- Tunable Electrosynthesis of Anthranilic Acid Derivatives via a C-C Bond Cleavage of Isatins
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A facile and direct electrocatalytic C-C bond cleavage/functionalization reaction of isatins was developed. With isatins as the amino-attached C1 sources, a variety of aminobenzoates, and aminobenzamides were synthesized in moderate to good yields under mild conditions.
- Qian, Peng,Liu, Jiaojiao,Zhang, Yan,Wang, Zhiyong
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p. 16008 - 16015
(2021/07/31)
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- COMBINATION THERAPY FOR TREATING MPS1
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The application is directed to compounds of formula (I) and their salts and solvates, wherein B, R1, R2, R3, R3', R4, R4', and R5 are as set forth in the specification, as well as to methods for their preparation, pharmaceutical compositions comprising the same, and use thereof for the treatment and/or prevention of, e.g., MPS1, optionally in combination with α-L-iduronidase or an analog or variant thereof, e.g., laronidase.
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Paragraph 0603; 0611-0613
(2021/08/14)
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- Oxidative ring-opening of isatins for the synthesis of 2-aminobenzamides and 2-aminobenzoates
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An efficient and practical isatin-based oxidative domino protocol has been developed for the facile synthesis of 2-aminobenzamides and 2-aminobenzoates. The robust nature of this reaction system is reflected by accessible starting materials, room temperature and high-yield gram-scale synthesis.
- Wang, Yu-Wei,Zheng, Lei,Jia, Feng-Cheng,Chen, Yun-Feng,Wu, An-Xin
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p. 1497 - 1503
(2019/02/13)
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- Trash to treasure: Eco-friendly and practical synthesis of amides by nitriles hydrolysis in WepPA
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The hydration of nitriles to amides in a water extract of pomelo peel ash (WEPPA) was realized with moderate to excellent yields without using external transition metals, bases or organic solvents. This reaction features a broad substrate scope, wide functional group tolerance, prominent chemoselectivity, and good reusability. Notably, a magnification experiment in this bio-based solvent at 100 mmol further demonstrated its practicability.
- Sun, Yajun,Jin, Weiwei,Liu, Chenjiang
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supporting information
(2019/11/11)
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- POLY-ADP RIBOSE POLYMERASE (PARP) INHIBITORS
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The present invention is related to a pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a compound represented by the following structural formula: The present invention is also related a method of treating a subject with a disease which can be ameliorated by inhibition of poly(ADP-ribose)polymerase (PARP). The definitions of the variables are provided herein.
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Page/Page column 51; 52
(2018/07/29)
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- Anthranilamide-based 2-phenylcyclopropane-1-carboxamides, 1,1'-biphenyl-4-carboxamides and 1,1'-biphenyl-2-carboxamides: Synthesis biological evaluation and mechanism of action
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Several anthranilamide-based 2-phenylcyclopropane-1-carboxamides 13a-f, 1,1’-biphenyl-4-carboxamides 14a-f and 1,1’-biphenyl-2-carboxamides 17a-f were obtained by a multistep procedure starting from the (1S,2S)-2-phenylcyclopropane-1-carbonyl chloride 11, the 1,1'-biphenyl-4-carbonyl chloride 12 or the 1,1'-biphenyl-2-carbonyl chloride 16 with the appropriate anthranilamide derivative 10a-f. Derivatives 13a-f, 14a-f and 17a-f showed antiproliferative activity against human leukemia K562?cells. Among these derivatives 13b, 14b and 17b exerted a particular cytotoxic effect on tumor cells. Derivative 17b showed a better antitumoral effect on K562?cells than 13b and 14b. Analyses performed to explore 17b mode of action revealed that it induced an arrest in G2/M phase of cell cycle which was consequent to DNA lesions as demonstrated by the increase in phospho-ATM and γH2AX, two known markers of DNA repair response system. The effect of 17b was also related to ROS generation, activation of JNK and induction of caspase-3 dependent apoptosis.
- Raffa, Demetrio,Plescia, Fabiana,Maggio, Benedetta,Raimondi, Maria Valeria,D'Anneo, Antonella,Lauricella, Marianna,Daidone, Giuseppe
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p. 262 - 273
(2017/04/03)
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- On the Synthesis and Reactivity of 2,3-Dihydropyrrolo[1,2- a ]quinazolin-5(1 H)-ones
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An improved, scalable synthetic route to the quinazolinone natural product 2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-one is reported. The applicability of this method to analogue synthesis and the synthesis of related natural products is explored. Finally, reactivity of the scaffold to a variety of electrophilic reagents, generating products stereoselectively, is reported.
- Sutherell, Charlotte L.,Ley, Steven V.
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supporting information
p. 135 - 144
(2016/12/24)
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- One-Pot Cascade Synthesis of Quinazolin-4(3H)-ones via Nickel-Catalyzed Dehydrogenative Coupling of o-Aminobenzamides with Alcohols
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In this paper, we report a general, efficient, and environmentally benign method for the one-pot cascade synthesis of quinazolin-4(3H)-ones via acceptorless dehydrogenative coupling of o-aminobenzamide with alcohols catalyzed by a simple Ni(II) catalyst, [Ni(MeTAA)], featuring a tetraaza macrocyclic ligand (tetramethyltetraaza[14]annulene (MeTAA)). A wide variety of substituted quinazolin-4(3H)-ones were synthesized in high yields starting from readily available benzyl alcohols and o-aminobenzamides. Several controlled reactions along with deuterium labeling studies were carried out to establish the acceptorless dehydrogenative nature of the reactions.
- Parua, Seuli,Das, Siuli,Sikari, Rina,Sinha, Suman,Paul, Nanda D.
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p. 7165 - 7175
(2017/07/26)
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- Structure-activity relationships of 2-arylquinazolin-4-ones as highly selective and potent inhibitors of the tankyrases
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Tankyrases (TNKSs), members of the PARP (Poly(ADP-ribose)polymerases) superfamily of enzymes, have gained interest as therapeutic drug targets, especially as they are involved in the regulation of Wnt signalling. A series of 2-arylquinazolin-4-ones with varying substituents at the 8-position was synthesised. An 8-methyl group (compared to 8-H, 8-OMe, 8-OH), together with a 4′-hydrophobic or electron-withdrawing group, provided the most potency and selectivity towards TNKSs. Co-crystal structures of selected compounds with TNKS-2 revealed that the protein around the 8-position is more hydrophobic in TNKS-2 compared to PARP-1/2, rationalising the selectivity. The NAD+-binding site contains a hydrophobic cavity which accommodates the 2-aryl group; in TNKS-2, this has a tunnel to the exterior but the cavity is closed in PARP-1. 8-Methyl-2-(4-trifluoromethylphenyl)quinazolin-4-one was identified as a potent and selective inhibitor of TNKSs and Wnt signalling. This compound and analogues could serve as molecular probes to study proliferative signalling and for development of inhibitors of TNKSs as drugs.
- Nathubhai, Amit,Haikarainen, Teemu,Hayward, Penelope C.,Mu?oz-Descalzo, Silvia,Thompson, Andrew S.,Lloyd, Matthew D.,Lehti?, Lari,Threadgill, Michael D.
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supporting information
p. 316 - 327
(2016/05/19)
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- Synthesis and Nematicidal Activities of 1,2,3-Benzotriazin-4-one Derivatives against Meloidogyne incognita
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A series of novel 1,2,3-benzotriazin-4-one derivatives were synthesized by the reaction of 3-bromoalkyl-1,2,3-benzotriazin-4-ones with potassium salt of 2-cyanoimino-4-oxothiazolidine in the presence of potassium iodide. Nematicidal assays in vivo showed that some of them exhibited good control efficacy against the cucumber root-knot nematode disease caused by Meloidogyne incognita, up to 100% at the concentration of 10.0 mg L-1, which indicated that 1,2,3-benzotriazin-4-one derivatives might be potential for novel promising nematicides. The nematicidal activity was influenced by the combination of substituent type, substituted position, and linker length in the molecule. The inhibition rate data at the concentrations of 5.0 and 1.0 mg L-1 for the compounds with high inhibitory activities were also provided. When tested in vitro, none of them showed direct inhibition against M. incognita. The investigation of a significant difference between in vivo and in vitro data is in progress.
- Wang, Gaolei,Chen, Xiulei,Deng, Yayun,Li, Zhong,Xu, Xiaoyong
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p. 6883 - 6889
(2015/08/18)
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- SUBSTITUTED 2- AMIDOQUINAZOL-4-ONES AS MATRIX METALLOPROTEINASE-13 INHIBITORS
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The present invention provides a novel amide derivative having a matrix metalloproteinase inhibitory activity, and useful as a pharmaceutical agent, which is a compound represented by the formula (I) wherein ring A is an optionally substituted, nitrogen containing heterocycle, ring B is an optionally substituted monocyclic homocycle or an optionally substituted monocyclic heterocycle, Z is N or NR1 (R1 is a hydrogen atom or an optionally substituted hydrocarbon group), is a single bond or a double bond, R2 is a hydrogen atom or an optionally substituted hydrocarbon group, X is an optionally substituted spacer having 1 to 6 atoms, ring C is (1) an optionally substituted homocycle or (2) an optionally substituted heterocycle other than a ring represented by (II) (X′ is S, O, SO, or CH2), and at least one of ring B and ring C has substituent(s), provided that N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]2 hydroxypropyl}5,6 dimethyl 4 oxo 1,4 dihydrothieno[2,3-d]pyrimidine-2-carboxamide is excluded, or a salt thereof.
- -
-
Paragraph 1532
(2015/12/23)
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- Synthesis, antiproliferative activity and possible mechanism of action of novel 2-acetamidobenzamides bearing the 2-phenoxy functionality
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Several new 2-(2-phenoxyacetamido)benzamides 17a-v, 21 and 22 were synthesized by stirring in pyridine the acid chlorides 16a-e and the appropriate5-R-4-R1-2-aminobenzamide 15a-e and initially evaluated in vitro for antiproliferative activity against the K562 (human chronic myelogenous leukemia) cell line. Some of synthesized compounds were evaluated for their in vitro antiproliferative activity against the full NCI tumor cell line panel derived from nine clinically isolated cancer types (leukemia, non-small cell lung, colon, CNS, melanoma, ovarian, renal, prostate and breast). The most active compounds caused an arrest of K562 cells in the G0-G1 phase of cell cycle and induction of apoptosis, which was mediated by caspase activation.
- Raffa, Demetrio,Maggio, Benedetta,Plescia, Fabiana,Cascioferro, Stella,Raimondi, Maria Valeria,Cancemi, Gabriella,D'Anneo, Antonella,Lauricella, Marianna,Cusimano, Maria Grazia,Bai, Ruoli,Hamel, Ernest,Daidone, Giuseppe
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p. 6305 - 6316
(2015/10/05)
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- 2-Cinnamamido, 2-(3-phenylpropiolamido), and 2-(3-phenylpropanamido) benzamides: Synthesis, antiproliferativeactivity, and mechanism of action
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Several new benzamides 4a-q were synthesized by stirring in pyridine the acid chlorides 3a-q with the appropriate anthranilamide derivatives 2a-g. Some of the synthesized compounds were evaluated for their in vitro antiproliferative activity against a panel of 5 human cell lines (K562 human chronic myelogenous leukemia cells, MCF-7 breast cancer cells, HTC-116 and HT26 colon cancer cells and NCI H460 non-small cell lung cancer cells).
- Raffa, Demetrio,Maggio, Benedetta,Raimondi, Maria Valeria,Cusimano, Maria Grazia,Amico, Giandomenico,Carollo, Anna,Conaldi, Pier Giulio,Bai, Ruoli,Hamel, Ernest,Daidone, Giuseppe
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p. 427 - 435
(2013/10/01)
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- Direct one-pot synthesis of luotonin F and analogues via rational logical design
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An efficient one-pot synthetic protocol has been proposed for the synthesis of luntonin F from easily available starting materials. Through a rational logical design, multifundamental reactions (iodination, Kornblum oxidation, and annulation) were assembled in one-pot. The developed approach can efficiently synthesize luntonin F and a diversity of analogues.
- Zhu, Yan-Ping,Fei, Zhuan,Liu, Mei-Cai,Jia, Feng-Cheng,Wu, An-Xin
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supporting information
p. 378 - 381
(2013/03/13)
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- Synthesis, antiproliferative activity, and mechanism of action of a series of 2-{[(2E)-3-phenylprop-2-enoyl]amino}benzamides
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Several new 2-{[(2E)-3-phenylprop-2-enoyl]amino}benzamides 12a-s and 17t-v were synthesized by stirring in pyridine the (E)-3-(2-R1-3-R2-4-R3-phenyl) acrylic acid chlorides 11c-k and 11t-v with the appropriate anthranilamide derivatives 10a-c or the 5-iodoanthranilic acid 13. Some of the synthesized compounds were evaluated for their in vitro antiproliferative activity against the full NCI tumor cell line panel derived from nine clinically isolated cancer types (leukemia, non-small cell lung, colon, CNS, melanoma, ovarian, renal, prostate and breast). COMPARE analysis, effects on tubulin polymerization in cells and with purified tubulin, and effects on cell cycle distribution for 17t, the most active of the series, indicate that these new antiproliferative compounds act as antitubulin agents.
- Raffa, Demetrio,Maggio, Benedetta,Plescia, Fabiana,Cascioferro, Stella,Plescia, Salvatore,Raimondi, Maria Valeria,Daidone, Giuseppe,Tolomeo, Manlio,Grimaudo, Stefania,Di Cristina, Antonietta,Pipitone, Rosaria Maria,Bai, Ruoli,Hamel, Ernest
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supporting information; experimental part
p. 2786 - 2796
(2011/07/08)
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- Direct catalytic asymmetric synthesis of cyclic aminals from aldehydes
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A highly enantioselective Bronsted acid catalyzed direct synthesis of cyclic aminals from aldehydes has been developed. The methodology has been applied to the first asymmetric synthesis of several antihypertensive aminal drugs including (R)-Thiabutazide. Copyright
- Cheng, Xu,Vellalath, Sreekumar,Goddard, Richard,List, Benjamin
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supporting information; experimental part
p. 15786 - 15787
(2009/05/15)
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- HETEROCYCLIC AMIDE COMPOUND AND USE THEREOF
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The present invention provides a novel amide compound represented by the following formula, which has a matrix metalloproteinase inhibitory activity and is useful as a pharmaceutical agent. wherein each symbol is as defined in the specification.
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Page/Page column 130
(2008/12/07)
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- Discovery of quinazolines as a novel structural class of potent inhibitors of NF-κB activation
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We disclose here a new structural class of low-molecular-weight inhibitors of NF-κB activation that were designed and synthesized by starting from quinazoline derivative 6a. Structure-activity relationship (SAR) studies based on 6a elucidated the structural requirements essential for the inhibitory activity toward NF-κB transcriptional activation, and led to the identification of the 6-amino-4-phenethylaminoquinazoline skeleton as the basic framework. In this series of compounds, 11q, containing the 4-phenoxyphenethyl moiety at the C(4)-position, showed strong inhibitory effects on both NF-κB transcriptional activation and TNF-α production. Furthermore, 11q exhibited an anti-inflammatory effect on carrageenin-induced paw edema in rats.
- Tobe, Masanori,Isobe, Yoshiaki,Tomizawa, Hideyuki,Nagasaki, Takahiro,Takahashi, Hirotada,Fukazawa, Tominaga,Hayashi, Hideya
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p. 383 - 391
(2007/10/03)
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- Method for inhibiting neoplastic cells and related conditions by exposure to 4-aminoquinazoline derivatives
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A method for inhibiting neoplastic cells and related conditions by exposing them to 4-aminoquinazoline derivatives.
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- FUSED HETEROCYCLIC COMPOUNDS, HAVING ANGIOTENSIN II ANTAGONISTIC ACTIVITY
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Fused heterocyclic compounds of the formula (I): STR1 wherein R. sup.1 is an optionally substituted hydrocarbon residue which may be attached through a hetero atom; R 2 is a group capable of forming an anion or a group convertible thereinto; R 3 is an optionally substituted aromatic hydrocarbon or heterocyclic residue which contains at least one hetero atom; X is a direct bond or a spacer having an atomic length of two or less between the R 3 group and the ring W group; W is an optionally substituted aromatic hydrocarbon or heterocyclic residue which contains at least one hereto atom; a,c and d are independently selected from the group consisting of one or two optionally substituted carbon atoms and one or two optionally substituted hetero atoms; b and e are independently selected from the group consisting of one optionally substituted carbon atom and one optionally substituted nitrogen atom wherein one of b or e must be nitrogen; the dotted line is a bond to form one double bond; n is an integer of 1 or 2 and when a, which is an optionally substituted carbon atom, is taken together with R 1, the following group: STR2 may form a ring group; provided that when STR3 is a benzimidazole, thieno[3,4-d] imidazole, or thieno[2,3-d] imidazole ring, at least one of the group: STR4 and R 3 is an optionally substituted heterocyclic residue; and the pharmaceutically acceptable salts thereof, have potent angiotensin II antagonistic activity and antihypertensive activity, thus being useful as therapeutic agents for treating circulatory system diseases such as hypertensive diseases, heart diseases (e.g. hypercardia, heart failure, cardiac infarction, etc.), strokes, cerebral apoplexy, nephritis, etc.
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- 4-aminoquinazoline derivatives
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The compounds of the formula: STR1 wherein R1, Y, A, R4, n, Z, CyB, R3, and m are defined in the specification.
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- 2-aza-2-desamino analogues of 5,8-dideazafolic acid
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2-Aza-2-desamino analogues of 5,8-dideazafolic acid, which analogues have the formula STR1 wherein X is an aryl or heteroaryl moiety; R1 is H, C1 -C4 alkyl, C3 -C4 alkenyl, or C3 -C4/
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- N-amino>benzoyl>-L-glutamic Acid, a Novel A-Ring Analogue of 2-Desamino-5,8-dideazafolic Acid
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N-amino>benzoyl>-L-glutamic acid ("2-aza-2-desamino-5,8-dideazafolic acid", ADDF) was synthesized from 2-amino-5-methylbenzamide via a four-step sequence consisting of diazotization, benzylic bromination, condensation with dimethyl N-(4-aminobenzoyl)-L-glutamate, and ester hydrolysis.ADDF was an inhibitor of recombinant mouse thymidylate synthase; inhibition was competitive with 5,10-methylenetetrahydrofolate as variable substrate (Ki=2.3μM).It was a substrate for murine folypolyglutamate synthetase with kinetic characteristics (Km=28μM) comparable to those of aminopterin, and it inhibited the growth of L1210 cells in culture (IC50=0.052μM).The structural modification of the A-ring embodied in ADDF appears to offer a novel, heterofore unexplored approach to the design of TS inhibitors.
- Rosowsky, Andre,Forsch, Ronald A.,Moran, Richard G.
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p. 2626 - 2630
(2007/10/02)
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- Substituted N-[[2-(aminocarbonyl)phenylamino]thioxomethyl]benzamides
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New substituted N-[[2-(aminocarbonyl)phenylamino]-thioxomethyl]benzamides which are useful as congnition stimulators in mammals.
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- Intramolecular 1,3-Dipolar Cycloadditions. Part 1. A Facile Synthesis of Benzimidazo- and Quinazolinotriazolobenzodiazepines
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The synthesis of hitherto unknown 9H-benzimidazotriazolobenzodiazepines (4, 11a-e and 12a-c) and 9H-quinazolinotriazolobenzodiazepin-11-ones (5 and 18a-g) is reported. 2-(2-Azidoaryl)benzimidazoles (6 and 10a-h) and 2-(2-azidoaryl)quinazolin-4(3H)-ones (7 and 17a-g) react with propargyl bromide to give non-isolable intermediates which undergo an intramolecular 1,3-dipolar cycloaddition to the title compounds.
- Mohiuddin, Ghulam,Reddy, Padala Satyanarayana,Ahmed, Khalil,Ratnam, Chengalvala Venkata
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p. 1839 - 1868
(2007/10/02)
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