- N-ALKYL-N-CYANOALKYLBENZAMIDE COMPOUND AND USE THEREOF
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The present invention discloses an N-alkyl-N-cyanoalkylbenzamide compound of General Formula I, an intermediate of General Formula II used to prepare the compound, wherein R1 is selected from halo or C1-C3 alkyl; R2
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Paragraph 0051-0052
(2021/01/25)
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- Exploiting the HSP60/10 chaperonin system as a chemotherapeutic target for colorectal cancer
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Over the past few decades, an increasing variety of molecular chaperones have been investigated for their role in tumorigenesis and as potential chemotherapeutic targets; however, the 60 kDa Heat Shock Protein (HSP60), along with its HSP10 co-chaperone, have received little attention in this regard. In the present study, we investigated two series of our previously developed inhibitors of the bacterial homolog of HSP60/10, called GroEL/ES, for their selective cytotoxicity to cancerous over non-cancerous colorectal cells. We further developed a third “hybrid” series of analogs to identify new candidates with superior properties than the two parent scaffolds. Using a series of well-established HSP60/10 biochemical screens and cell-viability assays, we identified 24 inhibitors (14%) that exhibited > 3-fold selectivity for targeting colorectal cancer over non-cancerous cells. Notably, cell viability EC50 results correlated with the relative expression of HSP60 in the mitochondria, suggesting a potential for this HSP60-targeting chemotherapeutic strategy as emerging evidence indicates that HSP60 is up-regulated in colorectal cancer tumors. Further examination of five lead candidates indicated their ability to inhibit the clonogenicity and migration of colorectal cancer cells. These promising results are the most thorough analysis and first reported instance of HSP60/10 inhibitors being able to selectively target colorectal cancer cells and highlight the potential of the HSP60/10 chaperonin system as a viable chemotherapeutic target.
- Ray, Anne-Marie,Salim, Nilshad,Stevens, Mckayla,Chitre, Siddhi,Abdeen, Sanofar,Washburn, Alex,Sivinski, Jared,O'Hagan, Heather M.,Chapman, Eli,Johnson, Steven M.
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- Rh(iii)-catalyzed diastereoselective cascade annulation of enone-tethered cyclohexadienonesviaC(sp2)-H bond activation
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Herein, we report highly diastereoselective arylative cyclization of enone-tethered cyclohexadienonesviaRh(iii)-catalyzed C-H activation ofN-methoxybenzamides. This reaction proceeds through the formation of a five-membered rhodacycle followed by bis-Michael cascade annulation to access functionalized bicyclic scaffolds with four contiguous stereocenters with a broad substrate scope. These products have excellent functional handles, allowing further synthetic transformation to increase the structural complexity. Furthermore, mechanistic studies of arylative cyclization and a gram-scale experiment are also presented.
- Chegondi, Rambabu,Jadhav, Sandip B.,Maurya, Sundaram,Navaneetha, N.
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supporting information
p. 13598 - 13601
(2021/12/23)
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- PYRAZOLAMIDE COMPOUND HAVING INSECTICIDAL ACTIVITY AND USE THEREOF
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The present invention discloses a pyrazolamide compound of General Formula I having an insecticidal activity and an intermediate of General Formula II used to preparing the compound of General Formula I, wherein R1 is selected from chloro or CN
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Paragraph 0039-0040; 0053-0054
(2020/11/29)
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- PROCESS FOR PREPARATION OF ERIBULIN AND INTERMEDIATES THEREOF
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The present application relate to a process for preparation of 4-methylene tetrahydrofuran compound of formula II, which is useful as an intermediate for the preparation of halichondrin B analogues such as eribulin and its pharmaceutically acceptable salts thereof. The present application also provide crystalline compound of formula III and crystalline compound of formula II.
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Page/Page column 23
(2020/01/31)
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- One-Pot Synthesis of Seven-Membered Heterocyclic Derivatives of Diazepines Involving Copper-Catalyzed Rearrangement Cascade Allyl-Amination
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A novel and efficient method has been proposed for the synthesis of 1,4-benzodiazepine-5-ones from o-nitrobenzoic N-allylamides by using molybdenyl acetylacetonate and copper(II) trifluoromethanesulfonate as catalysts in the presence of triphenylphosphine. This synthesis process involves nitrene formation, C-H bond insertion, C≠C bond rearrangement, and C-N bond formation cascade reactions via copper- and molybdenum-catalyzed mediation. The method features a wide substrate scope and a moderate to high yield (up to 90%), exhibiting the possibility for practical applications.
- Chen, Yuepeng,Liu, Xinglei,Shi, Wei,Zheng, Shilong,Wang, Guangdi,He, Ling
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p. 5146 - 5157
(2020/05/19)
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- Phosphine Sequentially Catalyzed Domino 1,6-Addition/Annulation: Access to Functionalized Chromans and Tetrahydroquinolines with an Ethynyl-Substituted All-Carbon Quaternary Center
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A novel phosphine sequentially catalyzed domino 1, 6-addition/annulation process has been developed using p-quinone methides (p-QMs) and α-substituted allenoates which generates a series of chroman and tetrahydroquinoline derivatives containing an ethynyl-substituted all-carbon quaternary center with up to 97% yield and 20:1 dr. value. In this reaction, allenoates act as C2 synthons.
- Zhu, Yannan,Wang, Dan,Huang, You
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supporting information
p. 908 - 912
(2019/05/16)
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- Heavily Substituted Atropisomeric Diarylamines by Unactivated Smiles Rearrangement of N-Aryl Anthranilamides
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Diarylamines find use as metal ligands and as structural components of drug molecules, and are commonly made by metal-catalyzed C?N coupling. However, the limited tolerance to steric hindrance of these couplings restricts the synthetic availability of more substituted diarylamines. Here we report a remarkable variant of the Smiles rearrangement that employs readily accessible N-aryl anthranilamides as precursors to diarylamines. Conformational predisposition of the anthranilamide starting material brings the aryl rings into proximity and allows the rearrangement to take place despite the absence of electron-withdrawing substituents, and even with sterically encumbered doubly ortho-substituted substrates. Some of the diarylamine products are resolvable into atropisomeric enantiomers, and are the first simple diarylamines to display atropisomerism.
- Costil, Romain,Dale, Harvey J. A.,Fey, Natalie,Whitcombe, George,Matlock, Johnathan V.,Clayden, Jonathan
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supporting information
p. 12533 - 12537
(2017/09/13)
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- TRIAZOLO- AND PYRAZOLOQUINAZOLINE DERIVATIVES AS PDE10A ENZYME INHIBITOR
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The invention relates to compounds of the formula (I) and their use as pharmaceutical ingredients, in particular for the treatment of CNS related diseases.
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Page/Page column 39
(2012/02/02)
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- Tricyclic dihydroquinazolinones as novel 5-HT2C selective and orally efficacious anti-obesity agents
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Agonists of the 5-HT2C receptor have been shown to suppress appetite and reduce body weight in animal models as well as in humans. However, agonism of the related 5-HT2B receptor has been associated with valvular heart disease. Synthesis and biological evaluation of a series of novel and highly selective dihydroquinazolinone-derived 5-HT2C agonists with no detectable agonism of the 5-HT2B receptor is described. Among these, compounds (+)-2a and (+)-3c were identified as potent and highly selective agonists which exhibited weight loss in a rat model upon oral dosing.
- Ahmad, Saleem,Ngu, Khehyong,Miller, Keith J.,Wu, Ginger,Hung, Chen-pin,Malmstrom, Sarah,Zhang, Ge,O'Tanyi, Eva,Keim, William J.,Cullen, Mary Jane,Rohrbach, Kenneth W.,Thomas, Michael,Ung, Thao,Qu, Qinling,Gan, Jinping,Narayanan, Rangaraj,Pelleymounter, Mary Ann,Robl, Jeffrey A.
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scheme or table
p. 1128 - 1133
(2010/06/15)
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- Intermolecular SNAr of the heterocycle-activated nitro and fluoro groups-application in the synthesis of polyazamacrocyclic ligands
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A new class of tetracylic benzimidazole compounds and derivatives thereof. Additionally provided is a synthetic route for the generation of these and related compounds via Intramolecular Aromatic Nucleophilic Substitution (SNAr) of the Benzimid
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Page/Page column 9; 10
(2010/02/14)
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- Ruffling-Induced Chirality: Synthesis, Metalation, and Optical Resolution of Highly Nonplanar, Cyclic, Benzimidazole-Based Ligands
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Expedient five-step syntheses of a cyclic bis(benzimidazole)-based amide 5 and two sterically more hindered analogues 23-24 have been developed. These amides are chiral due to the inherent ruffling of the macrocyclic plane. Racemization of the optical ant
- Fekner, Tomasz,Gallucci, Judith,Chan, Michael K.
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p. 223 - 236
(2007/10/03)
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- Structure-activity relationships of substituted benzothiophene-anthranilamide factor Xa inhibitors
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Compound 1 was identified by high throughput screening as a novel, potent, non-amidine factor Xa inhibitor with good selectivity against thrombin and trypsin. A series of modifications of the three aromatic groups of 1 was investigated. Substitution of chlorine or bromine for fluorine on the aniline ring led to the discovery of subnanomolar factor Xa inhibitors. Positions on the anthranilic acid ring that can accommodate further substitution were also identified.
- Chou, Yuo-Ling,Davey, David D.,Eagen, Keith A.,Griedel, Brian D.,Karanjawala, Rushad,Phillips, Gary B.,Sacchi, Karna L.,Shaw, Kenneth J.,Wu, Shung C.,Lentz, Dao,Liang, Amy M.,Trinh, Lan,Morrissey, Michael M.,Kochanny, Monica J.
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p. 507 - 511
(2007/10/03)
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- Intramolecular Aromatic Nucleophilic Substitution of the Benzimidazole-Activated Nitro Group
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(Equation Presented) A wide range of 2-(2-nitrophenyl)-1H-benzimidazoles undergo high-yielding intramolecular SNAr of nitrite with N-pendant alkoxides under mild conditions (DMF, rt). When this operationally simple process is carried out at ele
- Fekner, Tomasz,Gallucci, Judith,Chan, Michael K.
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p. 4795 - 4798
(2007/10/03)
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- Asymmetric Ni(II)/Cr(II)-mediated coupling reaction: stoichiometric process.
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[reaction: see text] Via an X-ray analysis, the sulfonamide bearing R(1) = i-Pr, R(2) = Me, and R(3) = Me is shown to be a tridentate ligand to a Cr(III) salt. This class of ligands, represented by R(1) = t-Bu, R(2) = 2-naphthyl, and R(3) = Me, is effecti
- Wan, Zhao-Kui,Choi, Hyeong-Wook,Kang, Fu-An,Nakajima, Katsumasa,Demeke, Damtew,Kishi, Yoshito
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p. 4431 - 4434
(2007/10/03)
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- N-aryl(thio)anthranilic acid amide derivatives, their preparation and their use as VEGF receptor tyrosine kinase inhibitors
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Described are compounds of formula (I), wherein W is O or S; X is NR8; Y is CR9R10-(CH2)n wherein R9 and R10 are independently of each other hydrogen or lower alkyl, and n is an integer of
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- A new facile procedure for the preparation of pyrrolo[2,1-c][1,4]benzodiazepines : Synthesis of the antibiotic DC-81 and its thio analogue
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An efficient synthesis of the imine form of the pyrrolo[2,1-c][1,4] benzodiazepine ring system based on a new reductive cyclization procedure is described. The naturally occuring antibiotic DC-81(5c) and its 5-thio analogue (7c) have also been synthesized to illustrate the usefulness of this methodology.
- Kamal, Ahmed,Reddy, B. S. Praveen,Reddy, B. S. Narayan
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p. 2281 - 2284
(2007/10/03)
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- A new route for the synthesis of pyrrolo[2,1-c][1,4]benzodiazepine antibiotics via oxidation of cycle secondary amine
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The synthesis of the imine-containing pyrrolo[2,1-c][1,4]benzodiazepine DNA-binding antitumour antibiotics was achieved by a new method of oxidation of cyclic secondary amines which does not endanger the stereochemical integrity of the C-11a position.
- Kamal,Rao
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p. 385 - 386
(2007/10/03)
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- Synthesis of new indolemethanamines using the Leimgruber-Batcho reaction
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A short and efficient synthesis of the title compounds is reported starting with commercially available cahboxylic acids 1 and 5, respectively. By appropriate modifications in the course of the Leimgruber-Batcho reaction used in the key step quite stable
- Stanetty,Koller
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p. 433 - 437
(2007/10/02)
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- 3-(1H-Tetrazol-5-yl)-4(3H)-quinazolinone Sodium Salt (MDL 427): A New Antiallergic Agent
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Syntheses for 3-(1H-tetrazol-5-yl)-4(3H)-quinazolinone sodium salt monohydrate (9; MDL 427) and the related formamido compound, 2-(formylamino)-N-1H-tetrazol-5-ylbenzamide (10), are described.Both compounds are active in the rat passive cutaneous anaphylaxis and passive peritoneal anaphylaxis tests.A 94:6 equilibrium mixture of 9 and ionized 10, respectively, forms in aqueous buffer systems at a pH-dependent rate.In addition, analogues of 3-(1H-tetrazol-5-yl)-4(3H)-quinazolinone (8) bearing substituents on the benzene ring, substituents at the 2-position, and heteroaryl groups at the 3-position other than tetrazole were prepared.These analogue sets demonstrated that an accessible electrophilic center and an acidic functionality were requirements for good antiallergic activity.
- Peet, Norton P.,Baugh, Larry E.,Sunder, Shyam,Lewis, Jon E.,Matthews, Emily H.,et al.
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p. 2403 - 2409
(2007/10/02)
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- o-Nitroaniline Derivatives. Part 8. Synthesis of Some Unsymmetrical Dimethylquinoxalines: A Long-Standing Problem Resolved
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Reduction of N-acetonyl-4-methyl-2-nitro-N-p-tolylsulphonylaniline, using tin(II) chloride in hydrochloric acid, gives 2,7-dimethylquinoxaline (42percent) together with di-p-tolyl disulphide and toluene-p-thiol. 2,6- and 2,5-Dimethylquinoxalines are similarly obtained from the appropriately substituted nitroanilines; the 2,8-dimethyl isomer, however, is obtained impure and in very low yield.
- Blaikley, David C.W.,Currie, David W,Smith, David M.,Watson, Susan A.,McNab, Hamish
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p. 367 - 369
(2007/10/02)
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- Herbicidal N-haloacetyl-2-methyl-6-substituted methoxymethylanilines
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Compounds of the formula STR1 wherein R1 is alkyl or alkoxy; R2 is alkenyl having 2 to 10 carbon atoms, substituted alkyl of 1 to 10 carbon atoms or substituted alkenyl of 1 to 10 carbon atoms substituted with 1 or 2 hydroxy groups or 1 or 2 alkoxy groups of 1 to 4 carbon atoms or 1 or 2 alkenyloxy groups of 2 to 4 carbon atoms; acyl, and ketal group of the formula STR2 wherein n=2, 3 or 4, R4 is alkyl and R5 is hydrogen or alkyl, an oxime of the formula STR3 wherein R6 is hydrogen or alkyl; R3 is hydrogen or alkyl; X is halo have herbicidal activity.
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- 3-(1H-Tetrazol-5-yl)-4(3H)-quinazolinones
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3-(1H-tetrazol-5-yl)-4(3H)-quinazolinones useful as antiallergic agents are described herein. The compounds are prepared by the reaction of an appropriate 2-amino-N-(1H-tetrazol-5-yl)benzamide with an appropriate ortho ester.
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- Conformational Behaviour of Medium-sized Rings. Part 12. Tri-3-methyltrianthranilide
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The stepwise synthesis of the N,N'-di- and N,N',N''-tri-substituted tri-3-methyltrianthranilides (13)-(19) are described.The amino-acid derivatives (34), (38), and (45), which are the key acyclic precursors in the synthesis of the tri-3-methyltrianthranilides, were all prepared from 2-amino-m-toluic acid (22) and 2-nitro-m-toluoyl chloride as starting materials.Tri-3-methyltrianthranilide derivatives with three equivalent N,N',N''-substituents can exist in either propeller or helical conformations.The N,N',N''-trimethyl derivative (14) adopts enantiomeric helical conformations in solution and the barrier to ring inversion is 26.8 kcal mol-1.The N,N',N''-tribenzyl derivative (19) populates both propeller and helical conformations in solution: these two conformational diastereoisomers have been separated by chromatography and isolated as crystalline compounds.Tri-3-methyltrianthranilide derivatives with two or three non-equivalent N,N',N''-substituents can, in principle, exist in either propeller or three different helical conformations.One of these three helical conformations is specifically populated in deuteriochloroform solution by compounds (13) and (15)-(17).The N,N'-dibenzyl derivative (18) populates the propeller and one helical conformation in solution: two conformational diastereoisomers have been isolated, one as an oil and the other as a crystalline compound.The N,N'-dimethyl-N''-benzyl derivative (15) undergoes spontaneous resolution when it crystallises as a 1:1 adduct from toluene.The N-methyl-N'-benzyl derivative (16) also forms a 1:1 inclusion compound on crystallisation from toluene.Although this derivative exists as only one conformational diastereoisomer of the helical type in deuteriochloroform solution, two different diastereoisomeric conformations undergo equilibration in hexadeuteriodimethyl sulphoxide with a barrier to interconversion of 16.1 kcal mol-1.
- Edge, Simon J.,Ollis, W. David,Stephanatou, Julia Stephanidou,Stoddart, J. Fraser
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p. 1701 - 1714
(2007/10/02)
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