ion coordinating residue at site 4 (Figure 8).
Sauve [15] showed that the β-elimination in electrophilic fluorination of 2-deoxyribonolactone can be successfully mitigated by steric triisopropylsilyl (TIPS) bulk at the susceptible β-position.
Increasing the steric bulk around a tertiary alcohol at the 5-indole position dramatically improved selectivity toward Lyk and Syk, but not Txk.
CoMFA results suggest that the antiamoebic activity is favored with steric bulk at position 5 of the benzimidazole ring and low electron density on the group at position 2. To the best of our knowledge this is the first 3D-QSAR study performed for benzimidazoles as antiamoebic agents.
The diminished progress along the reaction sequence as the product arrays of F96Y, F96L, F96V, and F96A are compared suggests that steric bulk at position 96 is functionally important, presumably for ensuring the close contact between the C1 and C6 atoms allowing (R -bisabolyl cation foR -bisabolyl
