15761-39-4Relevant articles and documents
Design, Synthesis, and Biological Evaluations of Several Y-26732 Analogues
Wang, Xinran,Chen, Ligong,Li, Hang,Sun, Changhai,Qi, Haofei,Wang, Donghua
, p. 1212 - 1218 (2015)
A series of pyridine Rho kinase inhibitors were designed and synthesized utilizing the ligand-binding pocket model with Y-26732 as the lead compound. These compounds were evaluated on cell lines for their biological activities.
Direct evidence of significantly different chemical behavior and excited-state dynamics of 1,7- and 1,6-regioisomers of pyrrolidinyl-substituted perylene diimide
Dubey, Rajeev K.,Niemi, Marja,Kaunisto, Kimmo,Efimov, Alexander,Tkachenko, Nikolai V.,Lemmetyinen, Helge
, p. 6791 - 6806 (2013)
Novel bay-functionalized perylene diimides with additional substitution sites close to the perylene core have been prepared by the reaction between 1,7(6)-dibromoperylene diimide 6 (dibromo-PDI) and 2-(benzyloxymethyl) pyrrolidine 5. Distinct differences in the chemical behaviors of the 1,7- and 1,6-regioisomers have been discerned. While the 1,6-dibromo-PDI produced the corresponding 1,6-bis-substituted derivative more efficiently, the 1,7-dibromo-PDI underwent predominant mono-debromination, yielding a mono-substituted PDI along with a small amount of the corresponding 1,7-bis-substituted compound. By varying the reaction conditions, a controlled stepwise bis-substitution of the bromo substituents was also achieved, allowing the direct synthesis of asymmetrical 1,6- and 1,7-PDIs. The compounds were isolated as individual regioisomers. Fullerene (C60) was then covalently linked at the bay region of the newly prepared PDIs. In this way, two separate sets of perylene diimide-fullerene dyads, namely single-bridged (SB-1,7-PDI-C60 and SB-1,6-PDI-C60) and double-bridged (DB-1,7-PDI-C60 and DB-1,6-PDI-C60), were synthesized. The fullerene was intentionally attached at the bay region of the PDI to achieve close proximity of the two chromophores and to ensure an efficient photoinduced electron transfer. A detailed study of the photodynamics has revealed that photoinduced electron transfer from the perylene diimide chromophore to the fullerene occurs in all four dyads in polar benzonitrile, and also occurs in the single-bridged dyads in nonpolar toluene. The process was found to be substantially faster and more efficient in the dyads containing the 1,7-regioisomer, both for the singly- and double-bridged molecules. In the case of the single-bridged dyads, SB-1,7-PDI-C60 and SB-1,6-PDI-C60, different relaxation pathways of their charge-separated states have been discovered. To the best of our knowledge, this is the first observation of photoinduced electron transfer in PDI-C60 dyads in a nonpolar medium. Copyright
Design, synthesis and evaluation of novel 2-hydroxypyrrolobenzodiazepine-5, 11-dione analogues as potent angiotensin converting enzyme (ACE) inhibitors
Sun, Ying,Bai, Yujun,He, Xirui,Bai, Yajun,Liu, Pei,Zhao, Zefeng,Chen, Xufei,Zheng, Xiaohui
, (2017)
Under the guidance of combination of traditional Chinese medicine chemistry (CTCMC), this study describes the preparation of a phenolic acid/dipeptide/borneol hybrid consisting of phenolic acid and a bornyl moiety connected to the dipeptide N-terminal and C-terminal respectively. It also evaluates their angiotensin converting enzyme (ACE) inhibitory and synergistic antihypertensive activities. Briefly, a series of novel 2-hydroxypyrrolobenzodiazepine-5, 11-dione analogues were prepared and investigated for their ability to inhibit ACE. The influence of the phenolic acid and bornyl moiety on subsite selectivity is also demonstrated. Among all the new compounds, two compounds-7a and 7g-reveal good inhibition potency in in vitro ACE-inhibitory tests. Interestingly, favorable binding results in molecular docking studies also supported the in vitro results. Additionally, the bioassay showed that oral administration of the two compounds displayed high and long-lasting antihypertensive activity both in acute antihypertensive tests and in therapeutic antihypertensive tests by non-invasive blood pressure measurements in spontaneously hypertensive rats.
Contiguous generation of quaternary and tertiary stereocenters: One-pot synthesis of chroman-fused S-proline-derived chiral oxazepinones
Singh, Ritesh,Parai, Maloy Kumar,Mondal, Sankalan,Panda, Gautam
, p. 253 - 259 (2013)
A new class of chroman-fused S-proline-derived chiral oxazepinones has been synthesized in one pot through contiguous generation of quaternary and tertiary stereocenters.
Intramolecular Alkylation of Carboxylic Acids: Application to the Synthesis of Boc-Protected Cyclic Amino Acids
Nicola, A. De,Einhorn, C.,Einhorn, J.,Luche, J. L.
, p. 879 - 880 (1994)
A new synthesis of Boc-protected cyclic amino acids is described as an application of an unreported method of lithium diisopropylamide-induced cyclisation of ω-chloro carboxylic acids containing a protected amine function in the chain.
Synthesis of alexine-like compounds from chiral five-membered endocyclic enecarbamates
Valle, Marcelo Siqueira,Retailleau, Pascal,Correia, Carlos Roque Duarte
, p. 1957 - 1960 (2008)
Stereoselective syntheses of enantiomerically enriched trihydroxy pyrrolizidine and indolizidines were accomplished from a common chiral endocyclic enecarbamate. The synthetic strategy features an efficient [2+2] cycloaddition of ketenes to the endocyclic enecarbamate and a highly regioselective Baeyer-Villiger oxidation of the intermediate azabicyclic-cyclobutanones. These new heterocycles are compounds structurally related to the alexines.
Hydrolysis of Pro-Ala Dipeptides by Lysosomal Hydrolases. Models for the Study of Lysosomotropic Amino Acid Prodrugs of Penicillins
Renard, C,Michel, A.,Tulkens, P. M.
, p. 1291 - 1293 (1986)
Peptidic lysosomotropic prodrugs of antibiotics and antitumoral agents could be of advantage in chemotherapy, providing that free, active drug is released at, or close to, the desired site of action.Thus, aminoacyl derivatives of doxorubicin, e.g., where the drug is attached to the amino acid by a primary amino function, are sensitive to lysosomal hydrolases.We have examined whether a similar approach can be used for drugs carrying a carboxyl group such as β-lactam antibiotics.Because the C adjacent to the carboxyl group in β-lactams has the D configuration, we have examined and report here the synthesis and susceptibility of model peptides, namely Boc-D-Pro-L-Ala and Boc-L-Pro-L-Ala to lysosomal hydrolases.Hydrolysis of the D isomer proceeds considerably more slowly than that of the L isomer.Lysosomal carboxypeptidase(s) and/or amidases appear therefore to have a much narrower specificity than aminopeptidase(s), which will severely limit the applicability of the concept of peptidic lysosomotropic prodrugs.
Synthesis and biological evaluation of pyrrolidine-2-carbonitrile and 4-fluoropyrrolidine-2-carbonitrile derivatives as dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes
Wang, Jiang,Feng, Ying,Ji, Xun,Deng, Guanghui,Leng, Ying,Liu, Hong
, p. 7418 - 7429 (2013)
A novel series of pyrrolidine-2-carbonitrile and 4-fluoropyrrolidine-2- carbonitrile derivatives was designed, synthesized, and found to act as dipeptidyl peptidase-4 (DPP-4) inhibitors. From this series of compounds, compound 17a was identified as an efficacious, safe, and selective inhibitor of DPP-4. In vivo studies in ICR and KKAy mice showed that administration of this compound resulted in decreased blood glucose in these mice after an oral glucose challenge. Compound 17a showed high DPP-4 inhibitory activity (IC50 = 0.017 μM), moderate selectivity against DPP-4 (selective ratio: DPP-8/DPP-4 = 1324; DPP-9/DPP-4 = 1164), and good efficacy in oral glucose tolerance tests in ICR and KKAy mice. These in vivo anti-diabetic properties and its desirable pharmacokinetic profile in Sprague-Dawley rats demonstrate that compound 17a is a promising candidate for development as an anti-diabetic agent.
Enantioselective synthesis of (R)-homoboroproline from (S)-proline using a borylation approach
Georgiou, Irene,Whiting, Andrew
, p. 4110 - 4113 (2012)
(S)-Proline was converted through a five-step sequence into (R)-homoboroproline hydrochloride in 29% overall yield with 97% The key step was the conversion of N-Boc iodomethylpyrrolidine into the corresponding pinacol boronate ester by an efficient copper(I)-catalyzed borylation reaction by using bispinacolatodiboron.
Formal Fluorinative Ring Opening of 2-Benzoylpyrrolidines Utilizing [1,2]-Phospha-Brook Rearrangement for Synthesis of 2-Aryl-3-fluoropiperidines
Kondoh, Azusa,Ojima, Rihaku,Terada, Masahiro
supporting information, p. 7894 - 7899 (2021/10/20)
A ring expansion of 2-benzoylpyrrolidines, which involves the formal fluorinative ring opening utilizing the [1,2]-phospha-Brook rearrangement under Br?nsted base catalysis and a subsequent intramolecular reductive amination, was developed. The operationally simple three-step protocol provides an efficient access to 2-aryl-3-fluoropiperidines. The methodology was further applied to the syntheses of azepanes and tetrahydroquinolines.
