167303-65-3Relevant articles and documents
PdII-Catalyzed Enantioselective C(sp3)–H Arylation of Cyclobutyl Ketones Using a Chiral Transient Directing Group
Ewing, William R.,Hong, Kai,Hu, Liang,Luo, Fan,Xiao, Li-Jun,Yeung, Kap-Sun,Yu, Jin-Quan
, p. 9594 - 9600 (2020)
The use of chiral transient directing groups (TDGs) is a promising approach for developing PdII-catalyzed enantioselective C(sp3)?H activation reactions. However, this strategy is challenging because the stereogenic center on the TDG is often far from the C?H bond, and both TDG covalently attached to the substrate and free TDG are capable of coordinating to PdII centers, which can result in a mixture of reactive complexes. We report a PdII-catalyzed enantioselective β-C(sp3)?H arylation reaction of aliphatic ketones using a chiral TDG. A chiral trisubstituted cyclobutane was efficiently synthesized from a mono-substituted cyclobutane through sequential C?H arylation reactions, thus demonstrating the utility of this method for accessing structurally complex products from simple starting materials. The use of an electron-deficient pyridone ligand is crucial for the observed enantioselectivity. Interestingly, employing different silver salts can reverse the enantioselectivity.
Benzoheterocyclic Oxime Carbamates Active against Mycobacterium tuberculosis: Synthesis, Structure-Activity Relationship, Metabolism, and Biology Triaging
Van Der Westhuyzen, Renier,Mabhula, Amanda,Njaria, Paul M.,Müller, Rudolf,Ngumbu Muhunga, Denis,Taylor, Dale,Lawrence, Nina,Njoroge, Mathew,Brunschwig, Christel,Moosa, Atica,Singh, Vinayak,Rao, Srinivasa P.S.,Manjunatha, Ujjini H.,Smith, Paul W.,Warner, Digby F.,Street, Leslie J.,Chibale, Kelly
supporting information, p. 9444 - 9457 (2021/07/19)
Screening of a library of small polar molecules against Mycobacterium tuberculosis (Mtb) led to the identification of a potent benzoheterocyclic oxime carbamate hit series. This series was subjected to medicinal chemistry progression underpinned by structure-activity relationship studies toward identifying a compound for proof-of-concept studies and defining a lead optimization strategy. Carbamate and free oxime frontrunner compounds with good stability in liver microsomes and no hERG channel inhibition liability were identified and evaluated in vivo for pharmacokinetic properties. Mtb-mediated permeation and metabolism studies revealed that the carbamates were acting as prodrugs. Toward mechanism of action elucidation, selected compounds were tested in biology triage assays to assess their activity against known promiscuous targets. Taken together, these data suggest a novel yet unknown mode of action for these antitubercular hits.
Zn-ProPhenol Catalyzed Enantioselective Mannich Reaction of 2 H-Azirines with Alkynyl Ketones
Trost, Barry M.,Zhu, Chuanle
supporting information, p. 9683 - 9687 (2020/12/21)
The enantioselective Mannich reaction of 2H-azirines with alkynyl ketones is achieved under Zn-ProPhenol catalysis, delivering various aziridines with vicinal tetrasubstituted stereocenters in high yields with excellent enantioselectivities. The bimetalli
Potent Analogues of Abscisic Acid – Identifying Cyano-Cyclopropyl Moieties as Promising Replacements for the Cyclohexenone Headgroup
Frackenpohl, Jens,Bojack, Guido,Baltz, Rachel,Bickers, Udo,Busch, Marco,Dittgen, Jan,Franke, Jana,Freigang, J?rg,Grill, Erwin,Gonzalez, Susana,Helmke, Hendrik,Hills, Martin J.,Hohmann, Sabine,von Koskull-D?ring, Pascal,Kleemann, Jochen,Lange, Gudrun,Lehr, Stefan,Schmutzler, Dirk,Schulz, Arno,Walther, Kerstin,Willms, Lothar,Wunschel, Christian
, p. 1416 - 1425 (2018/04/06)
Synthetic analogues of plant hormone abscisic acid (ABA) bearing a yet unexplored head group motif were prepared based on a combination of agrochemical experience, in vivo hits and structure-based design. It could thus be explored how modifying key parts of ABA's cyclohexenone unit influenced receptor affinity and in vivo efficacy against drought stress in selected crops. Cyano-cyclopropyl groups proved to be suitable replacements of the cyclohexanone moiety leading to ABA analogues with strong activity in vitro and in vivo. Their efficient and versatile synthesis proceeded via Stille or Sonogashira couplings as the key steps. Combining novel cyano-cyclopropyl headgroups with previously identified substituents in the terpenoid side chain afforded the most promising effects against drought stress in crops, particularly canola and wheat.
Copper(I)-Catalyzed Enantioselective Nucleophilic Borylation of Aliphatic Ketones: Synthesis of Enantioenriched Chiral Tertiary α-Hydroxyboronates
Kubota, Koji,Osaki, Shun,Jin, Mingoo,Ito, Hajime
supporting information, p. 6646 - 6650 (2017/05/29)
A new method was developed for the first catalytic enantioselective borylation of aliphatic ketones. A variety of substrates reacted efficiently with bis(pinacolato)diboron in the presence of a copper(I)/chiral N-heterocyclic carbene complex catalyst to furnish optically active tertiary α-hydroxyboronates with moderate to high enantioselectivities (up to 94 % ee). Notably, the product could be converted into the chiral tertiary alcohol derivative using a stereospecific boron functionalization process. The theoretical study of the mechanism for the enantioselectivity is also described.
Gold-Catalyzed Dehydrogenative Cycloisomerization of 1,4-Enyne Esters to 3,5-Disubstituted Phenol Derivatives
Chen, Cuili,Chen, Xianxiao,Zhang, Xiaoxiang,Wang, Shifa,Rao, Weidong,Chan, Philip Wai Hong
supporting information, p. 4359 - 4368 (2017/12/26)
A method to prepare synthetically important 3,5-disubstituted phenol derivatives that relies on the sequential gold(I)-catalyzed dehydrogenative cycloisomerization of 1,4-enyne esters in the presence of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) or N-fluorobenzenesulfonimide (NFSI) is described. The synthetic versatility of the methodology was exemplified by a gram-scale reaction of one example, the ease to realize subsequent functional transformations of an adduct, and the application of the method to the synthesis of the bioactive molecule LUF5771. (Figure presented.).
Thiophene [2, 3-c] pyridine derivative and application thereof for being used as CDK inhibitor
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Paragraph 0038; 0039; 0040, (2016/10/27)
The invention relates to the field of medicinal chemistry, in particular to a cyclin dependent kinase inhibitor, namely a thiophene [2, 3-c] pyridine derivative. Pharmacodynamic experiments prove that the compound has the efficient and high-selectivity inhibiting effect on CDK, and can be applied to lowering or inhibiting the activity of CDK in cells and treating or preventing CDK-mediated cancer related diseases.
2-AMINO-BENZIMIDAZOLE DERIVATIVES AND THEIR USE AS 5-LIPOXYGENASE AND/OR PROSTAGLANDIN E SYNTHASE INHIBITORS
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Page/Page column 44; 45, (2016/03/12)
The present invention relates to benzimidazole derivatives having the general formula I, wherein n is 0 or 1; X1 and X2 are independently, at each occurrence, CR5 or N; Y is C1-C6 alkylene, wherein alkylene is optionally substituted with one to two C1-C3 alkyl groups; R1 is selected from the group consisting of hydrogen, halogen, C1-C6 alkoxy, -NH2, -NHR6, -NR7R8 and -NH-(R9)n-R10, n being 0 or 1; R2 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, -NH2, -NHR6, - NR7R8 and -NH-(R9)n-R10; R3 is selected from the group consisting of hydrogen, hydroxyl, OR11, -NR7R8, C1-C6 alkoxy, C1-C6 alkyl, C3-C10 cycloalkyl, C1-C3 haloalkyl, -C(O)NHR11, aryl, heteroaryl and heterocyclyl, wherein each of said cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four Ra groups; and R4 is selected from the group consisting of -NH2, -N(R12)(V)pR13, - NH(V)p-OR14, -NHC(O)R15, and groups of formula la shown below, and their use in the treatment of diseases, in particular inflammatory diseases, cancer, stroke and/or Alzheimer's disease.
Analogs of 4-hydroxyisoleucine and uses thereof
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Page/Page column 43, (2008/06/13)
The invention relates to analogs of 4-hydroxyisoleucine, and to lactones, pharmaceutically acceptable salts, and prodrugs thereof, to processes for their preparation, and to pharmaceutical compositions comprising the same. The analogs of the invention stimulate both glucose uptake and insulin secretion, and may thus be useful for the prevention and treatment of disorders of carbohydrate or lipid metabolism, including diabetes mellitus (type 1 and type 2 diabetes), pre-diabetes, and Metabolic Syndrome.
Compounds and compositions for use in the prevention and treatment of obesity and related syndromes
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Page/Page column 56, (2010/11/24)
The invention relates to 4-hydroxyisoleucine, isomers, analogs, lactones, salts, and prodrugs thereof, to processes for their preparation, and to pharmaceutical compositions comprising the same. More particularly, the invention relates to the use of those compounds in the prevention and treatment of obesity and related syndromes.
