- Design, Synthesis, and Structural Analysis of Cladosporin-Based Inhibitors of Malaria Parasites
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Here we have described a systematic structure activity relationship (SAR) of a set of compounds inspired from cladosporin, a tool compound that targets parasite (Plasmodium falciparum) lysyl tRNA synthetase (KRS). Four sets of analogues, synthesized based on point changes in the chemical scaffold of cladosporin and other logical modifications and hybridizations, were assessed using high throughput enzymatic and parasitic assays along with in vitro pharmacokinetics. Co-crystallization of the most potent compound in our series (CL-2) with PfKRS revealed its structural basis of enzymatic binding and potency. Further, we report that CL-2 has performed better than cladosporin in terms of metabolic stability. It thus represents a new lead for further optimization toward the development of antimalarial drugs. Collectively, along with a lead compound, the series offers insights on how even the slightest chemical modification might play an important role in enhancing or decreasing the potency of a chemical scaffold.
- Babbar, Palak,Das, Pronay,Manickam, Yogavel,Mankad, Yash,Yadav, Swati,Parvez, Suhel,Sharma, Amit,Reddy, D. Srinivasa
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p. 1777 - 1794
(2021/05/10)
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- 4-benzylideneisoquinoline-1,3(2H,4H)-diones as tyrosyl DNA phosphodiesterase 2 (TDP2) inhibitors
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Tyrosyl-DNA phosphodiesterase 2 (TDP2) repairs topoisomerase II (Top2) mediated DNA damages, including double-strand breaks (DSBs) that underpin the anticancer mechanism of clinical Top2 poisons such as etoposide (ETP). Inhibition of TDP2 could sensitize
- Senaweera, Sameera,He, Tianyu,Cui, Haixi,Aihara, Hideki,Wang, Zhengqiang
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p. 371 - 386
(2020/11/23)
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- IDO/TDO Inhibitor
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A compound of formula (I) given below or a pharmaceutically acceptable salt of the compound is useful as an IDO/TDO inhibitor. Thus, the compound of formula (I) or the pharmaceutically acceptable salt of the compound can be used as, for example, a therapeutic agent for a disease or a disorder selected from tumor, infectious disease, neurodegenerative disorder, cataract, organ transplant rejection, autoimmune disease, postoperative cognitive impairment, and disease related to women's reproductive health [in the following formula (I), ring A represents an aromatic ring, an aliphatic ring, a heterocyclic ring, or a condensed ring of two or more rings selected from an aromatic ring, an aliphatic ring and a heterocyclic ring; X, R1 and R2 represent a substituent on a ring atom constituting ring A; m represents an integer of 0 to 6; X represents, for example, a halogen atom; and R1 and R2 are the same or different and are selected from, for example, the group consisting of groups of formula (a) or formula (b); and in the following formula (a) and formula (b), Y is selected from the group consisting of O, S, and Se, Z is selected from the group consisting of O, S, and Se, n represents an integer of 1 to 8, r represents an integer of 1 to 8, s represents an integer of 1 to 8, R4 represents, for example, —C(═NH)—HN2, and R6 represents, for example, a substituted or unsubstituted aryl group].
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-
Paragraph 0493-0496; 0581-0584
(2020/08/19)
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- Efficient flow fischer esterification of carboxylic acids with alcohols using sulfonic acid-functionalized silica as supported catalyst
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Flow Fischer esterification of carboxylic acids using hydroxy-substituted sulfonic acid-functionalized silica (HOSAS) packed into a stainless steel column reactor was investigated. HO-SAS well catalyzed flow esterification of long chain carboxylic acids with methanol within 3min of residence time at 110°C, and the methyl esters were quantitatively obtained. The flow esterification protocol was applied to the synthesis of a variety of esters (19 examples) and scalable synthesis was also successful.
- Furuta, Akihiro,Fukuyama, Takahide,Ryu, Ilhyong
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p. 607 - 612
(2017/06/19)
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- Crystal Photodimerization Reactions of Spatially Engineered Isocoumarin Assemblies
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We report the single-crystal-to-single-crystal (SCSC) photodimerization of a sulfonamide isocoumarin. When recrystallized, this material forms centrosymmetrically related supramolecular dimers that assemble via the complementary features of molecular shap
- Weerasinghe, Mihiri S.,Karlson, Steven T.,Lu, Yuhua,Wheeler, Kraig A.
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p. 1781 - 1785
(2016/05/09)
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- Compositions and methods for the protection of nucleophilic groups
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The present invention provides compositions, methods, and kits relating to the protection and deprotection of molecules comprising nucleophilic groups, such as the protection and deprotection of thermostable polymerases. Also provided are methods of performing nucleic acid amplification using polymerases protected according to the invention.
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Page/Page column 7; 26
(2016/01/25)
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- Biomass derived β-cyclodextrin-SO3H as a solid acid catalyst for esterification of carboxylic acids with alcohols
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A novel β-cyclodextrin-SO3H carbon based solid acid catalyst was prepared in a convenient and ecofriendly manner and was characterized using FTIR, PXRD, EDAX and NH3TPD to illustrate that the carbon material has been functionalized with -SO3H, -COOH and -OH groups. The catalyst was studied for esterification of various carboxylic acids and alcohols under solvent free conditions and showed excellent catalytic performance and gave good yields of esters in the range 78-99% at 70°C. No solvent was used either for catalyst preparation nor for esterification reaction. The catalyst can be easily recovered by simple filtration and reused for subsequent three runs without any significant impact on yields of products. The main advantage of this methodology is easy and ecofriendly catalyst preparation, easy catalyst separation, practical simplicity, safe reaction conditions, recyclable catalyst and high product yields.
- Thombal, Raju S.,Jadhav, Amol R.,Jadhav, Vrushali H.
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p. 12981 - 12986
(2015/02/19)
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- Compositions and methods for the protection of nucleophilic groups
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The present invention provides compositions, methods, and kits relating to the protection and deprotection of molecules comprising nucleophilic groups, such as the protection and deprotection of thermostable polymerases. Also provided are methods of performing nucleic acid amplification using polymerases protected according to the invention.
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Page/Page column
(2014/04/17)
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- A convenient procedure for bis-esterification of cyclic anhydrides
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Aromatic and aliphatic cyclic anhydrides are chemoselectively and conveniently transformed to the corresponding diesters by the use of DBU and appropriate alkyl/allyl halides. This bis-esterification reaction has been exemplified mostly with dimethyl esters. But in some cases, mixed dialkyl esters are also prepared.
- Jana, Amit Kumar,Karmakar, Raju,Dinda, Bidyut Kumar,Mitra, Prithiba,Ghosh, Ketaki,Karmakar, Rajdip,Mal, Dipakranjan
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p. 975 - 979
(2012/10/29)
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- 2-HYDROXYISOQUINOLINE-1,3(2H,4H)-DIONES AND RELATED COMPOUNDS USEFUL AS HIV REPLICATION INHIBITORS
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The present invention relates to compounds and compositions acting as inhibitors of HIV integrase. The compound of the invention is of Formula (I), or a tautomer (I') thereof, or a pharmaceutically acceptable salt, or solvate of said compound or tautomer
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Page/Page column 62
(2012/07/13)
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- Synthesis of indolin-2-one, isoindolin-1-one, and indole derivatives from homophthalic acid
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We hereby report the preparation of indolin-2-one and isoindolin-1-one and their derivatives starting from 2-(carboxymethyl)benzoic acid, which was first regiospecifically converted into the isomeric half esters. Transformation of the acid functionalities to the acyl azides followed by Curtius rearrangement gave the regioisomeric isocyanates. Reaction of the isocyanates with aniline produced urethane derivatives. Intramolecular cyclization provided the target compounds. Georg Thieme Verlag Stuttgart. New York.
- Kilikli, Alper A.,Dengiz, Cagatay,Oezcan, Sevil,Balci, Metin
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experimental part
p. 3697 - 3705
(2011/12/21)
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- 2-Hydroxyisoquinoline-1,3(2H,4H)-diones as inhibitors of HIV-1 integrase and reverse transcriptase RNase H domain: Influence of the alkylation of position 4
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We report herein the synthesis of a series of fifteen 2- hydroxyisoquinoline-1,3(2H,4H)-dione derivatives. Alkyl and arylalkyl groups were introduced on position 4 of the basis scaffold. All the compounds presented poor inhibitory properties against HIV-1 reverse transcriptase ribonuclease H (RNase H). Four compounds inhibited HIV-1 integrase at a low micromolar level. A docking study using the later crystallographic data available for PFV integrase allowed us to explain the slightly improved integrase inhibitory activities of 4-pentyl and 4-(3-phenylpropyl)-2-hydroxyisoquinoline-1,3(2H,4H)-diones, when compared to the basis scaffold. Physicochemical studies were consistent with 1:1 and 1:2 (metal/ligand) stoichiometries of the magnesium complexes in solution. Unfortunately all tested compounds exhibited high cellular cytotoxicity in cell culture which limited their applications as antiviral agents. However these identified integrase inhibitors provide a very good basis for the development of new hits.
- Billamboz, Muriel,Bailly, Fabrice,Lion, Cedric,Calmels, Christina,Andreola, Marie-Line,Witvrouw, Myriam,Christ, Frauke,Debyser, Zeger,De Luca, Laura,Chimirri, Alba,Cotelle, Philippe
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experimental part
p. 535 - 546
(2011/03/19)
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- Construction of 1,2,5-tricarbonyl compounds using methyl cyanoacetate as a glyoxylate anion synthon combined with copper(I) iodide-catalyzed aerobic oxidation
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A practical and efficient synthesis of various 1,2,5-tricarbonyl compounds is described. The synthesis has been carried out by a conjugate addition of methyl cyanoacetate to the β-position of α,β-unsaturated carbonyl compounds and a subsequent copper(I) iodide-catalyzed aerobic oxidation. In addition, various α-aryl- and α-alkyl-α-keto esters have been synthesized using a similar approach. Copyright
- Kim, Se Hee,Kim, Ko Hoon,Kim, Jae Nyoung
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supporting information; scheme or table
p. 3335 - 3339
(2012/01/19)
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- Chemically-enabled synthesis of 1,2,3,4-tetrahydroisoquinolin-1-ones
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We have developed a number of efficient protocols for the facile synthesis of 1,2,3,4-tetrahydroisoquinolin-1-ones. This synthetic methodology allowed concise and efficient exploration of the SAR in all areas of the molecule. A number of these methods pro
- Humphries, Paul S.,Balan, Gayatri,Bechle, Bruce M.,Conn, Edward L.,Dirico, Kenneth J.,Hui, Yu,Oliver, Robert M.,Southers, James A.,Yang, Xiaojing
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scheme or table
p. 2140 - 2143
(2009/07/26)
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- Facile synthesis of 4-alkoxycarbonylisoquinoline-1,3-diones and 5-alkoxycarbonyl-2-benzazepine-1,3-diones via a mild alkaline cyclization
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(Chemical Equation Presented) A series of 4-methoxycarbonylisoquinoline-1, 3-diones was obtained from homophthalic acid in four steps. The key step was the quantitative and rapid alkaline cyclization of 2-methoxycarbonyl-2-(2- methoxycarbonylphenyl) aceta
- Billamboz, Muriel,Bailly, Fabrice,Cotelle, Philippe
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experimental part
p. 392 - 398
(2009/09/08)
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- An expedient synthesis of poly-substituted 1-arylisoquinolines from δ-ketonitriles via indium-mediated Barbier reaction protocol
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We developed an efficient synthetic strategy of poly-substituted 1-arylisoquinolines via an indium-mediated Barbier type allylation from δ-ketonitriles. Initial attack of allylindium species occurred at the nitrile group selectively to form the enamine intermediate, which reacted with the ketone group intramolecularly to furnish the isoquinolines.
- Kim, Sung Hwan,Lee, Hyun Seung,Kim, Ko Hoon,Kim, Jae Nyoung
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experimental part
p. 6476 - 6479
(2011/02/23)
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- 1-Oxo-3-substitute-isothiochroman-4-carboxylic acid compounds: Synthesis and biological activities of FAS inhibition
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A new series 1-oxo-3-substitute-isothiochroman-4-carboxylic acid compounds have been designed and synthesized. Screening of these molecules for FAS inhibition in vitro has indicated that compounds 2c and 2d showed more effective FAS inhibition activities
- Wang, Xiaokui,Zhao, Guoming,Chen, Yao,Xu, Xiaowei,Zhong, Wu,Wang, Lili,Li, Song
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scheme or table
p. 770 - 772
(2009/08/15)
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- DBU-CH3I, a potential substitute for CH2N2 in the preparation of methyl esters and methyl aryl ethers: Studies with assorted acids
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DBU-CH3I has been poised to be a substitute for diazomethane in the preparation of methyl esters from carboxylic acids. The reactions can be carried out in commercial untreated acetone and acetonitrile, which have been exemplified with several methyl esters, otherwise it is difficult to prepare. Bis-esterification using diiodomethane can also be achieved in a similar fashion. Sufficiently acidic phenols are also conveniently O-methylated by the method. Copyright Taylor & Francis Group, LLC.
- Mal, Dipakranjan,Jana, Amit,Ray, Sutapa,Bhattacharya, Sourav,Patra, Asit,De, Saroj R.
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experimental part
p. 3937 - 3946
(2009/04/11)
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- METHODS FOR TREATING OR PREVENTING ERECTILE DYSFUNCTION OR URINARY INCONTINENCE
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The invention relates to methods for treating or preventing erectile dysfunction or urinary incontinence, comprising administering to a subject in need thereof an effective amount of a compound of the invention.
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Page/Page column 107
(2010/11/28)
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- Tetracyclic lactam derivatives and uses thereof
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The present invention relates to Tetracyclic Lactam Derivatives, compositions comprising an effective amount of a Tetracyclic Lactam Derivative and methods for treating or preventing an inflammatory disease, a reperfusion injury, an ischemic condition, re
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Page/Page column 35
(2010/02/14)
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- Highly efficient esterification of carboxylic acids with alcohols by montmorillonite enwrapped titanium as a heterogeneous acid catalyst
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Montmorillonite-enwrapped titanium catalyst was found to efficiently promote the esterification of carboxylic acids with alcohols. In comparison to other catalysts reported to date, this heterogeneous catalyst offers a remarkably simple workup procedure, and is reusable without any appreciable loss in its activity and selectivity.
- Kawabata, Tomonori,Mizugaki, Tomoo,Ebitani, Kohki,Kaneda, Kiyotomi
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p. 9205 - 9208
(2007/10/03)
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- Process for the manufacture of hypoxyxylerone derivatives
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The present invention relates to the total synthesis of hypoxyxylerone derivatives (formula I) and their biological activities. R1-R5 are as described in the description.
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- Silica Chloride: A Versatile Heterogeneous Catalyst for Esterification and Transesterification
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Silica chloride has been found to be an efficient catalyst for esterification of carboxylic acids (aliphatic, aromatic and conjugated) with alcohols (primary, secondary and tertiary) as well as for transesterification of esters (by both alcoholysis and acidolysis).
- Srinivas,Mahender,Das, Biswanath
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p. 2479 - 2482
(2007/10/03)
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- A simple method for the preparation of monomethyl esters of dicarboxylic acids by selective esterification of the nonconjugated carboxyl group in the presence of an aromatic or conjugated carboxyl group
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Various dicarboxylic acids have been converted selectively into monomethyl esters in which the nonconjugated carboxyl group is selectively esterified in the presence of an aromatic or conjugated carboxyl group at room temperature (~ 25-27°C) in methanol using a catalytic amount of thionyl chloride.
- Ram, Ram N.,Meher, Nabin Kumar
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p. 282 - 283
(2007/10/03)
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- Aqueous organotin chemistry: Tin hydride mediated dehalogenation of organohalides and a novel organotin mediated nucleophilic substitution on 2- iodobenzoates in water
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This paper describes the dehalogenation of water soluble and water insoluble organohalides in water by tri-n-butyltin hydride (TBTH), preformed TBTH and triphenyltin hydride (TPTH) in water. TBTH in the presence of a radical trap, and Ph4Sn were also found to effect nucleophilic substitution of 2-iodobenzoates in the presence of various nucleophiles.
- Sarma, Koushik Das,Maitra, Uday
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p. 4965 - 4976
(2007/10/03)
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- A practical photochemical synthesis of 6-aza-1,10-phenanthroic anhydride
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A high yield synthesis of 6-aza-1,10-phenanthroic anhydride has been developed. The key step is a volume-efficient photochemical cyclization of azastilbene 5 to the photochemically stable dihydroazaphenanthrene 9.
- Pierce, Michael E.,Fortunak, Joseph M. D.,Islam, Qamrul
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p. 3645 - 3652
(2007/10/03)
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- Laser flash photolysis study of the reactivity of α-ketenylbenzocyclobutenone with water and alcohols
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Photolysis of 2-diazo-1,3-indandione leads to ketene formation via the Wolff rearrangement. Ketene 2 hydrates to produce enol 3a that rearranges to 4a. Homophthalic acid 5a is formed by photodecomposition of 4a upon prolonged irradiation.
- De Lucas, Nanci Camara,Andraos, John,Netto-Ferreira,Scaiano
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p. 677 - 680
(2007/10/02)
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- ANGIOTENSIN II ANTAGONISTS INCORPORATING A SUBSTITUTED PYRIDOIMIDAZOLYL RING
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Substituted heterocycles attached through a methylene bridge to novel substituted phenyl derivatives of the Formula I are useful as angiotensin II antagonists. STR1
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- PLA2 INHIBITORS AS ANTIINFLAMMATORIES
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This invention relates to novel compounds for treating inflammatory conditions by inhibition of phospholipase A2 activity of the formula (I), compositions comprised of the novel compounds; and methods of treating inflammatory conditions with these composition
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- Use of Phosphorus Pentoxide. Preparation of Half-esters through Selective Esterification
-
Methyl 2-,3-,4-carboxyphenylacetate and methyl 2-,3-,4-carboxyphenoxyacetate have been prepared through selective esterification of the aliphatic carboxylic acid function of the corresponding dicarboxylic acids using a mixture of phosphorus pentoxide (1 part), anhydrous copper sulphate (5 parts) and anhydrous sodium sulphate (5 parts).All the isomeric half-esters have been prepared through partial hydrolysis of the corresponding dimethylesters.
- Banerjee, Amalendu,Adak, Mohini Mohan,Das, Sankar,Banerjee, Santa,Sengupta, Saumitra
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-
- Studies on Lactam Acetals: Part V - Use in N-, O- and S-Alkylations and Esterification
-
The utility of 2,2-dimethoxy-1-methylpyrrolidine as a reagent for facile N-, O-, S-alkylations and esterification, or both simultaneously, of a wide variety of substrates has been demonstrated.
- Singh, Jujhar,Nigam, M. B.,Sardana, Vinod,Jain, Padam C.,Anand, Nitya
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p. 596 - 597
(2007/10/02)
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