- Innovative bio-based organic UV-A and blue light filters from Meldrum's acid
-
Faced with the ban of some organic UV filters such as octinoxate or avobenzone, especially in Hawaii, it became essential to offer new alternatives that are both renewable and safe for humans and the environment. In this context, a class of bio-based mole
- Allais, Florent,Balaguer, Patrick,Brunissen, Fanny,Mention, Matthieu M.,Peyrot, Cédric
-
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- Discovery of novel potent GPR40 agonists containing imidazo[1,2-a]pyridine core as antidiabetic agents
-
Free fatty acid receptor 1 (FFA1 or GPR40) has been studied for many years as a target for the treatment of type 2 diabetes mellitus. In order to increase potency and reduce hepatotoxicity, a series of novel compounds containing imidazo[1,2-a]pyridine sca
- Ye, Zhiwen,Liu, Chunxia,Zou, Feng,Cai, Yan,Chen, Bin,Zou, Yuxing,Mo, Jiaxian,Han, Ting,Huang, Wenlong,Qiu, Qianqian,Qian, Hai
-
-
- Microwave-associate synthesis of Co3O4 nanoparticles as an effcient nanocatalyst for the synthesis of arylidene barbituric and Meldrum's acid derivatives in green media
-
In this study, Co3O4 nanocatalysts were constructed in environmentally appropriate conditions using controlled, effective, and facile microwave method. The final nanostructures were characterized by SEM, XRD, and TEM analyses. The products had a small size distribution, homogeneous morphology, and crystallographic structures associated with the formation of Co3O4 nanostructures. Moreover, EDS mapping analysis confirmed the existence of Co and O elements in the final structure, and the magnetic properties of the samples were investigated by VSM. The application of this nanostructure in a catalytic process was further examined, and the results suggested that it could be used as a novel candidate for the synthesis of arylidene barbituric and Meldrum,s acid through Knoevenagel condensation of aldehydes by barbituric and Meldrum,s acid in aqueous media. The high yield of these nanocatalysts would be justified by the nature of the nanostructure as well as the experimental procedure developed in this study, which affected the physicochemical features of the products.
- Yahyazadehfar, Mahdieh,Sheikhhosseini, Enayatollah,Ahmadi, Sayed Ali,Ghazanfari, Dadkhoda
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-
- 3-PHENYL-4-HEXYNOIC ACID DERIVATIVES AS GPR40 AGONISTS
-
A compound of the formula (I)wherein R represents a straight or branched, primary or secondary acyclic hydrocarbyl C3–C15 group, which can be saturated or unsaturated, or a straight or branched, primary or secondary acyclic hydrocarbyl C3–C15 group, which can be saturated or unsaturated and wherein one or more of hydrogen atoms is replaced with fluorine atom; X represents hydrogen atom or halogen atom,and* denotes chiral center, and salts thereof. The compound is useful for the treatment of diseases mediated by GPR40, in particular type II diabetes. (I)
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Page/Page column 38
(2019/07/23)
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- An alternative, practical, and ecological protocol for synthesis of arylidene analogues of Meldrum’s acid as useful intermediates
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This paper presents an ecological protocol for Knoevenagel condensation using a catalytic amount of 4,4′-trimethylenedipiperidine as a versatile, efficient, safe, commercially available, inexpensive, and recyclable organocatalyst by a ball-milling process
- Khaligh, Nader Ghaffari,Mihankhah, Taraneh,Johan, Mohd Rafie
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- A class of GPR40 agonist compounds with amide structure, and uses thereof
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The present invention relates to a class of amide compounds with a novel structure, and a pharmaceutical composition thereof, wherein the structure of the amide compound is represented by a general formula (I). According to the present invention, the amide compound (I) can regulate GPR40 activity, and can be used for GPR40 activity related diseases such as diabetes and metabolic syndrome. The formula I is defined in the specification.
- -
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Paragraph 0122; 0123; 0124
(2019/05/02)
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- Identification of highly potent and orally available free fatty acid receptor 1 agonists bearing isoxazole scaffold
-
The free fatty acid receptor 1 (FFA1) is being considered to be a novel anti-diabetic target based on its role in amplifying insulin secretion. We have previously identified several series of FFA1 agonists with different heterocyclic scaffolds. Herein, we describe the structural exploration of other heterocyclic scaffolds directed by drug-like physicochemical properties. Further structure-based design and chiral resolution provided the most potent compound 11 (EC50 = 7.9 nM), which exhibited improved lipophilicity (LogD7.4: 1.93), ligand efficiency (LE = 0.32) and ligand lipophilicity efficiency (LLE = 6.2). Moreover, compound 11 revealed an even better pharmacokinetic property than that of TAK-875 in terms of plasma clearance, maximum concentration, and plasma exposure. Although robust agonistic activity and PK profiles for compound 11, the glucose-lowering effects in vivo is not ideal, and the exact reason for in vitro/in vivo difference was worthy for further exploration.
- Li, Zheng,Liu, Chunxia,Shi, Wei,Cai, Xingguang,Dai, Yuxuan,Liao, Chen,Huang, Wenlong,Qian, Hai
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p. 703 - 711
(2018/01/03)
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- Improving metabolic stability with deuterium: The discovery of HWL-066, a potent and long-acting free fatty acid receptor 1 agonists
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The free fatty acid receptor 1 (FFA1) is a potential target due to its function in enhancing of glucose-stimulated insulin secretion. The FFA1 agonist GW9508 has great potential for the treatment of type 2 diabetes mellitus, but it has been suffering from high plasma clearance probably because the phenylpropanoic acid is vulnerable to β-oxidation. To identify orally available analog without influence on the unique pharmacological mechanism of GW9508, we tried to interdict the metabolically labile group by incorporating two deuterium atoms at the α-position of phenylpropionic acid affording compound 4 (HWL-066). As expected, HWL-066 revealed a lower clearance (CL?=?0.23?L?1?hr?1?kg?1), higher maximum concentration (Cmax?=?5907.47?μg/L), and longer half-life (T1/2?=?3.50?hr), resulting in a 2.8-fold higher exposure than GW9508. Moreover, the glucose-lowering effect of HWL-066 was far better than that of GW9508 and comparable with TAK-875. Different from glibenclamide, no side-effect of hypoglycemia was observed in mice after oral administrating HWL-066 (80?mg/kg).
- Liu, Chunxia,Li, Zheng,Shi, Wei,Li, Huilan,Wang, Nasi,Dai, Yuxuan,Liao, Chen,Huang, Wenlong,Qian, Hai
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p. 1547 - 1554
(2018/07/31)
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- NOVEL PHENYL PROPIONIC ACID DERIVATIVES AND USES THEREOF
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The present invention relates to the compounds according to Formula (I), the racemates, enantiomers, diastereomers thereof or pharmaceutical acceptable salts thereof, or pharmaceutical compositions comprising these, for the treatment or prevention of meta
- -
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Paragraph 129-133
(2018/07/05)
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- Novel deuterated phenylpropionic acid derivative, preparation method thereof, and use of derivative as medicine
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The invention relates to a novel deuterated phenylpropionic acid derivative represented by general formula (I), a preparation method thereof, and a use of a medicinal composition containing the derivative as a medicine for treating diabetes and metabolic syndrome. The deuterated phenylpropionic acid derivative has excellent in vivo blood sugar lowering activity, and can be used for preparing medicines for preventing or treating diabetes.
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-
Paragraph 0105; 0106
(2017/10/07)
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- ANTIDIABETIC BICYCLIC COMPOUNDS
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Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are agonists of G-protein coupled receptor 40 (GPR40) and may be useful in the treatment, prevention and suppression of diseases mediated by the G-protein-coupled receptor 40. The compounds of the present invention may be useful in the treatment of Type 2 diabetes mellitus, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia.
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Page/Page column 70
(2016/04/26)
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- Synthesis of 5-arylidene-2,2-dimethyl-1,3-dioxane-4,6-diones and coumarin-3-carboxylic acids via reaction of nitrones and Meldrum's acid
-
A variety of nitrones have been synthesized and reacted with Meldrum's acid without the aid of any catalysts. Selectively, 5- arylidene-2,2-dimethyl-1,3- dioxane-4,6-diones have been obtained with excellent yields under environmentally benign reaction conditions. Whereas, nitrone of salisylaldehydes with Meldrum's acid afford cyclized products i.e. coumarin-3- carboxylic acids.
- Kumar, Dhruva,Suresh,Sandhu, Jagir S.
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p. 1157 - 1160
(2013/09/24)
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- COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF CANCER
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New uses for phenylketone carboxylate compounds and substituted aromatic compounds of Formula I, Formula I.1, Formula I.2, Formula IA, Formula IB, Formula IC and Formula II and their pharmaceutical acceptable salts for the treatment of cancer. The use of
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Page/Page column 39-40
(2012/08/07)
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- AMG 837: A potent, orally bioavailable GPR40 agonist
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The discovery that certain long chain fatty acids potentiate glucose stimulated insulin secretion through the previously orphan receptor GPR40 sparked interest in GPR40 agonists as potential antidiabetic agents. Optimization of a series of β-substituted p
- Houze, Jonathan B.,Zhu, Liusheng,Sun, Ying,Akerman, Michelle,Qiu, Wei,Zhang, Alex J.,Sharma, Rajiv,Schmitt, Michael,Wang, Yingcai,Liu, Jiwen,Liu, Jinqian,Medina, Julio C.,Reagan, Jeff D.,Luo, Jian,Tonn, George,Zhang, Jane,Lu, Jenny Ying-Lin,Chen, Michael,Lopez, Edwin,Nguyen, Kathy,Yang, Li,Tang, Liang,Tian, Hui,Shuttleworth, Steven J.,Lin, Daniel C.-H.
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supporting information; experimental part
p. 1267 - 1270
(2012/03/26)
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- AGONISTS OF GPR40
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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.
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Page/Page column 151-152
(2012/02/05)
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- Discovery and preliminary SAR of 5-arylidene-2,2-dimethyl-1,3-dioxane-4,6- diones as platelet aggregation inhibitors
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We herein document the discovery of 5-arylidene-2,2-dimethyl-1,3-dioxane-4, 6-diones as a novel family of platelet aggregation inhibitors. The preliminary optimization study enabled us to establish the most salient features of the structure-activity relat
- El Maatougui, Abdelaziz,Azuaje, Jhonny,Coelho, Alberto,Yaziji, Vicente,Carbajales, Carlos,Sotelo, Eddy,Lopez, Carmen,Cano, Ernesto,Yanez, Matilde
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p. 551 - 554,4
(2020/08/31)
-
- Development of a scalable synthesis of a GPR40 receptor agonist
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Early process development and salt selection for AMG 837, a novel GPR40 receptor agonist, is described. The synthetic route to AMG 837 involved the convergent synthesis and coupling of two key fragments, (S)-3-(4-hydroxyphenyl) hex-4-ynoic acid (1) and 3-
- Walker, Shawn D.,Borths, Christopher J.,Divirgilio, Evan,Huang, Liang,Liu, Pingli,Morrison, Henry,Sugi, Kiyoshi,Tanaka, Masahide,Woo, Jacqueline C. S.,Faul, Margaret M.
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experimental part
p. 570 - 580
(2011/12/04)
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- Novel Spiropiperidine Compounds
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A compound of the formula: or a pharmaceutically acceptable salt thereof as well as a pharmaceutical composition, and a method for treating diabetes.
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Page/Page column 9
(2011/05/03)
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- Nickel nanoparticles catalyzed chemoselective Knoevenagel condensation of Meldrum's acid and tandem enol lactonizations via cascade cyclization sequence
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A novel protocol has been reported wherein, polyethylene glycol (PEG) stabilized nickel nanoparticles have been used as catalyst for chemoselective Knoevenagel condensation of aromatic aldehydes and Meldrum's acid to give 5-arylidene Meldrum's acid which underwent tandem enol lactonization by Michael addition/cyclization sequence with active methylene compounds in the presence of Ni nanoparticles to give corresponding enol lactone derivatives.
- Khurana, Jitender M.,Vij, Kanika
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experimental part
p. 3666 - 3669
(2011/07/29)
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- PPAR AGONIST COMPOUNDS, PREPARATION AND USES
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The present invention relates to novel PPAR agonist compounds as well as pharmaceutical compositions containing them. The compounds according to the invention are of quite particular therapeutic interest, notably for treating diabetes and/or dyslipidemias, as well as for preventing cardiovascular pathologies.
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Page/Page column 22
(2011/08/22)
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- Facile Knoevenagel and domino Knoevenagel/Michael reactions using gel-entrapped base catalysts
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An efficient method for Knoevenagel condensation of arenecarbaldehydes with active methylene compounds such as barbituric acid and Meldrum's acid in the presence of gel-entrapped base catalysts is reported. The method has been extended to the one-pot synthesis of arylmethylene-bis[3-hydroxycyclohex-2-en-1- one] derivatives from dimedone (=5,5-dimethylcyclohexane-1,3-dione) and arenecarbaldehydes by using domino Knoevenagel/Michael reaction sequence. Copyright
- Shinde, Shital,Rashinkar, Gajanan,Kumbhar, Arjun,Kamble, Santosh,Salunkhe, Rajashri
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experimental part
p. 1943 - 1951
(2012/01/04)
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- 3-Substituted 3-(4-aryloxyaryl)-propanoic acids as GPR40 agonists
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The design, synthesis, and structure-activity relationship (SAR) for a series of β-substituted 3-(4-aryloxyaryl)propanoic acid GPR40 agonists is described. Systematic replacement of the pendant aryloxy group led to identification of potent GPR40 agonists. In order to identify candidates suitable for in vivo validation of the target, serum shifted potency and pharmacokinetic properties were determined for several compounds. Finally, further profiling of compound 7 is presented, including demonstration of enhanced glucose tolerance in an in vivo mouse model.
- Walsh, Shawn P.,Severino, Alexandra,Zhou, Changyou,He, Jiafang,Liang, Gui-Bai,Tan, Carina P.,Cao, Jin,Eiermann, George J.,Xu, Ling,Salituro, Gino,Howard, Andrew D.,Mills, Sander G.,Yang, Lihu
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scheme or table
p. 3390 - 3394
(2011/06/24)
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- Synthesis and biological evaluation of arylidene analogues of Meldrum's acid as a new class of antimalarial and antioxidant agents
-
A series of arylidene analogues of Meldrum's acid were synthesized and evaluated for in vitro antimalarial and antioxidant activities for the first time. The influence of various physico-chemical parameters such as dielectric constant (), donor number (DN
- Sandhu, Harmeet S.,Sapra, Sameer,Gupta, Mukesh,Nepali, Kunal,Gautam, Raju,Yadav, Sunil,Kumar, Raj,Jachak, Sanjay M.,Chugh, Manoj,Gupta, Manish K.,Suri, Om P.,Dhar
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experimental part
p. 5626 - 5633
(2010/09/11)
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- Knoevenagel condensation of aldehydes with Meldrum's acid in ionic liquids
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The Knoevenagel condensation of Meldrum's acid with aromatic aldehydes proceeded efficiently in the recyclable ionic liquid [bmim]BF4 at room temperature in the presence of catalytic amounts of piperidine.
- Tahmassebi, Daryoush,Wilson, Levi J. A.,Kieser, Jerod M.
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experimental part
p. 2605 - 2613
(2009/12/04)
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- SPIRO COMPOUNDS AND PHARMACEUTICAL USE THEREOF
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The Spiro compound represented by the following general formula [Ia], its pharmaceutically acceptable salt or a solvate thereof
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Page/Page column 37
(2009/07/17)
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- SUBSTITUTED BIPHENYL PHENOXY-, THIOPHENYL- AND AMINOPHENYLPROPANOIC ACID GPR40 MODULATORS
-
The present invention provides compounds useful, for example, for treating metabolic disorders in a subject. Such compounds have the general formula (I) where the definitions of the variables are provided herein. The present invention also provides compositions that include, and methods for using, the compounds in preparing medicaments and for treating metabolic disorders such as, for example, type II diabetes.
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Page/Page column 100
(2008/12/08)
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- Conformationally constrained 3-(4-hydroxy-phenyl)-substituted-propanoic acids useful for treating metabolic disorders
-
The present invention provides compounds useful, for example, for treating metabolic disorders in a subject. Such compounds have the general formula I: where the definitions of the variables Q, L1, L2, M, X, L3, and A are provided herein. The present invention also provides compositions that include, and methods for using, the compounds in preparing medicaments and for treating metabolic disorders such as, for example, type II diabetes.
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Page/Page column 34
(2008/06/13)
-
- Compounds, pharmaceutical compositions and methods for use in treating metabolic disorders
-
The present invention provides compounds useful, for example, for modulating insulin levels in a subject and that have the general formula [in-line-formulae]Q-L1-P-L2-M-X-L3-A [/in-line-formulae] wherein the definitions of
- -
-
Page/Page column Figure 1; 22
(2010/02/15)
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- Ionic liquid-mediated knoevenagel condensation of Meldrum's acid and aldehydes
-
A simple, efficient, and green protocol for Knoevenagel condensation of Meldrum's acid and aldehydes in ionic liquid at room temperature without any catalyst is described. The reaction has been performed in different ionic liquids. The enhancement in the
- Darvatkar, Nitin B.,Deorukhkar, Amol R.,Bhilare, Sachin V.,Salunkhe, Manikrao M.
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p. 3043 - 3051
(2007/10/03)
-
- Compounds, pharmaceutical compositions and methods for their use in treating metabolic disorders
-
The present invention provides compounds useful, for example, for modulating insulin levels in a subject, having the general formula I: wherein Q is an optionally substituted phenyl; L is a bond or O; P is a benzene or an optionally substituted thiazole r
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Page/Page column 16
(2008/06/13)
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- Organic reactions in ionic liquids: Ionic liquids ethylammonium nitrate promoted Knoevenagel condensation of aromatic aldehydes with active methylene compounds
-
The Knoevenagel condensation of aromatic aldehydes with active methylene compounds proceeded efficiently in a reusable ionic liquid, ethylammonium nitrate, at room temperature in the absence of any catalyst with high yields.
- Hu, Yi,Chen, Jue,Le, Zhang-Gao,Zheng, Qin-Guo
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p. 739 - 744
(2007/10/03)
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- Organic reactions in ionic liquids: Ionic liquid ethylammonium nitrate-promoted knoevenagel condensation of meldrum's acid with aromatic aldehydes
-
The Knoevenagel condensation of Meldrum's acid with aromatic aldehydes proceeded efficiently in a reusable ionic liquid, ethylammonium nitrate, at room temperature in the absence of any catalyst with high yields. Copyright Taylor & Francis, Inc.
- Hu, Yi,Wei, Ping,Huang, He,Le, Zhang-Gao,Chen, Zhen-Chu
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p. 2955 - 2960
(2007/10/03)
-
- One Pot Synthesis of Monoalkylated and Mixed, Dialkylated Meldrum's Acid Derivatives
-
A simple one pot method, involving sequential Knoevenagel condensation of Meldrum's acid with aromatic aldehydes, conjugate reduction of ylidene Meldrum's acid using sodium borohydride followed by alkylation, to prepare mixed dialkylated derivatives of Meldrum's acid is described.
- Desai, Uday V.,Pore,Mane,Solabannavar,Wadgaonkar
-
-
- Solvent-free Knoevenagel condensations and Michael additions in the solid state and in the melt with quantitative yield
-
Numerous Knoevenagel condensations of solid or liquid aromatic aldehydes are performed with four barbituric acids, Meldrum's acid, dimedone, cyanoacetamide, malodinitrile and methyl cyanoacetate in stoichiometric mixtures of the solids or of stoichiometri
- Kaupp, Gerd,Naimi-Jamal, M. Reza,Schmeyers, Jens
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p. 3753 - 3760
(2007/10/03)
-
- Knoevenagel condensation of aldehydes with cyclic active methylene compounds in water
-
A new route of Knoevenagel condensation of aromatic aldehydes with Meldrum's acid, barbituric acid and dimedone in the presence of cetyltrimethyl ammonium bromide at room temperature in water is described.
- Ren, Zhongjiao,Cao, Weiguo,Tong, Weiqi,Jing, Xiuping
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p. 1947 - 1952
(2007/10/03)
-
- Kinetic studies of condensation of aromatic aldehydes with Meldrum's acid
-
The condensation reaction of Meldrum's acid with aromatic aldehydes in the presence of a catalyst has been investigated spectrophotometrically at 25-50 °C. The reaction follows overall second order kinetics, first order in each of the reactants. Electron-
- Medien
-
p. 1320 - 1326
(2007/10/03)
-
- Clean synthesis in water. Part 2: Uncatalysed condensation reaction of Meldrum's acid and aldehydes
-
The environment-friendly condensation of Meldrum's acid and aromatic, heteroaromatic and hindered aliphatic aldehydes is performed carrying out the reaction in water at 75°C for 2 h, avoiding the addition of any catalyst.
- Bigi, Franca,Carloni, Silvia,Ferrari, Leonetto,Maggi, Raimondo,Mazzacani, Alessandro,Sartori, Giovanni
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p. 5203 - 5205
(2007/10/03)
-
- Condensation of aromatic aldehydes with acidic methylene compounds without catalyst
-
The condensation of aromatic aldehyde with isopropylidene malonate or 5,5-dimethyl-1,3-cyclohexanedione is carried out in DMF as solvent without catalyst.
- Shi, Daqing,Wang, Yucheng,Lu, Zaisheng,Dai, Guiyuan
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p. 713 - 726
(2007/10/03)
-