141-75-3Relevant articles and documents
Stereoselective, solid phase-based synthesis of trans 3-alkyl-substituted β-lactams as analogues of cholesterol absorption inhibitors
Delpiccolo, Carina M.L.,Testero, Sebastián A.,Leyes, Federico N.,Boggián, Dora B.,Camacho, Cristián M.,Mata, Ernesto G.
, p. 10780 - 10786 (2012)
A straightforward solid phase-based strategy for the rapid generation of two small libraries of trans 3-alkyl-substituted β-lactams is described. For the glycine-derived library, a controlled excess of nonactivated acid chlorides was used to prevent oxazinone formation. The second library involved the attachment of Fmoc-protected p-aminophenol to Wang resin for the preparation of structurally-closed analogues of known cholesterol absorption inhibitors. This strategy allowed us to introduce diversity in the three variable positions of the β-lactam ring.
Novel inhibitors of tyrosinase produced by the 4-substitution of TCT (П)
Liu, Jing,Li, Mengrong,Yu, Yanying,Cao, Shuwen
, p. 1096 - 1106 (2017)
Novel Tyrosinase Inhibitors of 4-functionalized Thiophene-2-carbaldehyde thiosemicarbazone (TCT) derivatives (1–8) had been synthesized and Spectrofluorimetry, 1H and 13C NMR titration and Molecular docking had been used to investigate their inhibitory activities and mechanisms on tyrosinase. The results showed that the inter-molecular interactions or hydrogen bond formation by increasing length of carbon chain or introducing benzene ring to the 4-functionalized ester group promoted or stabilized formation of complexes between modifier and tyrosinase, and enhanced the inhibitory activity of modifiers. The inhibitory activity of 4-benzoy methoxy-TCT was much stronger than that of any other synthesized tested modifiers, which was well explained by molecular docking and further verified by spectrofluorimetry and NMR titration by assuming that there existed an inter-molecular interaction besides formation of hydrogen bonds between the amino acid residues ASN260, GLU256, HIS85 of enzyme and the modifier.We concluded that 4-benzoy methoxy substitution of TCT was a good route obtaining novel tyrosinase inhibitors and deserved further studies.
Carboxamides as N-Alkylating Reagents of Secondary Amines in Indium-Catalyzed Reductive Amination with a Hydrosilane
Ogiwara, Yohei,Shimoda, Wataru,Ide, Keisuke,Nakajima, Takumi,Sakai, Norio
, p. 2866 - 2870 (2017)
A method for the catalytic reductive N-alkylation of amines by using secondary amides as the alkyl source was developed. A versatile type of carboxamide functioned as an N-alkylation reagent in the presence of an indium(III) catalyst and a hydrosilane to provide alkylated tertiary amines efficiently. This amide-based catalytic N-alkylation strategy is considered to be a highly useful protocol to access unsymmetrical tertiary amines.
Synthesis and bioactivities of diamide derivatives containing a phenazine-1-carboxamide scaffold
Zhu, Xiang,Zhang, Min,Yu, Linhua,Xu, Zhihong,Yang, Dan,Du, Xiaoying,Wu, Qinglai,Li, Junkai
, p. 2453 - 2460 (2019)
Taking natural product phenazine-1-carboxamide (PCN) as a lead compound, a series of novel phenazine-1-carboxylic acid diamide derivatives were designed and synthesised. Their structures were confirmed by 1H-NMR and HRMS. The bioassays showed that some of the target compounds exhibited promising in vitro fungicidal activities, and exhibited excellent and selective herbicidal activities. Particularly, compounds c, h, o and s displayed root length inhibition activities against barnyard grass with the rate of more than 80%. Compound c exhibited the best activity among all the target compounds against barnyard grass stalk length with the IC50 value of 0.158?mmol/L, and compound o exhibited the best and wide spectrum inhibition against barnyard grass root length and rape in both root length and stalk length herbicidal activities with its IC50 values of 0.067, 0.048 and 0.059?mmol/L respectively. The analysis of preliminary Structure-Activity Relationships provides the theoretical basis for further design of phenazine-1-carboxylic acid.
Computational discovery, structural optimization and biological evaluation of novel inhibitors targeting transient receptor potential vanilloid type 3 (TRPV3)
Zhang, Fang,Lin, Yiyu,Min, Wenjian,Hou, Yi,Yuan, Kai,Wang, Jin,Yang, Peng
, (2021)
Transient receptor potential vanilloid type 3 (TRPV3) is a Ca2+ permeable nonselective cation channel and expressed abundantly in skin keratinocytes. TRPV3 emerges as an attractive target for treatment of pruritic, inflammatory, pain and skin-related diseases. However, only a few reports of TRPV3 inhibitors exist at present besides some patents. Therefore, TRPV3 research has always been fraught with challenges. Through a combination of virtual screening and biological evaluation, compound P1 (10 μM) was identified as a top hit with 34.5% inhibitory effect on 2-APB (1 mM)-evoked currents of mTRPV3-WT. Further structural optimization provided the inhibitor PC5 with the best activity (IC50 = 2.63 ± 0.28 μM), and point mutation assays indicated that amino acids V629 and F633 are crucial for the binding of PC5 and TRPV3. In summary, these newly discovered inhibitors could serve as promising lead compounds for the development of TRPV3 inhibitors in the future.
Lead derivatization of ethyl 6-bromo-2-((dimethylamino)methyl)-5-hydroxy-1-phenyl-1H-indole-3-carboxylate and 5-bromo-2-(thiophene-2-carboxamido) benzoic acid as FabG inhibitors targeting ESKAPE pathogens
Varakala, Saiprasad Dasugari,Reshma, Rudraraju Srilakshmi,Schnell, Robert,Dharmarajan, Sriram
, (2021/11/26)
Our previous studies on FabG have identified two compounds 5-bromo-2-(thiophene-2-carboxamido) benzoic acid (A) and ethyl 6-bromo-2-((dimethylamino)methyl)-5-hydroxy-1-phenyl-1H-indole-3-carboxylate(B) as best hits with allosteric mode of inhibition. FabG is an integral part of bacterial fatty acid biosynthetic system FAS II shown to be an essential gene in most ESKAPE Pathogens. The current work is focussed on lead expansion of these two hit molecules which ended up with forty-three analogues (twenty-nine analogues from lead compound A and fourteen compounds from lead compound B). The enzyme inhibition studies revealed that compound 15 (effective against EcFabG, AbFabG, StFabG, MtFabG1) and 19 (inhibiting EcFabG and StFabG) had potency of broad-spectrum inhibition on FabG panel.
Synthesis, computational studies and enzyme inhibitory kinetics of benzothiazole-linked thioureas as mushroom tyrosinase inhibitors
Ujan, Rabail,Saeed, Aamer,Ashraf, Saba,Channar, Pervaiz Ali,Abbas, Qamar,Rind, Mahboob Ali,Hassan, Mubashir,Raza, Hussain,Seo, Sung-Yum,El-Seedi, Hesham R.
, p. 7035 - 7043 (2020/08/12)
Herein, we report synthesis of a set of benzothiazole-thiourea hybrids with aromatic and aliphatic side chains (BT1 to BT9) using an elegant synthetic strategy. The newly synthesized benzothiazole-thiourea conjugates were subjected to In-vitro tyrosinase inhibition and free radical scavenging activity. Majority of the compounds indicated inhibition considerably improved than the standard; compound (Kojic acid with IC50 = 16.8320 ± 1.1600 μM) BT2 with IC50 = 1.3431 ± 0.0254 μM was found to be the best inhibitor. A non-competitive mode of inhibition of BT2 was disclosed with Ki value of 2.8 μM. In order to study enzyme-inhibitor interactions SAR analysis molecular docking was carried out. The amino groups of thiourea were involved in hydrogen bonding with Glu322 showing the bond length of 1.74 and 2.70 ?, respectively. Moreover, the coupling of π-π was displayed between benzothiazole and benzene rings of His244 and His263, respectively. The outcome of this study might help to develop new inhibitors of melanogenesis, important for cosmetic and food products. Communicated by Ramaswamy H. Sarma.