- Novel 2,4-diaminopyrimidines bearing fused tricyclic ring moiety for anaplastic lymphoma kinase (ALK) inhibitor
-
In this study, a series of novel 2,4-diaminopyrimidines bearing fused tricyclic ring moiety was described for ALK inhibitor. The pyrazole, imidazole, 1,2,4-triazole, piperazine and phenanthridine moieties were employed at the 2-position of pyrimidine. Amo
- Achary, Raghavendra,Mathi, Gangadhar Rao,Lee, Dong Ho,Yun, Chang Soo,Lee, Chong Ock,Kim, Hyoung Rae,Park, Chi Hoon,Kim, Pilho,Hwang, Jong Yeon
-
-
Read Online
- Design, synthesis, and biological evaluation of 4-methoxy-3-arylamido-N-(substitutedphenyl)benzamide derivatives as potential antiplatelet agents
-
A series of 4-methoxy-3-arylamido-N-(substitutedphenyl)benzamides 6a–u were designed according to the splicing principle of structural design in the medicinal chemistry theory and were synthesized in five steps: nitration, acylation, ammoniation, reduction, and secondary ammoniation. The structures of the target compounds were characterized and verified by infrared, 1H nuclear magnetic resonance (NMR), 13C NMR, and electron spray ionization spectroscopy. Their in vitro antiplatelet aggregation activities induced by adenosine diphosphate (ADP) or arachidonic acid (AA) were assessed by Born's method. The biological evaluation revealed that all compounds exhibited certain levels of activities in both of the antiplatelet aggregation assays; compounds 6c (IC50 = 3.84 μM) and 6f (IC50 = 3.12 μM) displayed the strongest antiplatelet aggregation activities in the ADP-induced and AA-induced assay, separately. Moreover, compounds that had stronger activities were chosen for cell toxicity testing via the cell counting kit-8 assay. The results indicated that none of the compounds had obvious cell toxicity against L929 cells at the doses of 10 and 20 μM. It is worth pointing out that compound 6c showed the highest antiplatelet activity and the lowest cell toxicity. In general, 4-methoxy-3-arylamido-N-(substitutedphenyl)benzamides have the potential to become a kind of safer and more effective antiplatelet agents.
- Chen, Xin,Liu, Xiujie,Qiu, Kai,Zhang, Zhihao
-
-
- Tubulin inhibitors: Discovery of a new scaffold targeting extra-binding residues within the colchicine site through anchoring substituents properly adapted to their pocket by a semi-flexible linker
-
Bis-hydrazides 13a-h were designed and synthesized as potential tubulin inhibitors selectively targeting the colchicine site between α- and β-tubulin subunits. The newly designed ring-B substituents were assisted at their ends by ‘anchor groups’ which are expected to exert binding interaction(s) with new additional amino acid residues in the colchicine site (beyond those amino acids previously reported to interact with reference inhibitors as CA-4 and colchicine). Conformational flexibility of bis-hydrazide linker assisted these ‘extra-binding’ properties through reliving ligands’ strains in the final ligand-receptor complexes. Compound 13f displayed the most promising computational and biological study results in the series: MM/GBSA binding energy of ?62.362 kcal/mol (extra-binding to Arg α:221, Thr β:353 & Lys β:254); 34% NCI-H522 cells’ death (at 10 μM), IC50 = 0.073 μM (MTT assay); significant cell cycle arrest at G2/M phase; 11.6% preG1 apoptosis induction and 83.1% in vitro tubulin inhibition (at concentration = IC50). Future researchers in bis-hydrazide tubulin inhibitors are advised to consider the 2-chloro-N-(4-substituted-phenyl)acetamide derivatives as compound 13f due to extra-binding properties of their ring B.
- AbdelHafez, El-Shimaa M. N.,Abdelhamid, Dalia,Aly, Omar M.,Maklad, Raed M.
-
-
- Synthesis process of anti-tumor drug Sapanisertib
-
The invention discloses a synthesis process of anti-tumor drug Sapanisertib. The synthesis process comprises the following steps: step 1, carrying out carboxyl halogenation reaction on a compound I and a halogenating reagent in a proper solvent to obtain
- -
-
Paragraph 0072; 0073
(2020/09/12)
-
- Straightforward α-Amino Nitrile Synthesis Through Mo(CO)6-Catalyzed Reductive Functionalization of Carboxamides
-
The selective reduction of amides into an intermediate hemiaminal catalyzed by Mo(CO)6 together with the inexpensive and easy to handle TMDS (1,1,3,3-tetramethyldisiloxane) as reducing agent, followed by subsequent trapping of the hemiaminal with a cyanide source, allows for the straightforward synthesis of α-amino nitriles. The methodology presented here, displays high levels of chemoselectivity allowing for the reduction of amides in the presence of functional groups such as ketones, imines, aldehydes, and acids, which affords a simple route for the synthesis of α-amino nitriles with a broad scope of functionalities in high yields. Furthermore, the applicability of this methodology is demonstrated by scale up experiments and by derivatization of the target compounds into synthetically interesting products. The selective cyanation is successfully applied in late stage functionalizations of amide containing drugs and prolinol derivatives.
- Trillo, Paz,Slagbrand, Tove,Adolfsson, Hans
-
supporting information
p. 12347 - 12351
(2018/09/10)
-
- 3-AMIDOBENZAMIDES AND USES THEREOF FOR INCREASING CELLULAR LEVELS OF A3G
-
Disclosed are novel benzamide compounds and the uses thereof for treating diseases and disorders in a patient in need thereof by increasing cellular levels of A3G and/or other members of the A3 family of proteins in the patient. The disclosed compounds in
- -
-
Paragraph 0081; 0082; 0083
(2016/03/13)
-
- PIGMENT DISPERSANT, AND PIGMENT COMPOSITION, COLORING COMPOSITION AND COLOR FILTER USING THE SAME
-
PROBLEM TO BE SOLVED: To provide a pigment dispersant that exhibits an extremely good characteristic in enhancing the dispersibility of pigment, to provide a pigment composition, produced by using the pigment dispersant, that is excellent in the contrast
- -
-
Paragraph 0182
(2016/11/09)
-
- The pigment composition, a colored composition, color filter
-
PROBLEM TO BE SOLVED: To provide a pigment composition that is excellent, when used for a color filter, in its contrast ratio and luminance, has a good heat resistance and light stability, and does not generate a coated film foreign body, as well as to pr
- -
-
Paragraph 0145
(2016/11/14)
-
- A practical in situ generation of the schwartz reagent. reduction of tertiary amides to aldehydes and hydrozirconation
-
A new, highly efficient in situ protocol (Cp2ZrCl2/LiAlH(OBu-t)3) is described for the generation of the Schwartz reagent which provides a convenient method for the amide to aldehyde reduction and the regioselective hydrozirconation-iodination of alkynes and alkenes. Highlighted are chemoselective reductions of benzamides derived by directed ortho metalation (DoM) chemistry, allowing the synthesis of valuable 1,2,3-substituted benzaldehydes. The single-step, three-component process proceeds in a very short reaction time, shows excellent functional group compatibility, and uses inexpensive and long-storage stable reducing reagents.
- Zhao, Yigang,Snieckus, Victor
-
supporting information
p. 390 - 393
(2014/04/03)
-
- NOVEL COMPOUNDS
-
The present invention relates substituted N-biphenyl-3-acetylamino-benzamides and N-[3-(acetylamino)phenyl]-biphenyl-carboxamides of general formula (I) as described and defined herein, to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of a hyper-proliferative disorder, as a sole agent or in combination with other active ingredients.
- -
-
Page/Page column 79; 80
(2014/10/03)
-
- NOVEL COMPOUNDS
-
The present invention relates to substituted N-(phenyl-heteroaryl)-3-acetylamino-benzamides and N- [3-(acetylamino)phenyl]-phenyl-heteroaryl-carboxamides of general formula(I) as described and defined herein,to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease.
- -
-
Page/Page column 105
(2014/10/03)
-
- Discovery, synthesis and biological evaluation of cycloprotoberberine derivatives as potential antitumor agents
-
A series of new 1,13-cycloprotoberberine derivatives defined through variations at the 9-position were designed, synthesized and evaluated for their cytotoxicities in human HepG2 (hepatoma), HT1080 (fibrosarcoma) and HCT116 (colon cancer) cells. The preliminary structure-activity relationship (SAR) revealed that the replacement of 9-methoxyl with an ester moiety might significantly enhance the antiproliferative activity in vitro. Notably, compound 7f demonstrated equipotent cytotoxicity activity against breast cancer MCF-7 (parent) and doxorubicin (DOX)-resistant MCF-7 (MCF-7/ADrR) cells, indicating a mode of action different from that of DOX. Further mechanism study showed that 7f significantly inhibited activity of DNA topoisomerase I (Top I) and Top II. G2/M phase arrest and tumor cell growth reduction was observed thereafter. Thus, we consider cycloprotoberberine analogues to be a new family of promising antitumor agents with an advantage of inhibiting drug-resistant cancer cells.
- Li, Yang-Biao,Zhao, Wu-Li,Wang, Yan-Xiang,Zhang, Cai-Xia,Jiang, Jian-Dong,Bi, Chong-Wen,Tang, Sheng,Chen, Ru-Xian,Shao, Rong-Guang,Song, Dan-Qing
-
p. 463 - 472
(2013/10/01)
-
- Synthesis of linear and cyclic aromatic peptides with fixed conformation owing to intramolecular hydrogen bonding by condensation polymerization method
-
Chain-growth condensation polymerization of 3-(4-octyloxybenzylamino) benzoic acid esters bearing an alkoxy group on the benzene ring was investigated for the synthesis of polyamides having a specific conformation owing to intramolecular hydrogen bonding
- Ohishi, Tomoyuki,Suzuki, Toshiya,Niiyama, Tetsurou,Mikami, Koichiro,Yokoyama, Akihiro,Katagiri, Kosuke,Azumaya, Isao,Yokozawa, Tsutomu
-
supporting information; experimental part
p. 7067 - 7070
(2012/01/13)
-
- Design and synthesis of 2-arylbenzimidazoles and evaluation of their inhibitory effect against Chlamydia pneumoniae
-
Chlamydia pneumoniae is an intracellular bacterium that responds poorly to antibiotic treatment. Insufficient antibiotic usage leads to chronic infection, which is linked to disease processes of asthma, atherosclerosis, and Alzheimer's disease. The Chlamydia research lacks genetic tools exploited by other antimicrobial research, and thus other approaches to drug discovery must be applied. A set of 2-arylbenzimidazoles was designed based on our earlier findings, and 33 derivatives were synthesized. Derivatives were assayed against C. pneumoniae strain CWL-029 in an acute infection model using TR-FIA method at a concentration of 10 μM, and the effects of the derivatives on the host cell viability were evaluated at the same concentration. Fourteen compounds showed at least 80% inhibition, with only minor changes in host cell viability. Nine most potential compounds were evaluated using immunofluorescence microscopy on two different strains of C. pneumoniae CWL-029 and CV-6. The N-[3-(1H-benzimidazol-2-yl)phenyl]-3-methylbenzamide (42) had minimal inhibitory concentration (MIC) of 10 μM against CWL-029 and 6.3 μM against the clinical strain CV-6. This study shows the high antichlamydial potential of 2-arylbenzimidazoles, which also seem to have good characteristics for lead compounds.
- Keurulainen, Leena,Salin, Olli,Siiskonen, Antti,Kern, Jan Marco,Alvesalo, Joni,Kiuru, Paula,Maass, Matthias,Yli-Kauhaluoma, Jari,Vuorela, Pia
-
supporting information; experimental part
p. 7664 - 7674
(2011/03/17)
-
- FUSED HETEROCYCLIC COMPOUND AND USE THEREOF
-
The present invention relates to wherein each symbol is as defined in the specification. The compound has a superior mineral corticoidreceptorantagonistic action and is useful as an agent for the prophylaxis or treatment of hypertension, cardiac failure and the like, a compound having a fused heterocycle, or a prodrug thereof, or a salt thereof; and an agent for the prophylaxis or treatment of hypertension, cardiac failure and the like.
- -
-
Page/Page column 232
(2008/06/13)
-
- Synthesis and structure-activity relationships of suramin-derived P2Y 11 receptor antagonists with nanomolar potency
-
Selective and potent P2Y11 receptor antagonists have yet to be developed, thus impeding an evaluation of this G protein-coupled receptor mainly expressed on immune cells. Taking suramin with moderate inhibitory potency as a template, 18 ureas with variations of the methyl groups of suramin and their precursors were functionally tested at P2Y11, P2Y1, and P2Y2 receptors. Fluorine substitution of the methyl groups of suramin led to the first nanomolar P2Y11 antagonist (8f, NF157, pK i: 7.35). For selectivity, 8f was also tested at various P2X receptors. 8f displayed selectivity for P2Y11 over P2Y1 (> 650-fold), P2Y2 (> 650-fold), P2X2 (3-fold), P2X3 (8-fold), P2X4 (>22-fold), and P2X7 (>67-fold) but no selectivity over P2X1. QSAR studies confirm that residues with favored resonance and size parameters in the aromatic linker region can indeed lead to an increased potency as is the case for 8f. A symmetric structure linking two anionic clusters seems to be required for bioactivity. 8f may be helpful for studies evaluating the physiological role of P2Y11 receptors.
- Ullmann, Heiko,Meis, Sabine,Hongwiset, Darunee,Marzian, Claudia,Wiese, Michael,Nickel, Peter,Communi, Didier,Boeynaems, Jean-Marie,Wolf, Christian,Hausmann, Ralf,Schmalzing, Günther,Kassack, Matthias U.
-
p. 7040 - 7048
(2007/10/03)
-
- SUBSTITUTED N-ARYL BENZAMIDES AND RELATED COMPOUNDS FOR TREATMENT OF AMYLOID DISEASES AND SYNUCLEINOPATHIES
-
Substituted diaryl compounds of the Formulae (I, II, III), where the variables are as defined in the claims, and their pharmaceutically acceptable derivatives, their synthesis, pharmaceutical compositions containing them, and their use in the treatment of amyloid diseases, including A? amyloidosis, such as observed in Alzheimer's disease, IAPP amyloidosis, such as observed in type 2 diabetes, and synucleinopathies, such as observed in Parkinson's disease, and the manufacture of medicaments for such treatment are provided.
- -
-
Page/Page column 67; 78-79
(2008/06/13)
-
- 2,3-Dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acid derivatives: A novel class of small molecule heparanase inhibitors
-
A novel class of 2,3-dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acids are described as inhibitors of the endo-β-glucuronidase heparanase. Several of the compounds, for example, 2-[4-propylamino-5-[5-(4-chloro)phenyl-benzoxazol-2- yl]phenyl]-2,3-dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acid (9c), display potent heparanase inhibitory activity (IC50 200-500nM) and have high selectivity (>100-fold) over human β-glucuronidase. They also show anti-angiogenic effects. Such compounds should serve as useful biological tools and may provide a basis for the design of novel therapeutic agents.
- Courtney, Stephen M.,Hay, Philip A.,Buck, Richard T.,Colville, Claire S.,Porter, David W.,Scopes, David I. C.,Pollard, Faye C.,Page, Martin J.,Bennett, James M.,Hircock, Margaret L.,McKenzie, Edward A.,Stubberfield, Colin R.,Turner, Paul R.
-
p. 3269 - 3273
(2007/10/03)
-
- Potential plant growth regulators: Synthesis and activity of new substituted N-(2-benzoyl-4-chlorophenyl)benzamides and N-[4-chloro-2-(α, α-hydroxyphenylmethyl)phenyl]benzamides
-
2-Amino-5-chlorobenzophenone 3 prepared in 2 steps from isatoic anhydride 1 on condensation with substituted benzoyl chlorides 6a-i in presence of Et 3N in 1,2-dichloroethane (DCE) affords substituted N-(2-benzoyl-4-chlorophenyl)-benzamides 7a-i which on reduction with NaBH 4 gives corresponding alcohols, N-[4-chloro-2-(α,α- hydroxyphenyl-methyl)phenyl]benzamides 8a-i. The structures of all the compounds are confirmed by 1H NMR spectra, and their cytokinin (plant growth promoting) activity is determined on seeds of Raphanus sativus, family Brassicaceae (common name white radish, variety Pusa Chetki), for concentrations varying between 0.1 to 10 mg/litre. Compounds 7c, 7d, 7g and 7h at all concentrations and 7i at 4 concentrations have been found to show higher plant growth promoting (PGP) activity than benzyladenine (standard). Compounds 8d and 8g also show moderate plant growth promoting (cytokinin) activity, while compounds 7a, 7b, 7e, 7f and 8a, 8b, 8c, 8e, 8f and 8i are found to have plant growth inhibiting (PGI) activity.
- Hatim, Jaywant Govind,Joshi, Vidya
-
p. 2689 - 2695
(2007/10/03)
-
- BENZOXAZOLE, BENZTHIAZOLE AND BENZIMIDAZOLE DERIVATIVES USEFUL AS HEPARANASE INHIBITORS
-
Compounds of formula (I): wherein R1, R2 and R3 are independently, hydrogen, halogen, CF3, OR6, NR7 R8, NR8COR10, NR8SO2R10 or C 1-6 alkyl optionally substituted by hydroxy, C 1-6 alkoxy or NR7R8; R4 is NR8CONR8R9; and R5 formula (Ia) is methods for their
- -
-
-
- PHTHALIMIDE CARBOXYLIC ACID DERIVATIVES
-
The present invention relates to phthalimide carboxylic acid derivatives of formula (I), methods for their preparation, pharmaceutical compositions containing them and their use in medicine, specifically in the treatment of cancer. (I), wherein X is O or S; R1 is a phthalimide carboxylic acid group of formula (II). R is hydrogen, C1-C6 alkyl, aryl or C1-C3 alkylaryl and R2, R3 and R4 represent various substituents.
- -
-
Page/Page column 20-21
(2008/06/13)
-
- Utility of Complementary Molecular Reactivity and Molecular Recognition (CMR/R) Technology and Polymer-Supported Reagents in the Solution-Phase Synthesis of Heterocyclic Carboxamides
-
The use of our recently reported chemical library purification strategy in the development of a herbicidal lead, N-(3-benzoylphenyl)-3-(1,1-dimethylethyl)-1-methyl-1H-pyrazole-5-carboxamide (3), is described. The approach applying fundamental properties of complementary molecular reactivity and molecular recognition (CMR/R) as the basis for a general purification strategy was utilized. Polymeric reagents were used in the synthesis to generate reactive species involved in product formation, and complementary molecular reactivity/molecular recognition polymer 8 (CMR/R polymer 8) was used in the solution-phase syntheses of building blocks, primary libraries, and lead refinement libraries. An extension of the CMR/R methodology was applied, utilizing a sequestration enabling reagent (SER), transforming a reactant into an electrophilic species sequestrable by CMR/R polymer 8. This library purification strategy enabled rapid lead generation and lead refinement to afford herbicide 27o. The CMR/R solid-phase purification technique enabled a simple, general, and powerful protocol, eliminating the usual tedious and time-consuming methods required for solution-phase product purification. The result was the synthesis of hundreds of compounds, prepared in a relatively short time, leading to a compound with a 4-fold improvement in herbicidal activity over the initial lead.
- Parlow, John J.,Mischke, Deborah A.,Woodard, Scott S.
-
p. 5908 - 5919
(2007/10/03)
-