- Pd/C-Catalyzed transfer hydrogenation ofN-H indoles with trifluoroethanol and tetrahydroxydiboron as the hydrogen source
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Under the guidance of the known mechanism of the hydrogenation of indoles and transfer hydrogenation with tetrahydroxydiboron (B2(OH)4), Pd/C catalyzed transfer hydrogenation ofN-H indoles with trifluoroethanol and tetrahydroxydiborane as the hydrogen source has been developed. This provides an efficient strategy and catalytic system for the reduction of un-activatedN-H indoles, andN-H indolines are obtained with good to excellent yields. In addition, a series of the isotopic labelling experiments were carried out to probe the mechanism.
- Zhou, Xiao-Yu,Chen, Xia
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supporting information
p. 548 - 551
(2021/02/06)
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- Palladium-Catalyzed Direct and Specific C-7 Acylation of Indolines with 1,2-Diketones
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The indole scaffold is a ubiquitous and useful substructure, and extensive investigations have been conducted to construct the indole framework and/or realize indole modification. Nevertheless, the direct selective functionalization on the benzenoid core must overcome the high activity of the C-3 position and still remains highly challenging. Herein, a palladium-catalyzed direct and specific C-7 acylation of indolines in the presence of an easily removed directing group was developed. This strategy usually is considered as a practical strategy for the preparation of acylated indoles because indoline can be easily converted to indole under oxidation conditions. In particular, our strategy greatly improved the alkacylation yield of indolines for which only an unsatisfactory yield could be achieved in the previous studies. Furthermore, the reaction can be scaled up to gram level in the standard reaction conditions with a much lower palladium loading (1 mol %).
- Xie, Guilin,Zhao, Yuhan,Cai, Changqun,Deng, Guo-Jun,Gong, Hang
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supporting information
p. 410 - 415
(2021/01/26)
-
- Covalent Organic Frameworks toward Diverse Photocatalytic Aerobic Oxidations
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Photoactive two-dimensional covalent organic frameworks (2D-COFs) have become promising heterogenous photocatalysts in visible-light-driven organic transformations. Herein, a visible-light-driven selective aerobic oxidation of various small organic molecules by using 2D-COFs as the photocatalyst was developed. In this protocol, due to the remarkable photocatalytic capability of hydrazone-based 2D-COF-1 on molecular oxygen activation, a wide range of amides, quinolones, heterocyclic compounds, and sulfoxides were obtained with high efficiency and excellent functional group tolerance under very mild reaction conditions. Furthermore, benefiting from the inherent advantage of heterogenous photocatalysis, prominent sustainability and easy photocatalyst recyclability, a drug molecule (modafinil) and an oxidized mustard gas simulant (2-chloroethyl ethyl sulfoxide) were selectively and easily obtained in scale-up reactions. Mechanistic investigations were conducted using radical quenching experiments and in situ ESR spectroscopy, all corroborating the proposed role of 2D-COF-1 in photocatalytic cycle.
- Liu, Shuyang,Tian, Miao,Bu, Xiubin,Tian, Hua,Yang, Xiaobo
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supporting information
p. 7738 - 7744
(2021/05/07)
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- Regioselective Formation of Substituted Indoles: Formal Synthesis of Lysergic Acid
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A Diels–Alder reaction-based strategy for the synthesis of indoles and related heterocycles is reported. An intramolecular cycloaddition of alkyne-tethered 3-aminopyrones gives 4-substituted indolines in good yield and with complete regioselectivity. Additional substitution is readily tolerated in the transformation, allowing synthesis of complex and non-canonical substitution patterns. Oxidative conditions give the corresponding indoles. The strategy also allows the synthesis of carbazoles. The method was showcased in a formal synthesis of lysergic acid.
- Beaudry, Christopher M.,Points, Gary L.,Stout, Kenneth T.
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supporting information
p. 16655 - 16658
(2020/12/01)
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- CANCER TREATMENTS TARGETING CANCER STEM CELLS
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Disclosed are compounds, methods, compositions, and kits that allow for treating cancer by, e.g., targeting cancer stem cells. In some embodiments, the cancer is colorectal cancer, gastric cancer, gastrointestinal stromal tumor, ovarian cancer, lung cancer, breast cancer, pancreatic cancer, prostate cancer, testicular cancer, or lymphoma. In some embodiments, the cancer is liver cancer, endometrial cancer, leukemia, or multiple myeloma. The compounds utilized in the disclosure are of Formula (0), (O'), and (I):
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-
Paragraph 0331; 0588-0590
(2019/11/19)
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- Synthesis and Pharmacological Evaluation of Noncatechol G Protein Biased and Unbiased Dopamine D1 Receptor Agonists
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Noncatechol heterocycles have recently been discovered as potent and selective G protein biased dopamine 1 receptor (D1R) agonists with superior pharmacokinetic properties. To determine the structure-activity relationships centered on G protein or β-arrestin signaling bias, systematic medicinal chemistry was employed around three aromatic pharmacophores of the lead compound 5 (PF2334), generating a series of new molecules that were evaluated at both D1R Gs-dependent cAMP signaling and β-arrestin recruitment in HEK293 cells. Here, we report the chemical synthesis, pharmacological evaluation, and molecular docking studies leading to the identification of two novel noncatechol D1R agonists that are a subnanomolar potent unbiased ligand 19 (PW0441) and a nanomolar potent complete G protein biased ligand 24 (PW0464), respectively. These novel D1R agonists provide important tools to study D1R activation and signaling bias in both health and disease.
- Wang, Pingyuan,Felsing, Daniel E.,Chen, Haiying,Raval, Sweta R.,Allen, John A.,Zhou, Jia
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supporting information
p. 792 - 799
(2019/05/02)
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- Sustainable Radical Cascades to Synthesize Difluoroalkylated Pyrrolo[1,2-a]indoles
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We disclose herein a photocatalytic difluoroalkylation and cyclization cascade reaction of N-(but-2-enoyl)indoles with broad substrate scopes in up to 90% isolated yield. This method provides sustainable and efficient access to synthesize difluoroalkylated pyrrolo[1,2-a]indoles with a quaternary carbon center under mild conditions.
- Huang, Honggui,Yu, Menglin,Su, Xiaolong,Guo, Peng,Zhao, Jia,Zhou, Jiabing,Li, Yi
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p. 2425 - 2437
(2018/02/23)
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- Gold-catalyzed C5-alkylation of indolines and sequential oxidative aromatization: Access to C5-functionalized indoles
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A novel protocol for the synthesis of C5-alkylated indole derivatives via a gold-catalyzed reaction of indolines with diazo compounds and subsequent oxidative aromatization has been developed. C-H bond functionalization selectively occurs at the C5-position of indolines without a directing group. The experimental operation is simple and the whole process can be manipulated in one-pot.
- Zhang, Wenzheng,Xu, Guangyang,Qiu, Lin,Sun, Jiangtao
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supporting information
p. 3889 - 3892
(2018/06/08)
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- Rh(III)-Catalyzed C7-Thiolation and Selenation of Indolines
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The rhodium(III)-catalyzed intermolecular C7-thiolation and selenation of indolines with disulfides and diselenides were developed. This protocol relies on the use of a removable pyrimidyl directing group to access valuable C-7 functionalized indoline scaffolds with ample substrate scope and broad functional group tolerance.
- Xie, Wucheng,Li, Bin,Wang, Baiquan
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p. 396 - 403
(2016/01/25)
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- NOVEL UREA COMPOUNDS
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The present invention provides a compound of Formula I: or a pharmaceutically acceptable salt thereof.
- -
-
Paragraph 0060-0062
(2015/04/28)
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- NOVEL UREA COMPOUNDS
-
The present invention provides a compound of Formula I: or a pharmaceutically acceptable salt thereof.
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Paragraph 0026
(2015/05/13)
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- Discovery of a novel series of indoline carbamate and indolinylpyrimidine derivatives as potent GPR119 agonists
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GPR119 has emerged as an attractive target for anti-diabetic agents. We identified a structurally novel GPR119 agonist 22c that carries a 5-(methylsulfonyl)indoline motif as an early lead compound. To generate more potent compounds of this series, structural modifications were performed mainly to the central alkylene spacer. Installation of a carbonyl group and a methyl group on this spacer significantly enhanced agonistic activity, resulting in the identification of 2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]propyl 7-fluoro-5-(methylsulfonyl)-2,3-dihydro-1H-indole-1-carboxylate (20). To further expand the chemical series of indoline-based GPR119 agonists, several heterocyclic core systems were introduced as surrogates of the carbamate spacer that mimic the presumed active conformation. This approach successfully produced an indolinylpyrimidine derivative 37, 5-(methylsulfonyl)-1-[6-({1-[3-(propan-2- yl)-1,2,4-oxadiazol-5-yl]piperidin-4-yl}oxy)pyrimidin-4-yl]-2, 3-dihydro-1H-indole, which has potent GPR119 agonist activity. In rat oral glucose tolerance tests, these two indoline-based compounds effectively lowered plasma glucose excursion and glucose-dependent insulin secretion after oral administration.
- Sato, Kenjiro,Sugimoto, Hiromichi,Rikimaru, Kentaro,Imoto, Hiroshi,Kamaura, Masahiro,Negoro, Nobuyuki,Tsujihata, Yoshiyuki,Miyashita, Hirohisa,Odani, Tomoyuki,Murata, Toshiki
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p. 1649 - 1666
(2014/03/21)
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- INDOLINE DERIVATIVES AND THEIR USE AS FLAVOURING AGENTS
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Organic compounds of formula (I) wherein: X is N, or C, R1 -R6 may be independently selected from the group consisting of, H, substituted, unsubstituted, branched or unbranched C1-C4 alkyl, methoxy, ethoxy, Br,
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Page/Page column 13-14
(2011/05/11)
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- Discovery of novel N -β- d -Xylosylindole derivatives as sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors for the management of hyperglycemia in diabetes
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A novel series of N-linked β-d-xylosides were synthesized and evaluated for inhibitory activity against sodium-dependent glucose cotransporter 2 (SGLT2) in a cell-based assay. Of these, the 4-chloro-3-(4-cyclopropylbenzyl) -1-(β-d-xylopyranosyl)-1H-indole 19m was found to be the most potent inhibitor, with an EC50 value similar to that of the natural SGLT2 inhibitor phlorizin. Further studies in Sprague-Dawley (SD) rats indicated that 19m significantly increased urine glucose excretion in a dose-dependent manner with oral administration. The antihyperglycemic effect of 19m was also observed in streptozotocin (STZ) induced diabetic SD rats. These results described here are a good starting point for further investigations into N-glycoside SGLT2 inhibitors.
- Yao, Chun-Hsu,Song, Jen-Shin,Chen, Chiung-Tong,Yeh, Teng-Kuang,Hung, Ming-Shiu,Chang, Chih-Chun,Liu, Yu-Wei,Yuan, Mao-Chia,Hsieh, Chieh-Jui,Huang, Chung-Yu,Wang, Min-Hsien,Chiu, Ching-Hui,Hsieh, Tsung-Chih,Wu, Szu-Huei,Hsiao, Wen-Chi,Chu, Kuang-Feng,Tsai, Chi-Hui,Chao, Yu-Sheng,Lee, Jinq-Chyi
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experimental part
p. 166 - 178
(2011/02/28)
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- ORGANIC COMPOUNDS
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Organic compounds of formula (I), wherein: X is C, R1 to R6 may be independently selected from the group consisting of, H, C1-C3 alkyl, Br, F, Cl, R7 is O R8 is NH R9 is a group having 5 to12 carbons selected from the group consisting of cycloalkyl or substituted alkyl, wherein the substituent is selected from the group consisting of aryl or cycloalkyl. The compounds create / modify flavour, in particular sweet flavour and may be used in compositions and consumable products.
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Page/Page column 17
(2011/05/11)
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- Discovery of SB-705498: A potent, selective and orally bioavailable TRPV1 antagonist suitable for clinical development
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Small molecule antagonists of the vanilloid receptor TRPV1 (also known as VR1) are disclosed. Pyrrolidinyl ureas such as 8 and 15 (SB-705498) emerged as lead compounds following optimisation of the previously described urea SB-452533. Pharmacological studies using electrophysiological and FLIPR-Ca2+-based assays showed that compounds such as 8 and 15 were potent antagonists versus the multiple chemical and physical modes of TRPV1 activation (namely capsaicin, acid and noxious heat). Furthermore, 15 possessed suitable developability properties to enable progression of this compound into in vivo studies and subsequently clinical development.
- Rami, Harshad K.,Thompson, Mervyn,Stemp, Geoffrey,Fell, Steve,Jerman, Jeffrey C.,Stevens, Alexander J.,Smart, Darren,Sargent, Becky,Sanderson, Dominic,Randall, Andrew D.,Gunthorpe, Martin J.,Davis, John B.
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p. 3287 - 3291
(2007/10/03)
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- Indoline and piperazine containing derivatives as a novel class of mixed D2/D4 receptor antagonists. Part 1: Identification and structure-activity relationships
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Optimization of the lead compound 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2,3-dihydro-indol-1-yl)-ethanone 1 by systematic structure-activity relation (SAR) studies lead to two potent compounds 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2-methy-2,3-dihydro-indol-1-yl)- ethanone 2n and 2-[-4-(4-chloro-benzyl)-piperazin-1-yl]-1-(2-methy-2,3-dihydro-indol-1-yl)- ethanone 7b. Their related synthesis was also reported.
- Zhao, He,Thurkauf, Andrew,He, Xiaoshu,Hodgetts, Kevin,Zhang, Xiaoyan,Rachwal, Stanislaw,Kover, Renata X.,Hutchison, Alan,Peterson, John,Kieltyka, Andrzej,Brodbeck, Robbin,Primus, Renee,Wasley, Jan W.F.
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p. 3105 - 3109
(2007/10/03)
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- ANTIMIGRAINE 1,2,5-THIADIAZOLE DERIVATIVES OF INDOLYLALKYL-PYRIDNYL AND PYRIMIDINYLPIPERAZINES
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A series of novel 5-(3,4-diamino-1,2,5-thiadiazole and S-oxide) derivatives of indolylalkylpiperazinyl pyridines and pyrimidines of Formula I are intended for use in the alleviation of vascular headaches. STR1 In Formula I, X is selected from S, SO and SO 2.
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- ANTIMIGRAINE CYCLOBUTENEDIONE DERIVATIVES OF INDOLYLALKYL-PYRIDINYL AND PYRIMIDINYLPIPERAZINES
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A series of novel 5-cyclobutenedione derivatives of indolylalkylpiperazinyl pyridines and pyrimidines of Formula I are intended for use in the alleviation of vascular headaches. STR1
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