- On the mixed oxides-supported niobium catalyst towards benzylamine oxidation
-
A series of mixed oxides-supported niobium-based catalysts has been synthesized and applied towards oxidation reactions of benzylamine derivatives. Under the optimized reaction conditions, the selectivity to oxime enhanced, leading to the main product with up to 72 %. Moreover, even α-substituted benzylamines were well tolerated and led to oximes in good isolated yields. It is important to mention; four equivalents of the harmless and inexpensive hydrogen peroxide were employed as oxidizing agent. Mechanism hypothesis suggested that the reaction proceed to selective benzylamine oxidation into nitroso intermediate, following by formation of the corresponding oxime tautomer mediated by an unstable water produced by NbOx supported catalyst. This consists the first mixed oxides-supported niobium-based catalyst for selective oxidation of benzylamines to oximes.
- Granato, álisson Silva,de Carvalho, Gustavo S. Gon?alves,Fonseca, Carla G.,Adrio, Javier,Leit?o, Alexandre A.,Amarante, Giovanni Wilson
-
p. 118 - 125
(2020/09/11)
-
- Design, synthesis, in vitro and in silico evaluation of new 3-phenyl-4,5-dihydroisoxazole-5-carboxamides active against drug-resistant mycobacterium tuberculosis
-
A new series of 3-phenyl-4,5-dihydroisoxazole-5-carboxamides were designed, synthesized, and evaluated for their potency against Mtb H37Rv. Designed molecules were synthesized by one-pot cycloaddition reaction in good to excellent yields. Anti-Tubercular evaluation of all synthesized derivatives identified 6k to be highly potent (MIC 1 μg/mL) against Mtb and drug-resistant strains. All potent derivatives were found to be non-toxic when tested against Vero cells. Also, in silico studies were employed to explore the binding patterns of designed compounds to target Mycobacterial membrane protein Large-3. All derivatives exhibited excellent binding patterns with the receptor. The excellent in silico Absorption, Distribution, Metabolism, and Excretion properties and druggability parameters positions these molecules as promising lead candidates for the future development of new drugs to treat drug-resistant Tuberculosis.
- Gaikwad, Nikhil Baliram,Afroz, Pathan,Ahmad, Mohammad Naiyaz,Kaul, Grace,Shukla, Manjulika,Nanduri, Srinivas,Dasgupta, Arunava,Chopra, Sidharth,Yaddanapudi, Venkata Madhavi
-
-
- Isoxazoline-pyrazole amide compound as well as preparation method and application thereof
-
The invention discloses an isoxazoline-pyrazole amide compound, which has the following structural formula (I) as shown in the specification. Each substituent group is shown in the specification. The invention also provides a preparation method and application of the compound. The compound provided by the invention is suitable for killing insects.
- -
-
Paragraph 0108-0112
(2021/05/15)
-
- Dibenzazepine-linked isoxazoles: New and potent class of α-glucosidase inhibitors
-
α-Glucosidase inhibition is a valid approach for controlling hyperglycemia in diabetes. In the current study, new molecules as a hybrid of isoxazole and dibenzazepine scaffolds were designed, based on their literature as antidiabetic agents. For this, a series of dibenzazepine-linked isoxazoles (33–54) was prepared using Nitrile oxide-Alkyne cycloaddition (NOAC) reaction, and evaluated for their α-glucosidase inhibitory activities to explore new hits for treatment of diabetes. Most of the compounds showed potent inhibitory potency against α-glucosidase (EC 3.2.1.20) enzyme (IC50 = 35.62 ± 1.48 to 333.30 ± 1.67 μM) using acarbose as a reference drug (IC50 = 875.75 ± 2.08 μM). Structure-activity relationship, kinetics and molecular docking studies of active isoxazoles were also determined to study enzyme-inhibitor interactions. Compounds 33, 40, 41, 46, 48–50, and 54 showed binding interactions with critical amino acid residues of α-glucosidase enzyme, such as Lys156, Ser157, Asp242, and Gln353.
- Umm-E-Farwa,Ullah, Saeed,Khan, Maria Aqeel,Zafar, Humaira,Atia-tul-Wahab,Younus, Munisaa,Choudhary, M. Iqbal,Basha, Fatima Z.
-
supporting information
(2021/05/10)
-
- Synthesis and SAR study of simple aryl oximes and nitrofuranyl derivatives with potent activity against Mycobacterium tuberculosis
-
Background: Oximes and nitrofuranyl derivatives are particularly important compounds in medicinal chemistry. Thus, many researchers have been reported to possess antibacterial, antiparasitic, insecticidal and fungicidal activities. Methods: In this work, we report the synthesis and the biological activity against Mycobacterium tuberculosis H37RV of a series of fifty aryl oximes, ArCH=N-OH, I, and eight nitrofuranyl compounds, 2-nitrofuranyl-X, II. Results: Among the oximes, I: Ar = 2-OH-4-OH, 42, and I: Ar = 5-nitrofuranyl, 46, possessed the best activity at 3.74 and 32.0 μM, respectively. Also, 46, the nitrofuran compounds, II; X = MeO, 55, and II: X = NHCH2Ph, 58, (14.6 and 12.6 μM, respectively), exhibited excellent biological activities and were non-cytotoxic. Conclusion: The compound 55 showed a selectivity index of 9.85. Further antibacterial tests were performed with compound 55 which was inactive against Enterococcus faecalis, Klebisiella pneumonae, Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella typhymurium and Shigel-la flexneri. This study adds important information to the rational design of new lead anti-TB drugs. Structure-activity Relationship (SAR) is reported.
- Calixto, Stephane Lima,Carvalho, Guilherme da Silva Louren?o,Coimbra, Elaine Soares,Granato, Juliana da Trindade,Louren?o, Maria Cristina da Silva,Wardell, James,da Costa, Cristiane Fran?a,de Souza, Marcus Vinicius Nora
-
-
- Potassium Poly(Heptazine Imide): Transition Metal-Free Solid-State Triplet Sensitizer in Cascade Energy Transfer and [3+2]-cycloadditions
-
Polymeric carbon nitride materials have been used in numerous light-to-energy conversion applications ranging from photocatalysis to optoelectronics. For a new application and modelling, we first refined the crystal structure of potassium poly(heptazine imide) (K-PHI)—a benchmark carbon nitride material in photocatalysis—by means of X-ray powder diffraction and transmission electron microscopy. Using the crystal structure of K-PHI, periodic DFT calculations were performed to calculate the density-of-states (DOS) and localize intra band states (IBS). IBS were found to be responsible for the enhanced K-PHI absorption in the near IR region, to serve as electron traps, and to be useful in energy transfer reactions. Once excited with visible light, carbon nitrides, in addition to the direct recombination, can also undergo singlet–triplet intersystem crossing. We utilized the K-PHI centered triplet excited states to trigger a cascade of energy transfer reactions and, in turn, to sensitize, for example, singlet oxygen (1O2) as a starting point to synthesis up to 25 different N-rich heterocycles.
- Antonietti, Markus,Guldi, Dirk M.,Hussain, Tanveer,Karton, Amir,Markushyna, Yevheniia,Mazzanti, Stefano,Oschatz, Martin,Sánchez Vadillo, José Manuel,Savateev, Aleksandr,Strauss, Volker,Tarakina, Nadezda V.,Tyutyunnik, Alexander P.,Walczak, Ralf,ten Brummelhuis, Katharina
-
supporting information
p. 15061 - 15068
(2020/06/17)
-
- Triazole alcohol derivative as well as preparation method and application thereof
-
The invention relates to a triazole alcohol derivative as well as a preparation method and application thereof. The chemical structure of the triazole alcohol derivative is shown as a formula I, R1 represents a benzene ring or a substituted benzene ring, and substituent groups of the substituted benzene ring can be located at all positions of the benzene ring, can be mono-substituted or multi-substituted, and can be selected from a) halogen which is F and Cl; b) an electron withdrawing group which is cyano or trifluoromethyl; c ) a lower alkyl of 1-4 carbon atoms or a halogen substituted loweralkyl; and d) lower alkoxy of 1-4 carbon atoms or halogen substituted lower alkoxy. The compound of the invention has strong antifungal activity, has the advantages of low toxicity, wide antibacterial spectrum and the like, and can be used for preparing antifungal drugs.
- -
-
Paragraph 0147-0148
(2020/03/11)
-
- Design, synthesis, and in vitro evaluation of novel triazole analogues featuring isoxazole moieties as antifungal agents
-
In order to develop novel antifungal agents, based on our previous work, a series of (2R,3R)-3-((3-substitutied-isoxazol-5-yl)methoxy)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl) butan-2-ol (a1-a26) were designed and synthesized. All of the compounds exhibited good in vitro antifungal activities against eight human pathogenic fungi. Among them, compound a6 showed excellent inhibitory activity against Candida albicans and Candida parasilosis with MIC80 values of 0.0313 μg/mL. In addition, compounds a6, a9, a12, a13 and a14 exhibited moderate inhibitory activities against fluconazole-resistant isolates with MIC80 values ranging from 8 μg/mL to 16 μg/mL. Furthermore, compounds a6, a12 and a23 exhibited low inhibition profiles for CYP3A4. Clear SARs were analyzed, and the molecular docking experiment was carried out to further investigate the relationship between a6 and the target enzyme CYP51.
- Chai, Xiaoyun,Ding, Zichao,Hao, Yumeng,Jiang, Yuanying,Jin, Yongsheng,Ni, Tingjunhong,Wang, Ruilian,Wang, Ruina,Wang, Ting,Xie, Fei,Yu, Shichong,Zhang, Dazhi
-
supporting information
(2020/06/17)
-
- Discovery of Natural Product-Based Fungicides (II): Semisynthesis and Biological Activity of Sarisan Attached 3-Phenylisoxazolines as Antifungal Agents
-
Many phytopathogenic fungi cause severe damage to crop yields. In continuation of our research aimed at the discovery and development of natural products-based fungicides, a series of thirty-one sarisan attached 3-phenylisoxazolines were synthesized and evaluated for their antifungal activities against five phytopathogenic fungi (B. cinerea, C. lagenarium, A. solani, F. solani, and F. graminearum). Among all title sarisan derivatives, compounds IV2, IV14 and IV23 showed potent antifungal activity against some phytopathogenic fungi. In particular, compound IV2 exhibited a broad-spectrum and more potent antifungal activity against A. solani, F. solani, and F. graminearum than the commercial fungicide Hymexazol. In addition, compounds IV2, IV14 and IV23 also displayed relative low toxicity on normal NRK-52E cells. This work will give some insights into the development of sarisan derivatives as new fungicide candidates in plant protection.
- Liu, Zhiyan,Cao, Jiangping,Yan, Xiaoting,Cheng, Wanqing,Wang, Xiaoguang,Yang, Ruige,Guo, Yong
-
-
- ISOXAZOLE DERIVATIVES AND PREPARATION PROCESS THEREOF
-
The present invention relates to an isoxazole derivative compound of Formula (1) useful as a substance for treating respiratory viral infectious disease caused by coronavirus, in particular, Middle East respiratory syndrome-coronavirus (MERS-CoV); a pharm
- -
-
Paragraph 114-116; 123-125
(2020/03/15)
-
- Synthesis and in vitro evaluation of neutral aryloximes as reactivators of Electrophorus eel acetylcholinesterase inhibited by NEMP, a VX surrogate
-
Casualties caused by nerve agents, potent acetylcholinesterase inhibitors, have attracted attention from media recently. Poisoning with these chemicals may be fatal if not correctly addressed. Therefore, research on novel antidotes is clearly warranted. Pyridinium oximes are the only clinically available compounds, but poor penetration into the blood-brain barrier hampers efficient enzyme reactivation at the central nervous system. In searching for structural factors that may be explored in SAR studies, we synthesized and evaluated neutral aryloximes as reactivators for acetylcholinesterase inhibited by NEMP, a VX surrogate. Although few tested compounds reached comparable reactivation results with clinical standards, they may be considered as leads for further optimization.
- Cavalcante, Samir F. de A.,Kitagawa, Daniel A.S.,Rodrigues, Rafael B.,Bernardo, Leandro B.,da Silva, Thiago N.,dos Santos, Wellington V.,Correa, Ana Beatriz de A.,de Almeida, Joyce S.F.D.,Fran?a, Tanos C.C.,Ku?a, Kamil,Simas, Alessandro B.C.
-
-
- Potassium iodate (KIO 3) as a novel reagent for the synthesis of isoxazolines: evaluation of antimicrobial activity of the products
-
Abstract : A novel reagent for the synthesis of isoxazolines has been reported. Aryl aldoximes were made to react with alkenes in the presence of KIO 3 as the oxidising agent. This new reagent has been useful as an oxidant in the synthesis of i
- Kotian, Sumana Y,Abishad,Byrappa,Rai, K M Lokanatha
-
-
- Stereospecific 1,4-Metallate Shift Enables Stereoconvergent Synthesis of Ketoximes
-
Reported herein is a stereospecific 1,4-metallate rearrangement for single-geometry ketoxime synthesis from oxime chlorides and arylboronic acids. This strategy exhibits broad substrate scope with excellent stereoselectivity under mild reaction conditions. In comparison with the conventional approaches, each configuration of unsymmetric diaryl oximes, as well as the thermodynamically less stable Z isomer of aryl alkyl ketoximes can be selectively and exclusively obtained. The reactivities of unsymmetric diaryl oximes and the Z isomer of aryl alkyl oximes, a class of underexplored molecules, enables efficient access to the corresponding isoquinolines, isoquinoline N-oxides, and amides having a single configuration.
- Yang, Kai,Zhang, Feng,Fang, Tongchang,Zhang, Guan,Song, Qiuling
-
supporting information
p. 13421 - 13426
(2019/08/20)
-
- Synthesis and cytotoxic evaluation of undecenoic acid-based oxime esters
-
A series of undecenoic acid-based aldoxime esters have been synthesized using various substituted benzaldehydes and undecenoic acid. These oxime esters have been evaluated for their cytotoxic activities against HeLa, B16-F10, SKOV3, MCF7 and CHO-K1 normal cell line using MTT assay. Most of the synthesized compounds exhibit cytotoxicity. Particularly, 2,3-dimethoxy (IC50 value 12.48μM) and 3-methoxy (IC50 value 13.58μM) derivatives exhibit promising activities against SKOV3 cell lines. All the synthesized compounds are non-toxic towards the Chinese hamster ovary (CHO-K1) normal cell line.
- Vijayendar, Venepally,Kaki, Shiva Shanker,Vamshi Krishna,Misra, Sunil,Prasad,Jala, Ram Chandra Reddy
-
p. 1015 - 1022
(2019/05/22)
-
- Synthesis and biological evaluation of novel 1-(aryl-aldehyde-oxime)uracil derivatives as a new class of thymidine phosphorylase inhibitors
-
A novel series of 1-(aryl aldehyd oxime) uracil derivatives were synthesized, characterized and evaluated for its inhibitory activity against thymidine phosphorylase. Among them, the compound 8d, 8e, 8f, 8g and 8l displayed potent thymidine phosphorylase
- Zhao, Shuyue,Li, Ke,Jin, Yi,Lin, Jun
-
-
- Synthesis, cytotoxic activity and binding model analysis of novel isoxazole-docetaxel analogues with C3′-N modification
-
Structure–activity relationship (SAR) studies confirm that modifications at C-3′ position can lead to the development of highly potent novel taxoids. We designed and synthesized a series of novel isoxazole-docetaxel analogues A1–A5 by introducing isoxazol
- Chen, Ming,Liu, Jiyuan,Tian, Zhen,Liu, Xueying,Zhang, Shengyong
-
p. 1355 - 1365
(2018/04/10)
-
- CALPAIN MODULATORS AND THERAPEUTIC USES THEREOF
-
Disclosed herein are small molecule calpain modulator compositions, pharmaceutical compositions, the use and preparation thereof.
- -
-
Paragraph 1422
(2018/04/17)
-
- Synthesis of new coumarin tethered isoxazolines as potential anticancer agents
-
A series of new coumarin tethered isoxazolines (7a-l) were synthesized and evaluated for their cytotoxic potency against human melanoma cancer cell line (UACC 903) as well as fibroblast normal cell line (FF2441). Preliminary results revealed that some of these coumarin tethered isoxazolines 7b, 7c, 7f and 7j exhibited significant antiproliferative effect against human melanoma cancer (UACC 903) with IC50 values of 8.8, 10.5, 9.2 and 4.5 μM respectively. However, compound 7c was non-toxic to normal human cells at the tested concentration. Further, we have chosen compound 7c to check its efficacy in Ehrlich Ascites Carcinoma animal model in-vivo for its antitumor and antiangiogenic properties. Our lead compound significantly reduced the cell viability, body weight, ascites volume and downregulated the formation of neovasculature such as regression of tumor volume. The present study indicates the scope of developing into potent anticancer drug in near future.
- Lingaraju, Gejjalagere S.,Balaji, Kyathegowdanadoddi S.,Jayarama, Shankar,Anil, Seegehalli M.,Kiran, Kuppalli R.,Sadashiva, Maralinganadoddi P.
-
supporting information
p. 3606 - 3612
(2018/11/06)
-
- Preparation technology for 3-aryl-4-nitro isoxazole compound
-
The invention discloses a preparation technology for a 3-aryl-4-nitro isoxazole compound. The preparation technology comprises the following steps: synthesizing a compound shown as formula II through the nucleophilic addition of hydroxylamine hydrochloride and the compound shown as formula I used as the raw material; acquiring the compound shown as formula III through the substitution reaction of the compound shown as formula II and N-chlorosuccinimide; preparing 1-dimethyl amino-2-nitro ethylene through the reaction of N,N-dimethylformamide dimethyl acetal and nitromethane used as the raw material; and acquiring a target product 3-aryl-4-nitro isoxazole compound through the cyclization reaction of the compound shown as formula III and 1-dimethyl amino-2-nitro ethylene. The raw materials in the synthesis route are low in cost and easily acquired, the operation condition is mild and is easily controlled, the product is easily purified and the preparation technology is a new method for synthesizing the 3-aryl-4-nitro isoxazole compound.
- -
-
Paragraph 0066; 0067
(2018/03/01)
-
- Synthesis and in vitro biological evaluation of novel coumarin derivatives containing isoxazole moieties on melanin synthesis in B16 cells and inhibition on bacteria
-
A novel series of coumarin derivatives 6a–o, bearing isoxazole moieties were designed and synthesized. After that, they were evaluated for melanin synthesis in murine B16 cells and inhibitory effect on the growth of CA (Candida albicans), EC (Escherichia coli), SA (Staphylococcus aureus). It was found that eleven compounds (6b–f, 6j–o) showed a better activity on melanin synthesis than positive control (8-MOP). Among them, compounds 6d (242%) and 6f (390%), with nearly 1.6 and 2.6-fold potency compared with 8-MOP (149%) respectively, were recognized as the most promising candidate hits for further pharmacological study of anti-vitiligo. Seven halogen substituted compounds exhibited moderate antimicrobial activity against CA. It is interesting that 6e–f and 6l–m, which had two halogens on the benzene showed a comparable activity with Amphotericin B against CA. The evaluation of melanin synthesis in B16 cells and inhibitory effect on bacteria of above structurally diverse derivatives had also led to an outline of structure-activity relationship.
- Pang, Guang Xian,Niu, Chao,Mamat, Nuramina,Aisa, Haji Akber
-
supporting information
p. 2674 - 2677
(2017/05/29)
-
- Synthesis of 3,5-Disubstituted isoxazoles containing privileged substructures with a diverse display of polar surface area
-
We designed and synthesized the molecular framework of 3,5-disubstituted isoxazoles containing privileged substructures with various substituents which uniquely display polar surface area in a diverse manner. A library of 3,5-disubstituted isoxazoles were systematically prepared via 1,3-dipolar cycloaddition of alkynes with nitrile oxides prepared by two complementary synthetic routes; method A utilized a halogenating agent with a base and method B utilized a hypervalent iodine reagent. Through the biological evaluation of corresponding isoxazoles via three independent phenotypic assays, the different pattern of biological activities was shown according to the type of privileged substructure and substituent. These results demonstrated the significance of molecular design via introducing privileged substructures and various substituents to make a diverse arrangement of polar surface area within a similar 3-dimensional molecular framework.
- Kim, Mingi,Hwang, Yoon Soo,Cho, Wansang,Park, Seung Bum
-
supporting information
p. 407 - 413
(2017/06/19)
-
- Catalytic Enantioselective [3 + 2] Cycloaddition of α-Keto Ester Enolates and Nitrile Oxides
-
An enantioselective [3 + 2] cycloaddition reaction between nitrile oxides and transiently generated enolates of α-keto esters has been developed. The catalyst system was found to be compatible with in situ nitrile oxide-generation conditions. A versatile array of nitrile oxides and α-keto esters could participate in the cycloaddition, providing novel 5-hydroxy-2-isoxazolines in high chemical yield with high levels of diastereo- and enantioselectivity. Notably, the optimal reaction conditions circumvented concurrent reactions via O-imidoylation and hetero-[3 + 2] pathways.
- Bartlett, Samuel L.,Sohtome, Yoshihiro,Hashizume, Daisuke,White, Peter S.,Sawamura, Miki,Johnson, Jeffrey S.,Sodeoka, Mikiko
-
supporting information
p. 8661 - 8666
(2017/07/06)
-
- 1,3-Dipolar cycloaddition of uracil derivatives with nitrile oxides: Synthesis of [1,2,4]oxadiazolo[4,5-c]pyrimidine-5,7(6H)-dione derivatives
-
An efficient method of synthesizing bicyclic fused [1,2,4]oxadiazolo[4,5-c]pyrimidine-5,7(6H)-dione derivatives was developed through a [3 + 2] cycloaddition of uracil derivatives and nitrile oxides. In the one step reaction, C[sbnd]N and C[sbnd]O bonds were constructed, the target compounds were efficiently obtained in good yields. The method represents a valuable way to obtain highly functional fused bicyclic heterocycle derivatives in a simple, rapid and practical manner. The method fusing bicyclic heterocycles can be applied for modification of uracil analogues that may have potential biological activities.
- Jiang, Kun-Ming,Jin, Yi,Lin, Jun
-
p. 6662 - 6668
(2017/10/23)
-
- Synthesis and bioactivity of novel isoxazole chalcone derivatives on tyrosinase and melanin synthesis in murine B16 cells for the treatment of vitiligo
-
A new series of chalcone derivatives 1–18, bearing isoxazole moieties were designed and synthesized, and biologically evaluated for their activity on mushroom tyrosinase and melanin synthesis in murine B16 cells. The result indicated that most of prepared compounds 1–18 showed potent activating effect on tyrosinase, especially for 1–2, 4, 6–7, 9 and 15. Among them, compounds 2, 4 and 9 demonstrated the best activity with EC50?=?1.3, 2.5 and 3.0?μmol·L?1respectively, much better than the positive control 8-methoxypsoralan (8-MOP, EC50?=?14.8?μmol·L?1); In B16 cells, all the tested compounds exhibited a stronger activity on melanogenesis than 8-MOP (with the value of 115%). It was interesting that derivatives substituted with halogen (1, 2, 4, 5, 7, 9) were generally more potent. Compounds 2 (463%) and 18 (438%) with 3 and 4-fold potency compared with 8-MOP respectively, were recognized as the most promising candidate hits for further pharmacological study of anti-vitiligo.
- Niu, Chao,Yin, Li,Nie, Li Fei,Dou, Jun,Zhao, Jiang Yu,Li, Gen,Aisa, Haji Akber
-
p. 5440 - 5448
(2016/10/24)
-
- Alkyl Nitrites: Novel Reagents for One-Pot Synthesis of 3,5-Disubstituted Isoxazoles from Aldoximes and Alkynes
-
An efficient, one-pot approach has been described for the synthesis of 3,5-disubstituted isoxazoles from substituted aldoximes (mixture of E and Z) and alkynes, using alkyl nitrites under conventional heating conditions. The key nitrile oxide intermediates that are required for the synthesis of isoxazoles are formed by treatment of substituted aldoxime with either tert-butyl nitrite or isoamyl nitrite. The generated nitrile oxides underwent in situ [3+2] dipolar cycloaddition to the substituted alkynes to give 3,5-disubstituted isoxazoles regioselectively in high to excellent yields. The developed synthetic methodology was applied for the synthesis of a previously reported potent hDGAT1 inhibitor.
- Kadam, Kishorkumar S.,Gandhi, Thirumanavelan,Gupte, Amol,Gangopadhyay,Sharma, Rajiv
-
p. 3996 - 4008
(2016/11/11)
-
- Substituent effect study on experimental 13C NMR chemical shifts of (3-(substituted phenyl)-cis-4,5-dihydroisoxazole-4,5-diyl)bis(methylene)diacetate derivatives
-
Abstract Eleven novel (3-(substituted phenyl)-cis-4,5-dihydroisoxazole-4,5-diyl)bis(methylene) diacetate derivatives were synthesized in the present study. These dihydroisoxazole derivatives were characterized by IR, 1H NMR, 13C NMR
- Kara, Yesim S.
-
p. 723 - 730
(2015/07/28)
-
- Synthesis of Novel 3-aryl-1-oxa-2,8-diazaspiro[4.5]dec-2-ene Derivatives and Their Biological Evaluation Against Protein Tyrosine Phosphatase 1B
-
A series of novel 3-aryl-1-oxa-2,8-diazaspiro[4.5]dec-2-ene derivatives were designed, synthesized, and evaluated as a new class of inhibitors against protein tyrosine phosphatase 1B. Among them, compound 6f displayed moderate inhibitory activity with IC50 of 2.87 ± 0.24 μm and can be used as a novel lead compound for the design of inhibitors of protein tyrosine phosphatase 1B. A series of novel 3-aryl-1-oxa-2,8-diazaspiro[4.5]dec-2-ene derivatives were designed, synthesized, and evaluated as a new class of inhibitors against PTP1B. Among them, compound 6f displayed moderate inhibitory activity with IC50 of 2.87 ± 0.24 μm and can be used as a novel lead compound for the design of inhibitors of PTP1B.
- Wang, Wen-Long,Chen, Xia,Gao, Li-Xin,Sheng, Li,Li, Jing-Ya,Li, Jia,Feng, Bainian
-
p. 1161 - 1167
(2015/10/28)
-
- Design, synthesis, and evaluation of hydroxamic acid derivatives as promising agents for the management of Chagas disease
-
Today, there are approximately 8 million cases of Chagas disease in the southern cone of South America alone, and about 100 million people are living with the risk of becoming infected. The present pharmacotherapy is sometimes ineffective and has serious side effects. Here, we report a series of 4,5-dihydroisoxazoles incorporating hydroxamate moieties, which act as effective inhibitors of the carbonic anhydrase (CA) from Trypanosoma cruzi (TcCA). One compound (5g) was evaluated in detail and shows promising features as an antitrypanosomal agent. Excellent values for the inhibition of growth for all three developmental forms of the parasite were observed at low concentrations of 5g (IC50 values from 7.0 to 1 μM). The compound has a selectivity index (SI) of 6.7 and no cytotoxicity to macrophage cells. Preliminary in vivo data showed that 5g reduces bloodstream parasites and that all treated mice survived; it was also more effective than the standard drug benznidazole.
- Rodrigues, Giseli Capaci,Feijó, Daniel Ferreira,Bozza, Marcelo Torres,Pan, Peiwen,Vullo, Daniela,Parkkila, Seppo,Supuran, Claudiu T.,Capasso, Clemente,Aguiar, Alcino Palermo,Vermelho, Alane Beatriz
-
p. 298 - 308
(2014/02/14)
-
- Organocatalytic, diastereo- and enantioselective synthesis of nonsymmetric cis -stilbene diamines: A platform for the preparation of single-enantiomer cis -imidazolines for protein-protein inhibition
-
The finding by scientists at Hoffmann-La Roche that cis-imidazolines could disrupt the protein-protein interaction between p53 and MDM2, thereby inducing apoptosis in cancer cells, raised considerable interest in this scaffold over the past decade. Initial routes to these small molecules (i.e., Nutlin-3) provided only the racemic form, with enantiomers being enriched by chromatographic separation using high-pressure liquid chromatography (HPLC) and a chiral stationary phase. Reported here is the first application of an enantioselective aza-Henry approach to nonsymmetric cis-stilbene diamines and cis-imidazolines. Two novel mono(amidine) organocatalysts (MAM) were discovered to provide high levels of enantioselection (>95% ee) across a broad range of substrate combinations. Furthermore, the versatility of the aza-Henry strategy for preparing nonsymmetric cis-imidazolines is illustrated by a comparison of the roles of aryl nitromethane and aryl aldimine in the key step, which revealed unique substrate electronic effects providing direction for aza-Henry substrate-catalyst matching. This method was used to prepare highly substituted cis-4,5-diaryl imidazolines that project unique aromatic rings, and these were evaluated for MDM2-p53 inhibition in a fluorescence polarization assay. The diversification of access to cis-stilbene diamine-derived imidazolines provided by this platform should streamline their further development as chemical tools for disrupting protein-protein interactions.
- Vara, Brandon A.,Mayasundari, Anand,Tellis, John C.,Danneman, Michael W.,Arredondo, Vanessa,Davis, Tyler A.,Min, Jaeki,Finch, Kristin,Guy, R. Kiplin,Johnston, Jeffrey N.
-
p. 6913 - 6938
(2014/08/18)
-
- PHENYL-ISOXAZOL DERIVATIVES AND PREPARATION PROCESS THEREOF
-
Disclosed are a phenyl-isoxazol derivative compound, which is useful as a treatment material for virus infection, especially, infection of an influenza virus, or its pharmaceutically acceptable derivative, a preparation method thereof, and an illness treatment pharmaceutical composition including the compound as an active ingredient.
- -
-
Paragraph 0057; 0058; 0061; 0062
(2014/02/16)
-
- Iodine(III)-Mediated [3 + 2] cyclization for one-pot synthesis of benzo[ d ]isoxazole-4,7-diols in aqueous medium
-
A one-pot [3 + 2] cycloadditive synthesis of benzo[d]isoxazole-4,7-diols in aqueous medium was carried out via nitrile oxides and benzoquinone intermediates by taking advantage of iodobenzene diacetate as an oxidant. This method can also be used to synthesize benzodiisoxazole-4,8-diols, isoxazolo[5,4-a]phenazines, and indazole-4,7-diols, which are difficult to obtain by classical methods.
- Hou, Yingwei,Lu, Shichao,Liu, Gang
-
p. 8386 - 8395
(2013/09/24)
-
- PROCESS FOR THE PREPARATION OF ISOXAZOLYL- METHOXY NICOTINIC ACIDS
-
The present invention relates to a process for the preparation of a compound of formula (I) wherein R1 and R2 are as defined herein, which is useful as an intermediate in the preparation of active pharmaceutical compounds.
- -
-
Paragraph 0207; 0208
(2013/05/08)
-
- PROCESS FOR THE PREPARATION OF ISOXAZOLYL-METHOXY-NICOTINIC ACIDS
-
The present invention relates to a process for the preparation of a compound of formula (I) which is useful as an intermediate in the preparation of active pharmaceutical compounds from a compound of formula (IV) wherein R1 and R2 ar
- -
-
Page/Page column 30
(2013/05/09)
-
- Scalable synthetic route to 2-amino-5-hydroxypropiophenone: Efficient formal synthesis of irinotecan
-
2-Amino-5-hydroxypropiophenone, a key precursor in the total synthesis of irinotecan, has been synthesized. Regioselective nitration and a SNAr displacement are the key steps involved in this strategy, which is high yielding, is economical, and has been performed on a plant scale. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications1 to view the free supplemental file. Copyright Taylor & Francis Group, LLC.
- Rao, A. V. Rama,Rao, Ramakrishna,Yadav,Khagga, Mukkanti
-
supporting information
p. 1661 - 1667
(2013/05/21)
-
- Discovery and characterization of a novel dihydroisoxazole class of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor potentiators
-
Positive allosteric modulators ("potentiators") of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPAR) enhance excitatory neurotransmission and may improve the cognitive deficits associated with various neurological disorders. Th
- Patel, Nandini C.,Schwarz, Jacob,Hou, Xinjun J.,Hoover, Dennis J.,Xie, Longfei,Fliri, Anton J.,Gallaschun, Randall J.,Lazzaro, John T.,Bryce, Dianne K.,Hoffmann, William E.,Hanks, Ashley N.,McGinnis, Dina,Marr, Eric S.,Gazard, Justin L.,Hajós, Mihály,Scialis, Renato J.,Hurst, Raymond S.,Shaffer, Christopher L.,Pandit, Jayvardhan,O'Donnell, Christopher J.
-
supporting information
p. 9180 - 9191
(2014/01/06)
-
- Selective tandem synthesis of oximes from benzylic alcohols catalyzed with 2, 3-dichloro-5, 6-dicyanobenzoquinone
-
In spite of many reports in the literature concerning with oxidation of benzylic alcohols to carbonyl compounds with 2,3-dichloro-5,6- dicyanobenzoquinone (DDQ) in stoichiometric amounts or even more, we surprisingly found that benzylic alcohols are directly oxidized to oximes using a catalytic amount of DDQ in the presence of hydroxylamine hydrochloride under solvent-free conditions. The present tandem catalytic method can be efficiently used for preparation of oximes in the presence of some other functional groups with excellent chemoselectivity.
- Aghapour, Ghasem,Mohamadian, Samaneh
-
experimental part
p. 1209 - 1212
(2012/07/13)
-
- PHENYL-ISOXAZOL DERIVATIVES AND PREPARATION PROCESS THEREOF
-
Disclosed are a phenyl-isoxazol derivative compound, which is useful as a treatment material for virus infection, especially, infection of an influenza virus, or its pharmaceutically acceptable derivative, a preparation method thereof, and an illness treatment pharmaceutical composition including the compound as an active ingredient
- -
-
Page/Page column 14-15
(2012/11/07)
-
- Oxime Carbamate-Discovery of a series of novel FAAH inhibitors
-
A series of novel oxime carbamates have been identified as potent inhibitors of the key regulatory enzyme of the endocannabinoid signaling system, fatty acid amide hydrolase (FAAH). In this Letter, the rationale behind the discovery and the biological evaluations of this novel class of FAAH inhibitors are presented. Both in vitro and in vivo results of selected targets are discussed, along with inhibition kinetics and molecular modeling studies.1.
- Sit,Conway, Charles M.,Xie, Kai,Bertekap, Robert,Bourin, Clotilde,Burris, Kevin D.
-
supporting information; experimental part
p. 1272 - 1277
(2010/06/17)
-
- ISOXAZOLE-PYRIDINE DERIVATIVES
-
The present invention is concerned with isoxazole-pyridine derivatives of formula I wherein X, R1 to R6 are as described herein. The compounds are active on the GABA A α5 receptor binding site and useful for the treatment of cognitive disorders, such as Alzheimer's disease.
- -
-
Page/Page column 30-31
(2009/06/27)
-
- ISOXAZOLO-PYRIDAZINE DERIVATIVES
-
The invention relates to isoxazolo-pyridazine compounds, in particular those of formula I as described above and to a pharmaceutically acceptable salts thereof, having affinity and selectivity for the GABA A α5 receptor binding site, their manufacture, pharmaceutical compositions containing them and their use as cognitive enhancers or for the treatment of cognitive disorders like Alzheimer's disease.
- -
-
-
- Effect of the aryl group substituent in the dimerization of 3-arylisoxazoles to syn 2,6-diaryl-3,7-diazatricyclo[4.2.0.02,5]octan-4,8-diones induced by LDA
-
3-Arylisoxazoles react with LDA in THF at 0 °C affording syn-2,6-diaryl-3,7-diazatricyclo[4.2.0.02,5]octan-4,8-diones (bis-azetidinones), via stereoselective dimerization of an azetinone anion intermediate. A?fragmentation reaction affording arylnitriles may compete with electronic and steric effects of the substituent present in the aryl group being pivotal in determining the outcome of this reaction. An interesting behaviour with LDA of arylnitriles arising from the fragmentation reaction of some 3-arylisoxazoles was also observed. N,N-Diisopropylaminobenzonitriles were in fact formed (plausibly via a benzyne mechanism) from 3-(4-chlorophenyl)isoxazole and 3-(2-chlorophenyl)isoxazole, whereas 3-(2-methylphenyl)isoquinolin-1-amine was isolated starting from 3-(2-methylphenyl)isoxazole and LDA.
- Di Nunno, Leonardo,Vitale, Paola,Scilimati, Antonio
-
experimental part
p. 11198 - 11204
(2009/04/11)
-
- Aryl-isoxazol-4-yl-imidazole derivatives
-
The present invention is concerned with aryl-isoxazol-4-yl-imidazole derivatives of formula I: wherein R1 to R6 are as defmed in the specification and pharmaceutically acceptable acid addition salts thereof. This class of compounds h
- -
-
Page/Page column 18
(2010/11/28)
-
- Effect of structure in benzaldehyde oximes on the formation of aldehydes and nitriles under photoinduced electron-transfer conditions
-
(Chemical Equation Presented) The mechanistic aspects of the photosensitized reactions of a series of benzaldehyde oximes (1a-o) were studied by steady-state (product studies) and laser flash photolysis methods. Nanosecond laser flash photolysis studies have shown that the reaction of the oxime with triplet chloranil (3CA) proceeds via an electron-transfer mechanism provided the free energy for electron transfer (ΔGET) is favorable; typically, the oxidation potential of the oxime should be below 2.0 V. Substituted benzaldehyde oximes with oxidation potentials greater than 2.0 V quench 3CA at rates that are independent of the substituent and the oxidation potential. The most likely mechanism under these conditions is a hydrogen atom transfer mechanism as this reaction should be dependent on the O-H bond strength only, which is virtually the same for all oximes. Product studies have shown that aldoximes feact to give both the corresponding aldehyde and the nitrile. The important intermediate in the aldehyde pathway is the iminoxyl radical, which is formed via an electron transfer-proton transfer (ET-PT) sequence (for oximes with low oxidation potentials) or via a hydrogen atom transfer (HAT) pathway (for oximes with larger oxidation potentials). The nitriles are proposed to result from intermediate iminoyl radicals, which can be formed via direct hydrogen atom abstraction or via an electron-transfer-proton- transfer sequence. The experimental data seems to support the direct hydrogen atom abstraction as evidenced by the break in linearity in the plot of the quenching rates against the oxidation potential, which suggests a change in mechanism. The nitrile product is favored when electron-accepting substituents are present on the benzene ring of the benzaldehyde oximes or when the hydroxyl hydrogen atom is unavailable for abstraction. The latter is the case in pyridine-2-carboxaldoxime (2), where a strong intramolecular hydrogen bond is formed. Other molecules that form weaker intramolecular hydrogen bonds such as 2-furaldehyde oxime (3) and thiophene-2-carboxaldoxime (4) tend to yield increasing amounts of aldehyde.
- De Lijser, H.J. Peter,Hsu, Susan,Marquez, Bernadette V.,Park, Adriana,Sanguantrakun, Nawaporn,Sawyer, Jody R.
-
p. 7785 - 7792
(2007/10/03)
-
- Discovery of 3-amino-4-chlorophenyl P1 as a novel and potent benzamidine mimic via solid-phase synthesis of an isoxazoline library
-
In an effort to identify orally bioavailable factor Xa inhibitors, two isoxazolines libraries were prepared to scan for novel P1 ligands. From this work, 4-chloro-3-aniline was identified as a novel and potent benzamidine mimic.
- Lam, Patrick Y. S.,Adams, Jessica J.,Clark, Charles G.,Calhoun, W. Jason,Luettgen, Joseph M.,Knabb, Robert M.,Wexler, Ruth R.
-
p. 1795 - 1799
(2007/10/03)
-