U-87947E, a protein quinolone antibacterial agent incorporating a bicyclo[1.1.1]pent-1-yl (BCP) subunit

Nonconjugated Hydrocarbons as Rigid‐Linear Motifs: Isosteres for Material Sciences and Bioorganic and Medicinal Chemistry

“…[363] Following this, aB CP analogue 292 was synthesized, replacing the tert-butylg roup. [362] This compound showede nhanceda ctivity against gram-positive aerobic bacteria and anaerobic organisms, relative to that of ciprofloxacin. Moreover,t ime-killk inetic studies revealed that BCP 292 is extremely potent against ciprofloxacin-resistant Staphylococcus aureus.…”

“…While tert-butyl is widely employed as am otif in medicinal chemistry it can affect the properties of the molecule causing drawbacks such as increased lipophilicity and enhanced metabolism rates. [362] From the family of fluoroquinones,C iprofloxacin 290 is ap otent antibacteriald rug with broad spectrum activity ( Figure 59). However,b acterialr esistance is always an ongoing problem.A na lternative quinolone analogue 291 was prepared with a tert-butyl group at the N-1 position.…”

Evaluation of tert‐Butyl Isosteres: Case Studies of Physicochemical and Pharmacokinetic Properties, Efficacies, and Activities

“…[23,24] Recently, Zanda and colleagues disclosed work on cannabinoid receptor ligands in which the SF 5 group was compared with CF 3 and tert-butyl. [28] Compounds incorporating bicyclo[1.1.1]pentane were also compared with counterparts including fluorinated cyclic and open-chain alkyl groups, and this group was found to be a reasonable surrogate with respect to calculated log P, clearance rates, and Caco-2 permeability. [6] Herein, we substantiate this finding by providing additional, directly comparable physicochemical data.…”

“…[8] In addition, it was used in a study on quinolone antibacterials and shown to be more active than structurally closely related ciprofloxacin. [28] Compounds incorporating bicyclo[1.1.1]pentane were also compared with counterparts including fluorinated cyclic and open-chain alkyl groups, and this group was found to be a reasonable surrogate with respect to calculated log P, clearance rates, and Caco-2 permeability. [29] Despite the wide ranging studies, there has been no direct comprehensive comparison of the various groups.…”

Synthesis of BCP Benzylamines From 2‐Azaallyl Anions and [1.1.1]Propellane

“…[1] Most recently,B CP substitution in resveratrol [2] and the LpPLA 2 inhibitor darapladib [3] were reported to enhance drug-like qualities,f urther confirming the utility of BCPs as phenyl isosteres.BCPs have also been studied as tert-butyl isosteres. [4,5] Though BCPs continue to emerge as as tandard candidate for spacer group replacement in drug evaluation, the synthesis of BCP-containing scaffolds remains asignificant obstacle.…”