- NEW SYNTHESIS OF 1-TRIACONTANOL
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Succinic anhydride and behenic acid have been used to attach C4 and C22 carbon chains on to 2 and 5 positions of thiophene through two alternate acylation sequences.Raney nickel desulphurization to the 2,5-disubstituted thiophene yielded triacontanoic acid esters which on LAH reduction gave 1-triacontanol.
- Bhalerao, U. T.,Rao, Jagadishwar S.,Tilak, B. D.
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Read Online
- NEAR-INFRARED ABSORBING DYE, OPTICAL FILTER, AND IMAGING DEVICE
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A near-infrared absorbing dye includes a compound represented by formula (A). Each of R11 to R14 is independently a hydrogen atom, a halogen atom, a hydroxyl group, or an alkyl, aryl or alaryl group. Each of pairs R11 and R12, R12 and R13, and R13 and R14 may combine with one another to form a monocyclic ring or a polycyclic ring in which from 2 to 4 rings are fused. Each of R15 and R16 is independently an alkyl or alaryl group. R15 and R16 may combine with one another to form a cyclohetero ring having from 5 to 10 members together with the nitrogen atom.
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Paragraph 0192; 0194
(2021/03/13)
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- Visible Light-Driven, Copper-Catalyzed Aerobic Oxidative Cleavage of Cycloalkanones
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A visible light-driven, copper-catalyzed aerobic oxidative cleavage of cycloalkanones has been presented. A variety of cycloalkanones with varying ring sizes and various α-substituents reacted well to give the distal keto acids or dicarboxylic acids with moderate to good yields.
- Xin, Hong,Duan, Xin-Hua,Yang, Mingyu,Zhang, Yiwen,Guo, Li-Na
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p. 8263 - 8273
(2021/06/30)
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- Synthesis, anti-convulsant activity and molecular docking study of novel thiazole pyridazinone hybrid analogues
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Pyridazinone analogues have been known to be potential candidates for anticonvulsant agents. We have identified several pyridazinone-based anticonvulsant agents. As a continuation to our previous research, a series of hybrid pyridazinone-thiazole connected through amide linkage were designed and synthesized. Among these, compound SP-5F demonstrated significant anticonvulsant activity with median effective dose of 24.38 mg/kg (MES) and 88.23 mg/kg (scPTz). Results of GABA estimation showed a marked increase in the GABA level when compared with control. Molecular docking studies at the active site of GABA receptor, further confirmed the GABA modulatory effects of SP-5F.
- Khisal, Subuhi,Mishra, Ravinesh,Partap, Sangh,Siddiqui, Aness Ahmad,Yar, Mohammad Shahar
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- Novel synthetic method for duloxetine intermediate
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The invention provides a novel synthetic method for a duloxetine intermediate (S)-N-methyl-3-hydroxy-3-(2-thienyl)-1-propylamine (a compound 1 as described in the specification). According to the method, thiophene and succinic anhydride are used as raw materials and undergo Friedel-Crafts acylation, esterification, aminolysis, asymmetric hydrogenation, and oxidative degradation so as to obtain theduloxetine intermediate (the compound 1).
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Paragraph 0008; 0017
(2018/09/08)
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- AGONISTS OF THE CHEMOKINE RECEPTOR CXCR3
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The present invention relates to agonists of the chemokine receptor CXCR3, methods of their synthesis and uses thereof.
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Page/Page column 19
(2017/05/02)
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- Design, Synthesis, and Pharmacological Screening of Pyridazinone Hybrids as Anticonvulsant Agents
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A series of new hybrid benzimidazole containing pyridazinones derivatives were designed and synthesized in accordance with the pharmacophoric requirements essential for the anticonvulsant activity. The synthesized compounds were evaluated for anticonvulsant activity on mice by the gold standard maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ)-induced seizure models. Among the compounds tested, SS-4F showed significant anticonvulsant activity in both the screens with ED50 values of 25.10 and 85.33 mg/kg in the MES and scPTZ screens, respectively. Compound SS-4F emerged as safer and effective anticonvulsant due to its several-fold higher protective indices. Further, the gamma-aminobutyric acid (GABA) estimation result showed a marked increase in the GABA level (1.7-fold) as compared to the control, which was further confirmed by good binding properties with the GABAA receptor.
- Partap, Sangh,Yar, Mohammad Shahar,Hassan, Md. Zaheen,Akhtar, Md. Jawaid,Siddiqui, Anees A.
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- Discovery and Characterization of Biased Allosteric Agonists of the Chemokine Receptor CXCR3
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In this work we report a design, synthesis, and detailed functional characterization of unique strongly biased allosteric agonists of CXCR3 that contain tetrahydroisoquinoline carboxamide cores. Compound 11 (FAUC1036) is the first strongly biased allosteric agonist of CXCR3 that selectively induces weak chemotaxis and leads to receptor internalization and the β-arrestin 2 recruitment with potency comparable to that of the chemokine CXCL11 without any activation of G proteins. A subtle structural change (addition of a methoxy group, 14 (FAUC1104)) led to a contrasting biased allosteric partial agonist that activated solely G proteins, induced chemotaxis, but failed to induce receptor internalization or β-arrestin 2 recruitment. Concomitant structure-activity relationship studies indicated very steep structure-activity relationships, which steer the ligand bias between the β-arrestin 2 and G protein pathway. Overall, the information presented provides a powerful platform for further development and rational design of strongly biased allosteric agonists of CXCR3.
- Milanos, Lampros,Brox, Regine,Frank, Theresa,Poklukar, Ga?per,Palmisano, Ralf,Waibel, Reiner,Einsiedel, Jürgen,Dürr, Maximilian,Ivanovi?-Burmazovi?, Ivana,Larsen, Olav,Hjort?, Gertrud Malene,Rosenkilde, Mette Marie,Tschammer, Nuska
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p. 2222 - 2243
(2016/03/25)
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- NOVEL TRICYCLIC CALCIUM SENSING RECEPTOR ANTAGONISTS
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Novel tricyclic compounds of Formula (I) and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing osteoporosis and similar conditions. The compounds are effective as calcium sensing receptor antagonists. Pharmaceutical compositions and methods of treatment are also included.
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Page/Page column 100
(2015/07/07)
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- NOVEL TRICYCLIC CALCIUM SENSING RECEPTOR ANTAGONISTS FOR THE TREATMENT OF OSTEOPOROSIS
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Novel tricyclic compounds of the formula (I): and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing osteoporosis and similar conditions. The compounds are effective as calcium sensing receptor antagonists. Pharmaceutical compositions and methods of treatment are also included.
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Page/Page column 98-99
(2015/07/07)
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- Identification of a novel GPR81-selective agonist that suppresses lipolysis in mice without cutaneous flushing
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GPR81, which exhibits a high degree of homology with GPR109a, has been recently identified as a lactate receptor. Similar to GPR109a, the activation of GPR81 by lactate suppresses lipolysis, suggesting that GPR81 may be a potential drug target for treating dyslipidemia. In addition, the fact that GPR81 is expressed only in adipocytes, whereas GPR109a is expressed in various tissues and cells, including Langerhans cells, which are considered responsible for flushing, indicates that targeting GPR81 could lead to the development of antidyslipidemia agents with a reduced risk of this side effect. However, the pharmacological role of GPR81 remains largely unclear, mainly because of the lack of potent and selective surrogate GPR81 agonists suitable for in vivo studies. In the present study, we showed that lactate-induced suppression of lipolysis in explants of white adipose tissue (WAT) depends on the presence of GPR81. We also performed high-throughput screening (HTS) and identified four novel chemical clusters as GPR81 agonists. Chemical optimization of aminothiazole derivatives led to the discovery of a lead compound with improved potency. The compound inhibited lipolysis in differentiated 3T3-L1 adipocytes. Finally, intraperitoneal administration of this compound suppressed lipolysis in mice at doses that did not cause cutaneous flushing. This is the first description of a 50 nM GPR81 selective agonist with in vivo efficacy, without the side effect, i.e., flushing. These results suggest that GPR81 is an attractive drug target for treating dyslipidemia without the risk of flushing.
- Sakurai, Taku,Davenport, Richard,Stafford, Stuart,Grosse, Johannes,Ogawa, Kazumasa,Cameron, Jennifer,Parton, Laura,Sykes, Andy,Mack, Stephen,Bousba, Sarah,Parmar, Alka,Harrison, David,Dickson, Louise,Leveridge, Mathew,Matsui, Junji,Barnes, Matt
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supporting information
p. 1 - 7
(2014/03/21)
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- New combination of pharmacophoric elements of potent σ1 ligands: Design, synthesis and σ receptor affinity of aminoethyl substituted tetrahydrobenzothiophenes
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The aminoethyl substituted tetrahydrobenzothiophenes 4 resulted from combination of the pharmacophoric elements of the potent σ1 ligands 2 and 3. The aminoethyl substituted tetrahydrobenzothiophenes 4 were prepared in an 8-step synthesis starting with thiophene. Whereas the σ1 affinity of the N-benzyl derivative 4a is in the medium nanomolar range (Ki = 49 nM), the analogous N-cyclohexylmethyl derivative 4d exhibits low nanomolar affinity (Ki = 5.0 nM). The reduced σ1 affinity and σ2/σ1 selectivity of tetrahydrobenzothiophenes 4 compared to analogous spirocyclic piperidines 3 is attributed to the increased conformational flexibility of the aminoethyl side chain.
- Harel, Dipak,Schepmann, Dirk,Wünsch, Bernhard
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p. 490 - 497
(2013/10/22)
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- Peculiarities of the behavior of succinyl dichloride in Friedel-Crafts reaction with thiophenes
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The reactions of thiophene, 2-methyl-, and 2-bromothiophene with succinyl dichloride in the presence of AlCl3, TiCl4, and SnCl 4 have been studied. The effect of the acylation conditions, the relative amounts and nature of the Lewis acid on the ratio and yields of the 1,4-di(2-thienyl)-1,4-diones and 4-oxo-4-(2-thienyl)butyric acids formed have been demonstrated. Under the reaction conditions, the formation of 4,4-di(2-thienyl)but-3-enoic acids (the main products in many cases) and also 4,4-di(2-thienyl)-butyrolactones was demonstrated.
- Smirnov,Afanas'Ev,Belen'kii
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experimental part
p. 1199 - 1207
(2011/10/13)
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- COMPOUNDS AND METHODS
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Disclosed are compounds having the formula: wherein X1, X2, X3, R1, R2, R3, R4, Y, A, n and L are as defined herein, and methods of making and using the same.
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Page/Page column 60
(2011/08/04)
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- SYNTHESIS OF SUBSTITUTED TETRAHYDROINDENYL COMPLEXES
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This invention relates to the synthesis of substituted tetrahydroindenyls and the use of the synthesised complexes in the homo- and co-polymerisation of ethylene and alpha-olefins.
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Page/Page column 17-19
(2010/08/04)
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- Synthesis and evaluation of some novel isochroman carboxylic acid derivatives as potential anti-diabetic agents
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A series of novel isochroman mono-carboxylic acid derivatives were synthesized, characterized and evaluated for their ability to inhibit protein tyrosine phosphatase 1B (PTP1B) in vitro in order to use them as potential anti-diabetic agents. Analysis of structure-activity relationships led to the identification of potent compound 4n which inhibited PTP1B with IC50 value of 51.63 ± 0.91 nM. In general, high potency was associated with a dithiolane ring with a spacer of five carbons to the isochroman ring. Compound 4n has been selected for in vivo evaluation as drug candidate for anti-diabetic activity.
- Lakshminarayana,Rajendra Prasad,Gharat, Laxmikant,Thomas, Abraham,Ravikumar,Narayanan, Shridhar,Srinivasan,Gopalan, Balasubramanian
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scheme or table
p. 3147 - 3157
(2009/12/04)
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- Facile synthesis of substituted thiophenes via Pd/C-mediated sonogashira coupling in water
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The first successful Pd/C-mediated Sonogashira coupling of iodothiophene with terminal alkynes in water is described here. Pd/C-CuI-PPh3 was found to be an efficient catalyst system for this coupling reaction. Using this economic and reliable process a variety of acetylenic thiophenes with a wide range of functional groups were prepared in good yields. Synthetic applications and in vitro anticancer properties of some of the compounds synthesized are described.
- Raju, Sirisilla,Kumar, P. Rajender,Mukkanti,Annamalai, Pazhanimuthu,Pal, Manojit
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p. 6185 - 6189
(2012/05/07)
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- OXAZOLIDINONE DERIVATIVES, PROCESS FOR THEIR PREPERATION AND THEIR USE AS ANTIMYCOBACTERIAL AGENTS
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Novel compounds belonging to the class of oxazolidinones possessing potent antimycobacterial properties especially useful in the treatment of acid fast organisms such as Mycobacterium tuberculosis, Mycobacterium avium-intracellular complex, M. fortuitum and M. kansai. The compound and its pharmaceutically acceptable salts thereof act as antibacterial agents. Also disclosed is a method for inhibiting growth of mycobacterial cells a well as a method of treating mycobacterial conditions such as Mycobacterium tuberculoses, drug resistant Mycobacterium tuberculosis, Mycobacterium avium-intracellular complex, M. fortuitum and M. kansai, comprising administering an antimycobacterially effective amount of the said compound and/or pharmaceutically acceptable salts thereof. There is also disclosed a process for the manufacture of the said compound or its pharmaceutically acceptable salts.
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- A combination of Friedel-Crafts and Lawesson reactions to 5-substituted 2,2′-bithiophenes
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γ-Keto esters (2) derivatives of thiophene were obtained from hemisuccinic esters and transformed to the corresponding amides (4). Lawesson's treatment of 2 and 4 gave the corresponding bithiophenes (5) with alkoxy or amino substituents.
- Raposo, M. Manuela M.,Kirsch
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p. 1487 - 1498
(2007/10/03)
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- Syntheses and antiinflammatory activity of some 6-aryl-2,3,4,5-tetrahydro-3-pyridazinones
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6-Aryl-2, 3, 4, 5-tetrahydro-3-pyridazinones (2c-22c) are obtained by dehydrocyclisation of various hydrazides formed by the reaction of appropriate methyl β-aroylpropionate and hydrazine hydrate in the presence of anhydrous sodium acetate. They show promising antiinflammatory activity during their evaluation by carrageenin induced paw edema test in rats.
- Khan,Siddiqui
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p. 614 - 619
(2007/10/03)
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- Synthesis of tri- and tetracyclic heterocycles related to cyclohexa- and cyclohepta[b]thiophenes
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Synthesis of a number of tri- and tetracyclic compounds with a fused thiophene ring starting from spiro[benzo[b]thiophene-6(5H), 1'-cycloalkyl]-4(7H)-one 1(R = H, Me, Et and n = 4, 5) and cyclohepta[b]thiophenone 2 (R1 = H, R2 = Me and R1R2 = -(CH2)4-) is described.
- Sen,Saha,Das
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p. 334 - 338
(2007/10/03)
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- New structures able to prevent the inhibition by hydroxyl radicals of glutamate transport in cultured astrocytes
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4,5,6,7-Tetrahydro-benzothiophen-7-ylamines, 4,5,6,7-tetrahydro- benzothiophen-4-ylamines, and 5,6-dihydro-4H-thieno[2,3-b] thiopyran-4- ylamines were designed, synthesized, and tested as OH radical scavengers. Most of them displayed chemical scavenging properties better than or in the same range as salicylic acid. Moreover, some compounds were able to protect in vitro the astroglial glutamate transporters against inhibitory action of radicals promoted by xanthine/xanthine oxidase. Thus, such compounds might be useful for lowering the large amounts of excitotoxic glutamate liberated during acute CNS diseases: they might protect the glutamate reuptake in astrocytes from the inhibitory action due to radicals co-liberated with glutamate.
- Cauquil-Caubere, Isoline,Kamenka, Jean-Marc
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p. 867 - 877
(2007/10/03)
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- The Stereoselective Synthesis of 2-Alkyl γ-Keto Acid and Heterocyclic Ketomethylene Peptide Isostere Core Units Using Chiral Alkylation by 2-Triflyloxy Esters
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A simple and general protocol for the enentioselective preparation of γ-keto acids and heterocyclic γ-keto acids which have an alkyl group at C-2 is reported.The alkyl group is introduced by chiral alkylation using a scalemic 2-triflyoxy ester.The alkylation takes place with inversion of configuration and is compatible with a variety of alkyl groups.This methodology is thus wellsuited for the preparation of a wide variety of ketomethylene peptide isosteres.
- Hoffman, Robert V.,Kim, Hwa-Ok
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p. 5107 - 5113
(2007/10/02)
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- OMEGA-HETEROAROYL(PROPIONYL OR BUTYRYL)-L-PROLINES
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This disclosure describes novel substituted ω-heteroaroyl(propionyl or butyryl)-L-prolines and the esters and cationic salts thereof which are useful as hypotensive agents in mammals.
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