cas 20699-86-9, 5-NITRO-BENZO[B]THIOPHENE-2-CARBOXYLIC ACID METHYL ESTER

Articles about 20699-86-9Total 21 be found

Article title
Article abstract
Author
Journal number and time
Download

Ring closure strategy leads to potent RIPK3 inhibitors
Necroptosis is a form of regulated necrotic cell death that is independent of caspases. Receptor-interacting protein kinase 3 (RIPK3) has been identified as a key regulator for necroptosis, and has been proposed as a potential therapeutic target for the treatment of diseases associated with necroptosis. In this report, we describe the design, synthesis, and evaluation of a series of novel RIPK3 inhibitors. The lead compound 38 exhibited potent activity (EC50 = 0.42 μM) in blocking TNFα, Smac mimetic and z-VAD (TSZ) induced cell death in HT-29 cells. Mechanistic studies showed that compound 38 bound to RIPK3 with high affinity (Kd = 7.1 nM), and inhibited RIPK3 kinase activity in a ADP-Glo functional assay. In addition, compound 38 displayed good selectivity over another necroptosis regulator RIPK1 (Kd = 6000 nM). Furthermore, compound 38 demonstrated excellent in vitro safety profiles with minimal inhibition of CYP isozymes and hERG potassium channel. Lastly, compound 38 efficiently blocked hypothermia and death in mice in the TNFα-induced systemic inflammatory response syndrome model.
Wu, Shuwei,Xu, Chen,Xia, Kaijiang,Lin, Yu,Tian, Sheng,Ma, Haikuo,Ji, Yuting,Zhu, Fang,He, Sudan,Zhang, Xiaohu
(2021/03/16)

HETEROARYL COMPOUNDS AS INHIBITORS OF PROGRAMMED NECROSIS PATHWAY, COMPOSITION AND METHOD USING THE SAME
The present disclosure provides heteroaryl compounds of Formula (I), processes for their preparation, pharmaceutical compositions containing them, and their use in the treatment of diseases and disorders, arising from or related to the programmed necrosis pathway.
-
Paragraph 00152-00154

(2021/07/10)

Discovery of fluorescent coumarin-benzo[b]thiophene 1, 1-dioxide conjugates as mitochondria-targeting antitumor STAT3 inhibitors
STAT3 has been extensively studied as a potential antitumor target. Though studies on regulating STAT3 mainly focus on the inhibition of STAT3 phosphorylation at Tyr705 residue, the phosphorylation at Ser727 residue of STAT3 protein is also closely associated with the mitochondrial import of STAT3 protein. N, N-diethyl-7-aminocoumarin is a fluorescent mitochondria-targeting probe. In this study, a series of STAT3 inhibitors were developed by connecting N, N-diethyl-7-aminocoumarin fluorophore with benzo [b]thiophene 1, 1-dioxide moiety. All designed compounds displayed potent anti-proliferative activity against cancer cells. The representative compound 7a was mainly accumulated in mitochondria visualized by its fluorescence. STAT3 phosphorylation was inhibited by compound 7a at both Tyr705 and Ser727 residues. Compound 7a inhibited STAT3 phosphorylation whereas had no influence on the phosphorylation levels of STAT1, JAK2, Src and Erk1/2, indicating good selectivity of compound 7a. Moreover, compound 7a down-regulated the expression of STAT3 target genes Bcl-2 and Cyclin D1, increased ROS production and remarkably reduced the mitochondrial membrane potential to induce mitochondrial apoptotic pathway. Furthermore, compound 7a in vivo suppressed breast cancer 4T1 implanted tumor growth. Taken together, these results highlighted that compound 7a might be a promising mitochondria-targeting STAT3 inhibitor for cancer therapy.
Cai, Guiping,Yu, Wenying,Song, Dongmei,Zhang, Wenda,Guo, Jianpeng,Zhu, Jiawen,Ren, Yuhao,Kong, Lingyi
p. 236 - 251
(2019/05/02)

Bicyclic heterocyclic anthranilic diamides as ryanodine receptor modulators with insecticidal activity
The diamide insecticides act on the ryanodine receptor (RyR). The synthesis of various bicyclic anthranilic derivatives is reported. Their activity against the insect ryanodine receptor (RyR) and their insecticidal activity in the greenhouse is presented,
Jeanguenat, André,Durieux, Patricia,Edmunds, Andrew J.F.,Hall, Roger G.,Hughes, Dave,Loiseleur, Olivier,Pabba, Jagadish,Stoller, André,Trah, Stephan,Wenger, Jean,Dutton, Anna,Crossthwaite, Andrew
p. 403 - 427
(2016/01/25)

Benzo[b]thiophene-2-carboxamide derivatives as potent urotensin-II receptor antagonists
Members of a series of benzo[b]thiophene-2-carboxamide derivatives, possessing an N-(1-(3-bromo-4-(piperidin-4-yloxy)benzyl)piperidin-4-yl) group, were synthesized and evaluated as urotensin-II receptor antagonists. The results show that these substances have potent UT binding affinities. Observations made in a systematic SAR investigation of the effects of a variety of substituents (R1and R2) at the 5- and 6-positions in the benzo[b]thiophene-2-carboxamide moiety on UT binding affinities led to identification of the 5-cyano analog 7f as a highly potent UT antagonist with an IC50value of 25?nM. Despite having a good metabolic stability, 7f is a potent inhibitor of CYP isozyme and displays an unsuitable PK profile.
Lim, Chae Jo,Woo, Seong Eun,Ko, Su Ik,Lee, Byung Ho,Oh, Kwang-Seok,Yi, Kyu Yang
p. 4684 - 4686
(2016/09/13)

Microwave-assisted synthesis of 3-aminobenzo[b]thiophene scaffolds for the preparation of kinase inhibitors
Microwave irradiation of 2-halobenzonitriles and methyl thioglycolate in the presence of triethylamine in DMSO at 130°C provides rapid access to 3-aminobenzo[b]thiophenes in 58-96% yield. This transformation has been applied in the synthesis of the thieno
Bagley, Mark C.,Dwyer, Jessica E.,Molina, Maria D. Beltran,Rand, Alexander W.,Rand, Hayley L.,Tomkinson, Nicholas C. O.
p. 6814 - 6824
(2015/06/25)

1-(CYCLOALKYL-CARBONYL)PROLINE DERIVATIVE
A compound represented by formula (1) (in the formula: ring-D represents a three- to eight-membered hydrocarbon ring; Ra represents an optionally substituted amino C1-6 alkyl group or the like; Rb1 and Rb2 each independently represent a hydrogen atom, a halogen atom, or the like; Rc represents an optionally substituted C6-10 aryl group or the like; Rd represents a hydrogen atom or the like; and ring-Q represents a (hetero)aryl group or the like which may be substituted with a carboxyl group or the like) or a pharmaceutically acceptable salt thereof exhibits an excellent FXIa inhibitory activity, and is useful as a therapeutic agent against thrombosis or the like.
-
Paragraph 0945; 0946

(2015/06/03)

Novel 2-Carbonylbenzo[b]thiophene 1,1-Dioxide Derivatives as Potent Inhibitors of STAT3 Signaling Pathway
Signal transducer and activator of transcription 3 (STAT3) is considered to be an attractive therapeutic target for cancer therapy. In this study, a series of 2-carbonylbenzo[b]thiophene 1,1-dioxide derivatives (CBT) were designed to inhibit the STAT3 SH2 domain phosphorylation site Try 705. We demonstrated that incorporation of basic flexible groups through amide bond linkage to benzo[b]thiophene 1,1-dioxide (BTP) achieved compounds with higher antiproliferative potency than BTP itself. The most potent compound 6o, as indicated from luciferase reporter gene assay, inhibited the STAT3 pathway by decreasing the phosphorylation level of STAT3 Tyr705, while the phosphorylation level of other upstream tyrosine kinases in this pathway was not significantly inhibited. Compound 6o was also shown to trigger ROS generation and accumulation, thus consequently attributed partially to the observed cell apoptosis. This study provided important structural information for the development of inhibitors targeting the STAT3 pathway.
Ji, Peng,Xu, Xin,Ma, Shuhua,Fan, Junchao,Zhou, Qiang,Mao, Xinliang,Qiao, Chunhua
supporting information
p. 1010 - 1014
(2015/09/22)

METHOD FOR PROMOTING PLANT GROWTH
The present invention provides a method for promoting plant growth, which comprises treating a plant with at least one compound selected from a group consisting of a compound represented by the following Formula (1): and an agriculturally acceptable salt thereof, provided that a method for promoting plant growth which comprises treating plants with a compound corresponding to any one of the following (1) to (5) and an agriculturally acceptable salt thereof is excluded: (1) 4-(Trifluoromethyl)benzo[b]thiophene-2-carboxylic acid, (2) 5-(Trifluoromethyl)benzo[b]thiophene-2-carboxylic acid, (3) 6-(Trifluoromethyl)benzo[b]thiophene-2-carboxylic acid, (4) 7-(Trifluoromethyl)benzo[b]thiophene-2-carboxylic acid, and (5) Benzo[b]thiophene-2-carboxylic acid.
-
Paragraph 0271

(2015/11/16)

Hydroxybenzothiophene ketones are efficient pre-mRNA splicing modulators due to dual inhibition of Dyrk1A and Clk1/4
Dysregulated usage of pre-mRNA splicing sites contributes to the progression of cancer, neurodegenerative diseases, and viral infections. Serine/arginine-rich (SR) proteins play major roles in the splice site recognition and are largely regulated by phosp
Schmitt, Christian,Miralinaghi, Parisa,Mariano, Marica,Hartmann, Rolf W.,Engel, Matthias
supporting information
p. 963 - 967
(2014/12/10)

Solvent-free microwave synthesis of 3-(4-benzo[b]-thiophene-2-carbonyl)-1-piperazinyl-1-benzo[b]thiophen-2-YL-1-propanones. New hetero bis-ligands with potential 5-HT1A serotonergic activity
A novel series of 2-benzothiophenealkylpiperazine derivatives 11 (a-d) with potential affinity at 5-HT1A serotonin receptors have been synthesized via solvent-free, microwave-promoted Michael addition of benzo[b]thiophene piperazine derivatives 6(a-c) to substituted benzo[b]thiophen-2-yl propenones 10(b,c).
Pessoa-Mahana, Hernan,Kosche C., Johann,Ron H., Nadia,Recabarren-Gajardo, Gonzalo,Saitz B., Claudio,Araya-Maturana, Ramiro,Pessoa-Mahana, C. David
experimental part
p. 1913 - 1929
(2009/04/06)

BENZOTHIOPHENE DERIVATIVES: PREPARATION AND PHARMACEUTICAL APPLICATIONS
The present invention relates to hydroxamate compounds which are inhibitors of histone deacetylase. More particularly, the present invention relates to benzothiophene containing compounds and methods for their preparation. These compounds may be useful as
-
Page/Page column 45

(2008/06/13)

AMINOPYRIMIDINE COMPOUNDS AND METHODS OF USE
The invention relates to aminopyrimidine compounds useful for treating diseases mediated by polo-like kinase 1 (Plk1). The invention also relates to the therapeutic use of such aminopyrimidine compounds and compositions thereof in treating disease states associated with abnormal cell growth and unwanted cell proliferation.
-
Page/Page column 26-27

(2010/11/08)

6-(4-Chlorophenyl)-3-substituted-thieno[3,2-d]pyrimidin-4(3H)-one-based melanin-concentrating hormone receptor 1 antagonist
Genetic manipulation studies in mice at both the MCH receptor 1 (MCHR1) as well as the MCH peptide levels have implicated MCHR1 as a key player in energy homeostasis. The phenotype exhibited by these studies, that is, increased metabolic rate, resistance to high fat diet, and subsequent weight loss, has spurred considerable efforts to develop antagonists of MCHR1. In continuation of efforts directed toward this goal, the present work capitalizes on the putative binding mode of an MCH antagonist, resulting in the identification of several novel chemotypes that are potent and selective MCHR1 antagonists. In addition, the favorable pharmacokinetics of representative examples has allowed for the evaluation of an MCHR1 antagonist in a high fat diet-induced obese rodent model of obesity. The tolerability of the right-hand side of the template for diverse chemotypes accompanied by favorable effects on weight loss enhances the attractiveness of this template in the pursuit toward development of effective anti-obesity agents.
Tavares, Francis X.,Al-Barazanji, Kamal A.,Bishop, Michael J.,Britt, Christy S.,Carlton, David L.,Cooper, Joel P.,Feldman, Paul L.,Garrido, Dulce M.,Goetz, Aaron S.,Grizzle, Mary K.,Hertzog, Donald L.,Ignar, Diane M.,Lang, Daniel G.,McIntyre, Maggie S.,Ott, Ronda J.,Peat, Andrew J.,Zhou, Hui-Qiang
p. 7108 - 7118
(2011/05/18)

Inhibitors of histone deacetylase
The invention relates to the inhibition of histone deacetylase. The invention provides compounds and methods for inhibiting histone deacetylase enzymatic activity. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.
-
(2008/06/13)

Inhibitors of histone deacetylase
The invention relates to the inhibition of histone deacetylase. The invention provides compounds and methods for inhibiting histone deacetylase enzymatic activity. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.
-
(2008/06/13)

Inhibitors of histone deacetylase
The invention relates to the inhibition of histone deacetylase. The invention provides compounds and methods for inhibiting histone deacetylase enzymatic activity. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.
-
(2008/06/13)

Total synthesis of distamycin A and 2640 analogues: A solution-phase combinatorial approach to the discovery of new, bioactive DNA binding agents and development of a rapid, high-throughput screen for determining relative DNA binding affinity or DNA binding sequence selectivity
The development of a solution-phase synthesis of distamycin A and its extension to the preparation of 2640 analogues are described. Thus, solution-phase synthesis techniques with reaction workup and purification employing acid/base liquid - liquid extractions were used in the multistep preparation of distamycin A (8 steps, 40% overall yield) and a prototypical library of 2640 analogues providing intermediates and final products that are ≥95% pure on conventional reaction scales. The complementary development of a simple, rapid, and high-throughput screen for DNA binding affinity based on the loss of fluorescence derived from displacement of prebound ethidium bromide is disclosed which is applicable for assessing relative or absolute binding affinity to DNA homopolymers or specific sequences (hairpin oligonucleotides). Using hairpin oligonucleotides, this method permits the screening of a library of compounds against a single predefined sequence to identify high affinity binders, or the screening of a single compound against a full library of individual hairpin oligionucleotides to define its sequence selectivity. The combination permits the establishment of the complete DNA binding profile of each member of a library of compounds. Screening the prototypical library provided compounds that are 1000 times more potent than distamycin A in cytotoxic assays (67, IC50 = 29 nM, L1210), that bind to poly[dA]-poly[dT] with comparable affinity, and that exhibit an altered DNA binding sequence selectivity. Several candidates were identified which bound the five-base-pair AT-rich site of the PSA-ARE-3 sequence, and one (128, K = 3.2 x 106 M-1) maintained the high affinity binding (K = 4.5 x 106 M-1) to the ARE-consensus sequence containing a GC base-pair interrupted five-base-pair AT-rich site suitable for inhibition of gene transcription initiated by hormone insensitive androgen receptor dimerization and DNA binding characteristic of therapeutic resistant prostate cancer.
Boger, Dale L.,Fink, Brian E.,Hedrick, Michael P.
p. 6382 - 6394
(2007/10/03)

Telomerase inhibitors
Methods and compositions for treating cancer and other diseases in which inhibition of telomerase activity can ameliorate disease symptoms or prevent or treat the disease relate to compounds characterized by the following structure: STR1 and their pharmaceutically acceptable salts. Y is selected from the group consisting of oxygen, sulfur, sulfonyl, sulfinyl, and --NR7 --. R1 is --TR8, where T is --C(X1)-- or --SO2 --, and R8 is selected from the group consisting of --OR9, --NHNHSO2 R9, --NHNHC(X2)OR9, --NR9 R10, --NHNHC(X2)NR9 R10, --NHCR9 R10 C(X2)NR11 R12, --NHC(X2)NR9 R10, and the piperazinyl moiety shown below: STR2 where n is 0 or 1, and Qn, for n=1, is --SO2 --, --C(X2)-- or --C(X2)NR10 --. R2 -R6 are selected independently from the group consisting of hydrogen, alkyl, aryl, hydroxyl, alkoxyl, aryloxyl, aralkoxyl, halogen, cyano, nitro, alkylcarbamido, arylcarbamido, dialkylcarbamido, diarylcarbamido, alkylarylcarbamido, alkylthiocarbamido, arylthiocarbamido, dialkylthiocarbamido, diarylthiocarbamido, alkylarylthiocarbamido, amino, alkylamino, arylamino, dialkylamino, diarylamino, arylalkylamino, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, diarylaminocarbonyl, arylalkylaminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, carboxyl, alkoxycarbonyl, aryloxycarbonyl, sulfo, alkylsulfonylamido, arylsulfonylamido, alkylsulfonyl, arylsulfonyl, alkylsulfinyl, and arylsulfinyl. X1 and X2 are selected independently from the group consisting of oxygen, and sulfur. R7 -R12 are selected independently from the group consisting of hydrogen, alkyl, aryl, aralkyl, heterocycle, and heterocyclealkyl.
-
(2008/06/13)

The synthesis of 5-hydroxy-2,3-dihydrobenzo(B)thiophene (1) via an efficient one step preparation of 5-nitro-benzo(B) thiophene-2-carboxylate (3A)
The preparation of 5-hydroxy-2,3-dihydrobenzothiophene 1 from 5-nitro-benzothiophene-2-carboxylate 3a is described along with an efficient one pot synthesis of 3a.
Zambias,Hammond
p. 959 - 964
(2007/10/02)

Synthesis and in vitro LTD4 antagonist activity of bicyclic and monocyclic cyclopentylurethane and cyclopentylacetamide N-arylsulfonyl amides
The dissociation constants (K(B)) at the LTD4 receptor on guinea pig trachea of a series of monocyclic and bicyclic cyclopentylurathane and cyclopentylacetamide N-arylsulfonyl amides have been measured. The K(B) was found to be remarkably toler
Matassa,Brown,Bernstein,Shapiro,Maduskuie Jr.,Cronk,Vacek,Yee,Snyder,Krell,Lerman,Maloney
p. 2621 - 2629
(2007/10/02)