- Isatin derivatives as a new class of aldose reductase inhibitors with antioxidant activity
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In this work, isatin was employed as the scaffold to design aldose reductase inhibitors with antioxidant activity. Most of the isatin derivatives were proved to be excellent in the inhibition of aldose reductase (ALR2) with IC50 values at submi
- Liu, Wenchao,Chen, Huan,Zhang, Xiaonan,Zhang, Xin,Xu, Long,Lei, Yanqi,Zhu, Changjin,Ma, Bing
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- Accessing New 5-α-(3,3-Disubstituted Oxindole)-Benzylamine Derivatives from Isatin: Stereoselective Organocatalytic Three Component Petasis Reaction
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A one-step, three-component Petasis reaction of isatin derived 5-arylboronate-3-substituted oxindole derivatives with salicylaldehydes and secondary amines affords new enantiomerically pure structurally diverse 5-α-(3-substituted-oxindole)-benzylamine derivatives. The reaction shows good substrate and reagent scope affording the products with good to excellent yields (up to >99 % yield) and enantioselectivities (up to 99 % ee) using cheap and readily available (R)-BINOL as the organocatalyst. A diastereoselective version of the reaction was also developed where moderate yields (37 to 55 % yield), excellent enantioselectivities (up to 99 % ee) and good diastereoselectivities (up to 86 % de) were obtained for new 5-α-(3-hydroxy-oxindole)-benzylamine derivatives, having two stereocenters. The reaction is also feasible on gram-scale.
- Burke, Anthony J.,Erxleben, Andrea,Marques, Carolina S.,McArdle, Patrick
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- Triarylethylene-indolin-2,3-dione molecular conjugates: Design, synthesis, docking studies and anti-proliferation evaluation
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A series of 1H-1,2,3-triazole-linked ospemifene-isatin and O-methylated ospemifene-isatin conjugates were synthesized and assayed for their anti-proliferative activities against estrogen-responsive as well as estrogen-non-responsive cells. The non-cytotoxic conjugate 14e, with an optimal combination of bromo substituents at the C-5/C-7 positions of isatin, proved to be a promising hit with an IC50 value of 31.62 μM against MCF-7 and 19.23 μM against MDA-MB-231. The observed anti-proliferative activities of active conjugates were further corroborated via docking studies carried out on estrogen receptor subtypes α and β.
- Kumar, Sumit,Palma, Gabriella,Perumal, Shanen,Kaur, Mandeep,Singh-Pillay, Ashona,Raj, Raghu,Singh, Parvesh,Kumar, Vipan
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p. 42409 - 42414
(2020/01/08)
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- Cu(ii)-: TBu-PHOX catalyzed enantioselective malonate addition onto 3-hydroxy 2-oxindoles: Application in the synthesis of dimeric pyrroloindoline alkaloids
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An efficient Cu(ii)-PHOX-catalyzed malonate addition onto 3-hydroxy 3-indolyl-2-oxindoles is envisioned to afford excellent enantioselectivities (up to >99% ee) in high chemical yields. Detailed characterization techniques including X-ray, NMR, CV and EPR experiments suggest that a Cu(ii)-complex is involved as an active species in this process. Applying this strategy, an advanced intermediate of cyclotryptamine alkaloids has been synthesized in few steps for a general approach to bis-cyclotryptamine alkaloids.
- Babu, K. Naresh,Kinthada, Lakshmana K.,Pratim Das, Partha,Bisai, Alakesh
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supporting information
p. 7963 - 7966
(2018/07/25)
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- N-{[2-(PIPERIDIN-1-YL)PHENYL](PHENYL)METHYL}-2-(3-OXO-3,4-DIHYDRO-2H-1,4-BENZOXA ZIN-7-YL)ACETAMIDE DERIVATIVES AND RELATED COMPOUNDS AS ROR-GAMMA MODULATORS FOR TREATING AUTOIMMUNE DISEASES
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The present invention provides e.g. N-{[2-(piperidin-1-yl)phenyl] (phenyl)methyl}-2-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl)acetamide derivatives and related compounds as ROR-gamma modulators for treating e.g. autoimmune diseases, autoimmune-related diseases, inflammatory diseases, metabolic diseases, fibrotic diseases or cholestatic diseases, such as e.g. arthitis and asthma.
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Page/Page column 68; 111; 112
(2018/08/20)
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- Design, synthesis and anti-tumor activity study of novel histone deacetylase inhibitors containing isatin-based caps and o-phenylenediamine-based zinc binding groups
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As a hot topic of epigenetic studies, histone deacetylases (HDACs) are related to lots of diseases, especially cancer. Further researches indicated that different HDAC isoforms played various roles in a wide range of tumor types. Herein a novel series of HDAC inhibitors with isatin-based caps and o-phenylenediamine-based zinc binding groups have been designed and synthesized through scaffold hopping strategy. Among these compounds, the most potent compound 9n exhibited similar if not better HDAC inhibition and antiproliferative activities against multiple tumor cell lines compared with the positive control entinostat (MS-275). Additionally, compared with MS-275 (IC50 values for HDAC1, 2 and 3 were 0.163, 0.396 and 0.605?μM, respectively), compound 9n with IC50 values of 0.032, 0.256 and 0.311?μM for HDAC1, 2 and 3 respectively, showed a moderate HDAC1 selectivity.
- Gao, Shuai,Zang, Jie,Gao, Qianwen,Liang, Xuewu,Ding, Qinge,Li, Xiaoyang,Xu, Wenfang,Chou, C. James,Zhang, Yingjie
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p. 2981 - 2994
(2017/05/25)
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- PURINE INHIBITORS OF HUMAN PHOSPHATIDYLINOSITOL 3-KINASE DELTA
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The instant invention provides compounds of formula (I) which are PI3K-delta inhibitors, and as such are useful for the treatment of PI3K-delta-mediated diseases such as inflamation, asthma, COPD and cancer.
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Page/Page column 111-112
(2017/11/01)
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- Design, synthesis and preliminary biological evaluation of indoline-2,3-dione derivatives as novel HDAC inhibitors
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Histone deacetylases (HDACs) are zinc-dependent or NAD+ dependent enzymes and play a critical role in the process of tumor development. Herein a series of indoline-2,3-dione derivatives have been designed and synthesized as potential HDACs inhibitors. The preliminary biological evaluation showed that most compounds synthesized have exhibited moderate Hela cell nuclear extract inhibitory activities, among which compound 25a (IC50 = 10.13 nM) has shown the best efficacy. The anti-proliferative activities of some of these compounds were also discussed.
- Jin, Kang,Li, Shanshan,Li, Xiaoguang,Zhang, Jian,Xu, Wenfang,Li, Xuechen
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p. 4728 - 4736
(2015/08/03)
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- Identification of the First Highly Subtype-Selective Inhibitor of Human GABA Transporter GAT3
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Screening a library of small-molecule compounds using a cell line expressing human GABA transporter 3 (hGAT3) in a [3H]GABA uptake assay identified isatin derivatives as a new class of hGAT3 inhibitors. A subsequent structure-activity relationship (SAR) study led to the identification of hGAT3-selective inhibitors (i.e., compounds 20 and 34) that were superior to the reference hGAT3 inhibitor, (S)-SNAP-5114, in terms of potency (low micromolar IC50 values) and selectivity (>30-fold selective for hGAT3 over hGAT1/hGAT2/hBGT1). Further pharmacological characterization of compound 20 (5-(thiophen-2-yl)indoline-2,3-dione) revealed a noncompetitive mode of inhibition at hGAT3. This suggests that this compound class, which has no structural resemblance to GABA, has a binding site different from the substrate, GABA. This was supported by a molecular modeling study that suggested a unique binding site that matched the observed selectivity, inhibition kinetics, and SAR of the compound series. These compounds are the most potent GAT3 inhibitors reported to date that provide selectivity for GAT3 over other GABA transporter subtypes.
- Damgaard, Maria,Al-Khawaja, Anas,Vogensen, Stine B.,Jurik, Andreas,Sijm, Maarten,Lie, Maria E. K.,B?k, Mathias I.,Rosenthal, Emil,Jensen, Anders A.,Ecker, Gerhard F.,Fr?lund, Bente,Wellendorph, Petrine,Clausen, Rasmus P.
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p. 1591 - 1599
(2015/09/28)
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- Novel 2-oxoindoline-based hydroxamic acids: Synthesis, cytotoxicity, and inhibition of histone deacetylation
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In a continuation of a research program to discover novel small molecules targeting histone deacetylases, a series of 2′-oxospiro[1,3]dioxolane/dithiolane-2,3′-indoline-based hydroxamic acids have been designed and synthesized. These 2-oxoindoline-based hydroxamic acids displayed potent cytotoxicity against three human cancer cell lines, including SW620 (colon cancer), PC-3 (prostate cancer) and AsPC-1 (pancreatic cancer), with IC50 values as low as 0.05-0.07 μM, 74-fold lower than that of SAHA (1.64-3.70 μM). Additionally, compounds in this series exhibited good inhibition against histone-H3 and histone-H4 deacetylation, as evaluated by Western blot assay. These compounds also strongly inhibited HDAC2 with IC50 values as low as 0.03 μM. Docking studies performed using Autodock Vina showed all compounds bound to HDAC2 with relatively higher affinities (from -7.7 to -8.0 kcal/mol) compared to SAHA (-7.4 kcal/mol).
- Huong, Tran Thi Lan,Dung, Do Thi Mai,Dung, Phan Thi Phuong,Huong, Phung Thanh,Vu, Tran Khac,Hahn, Hyunggu,Han, Byung Woo,Kim, Jisung,Pyo, Minji,Han, Sang-Bae,Nam, Nguyen-Hai
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supporting information
p. 6425 - 6429
(2015/11/16)
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- NEUROPROTECTIVE AGENTS FOR TREATMENT OF NEURODEGENERATIVE DISEASES
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A compound having formula I is useful for treating a neurodegenerative disease: I, R1 is an C1-12 organyl group; is a C1-12 heterocyclic ring system containing 5 to 12 ring atoms and up to three heteroatoms individually selected from the group consisting of N, O, S, and Se; R2 are C1-12 organyl groups; R7, R8 are each independently, hydrogen (H), hydroxyl, oxo (i.e., carbonyl), C1-8 alkyl, C1-8 alkoxyl, C2-8 alkenyl, C2-10 alkynyl, C5-7 cycloalkyl, C5-7 cycloalkenyl, halo, C1-4 aldehyde, or -NR4q where R4 is H, C1-8 alkyl, C2-8 alkenyl, C4-8 cycloalkyl, C4-8 cycloalkenyl, or C6-10 aryl; o is 0, 1, 2, 3, or 4; A is a C6-12 aryl group, C5-12 heteroaryl group, or an optionally substituted 3-hydroxypyridin- 4(1H)-one; p is an integer from 1 to 6; and Zm is absent or a divalent linking moiety; and m is an integer representing the number of time Z is repeated.
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Paragraph 000163
(2014/06/23)
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- SUBSTITUTED5-(3,5-DIMETHYLISOXAZOL-4-YL)INDOLINE-2-ONES
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Disclosed are substituted5-(3,5-dimethylisoxazol-4-yl)indoline-2-one compounds, pharmaceutical compositions comprising at least one such4substituted5-(3,5-dimethylisoxazol- 4-yl)indoline-2-one compound processes for the preparation thereof,and the use the
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Paragraph 0146; 0147
(2014/11/13)
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- Novel indoline-2,3-dione derivatives as inhibitors of aminopeptidase N (APN)
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Aminopeptidase N (APN/CD13), as a zinc-containing ectoenzyme, plays a critical role in the process of tumor angiogenesis, invasion and metastasis. Through the docking-based virtual screening of chemical databases and the further activity assay, we discovered that compound 10c exhibits potent and selective inhibitory ability towards APN. In addition, a series of indoline-2,3-dione derivates have been designed and synthesized as APN inhibitors. The results of preliminary activity evaluation showed that compound 12a (IC50 = 0.074 ± 0.0026 μM) exhibited the best inhibitory activity against APN, which could be used for further anticancer agent research.
- Jin, Kang,Zhang, Xiaopan,Ma, Chunhua,Xu, Yingying,Yuan, Yumei,Xu, Wenfang
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p. 2663 - 2670
(2013/06/27)
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- Novel synthesis and functionalization of ortho-ortho disubstituted biphenyls and a highly condensed novel heterocycle using radical cyclization reaction
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This paper describes a novel synthetic route for the preparation of ortho-ortho disubstituted biphenyls and compounds possessing highly condensed ring system represented by structures X and Y, respectively. Several approaches, such as intermolecular Grubb's olefin metathesis, Heck and, Suzuki reactions were incorporated to functionalize the core structures of X and Y making it suitable for the preparation of a library of compounds.
- Wang, C. H.,White, A. R.,Schwartz, S. N.,Alluri, S.,Cattabiani, T. M.,Ganguly, A. K.,Zhang, L. K.,Chan, T. M.,Buevich, A. V.
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p. 9750 - 9762,13
(2020/08/20)
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- Potential anticonvulsants. 11. Synthesis and anticonvulsant activity of spiro[1,3-dioxolane-2,3'-indolin]-2'-ones and structural analogues
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A number of spiro[1,3-dioxolane-2,3'-indolin]-2'-ones were synthesized and tested for anticonvulsant activity in the maximal electroshock seizure (MES) and pentylenetetrazole seizure threshold (sc-Met) tests. 5'-Chlorospiro[1,3-dioxolane-2,3'-indolin]-2'-one was the most active compound in the MES test and had ED50 = 27.97 mg/kg. Structural analogues spiro[1,3-dioxane-2,3'-indolin]-2'-one, spiro[1,3-dithiolane-2,3'-indolin]-2'-one, spiro[indoline-3,2'-[1,3]-oxathiolan]-2-one, and 3,3-dimethoxyindolin-2-one were also evaluated for anticonvulsant activity. Almost all compounds submitted for screening exhibited the ability to protect mice against electrically and chemically induced seizures. The ED50 and TD50 values for some of the title compounds are reported. Anticonvulsant screenings were carried out through NINCDS, NIH.
- Rajopadhye,Popp
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p. 1001 - 1005
(2007/10/02)
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