5241-64-5Relevant articles and documents
A class of DL-tryptophan compounds, preparation method and applications thereof
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Paragraph 0058-0061, (2020/06/17)
The invention provides a DL-tryptophan compound represented by a general formula I or a pharmaceutically acceptable salt thereof, a preparation method and applications thereof, especially applicationsin preparation of RANKL inhibitors. According to the DL-tryptophan compound or the pharmaceutically acceptable salt thereof, an OPG-RANKL-RANK signal system can be intervened by inhibiting the interaction of RANKL-RANK, and the activity of RANKL in osteoclast precursor cells is regulated and controlled, so that formation of osteoclasts is inhibited, and bone resorption is reduced; and the DL-tryptophan compound or the pharmaceutically acceptable salt thereof is expected to play a role in preventing and treating bone metabolic diseases, and brings good news to bone metabolic disease patients.
A Facile Approach to the Synthesis of Benzothiazoles from N-Protected Amino Acids
Arfan, M.,Fatima, T.,Mannan, A.,Tahira, A.
, p. 292 - 297 (2020/04/21)
Abstract: –A simple trituration method for the synthesis of 2-substituted benzothiazoles derived from N-protected amino acids and 2-aminothiophenol using molecular iodine as a mild Lewis acid catalyst has been proposed. The reaction occurs in one step for 20–25 min in solve-free conditions and provides the target products in excellent yields.
Novel tacrine-tryptophan hybrids: Multi-target directed ligands as potential treatment for Alzheimer's disease
Chalupova, Katarina,Korabecny, Jan,Bartolini, Manuela,Monti, Barbara,Lamba, Doriano,Caliandro, Rosanna,Pesaresi, Alessandro,Brazzolotto, Xavier,Gastellier, Anne-Julie,Nachon, Florian,Pejchal, Jaroslav,Jarosova, Michaela,Hepnarova, Vendula,Jun, Daniel,Hrabinova, Martina,Dolezal, Rafael,Zdarova Karasova, Jana,Mzik, Martin,Kristofikova, Zdena,Misik, Jan,Muckova, Lubica,Jost, Petr,Soukup, Ondrej,Benkova, Marketa,Setnicka, Vladimir,Habartova, Lucie,Chvojkova, Marketa,Kleteckova, Lenka,Vales, Karel,Mezeiova, Eva,Uliassi, Elisa,Valis, Martin,Nepovimova, Eugenie,Bolognesi, Maria Laura,Kuca, Kamil
, p. 491 - 514 (2019/03/08)
A combination of tacrine and tryptophan led to the development of a new family of heterodimers as multi-target agents with potential to treat Alzheimer's disease. Based on the in vitro biological profile, compound S-K1035 was found to be the most potent inhibitor of human acetylcholinesterase (hAChE) and human butyrylcholinesterase (hBChE), demonstrating balanced IC50 values of 6.3 and 9.1 nM, respectively. For all the tacrine-tryptophan heterodimers, favorable inhibitory effect on hAChE as well as on hBChE was coined to the optimal spacer length ranging from five to eight carbon atoms between these two pharmacophores. S-K1035 also showed good ability to inhibit Aβ42 self-aggregation (58.6 ± 5.1% at 50 μM) as well as hAChE-induced Aβ40 aggregation (48.3 ± 6.3% at 100 μM). The X-ray crystallographic analysis of TcAChE in complex with S-K1035 pinpointed the utility of the hybridization strategy applied and the structures determined with the two K1035 enantiomers in complex with hBChE could explain the higher inhibition potency of S-K1035. Other in vitro evaluations predicted the ability of S-K1035 to cross blood-brain barrier and to exert a moderate inhibition potency against neuronal nitric oxide synthase. Based on the initial promising biochemical data and a safer in vivo toxicity compared to tacrine, S-K1035 was administered to scopolamine-treated rats being able to dose-dependently revert amnesia.
Development of Small-Molecules Targeting Receptor Activator of Nuclear Factor-κB Ligand (RANKL) - Receptor Activator of Nuclear Factor-κB (RANK) Protein-Protein Interaction by Structure-Based Virtual Screening and Hit Optimization
Jiang, Min,Peng, Lei,Yang, Kai,Wang, Tianqi,Yan, Xueming,Jiang, Tao,Xu, Jianrong,Qi, Jin,Zhou, Hanbing,Qian, Niandong,Zhou, Qi,Chen, Bo,Xu, Xing,Deng, Lianfu,Yang, Chunhao
supporting information, p. 5370 - 5381 (2019/06/24)
Targeting RANKL/RANK offers the possibility of developing novel therapeutic approaches to treat bone metabolic diseases. Multiple efforts have been made to inhibit RANKL. For example, marketed monoclonal antibody drug Denosumab could inhibit the maturation of osteoclasts by binding to RANKL. This study is an original approach aimed at discovering small-molecule inhibitors impeding RANKL/RANK protein interaction. We identified compound 34 as a potent and selective RANKL/RANK inhibitor by performing structure-based virtual screening and hit optimization. Disruption of the RANKL/RANK interaction by 34 effectively inhibits RANKL-induced osteoclastogenesis and bone resorption. The expression of osteoclast marker genes was also suppressed by treatment of 34. Furthermore, 34 markedly blocked the NFATc1/c-fos pathway. Thus, our current work demonstrates that the chemical tractability of the difficult PPI (RANKL/RANK) target by a small-molecule compound 34 offers a potential lead compound to facilitate the development of new medications for bone-related diseases.
Amino acid conjugated antimicrobial drugs: Synthesis, lipophilicity- activity relationship, antibacterial and urease inhibition activity
Ullah, Atta,Iftikhar, Fatima,Arfan, Muhammad,Batool Kazmi, Syeda Tayyaba,Anjum, Muhammad Naveed,Haq, Ihsan-ul,Ayaz, Muhammad,Farooq, Sadia,Rashid, Umer
, p. 140 - 153 (2018/01/10)
Present work describes the in vitro antibacterial evaluation of some new amino acid conjugated antimicrobial drugs. Structural modification was attempted on the three existing antimicrobial pharmaceuticals namely trimethoprim, metronidazole, isoniazid. Twenty one compounds from seven series of conjugates of these drugs were synthesized by coupling with some selected Boc-protected amino acids. The effect of structural features and lipophilicity on the antibacterial activity was investigated. The synthesized compounds were evaluated against five standard American type culture collection (ATCC) i.e. Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi strains of bacteria. Our results identified a close relationship between the lipophilicity and the activity. Triazine skeleton proved beneficial for the increase in hydrophobicity and potency. Compounds with greater hydrophobicity have shown excellent activities against Gram-negative strains of bacteria than Gram-positive. 4-amino unsubstituted trimethoprim-triazine derivative 7b have shown superior activity with MIC = 3.4 μM (2 μg/mL) for S. aureus and 1.1 μM (0.66 μg/mL) for E. coli. The synthesized compounds were also evaluated for their urease inhibition study. Microbial urease from Bacillus pasteurii was chosen for this study. Triazine derivative 7a showed excellent inhibition with IC50 = 6.23 ± 0.09 μM. Docking studies on the crystal structure of B. pasteurii urease (PDB ID 4UBP) were carried out.
Non-peptide tachykinin receptor antagonist preparation method
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Paragraph 0029; 0030; 0031; 0032, (2017/08/29)
The invention discloses a non-peptide tachykinin receptor antagonist preparation method. A synthetic route of a non-peptide tachykinin receptor antagonist is as shown in the specification. The non-peptide tachykinin receptor antagonist preparation method has advantages of simplicity and feasibility in operation, cheap and easy in acquisition of raw materials, high reaction efficiency and high repeatability.
The method of synthesis for preparing compound
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Paragraph 0054-0056, (2017/09/01)
A synthesis method of a compound shown as a formula I is provided. The method includes (1) bringing a compound shown as a formula 1 into contact with BOC anhydride to produce a compound shown as a formula 2; (2) bringing the compound shown as the formula 2 into contact with a compound shown as a formula 3 to produce a compound shown as a formula 4; (3) subjecting the compound shown as the formula 4 to amino deprotection to produce a compound shown as a formula 5; and (4) bringing the compound shown as the formula 5 into contact with a compound shown as a formula 6 to produce the compound shown as the formula I that is Tadalafil. The method prepares the Tadalafil through four steps of reactions. The total yield reaches 36.1%. Process steps of the method are simple. Initial raw materials are cheap and easily available. All the intermediates are easy to purify. After-treatment operation is simple. The content of impurities in a finished product is low. The target product is high in purity. Compared with other Tadalafil preparing processes at present, the method obviously reduces environment pollution and benefits industrial production.
Substrate Fragmentation for the Design of M. tuberculosis CYP121 Inhibitors
Kavanagh, Madeline E.,Gray, Janine L.,Gilbert, Sophie H.,Coyne, Anthony G.,McLean, Kirsty J.,Davis, Holly J.,Munro, Andrew W.,Abell, Chris
supporting information, p. 1924 - 1935 (2016/10/06)
The cyclo-dipeptide substrates of the essential M. tuberculosis (Mtb) enzyme CYP121 were deconstructed into their component fragments and screened against the enzyme. A number of hits were identified, one of which exhibited an unexpected inhibitor-like binding mode. The inhibitory pharmacophore was elucidated, and fragment binding affinity was rapidly improved by synthetic elaboration guided by the structures of CYP121 substrates. The resulting inhibitors have low micromolar affinity, good predicted physicochemical properties and selectivity for CYP121 over other Mtb P450s. Spectroscopic characterisation of the inhibitors′ binding mode provides insight into the effect of weak nitrogen-donor ligands on the P450 heme, an improved understanding of factors governing CYP121–ligand recognition and speculation into the biological role of the enzyme for Mtb.
Dual Catalytic Decarboxylative Allylations of α-Amino Acids and Their Divergent Mechanisms
Lang, Simon B.,O'Nele, Kathryn M.,Douglas, Justin T.,Tunge, Jon A.
supporting information, p. 18589 - 18593 (2016/01/25)
The room temperature radical decarboxylative allylation of N-protected α-amino acids and esters has been accomplished via a combination of palladium and photoredox catalysis to provide homoallylic amines. Mechanistic investigations revealed that the stability of the α-amino radical, which is formed by decarboxylation, dictates the predominant reaction pathway between competing mechanisms.
DI-AND TRI-HETEROARYL DERIVATIVES AS INHIBITORS OF PROTEIN AGGREGATION
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Paragraph 0125; 0128, (2014/02/15)
The present invention relates to certain di- and tri-heteroaryl derivatives, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, and multiple system atrophy.
