- Choline chloride based eutectic solvent for the efficient synthesis of 2-amino-4H-chromen-4-yl phosphonate derivatives via multicomponent reaction under mild conditions
-
Synthesis of 2-amino-4H-chromen-4-ylphosphonate derivatives has been accomplished by the one-pot three-component reaction of salicylaldehyde, malononitrile/ethylcyanoacetate and dialkyl phosphites in the presence of reusable deep eutectic solvent (DES) under mild conditions. The advantages of this method are mild reaction conditions, simple work-up procedure, use of DES as a green solvent and an economical protocol for the preparation of important biologically active phosphorus-containing compounds.
- Krishnammagari, Suresh Kumar,Cho, Byung Gwon,Jeong, Yeon Tae
-
-
Read Online
- A simple and efficient approach for the preparation of dihydroxanthyletin, xanthyletin, decursinol and marmesin
-
A simple and efficient approach has been developed for the preparation of coumarin natural products such as dihydroxanthyletin, xanthyletin, decursinol and marmesin starting from commercially available 2,4-dihydroxybenzaldehyde with very good yields. Wittig homologation and Claisen rearrangement are the protocols used to achieve these molecules.
- Kommera, Rajkumar,Bhimapaka, China Raju
-
supporting information
p. 3204 - 3211
(2020/08/05)
-
- Semicarbazone derivatives bearing phenyl moiety: Synthesis, anticancer activity, cell cycle, apoptosis-inducing and metabolic stability study
-
A series of semicarbazone derivatives bearing phenyl moiety were synthesized and evaluated for the vitro anticancer activities in four human cancer cell lines (human colon cancer (HT29), human neuroblastoma (SK-N-SH), human breast cancer (MDA-MB-231), and human gastric cancer (MKN45)). Biological evaluation led to the identification of 11q and 11s, which showed excellent anticancer activities against tested cancer cell lines with IC50 values ranging from 0.32 to 1.57μM, respectively, while exhibiting weak cytotoxicity on the normal cells (human umbilical vein endothelial cell (HUVEC)). Flow cytometric assay for cell cycle and apoptosis revealed that 11q and 11s caused an arrest in the Sub-G1 cell cycle and inhibited proliferation of cancer cells by inducing apoptosis in a dose-dependent manner. Further enzymatic assay suggested that 11q and 11s could significantly activated procaspase-3 to caspase-3. Metabolic stability study indicated that 11q and 11s showed moderate stability in vitro in human and rat liver microsomes. In view of promising pharmacological activities of 11q and 11s, which had emerged as the valuable lead for further development in the treatment for cancer.
- Ma, Junjie,Ni, Xin,Gao, Yali,Huang, Kun,Wang, Yu,Liu, Jiaan,Gong, Guowei
-
p. 351 - 360
(2019/05/07)
-
- 5-FLUORO-C-(ARYL OR HETEROCYCLYL)-GLYCOSIDE DERIVATIVES USEFUL AS DUAL SGLT1 / SGLT2 MODULATORS
-
The present invention is directed to 5-fluoro-C-(aryl or hetercyclyl)-glycoside derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by SGLT activity, more particularly dual SGLT1/2 activity.
- -
-
Paragraph 0405
(2019/02/28)
-
- Choline hydroxide: An efficient and biodegradable catalyst for the synthesis of 2-amino-3-nitro-4H-chromene derivatives in an aqueous medium
-
An expedient, eco-friendly and efficient procedure for the synthesis of novel 2-amino-3-nitro-4H-chromene derivatives has been developed through the reaction of various 2-hydroxybenzaldehydes and (E)-N-methyl-1-(methylthio)-2-nitroethenamine in the presence of the basic ionic liquid catalyst (choline hydroxide (ChOH)) at room temperature an aqueous medium. The advantageous of this method is a biodegradable and recyclable catalyst, mild, environmentally friendly and high products yields (83-96%) in short reaction times.
- Krishnammagari, Suresh Kumar,Lim, Kwon Taek,Cho, Byung Gwon,Tae Jeong, Yeon
-
supporting information
p. 574 - 581
(2018/09/25)
-
- Development of noviomimetics that modulate molecular chaperones and manifest neuroprotective effects
-
Heat shock protein 90 (Hsp90) is a chaperone under investigation for the treatment of cancer and neurodegenerative diseases. Neuroprotective Hsp90 C-terminal inhibitors derived from novobiocin (novologues) include KU-32 and KU-596. These novologues modulate molecular chaperones and result in an induction of Heat Shock Protein 70 (Hsp70). “Noviomimetics” replace the synthetically complex noviose sugar with a simple cyclohexyl moiety to maintain biological efficacy as compared to novologues KU-596 and KU-32. In this study, we further explore the development of noviomimetics and evaluate their efficacy using a luciferase refolding assay, immunoblot analysis, a c-jun assay, and an assay measuring mitochondrial bioenergetics. These new noviomimetics were designed and synthesized and found to induce Hsp70 and improve biological activity. Noviomimetics 39e and 40a were found to induce Hsp70 and exhibit promising effects in cellular assays.
- Forsberg, Leah K.,Anyika, Mercy,You, Zhenyuan,Emery, Sean,McMullen, Mason,Dobrowsky, Rick T.,Blagg, Brian S.J.
-
p. 1428 - 1435
(2017/11/17)
-
- SPIRO-COMPOUNDS AS S1P MODULATORS
-
The invention relates to heterocyclic compounds of formula (I) as SIP modulators, pharmaceutical compositions comprising such compounds, and uses thereof in the treatment or alleviation of diseases or disorders mediated by an SIP receptor.
- -
-
Page/Page column 48; 49
(2018/05/24)
-
- Functional group manoeuvring for tuning stability and reactivity: Synthesis of cicerfuran, moracins (D, E, M) and chromene-fused benzofuran-based natural products
-
The protecting group manoeuvring as a strategy was applied for tuning the stability and reactivity of 4-(2,2-dibromovinyl)benzene-1,3-diol (12a) and 6-(2,2-dibromovinyl)-2,2-dimethylchroman-7-ol (22) in the domino synthesis of benzofuran-based natural products (1-8). The functional group demands and their impact on the reactivity driven by electronic effects were successfully managed by varying the protecting groups with substituted gem-dibromovinylphenols in domino couplings and triarylbismuth reagents under palladium-catalyzed conditions. This approach paved the way for the synthesis of moracin M (1) and cicerfuran (2), and the first time synthesis of moracin D (3) and moracin E (4) along with chromene-fused benzofuran-based natural products (5-8) in overall good yields.
- Rao, Maddali L. N.,Murty, Venneti N.,Nand, Sachchida
-
p. 9415 - 9423
(2017/11/23)
-
- Semicarbazone derivatives and use thereof
-
The invention belongs to the technical field of medicine, and relates to semicarbazone derivatives disclosed as general formula I, and geometrical isomer, pharmaceutically acceptable salt, solvate or prodrug thereof, wherein the substituent groups M, R1, R2, R and n are defined in the specification. The invention also relates to a method for preparing compounds disclosed as Formula I, a pharmaceutical composition containing the compounds and application of the compounds and pharmaceutical composition in preparing drugs for treating and/or preventing cancers and other hyperplastic diseases.
- -
-
Paragraph 0437; 0438; 0439; 0440
(2017/08/14)
-
- Benzofuran compound and its preparation, use (by machine translation)
-
The invention relates to a benzofuran compound and its preparation, use, its structural formula such as formula (I) as shown: Wherein R1 , R2 , R4 Are selected from hydrogen, C1 - C5 Alkyl, nitro, halogen, ester, hydroxy, amino, amide base or alkoxyl; R3 Hydrogen, C1 - C5 Alkyl, benzyl, aromatic or heteroaromatic group. The invention also relates to the benzofuran compounds in inhibiting the application of gram-positive to be used repeatedly. The invention relates to 3 - oxime substituted benzene and furan structure aromatic ring as the center, the establishment and optimize the preparation method of the compound, and on the preparation of novel compound of the bacteriostatic screening experiment, through initial bacteriostatic test to confirm that preparation compound has broad-spectrum bacteriostatic activity. (by machine translation)
- -
-
Paragraph 0054-0055
(2017/08/18)
-
- Synthesis and antimicrobial evaluation of 3-substituted-imine-6-hydroxy-benzofuran derivatives
-
A series of 3-substituted-imine-6-hydroxy-benzofuran derivatives were chemically synthesized and biologically evaluated as antibacterial and antifungal agents against Candida albicans, Escherichia coli, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus and Bacillus subtilis. Most compounds showed a selective antibacterial activity to gram-positive bacteria and four compounds revealed great antibacterial activities against methicillin-resistant Staphylococcus aureus comparing to the positive control (Ceftazidime) with MIC80 = 12.5–25 μg/mL. Structure-activity relationship studies demonstrated that the free hydroxy group at the C-6 position is essential to the antibacterial activity, and the aromatic imine fragment at the C-3 position also greatly increases antibacterial activity.
- He, Wan,Xu, Buzhe,Bao, Jian,Deng, Xinxian,Liu, Wenlu,Zhang, Yong,Jiang, Faqin,Fu, Lei
-
p. 2485 - 2497
(2016/10/25)
-
- Aromatic-ring azacyclo derivatives and application thereof
-
Aromatic-ring azacyclo derivatives and an application thereof are provided. The invention relates to compounds represented by the formula (V), and a preparation method and an application thereof in medicines. In particular, the invention relates to derivatives of the compounds represented by the general formula (V), and a preparation method and the application thereof as therapeutic agents in prevention and treatment of hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, hepatic steatosis, type-II diabetes, hyperglycemia, obesity or insulin resistance syndromes and metabolic syndromes. The compounds disclosed by the invention also can reduce total cholesterol, LDL-cholesterol and triglycerides, increase the expression of hepatic LDL receptors and inhibit the expression of PCSK9.
- -
-
Paragraph 0318; 0319; 0320
(2016/10/09)
-
- BIPHENYL AMIDES WITH MODIFIED ETHER GROUPS AS HSP90 INHIBITORS AND HSP70 INDUCERS
-
Provided herein are compounds of the formulas: (I) wherein: n, X2, R3, R3', R4, R4', R5, R5', R6, and R6' are as defined herein. Pharmaceutical compositions of the compounds are also provided. In some aspects, these compounds may be used for the treatment of diseases, including diabetic peripheral neuropathy or cancer.
- -
-
Page/Page column 69
(2016/04/19)
-
- pH-responsive fluorescent false neurotransmitters and their use
-
This invention relates to compounds having the following structure: wherein Y is O, X is O, bond α is absent and bond β is present, or Y is H, X is CH, bond α is present, and bond β is absent; atom Z is a carbon and bonds χ, δ and γ are present, or atom Z is a nitrogen and bonds χ, δ and γ are absent, or atom Z is a nitrogen and bonds χ and δ are present and γ is absent. R1, R2, R3, R4, R5, and R6 are various substituents as described in the specification.
- -
-
Page/Page column 39
(2015/07/15)
-
- Condensation of salicylaldehydes with ethyl 4,4,4-trichloro-3-oxobutanoate: A facile approach for the synthesis of substituted 2H-chromene-3-carboxylates
-
A highly efficient and simple protocol has been developed for the preparation of ethyl 2-oxo-2H-chromene-3-carboxylates 3a-v by the condensation of salicylaldehydes 1a-v with ethyl 4,4,4-trichloro-3-oxobutanoate 2 for the first time. The reaction is proceeding via Knoevenagel pathway followed by a selective addition of the phenolic hydroxyl group to the carbonyl group adjacent to the CCl3 group rather than ester carbonyl due to a strong electron withdrawing effect and produced coumarin derivative 3a with the elimination of CHCl3.
- Sairam, Mudulkar,Saidachary, Gannerla,Raju, Bhimapaka China
-
supporting information
p. 1338 - 1343
(2015/03/04)
-
- Design, synthesis, and structure-activity relationships of novel benzothiazole derivatives bearing the ortho-hydroxy N-carbamoylhydrazone moiety as potent antitumor agents
-
A series of novel benzothiazole derivatives bearing the ortho-hydroxy N-carbamoylhydrazone moiety were designed and synthesized and their cytotoxic activities against five cancer cell lines (NCI-H226, SK-N-SH, HT29, MKN45, and MDA-MB-231) were screened in vitro. Most of them showed moderate to excellent activity against all the tested cell lines. Among them, compounds 15g (procaspase-3 EC50 = 1.42 μM) and 16b (procaspase-3 EC 50 = 0.25 μM) exhibited excellent antitumor activity with IC 50 values ranging from 0.14 μM to 0.98 μM against all cancer cell lines, which were 1.8-8.7 times more active than the first procaspase activating compound (PAC-1) (procaspase-3 EC50 = 4.08 μM). The structure-activity relationship (SAR) analyses indicated that the introduction of a lipophilic group (a benzyloxy or heteroaryloxy group) at the 4-position of the 2-hydroxy phenyl ring was beneficial to antitumor activity, and the presence of substituents containing nitrogen that are positively charged at physiological pH could also improve antitumor activity. It was also confirmed that the steric effect of the 4-position substituent of the benzyloxy group had a significant influence on cytotoxic activity.
- Ma, Junjie,Chen, Dong,Lu, Kuan,Wang, Lihui,Han, Xiaoqi,Zhao, Yanfang,Gong, Ping
-
p. 257 - 269
(2014/09/29)
-
- Synthesis and biological evaluation of benzothiazole derivatives bearing the ortho-hydroxy-N-acylhydrazone moiety as potent antitumor agents
-
A novel series of benzothiazole derivatives bearing the ortho-hydroxy-N-acylhydrazone moiety were designed, synthesized, and evaluated for their procaspase-3 kinase activation activities and antiproliferative activities against five cancer cell lines (NCI-H226, SK-N-SH, HT29, MKN-45, and MDA-MB-231). Most target compounds showed moderate to excellent cytotoxic activity against all five tested cancer lines. The most promising compound 18e (procaspase-3 EC50- 0.31μM) with IC50 values ranging from 0.24 to 0.92 μM against all tested cell lines was 4.24-12.2 times more active than PAC-1 (procaspase-3 EC50 - 0.41 μM). Structure-activity relationship studies indicated that the phenyl group on the 2-hydroxyphenyl ring (moiety A) was critical for pharmacological activity in vitro. In addition, introduction of a benzyloxyl group on moiety A and a mono-electron-withdrawing group at the 4-position of the benzyloxyl group were more favorable for antitumor activity. Moreover, reduction of the electron density in the phenyl ring of the benzyloxy group led to a dramatic decrease in the procaspase-3 kinase activation activity. -
- Ma, Junjie,Zhang, Guangyan,Han, Xiaoqi,Bao, Guanglong,Wang, Lihui,Zhai, Xin,Gong, Ping
-
p. 936 - 949
(2015/02/19)
-
- Novologues containing a benzamide side chain manifest anti-proliferative activity against two breast cancer cell lines
-
Hsp90 represents a promising target for the development of both anti-cancer and neuroprotective agents. Structure-activity relationship studies on novobiocin and novobiocin analogues, led to the development of KU-32 and recently, KU-596, as lead compounds for the potential treatment of neurodegenerative diseases. Similar to KU-32, we have demonstrated that upon replacement of the acetamide side chain present in KU-32 with a benzamide, this neuroprotective agent was transformed into a scaffold that manifests anti-proliferative activity. To assess structure-activity relationships for this new scaffold, a library of benzamide-containing novologues was prepared and evaluated against two breast cancer cell lines. Compound 14a manifested the most potent anti-proliferative activity from these studies and induced Hsp90-dependent client protein degradation in a concentration-dependent manner.
- Zhao, Huiping,Anyika, Mercy,Girgis, Antwan,Blagg, Brian S.J.
-
p. 3633 - 3637
(2015/02/05)
-
- 7-Substituted-sulfocoumarins are isoform-selective, potent carbonic anhydrase II inhibitors
-
A series of 7-substituted sulfocoumarins and 3,4-dihydrosulfocoumarins was obtained by cyclization of the methanesulfonate of 2,4-dihydroxy- or 2-hydroxy-4-methoxybenzaldehyde, followed by derivatization reactions. The new compounds incorporate a range of substituents in position 7 of the heterocyclic ring (hydroxyl, methoxy, carboxylic and alkylsulfonate ester). The compounds were tested for the inhibition of the zinc enzyme human (h) carbonic anhydrase (hCA, EC 4.2.1.1). Unlike the 6-substituted sulfocoumarins which were potent hCA IX and XII inhibitors and ineffective hCA I and II inhibitors, compounds from this series showed low nanomolar hCA II inhibitory properties, and inhibited the mitochondrial isoform hCA VA with KIs in the range of 91-9960 nM, but were ineffective as hCA I, IX and XII inhibitors. The structure activity relationship for this class of inhibitors was rather clear, with the nature of the 7-substituent strongly influencing hCA VA inhibition, whereas the nature of these groups were less relevant for hCA II inhibition (all reported compounds were highly effective hCA II inhibitors, with KIs in the range of 1.5-8.4 nM). Since both hCA II and hCA VA are important drug targets (hCA II for antiglaucoma agents; hCA VA for antiobesity drugs), these isoform-selective inhibitors reported here may be considered of interest for various biomedical applications.
- Tanc, Muhammet,Carta, Fabrizio,Bozdag, Murat,Scozzafava, Andrea,Supuran, Claudiu T.
-
p. 4502 - 4510
(2013/07/26)
-
- Synthesis of 6a-hydroxypterocarpans via intramolecular benzoin condensation
-
A novel approach for the syntheses of 6a-hydroxypterocarpans is reported. Its practicality is demonstrated by the synthesis of (±)-glycinol. The main feature is an intramolecular benzoin condensation catalyzed by nucleophilic carbenes to initiate assembly of the benzopyran and establish the 6a-hydroxy center. In addition, a one-pot method was developed to form an epoxide that facilitates subsequent cyclization leading to the benzofuran and direct production of (±)-glycinol.
- Malik, Neha,Erhardt, Paul
-
supporting information
p. 4121 - 4124
(2013/07/26)
-
- C-TERMINAL HSP90 INHIBITORS
-
Hsp90 C-terminal inhibitors and pharmaceutical compositions containing such compounds are provided. The compounds of the disclosure are useful for the treatment and/or prevention of neurodegenerative disorders such as diabetic peripheral neuropathy.
- -
-
Paragraph 00335; 00336
(2013/08/28)
-
- Synthesis and antimicrobial evaluation of 3-methanone-6-substituted- benzofuran derivatives
-
Seventeen benzofuran derivatives were synthesized and screened for their antibacterial activities against Escherichia coli, Staphylococcus aureus, Methicillin-resistant S. aureus, Bacillus subtilis, and Pseudomonas aeruginosa. Seven of them have showed excellent antibacterial activities compared to the positive controls (Cefotaxime and Sodium Penicillin). The substitutions at C-6 and C-3 positions of these derivatives were found to greatly impact on the antibacterial activity and strains specificity, respectively. Specifically, compounds bearing a hydroxyl group at C-6 (5a, 5b, 5c and 12) offered excellent antibacterial activities against all five above-mentioned strains (MIC 80 = 0.78-12.5 ug/mL), and those with imine (15) and (3, 4, 5-trimethoxyphenyl) methanone (7e), respectively, at C-3 position showed selective activity against S. aureus among five tested strains with great MIC80 values (3.12-12.5 ug/mL).
- Liu, Jingbao,Jiang, Faqin,Jiang, Xizhen,Zhang, Wei,Liu, Jingjing,Liu, Wenlu,Fu, Lei
-
experimental part
p. 879 - 886
(2012/09/10)
-
- Identification of fused-ring alkanoic acids with improved pharmacokinetic profiles that Act as G protein-coupled receptor 40/free fatty acid receptor 1 agonists
-
The G protein-coupled receptor 40 (GPR40)/free fatty acid receptor 1 (FFA1) has emerged as an attractive target for a novel insulin secretagogue with glucose dependency. We previously identified phenylpropanoic acid derivative 1 (3-{4-[(2′,6′-dimethylbiphenyl-3-yl)methoxy]-2-fluorophenyl} propanoic acid) as a potent and orally available GPR40/FFA1 agonist; however, 1 exhibited high clearance and low oral bioavailability, which was likely due to its susceptibility to β-oxidation at the phenylpropanoic acid moiety. To identify long-acting compounds, we attempted to block the metabolically labile sites at the phenylpropanoic acid moiety by introducing a fused-ring structure. Various fused-ring alkanoic acids with potent GPR40/FFA1 activities and good PK profiles were produced. Further optimizations of the lipophilic portion and the acidic moiety led to the discovery of dihydrobenzofuran derivative 53 ((6-{[4′-(2-ethoxyethoxy)-2′,6′-dimethylbiphenyl-3-yl]methoxy} -2,3-dihydro-1-benzofuran-3-yl)acetic acid), which acted as a GPR40/FFA1 agonist with in vivo efficacy during an oral glucose tolerance test (OGTT) in rats with impaired glucose tolerance.
- Negoro, Nobuyuki,Sasaki, Shinobu,Ito, Masahiro,Kitamura, Shuji,Tsujihata, Yoshiyuki,Ito, Ryo,Suzuki, Masami,Takeuchi, Koji,Suzuki, Nobuhiro,Miyazaki, Junichi,Santou, Takashi,Odani, Tomoyuki,Kanzaki, Naoyuki,Funami, Miyuki,Tanaka, Toshimasa,Yasuma, Tsuneo,Momose, Yu
-
scheme or table
p. 1538 - 1552
(2012/04/10)
-
- Design, synthesis and anticancer activities of diaryl urea derivatives bearing N-acylhydrazone moiety
-
A new series of diaryl urea derivatives bearing N-acylhydrazone moiety were designed and synthesized. All the target compounds were evaluated for their cytotoxic activities in vitro against human lung adenocarcinoma epithelial cell line (A549), human breast cancer cell line (MDA-MB-231) and human leukemia cell line (HL-60) by standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Several compounds (1a, 1f and 1h) were further evaluated against human embryonic fibroblast, lung-derived cell line (WI38). The pharmacological results indicated that some compounds exhibited promising anticancer activities. In particular, compound 1f showed the most potent cytotoxicity against the tested three cell lines with IC50 values of 0.41 μM, 0.24 μM and 0.23 μM, respectively.
- Zhang, Bei,Zhao, Yanfang,Zhai, Xin,Wang, Lihui,Yang, Jingyu,Tan, Zehui,Gong, Ping
-
experimental part
p. 1046 - 1054
(2012/09/07)
-
- Positional chemoselectivity in the Zn(II)-mediated removal of phenol protecting groups
-
A protocol was developed for the chemoselective ortho-deprotection of polyphenolic substrates using readily available ZnIIX2 salts. This procedure provides exceptional positional selectivity for the deprotection of phenols that reside adjacent to directing carbonyl functionality in the presence of similar protecting groups at the meta and para positions. Good to excellent yields of the desired free phenols were obtained (≤96%), and a wide assortment of protecting groups was readily removed under the reaction conditions.
- Fleury, Lauren M.,Gianino, Joseph B.,Ashfeld, Brandon L.
-
supporting information
p. 5376 - 5379
(2012/10/30)
-
- Synthesis and evaluation of novologues as C-terminal Hsp90 inhibitors with cytoprotective activity against sensory neuron glucotoxicity
-
Compound 2 (KU-32) is a first-generation novologue (a novobiocin-based, C-terminal, heat shock protein 90 (Hsp90) inhibitor) that decreases glucose-induced death of primary sensory neurons and reverses numerous clinical indices of diabetic peripheral neuropathy in mice. The current study sought to exploit the C-terminal binding site of Hsp90 to determine whether the optimization of hydrogen bonding and hydrophobic interactions of second-generation novologues could enhance neuroprotective activity. Using a series of substituted phenylboronic acids to replace the coumarin lactone of 2, we identified that electronegative atoms placed at the meta-position of the B-ring exhibit improved cytoprotective activity, which is believed to result from favorable interactions with Lys539 in the Hsp90 C-terminal binding pocket. Consistent with these results, a meta-3-fluorophenyl substituted novologue (13b) exhibited a 14-fold lower ED50 for protection against glucose-induced toxicity of primary sensory neurons compared to 2.
- Kusuma, Bhaskar Reddy,Zhang, Liang,Sundstrom, Teather,Peterson, Laura B.,Dobrowsky, Rick T.,Blagg, Brian S. J.
-
scheme or table
p. 5797 - 5812
(2012/07/30)
-
- AGONISTS OF GPR40
-
The present invention relates to compounds that have the ability to modulate the activity of GPR40 and are there-fore useful in the treatment of GPR40 related disorders. In addition the invention relates to the compounds, methods for their preparation, pharmaceutical compositions containing the compounds and the uses of these compounds in the treatment of certain disorders related to GPR40 activity.
- -
-
Page/Page column 145-146
(2012/02/05)
-
- Wharton-fragmentation-based approach to the carbocyclic core of the phomoidrides
-
The carbocyclic core of the phomoidrides has been synthesized efficiently and in high yield. Key steps include a phenolic oxidation/intramolecular Diels-Alder sequence, tandem radical cyclization, and a late-stage Wharton fragmentation of a densely functionalized isotwistane skeleton.
- Murphy, Graham K.,Hama, Naoto,Bedermann, Aaron,Dong, Ping,Schneider, Chris M.,McMahon, Travis C.,Tao, Ran N.,Twenter, Barry M.,Spiegel, David A.,Wood, John L.
-
supporting information
p. 4544 - 4547
(2012/11/06)
-
- Total syntheses of (±)-vestitol and bolusanthin III using a wittig strategy
-
An intramolecular Wittig olefination was utilized to -produce the key isoflav-3-ene intermediate needed to prepare (±)-vestitol and bolusanthin III in ca. 30% and 20% respective yields after eight steps. Georg Thieme Verlag Stuttgart ? New York.
- Luniwal, Amarjit,Erhardt, Paul W.
-
scheme or table
p. 1605 - 1607
(2011/08/03)
-
- Multigram synthesis of glyceollin i
-
Scaled-up procedures and preparation of glyceollin I in multigram quantities are described. The synthesis features construction of a cis-fused ring system in high enantiomeric excess after Sharpless asymmetric dihydroxylation of a key intermediate that is initially produced by an intramolecular Wittig reaction to afford the requisite alkene while simultaneously forming the first ring. The overall yield is 12% after 11 steps.
- Luniwal, Amarjit,Malik, Neha,Erhardt, Paul,Khupse, Rahul,Reese, Michael,Liu, Jidong,El-Dakdouki, Mohammad,Fang, Lei
-
experimental part
p. 1149 - 1162
(2012/01/05)
-
- METHODS FOR SYNTHESIZING GLYCINOLS, GLYCEOLLINS I AND II, COMPOSITIONS OF SELECTED INTERMEDIATES, AND THERAPEUTIC USES THEREOF
-
Two distinct methods are disclosed and claimed for synthesizing glyceollin I plus glyceollin II as a mixture and as their pure forms. Stereochemical isomers and various synthetic intermediates are also synthesized and claimed for their novel compositions of matter. All compounds and their mixtures are claimed for use in formulations that are useful to treat or prevent cancer, or that have utility as selective estrogen receptor modulators, such formulations including enhanced or medical foods, dietary supplements and ethical pharmaceutical agents.
- -
-
Page/Page column 2; 4; 11
(2011/06/26)
-
- PH RESPONSIVE FLUORESCENT FALSE NEUROTRANSMITTERS AND THEIR USE
-
This invention relates to compounds having the following structure: wherein Y is O, X is O, bond α is absent and bond β is present, or Y is H, X is CH, bond α is present, and bond β is absent; atom Z is a carbon and bonds χ, δ and γ are present, or atom Z is a nitrogen and bonds χ, δ and γ are absent, or atom Z is a nitrogen and bonds χ and δ are present and γ is absent. R1, R2, R3, R4, R5, and R6 are various substituents as described in the specification.
- -
-
Page/Page column 54
(2011/08/21)
-
- Improved total synthesis of racemic rutamarin
-
An improved, convenient and cost-effective process, using 2,4-dihydroxybenzaldehyde 2 as starting material for (±)-rutamarin 1, is described. The overall yield of 1 is 44% in eight steps, requiring no chromatographic purification. The Japan Institute of Heterocyclic Chemistry.
- Tong, Ling,Xiong, Ruisheng,Jiang, Hong,Jiang, Xiangrui,Sun, Hongbin,Jiang, Hualiang,Shen, Jingshan
-
experimental part
p. 1697 - 1702
(2011/03/22)
-
- Novel thiazolidinedione derivatives with anti-obesity effects: Dual action as PTP1B inhibitors and PPAR-γ activators
-
Benzylidene-2,4-thiazolidinedione derivatives with substitutions at both the ortho and para-positions of the phenyl group were synthesized as PTP1B inhibitors with IC50 values in a low micromolar range. Compound 18l, the lowest, bore an IC50 of 1.3 μM. In a peroxisome proliferator-activated receptor-γ (PPAR-γ) promoter reporter gene assay, 18l was found to activate the transcription of the reporter gene with potencies comparable to those of troglitazone, rosiglitazone, and pioglitazone. In vivo efficacy of 18l as an anti-obesity and hypoglycemic agent was evaluated in a mouse model system. Compound 18l significantly suppressed weight gain and significantly improved blood parameters such as TG, total cholesterol and NEFA without overt toxic effects.
- Bhattarai, Bharat Raj,Kafle, Bhooshan,Hwang, Ji-Sun,Ham, Seung Wook,Lee, Keun-Hyeung,Park, Hwangseo,Han, Inn-Oc,Cho, Hyeongjin
-
supporting information; experimental part
p. 6758 - 6763
(2010/12/20)
-
- Development of pH-responsive fluorescent false neurotransmitters
-
We introduce pH-responsive fluorescent false neurotransmitters (pH-responsive FFNs) as novel probes that act as vesicular monoamine transporter (VMAT) substrates and ratiometric fluorescent pH sensors. The development of these agents was achieved by systematic molecular design that integrated several structural elements, including the aminoethyl group (VMAT recognition), halogenated hydroxy-coumarin core (ratiometric optical pH sensing in the desired pH range), and N- or C-alkylation (modulation of lipophilicity). Of 14 compounds that were synthesized, the probe Mini202 was selected based on the highest uptake in VMAT2-transfected HEK cells and desirable optical properties. Using Mini202, we measured the pH of catecholamine secretory vesicles in PC-12 cells (pH -5.9) via two-photon fluorescence microscopy. Incubation with methamphetamine led to an increase in vesicular pH (pH - 6.4), consistent with a proposed mechanism of action of this psychostimulant, and eventually to redistribution of vesicular content (including Mini202) from vesicles to cytoplasm. Mini202 is sufficiently bright, photostable, and suitable for two-photon microscopy. This probe will enable fundamental neuroscience and neuroendocrine research as well as drug screening efforts.
- Lee, Minhee,Gubernator, Niko G.,Sulzer, David,Sames, Dalibor
-
supporting information; experimental part
p. 8828 - 8830
(2010/08/21)
-
- Discovery of a series of acrylic acids and their derivatives as chemical leads for selective EP3 receptor antagonists
-
A series of acrylic acids and their structurally related compounds were evaluated for their binding affinity to four EP receptor subtypes (EP1-4). Starting from the initial hit 3, which was discovered in our in-house library, compounds 4 and 5 were identified as new chemical leads as candidates for further optimization towards a selective EP3 receptor antagonist. The identification process of these compounds and their pharmacokinetic profiles are presented.
- Asada, Masaki,Obitsu, Tetsuo,Nagase, Toshihiko,Sugimoto, Isamu,Yamaura, Yoshiyuki,Sato, Kazutoyo,Narita, Masami,Ohuchida, Shuichi,Nakai, Hisao,Toda, Masaaki
-
experimental part
p. 6567 - 6582
(2009/12/09)
-
- ortho-Formylation of oxygenated phenols
-
Oxygenated phenols are mono-formylated using a mixture of paraformaldehyde, MgCl2, and Et3N in THF. In all cases but one, only one regioisomer of the salicylaldehyde is obtained in good to high yield.
- Akselsen, ?yvind W.,Skatteb?l, Lars,Hansen, Trond Vidar
-
experimental part
p. 6339 - 6341
(2010/02/27)
-
- Total syntheses of racemic and natural glycinol
-
Total syntheses of racemic and (-)-glycinol (1) are described. A Wittig reaction produced the isoflav-3-ene from which a Sharpless dihydroxylation introduced either the racemic or enantiomeric 6a-hydroxy group. A 5.5% overall yield of racemic material was obtained after 12 steps. A method was devised for a one-pot switch of protecting groups masking a sensitive resorcinolic para-functionality, and conditions were optimized to prompt spontaneous closure of the pterocarpanolic dihydrofuran upon subsequent exposure of its ortho-functionality. These improvements eliminated two steps and increased the overall yield to 9.8% during production of the natural enantiomer.
- Luniwal, Amarjit,Khupse, Rahul S.,Reese, Michael,Fang, Lei,Erhardt, Paul W.
-
scheme or table
p. 2072 - 2075
(2010/04/29)
-
- Total syntheses of racemic, natural (-) and unnatural (+) glyceollin I
-
(Chemical Equation Presented) The first total syntheses of racemic glyceollin I and its enantiomers are described. A Wittig approach was utilized as an entry to the appropriately substituted isoflav-3-ene so that an osmium tetroxide mediated asymmetric dihydroxylation could be deployed for stereospecific Introduction of the 6a-hydroxy group. While using triphenylphosphine hydrobromide, a novel method was found for gently removing MOM from protected phenolic hydroxyl groups present within sensitive systems.
- Khupse, Rahul S.,Erhardt, Paul W.
-
supporting information; experimental part
p. 5007 - 5010
(2009/05/31)
-
- Enantioselective total synthesis of hydramicromelin B
-
The first total synthesis of hydramicromelin B is described. An AuCl3/AgOTf-catalyzed intramolecular reaction was used as key step for the construction the coumarin ring.
- Huo, Xing,Ren, Xingfeng,Xu, Yanfen,Li, Xinyun,She, Xuegong,Pan, Xinfu
-
p. 343 - 347
(2008/09/19)
-
- Molecular design of potent tyrosinase inhibitors having the bibenzyl skeleton
-
In order to develop water soluble tyrosinase inhibitors, bibenzyl xyloside 1 isolated from Chlorophytum arundinaceum (liliaceae), and its derivatives 2 and 3 were synthesized by using Wittig reaction and trichloroimidate glycosylation procedure as key steps. Xylosides 1-3 showed potent tyrosinase inhibitory activity with IC50s of 1.6, 0.43, and 0.73 μM, respectively, although each NMR data of synthetic bibenzyls was not identical to that of naturally occurring xyloside 1.
- Oozeki, Hiromi,Tajima, Reiko,Nihei, Ken-ichi
-
scheme or table
p. 5252 - 5254
(2009/05/07)
-
- A facile two-step synthesis of 2-arylbenzofurans based on the selective cross McMurry couplings
-
(Chemical Equation Presented) A novel two-step synthesis of 2-arylbenzofurans has been developed. It involves a selective cross McMurry coupling of a salicylaldehyde or substituted salicylaldehyde with an aromatic aldehyde and a sequential oxidative cyclization of the resulting ortho-vinylphenols. Utilizing this synthetic protocol, a variety of 2-arylbenzofurans including cicerfuran (5) have been efficiently synthesized.
- Duan, Xin-Fang,Zeng, Jing,Zhang, Zhan-Bin,Zi, Guo-Fu
-
p. 10283 - 10286
(2008/04/05)
-
- COMPOUNDS AND METHODS FOR MODULATING FXR
-
Compounds of formula. wherein variables are as defined herein and their pharmaceutical compositions and methods of use are disclosed as useful for treating dyslipidemia and related diseases.
- -
-
Page/Page column 33
(2008/06/13)
-
- ORGANIC COMPOUNDS
-
Compounds of the formula are inhibitors of protein tyrosine phosphatases (PTPases) and, thus, may be employed for the treatment of conditions mediated by PTPase activity. The compounds of the present invention may also be employed as inhibitors of other enzymes characterized with a phosphotyrosine binding region such as the SH2 domain. Accordingly, the compounds of formula (I) may be employed for prevention and/or treatment of insulin resistance associated with obesity, glucose intolerance, diabetes mellitus, hypertension and ischemic diseases of the large and small blood vessels, conditions that accompany type-2 diabetes, including hyperlipidemia, hypertriglyceridemia, atherosclerosis, vascular restenosis, irritable bowel syndrome, pancreatitis, adipose cell tumors and carcinomas such as liposarcoma, dyslipidemia, and other disorders where insulin resistance is indicated. In addition, the compounds of the present invention may be employed to treat and/or prevent cancer (such as prostate or breast cancer), osteoporosis, neurodegenerative and infectious diseases, and diseases involving inflammation and the immune system.
- -
-
Page/Page column 112-113
(2010/11/27)
-
- 4-amino-thieno[3,2-c] pyridine-7-carboxylic acid derivatives
-
The present invention relates to compounds of the formula medicaments containing them and the use of these compounds as pharmaceutically active agents. The compounds exhibit activity as Raf kinase inhibitors and therefore may be useful for the treatment of diseases mediated by said kinases, especially as anticancer agents.
- -
-
Page/Page column 53
(2010/11/26)
-
- Design, synthesis, and conformational dynamics of a gated molecular basket
-
We have developed a synthesis and examined the conformational behavior and recognition properties of dynamic molecular containers 1-3. As follows from the 1H NMR dilution, diffusion NMR, and vapor pressure osmometry measurements, compound 1 has a low affinity for intermolecular aggregation and is mostly present in monomeric form in dilute chloroform solutions. Inspecting the O-H chemical shift resonances of 1, 3, and model compound 4 as a function of temperature afforded the Δδ/ΔT coefficients of 17.0, 17.3, and 4.7 ppb K-1, respectively. In combination with the results from variable temperature 1H NMR and IR measurements, the existence of conformers of 1 and 3 in equilibrium, each having a different extent of hydrogen bonding, was confirmed. Molecular mechanics calculations suggested 1 a as the most favorable conformation, with three additional conformers, 1b, 1C, and 1d, populating local energy minima. Further optimization of each of the four conformers using semiempirical PM3 and ab initio (HF/6-31G*) methods allowed a determination of their relative free energies and the corresponding Boltzmann population distributions which were heavily weighted toward 1a. A computed composite IR spectrum of a fraction-weighted mixture of the conformers of 1 reproduced the experimentally observed IR spectrum in its structural features, leading to a conclusion that conformer 1a indeed dominates the equilibrium. The egg-shaped cavity of 1 (136.6 A3) is complementary in size, shape, and electrostatic potential to chloroform (74.9 A3). A single-crystal X-ray study of 2 revealed a disordered chloroform molecule positioned inside the cavitand along its C3, axis.
- Maslak, Veselin,Yan, Zhiqing,Xia, Shijing,Gallucci, Judith,Hadad, Christopher M.,Badjic, Jovica D.
-
p. 5887 - 5894
(2007/10/03)
-
- BENZYLAMINE ANALOGUE
-
A compound of the formula (I): [wherein R1 represents a C1-C6 alkyl group etc., R2 and R3 are the same or different and represent a hydrogen atom etc., Ra represents a C1-C6 alkyl group etc., Arom represents an aryl group etc., A represents a C1-C6 alkylene group, E represents a single bond, an oxygen atom, a sulfur atom etc., X1 and X2 are the same or different and represent an oxygen atom or a sulfur atom] or a pharmacologically acceptable salt or ester thereof.
- -
-
Page/Page column 131-135
(2008/06/13)
-
- Chroman and benzofuran derivatives as 5-hydroxytryptamine-6 ligands
-
The present invention provides a compound of formula I and the use thereof for the therapeutic treatment of disorders relating to or affected by the 5-HT6 receptor.
- -
-
-
- A series of 2(Z)-2-benzylidene-6,7-dihydroxybenzofuran-3[2H]-ones as inhibitors of chorismate synthase
-
A series of 2(Z)-2-benzylidene-6,7-dihydroxybenzofuran-3[2H]-ones was identified as potent inhibitors of bacterial chorismate synthase. The 2′-hydroxy-4′-pentoxy analogue 33 is a potent inhibitor of Streptococcus pneumoniae chorismate synthase.
- Thomas, Michael G.,Lawson, Chris,Allanson, Nigel M.,Leslie, Bruce W.,Bottomley, Joanna R.,McBride, Andrew,Olusanya, Oyinkan A.
-
p. 423 - 426
(2007/10/03)
-
- Benzofuranylsulfonates
-
The invention relates to benzofuranylsulfonates of the general formula (I), their preparation and their use for the treatment of inflammation.
- -
-
-