- Synthesis, docking, 3-D-qsar, and biological assays of novel indole derivatives targeting serotonin transporter, dopamine D2 receptor, and mao-a enzyme: In the pursuit for potential multitarget directed ligands
-
A series of 27 compounds of general structure 2,3-dihydro-benzo[1,4]oxazin-4-yl)-2-{4-[3-(1H-3indolyl)-propyl]-1-piperazinyl}-ethanamides, Series I: 7(a-o) and (2-{4-[3-(1H-3-indolyl) -propyl]-1-piperazinyl}-acetylamine)-N-(2-morfolin-4-yl-ethyl)-fluorinated benzamides Series II: 13(a-l) were synthesized and evaluated as novel multitarget ligands towards dopamine D2 receptor, serotonin transporter (SERT), and monoamine oxidase-A (MAO-A) directed to the management of major depressive disorder (MDD). All the assayed compounds showed affinity for SERT in the nanomolar range, with five of them displaying Ki values from 5 to 10 nM. Compounds 7k, Ki = 5.63 ± 0.82 nM, and 13c, Ki = 6.85 ± 0.19 nM, showed the highest potencies. The affinities for D2 ranged from micro to nanomolar, while MAO-A inhibition was more discrete. Nevertheless, compounds 7m and 7n showed affinities for the D2 receptor in the nanomolar range (7n: Ki = 307 ± 6 nM and 7m: Ki = 593 ± 62 nM). Compound 7n was the only derivative displaying comparable affinities for SERT and D2 receptor (D2/SERT ratio = 3.6) and could be considered as a multitarget lead for further optimization. In addition, docking studies aimed to rationalize the molecular interactions and binding modes of the designed compounds in the most relevant protein targets were carried out. Furthermore, in order to obtain information on the structure-activity relationship of the synthesized series, a 3-D-QSAR CoMFA and CoMSIA study was conducted and validated internally and externally (q2 = 0.625, 0.523 for CoMFA and CoMSIA and r2ncv = 0.967, 0.959 for CoMFA and CoMSIA, respectively).
- Alarcón-Espósito, Jazmín,Araya-Maturana, Ramiro,Cabezas, David,Cerda-Cavieres, Christopher,Chung, Hery,Iturriaga-Vásquez, Patricio,Mella-Raipán, Jaime,Ojeda-Gómez, Claudia,Pessoa-Mahana, Carlos D.,Pessoa-Mahana, Hernán,Quiroz, Gabriel,Reyes-Parada, Miguel,Rodríguez-Lavado, Julio,Saitz, Claudio
-
-
Read Online
- Production process of flumioxazin herbicide
-
The invention discloses a production process of a flumioxazin herbicide. The process is characterized by comprising the following steps: S1, synthesizing 2-nitro-5-fluorophenol; S2, synthesizing ethyl 2-(5-fluoro-2-nitrophenoxy) acetate; S3, synthesizing 7-fluoro-2H-1, 4-benzoxazine-3 (4H)-ketone; S4, synthesizing 7-fluoro-6-nitro-2H-1, 4-benzoxazine-3 (4H)-ketone; S5, synthesizing 7-fluoro-6-amino-2H-1, 4-benzoxazine-3 (4H)-ketone; S6, synthesizing 7-fluoro-6-(3, 4, 5, 6-tetrahydro)phthalimido-1, 4-benzoxazine-3 (4H) ketone; and S7, synthesizing the flumioxazin. The method has the advantages of low raw material price, few byproducts and light pollution.
- -
-
-
- TETRALIN AND TETRAHYDROQUINOLINE COMPOUNDS AS INHIBITORS OF HIF-2ALPHA
-
Compounds that inhibit HIF-2a, and compositions containing the compound(s) and methods for synthesizing the compounds, are described herein. Also described are the use of such compounds and compositions for the treatment of a diverse array of diseases dis
- -
-
Paragraph 0262
(2021/09/26)
-
- Cycloalkane-pyrimidinedione compound as well as preparation method and application and pesticide herbicide thereof (by machine translation)
-
The invention relates to the field, discloses a cycloalkane-pyrimidinedione compound and a preparation method and application and a pesticide herbicide, and the compound has the structure shown in the formula (I). The cycloalkane pyrimidine diketone compo
- -
-
Paragraph 0102; 0103; 0105
(2019/09/14)
-
- Design, Herbicidal Activity, and QSAR Analysis of Cycloalka[ d]quinazoline-2,4-dione-Benzoxazinones as Protoporphyrinogen IX Oxidase Inhibitors
-
In continuation of our search for potent protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4) inhibitors, we designed and synthesized a series of novel herbicidal cycloalka[d]quinazoline-2,4-dione-benzoxazinones. The bioassay results of these synthesized compo
- Wang, Da-Wei,Zhang, Rui-Bo,Ismail, Ismail,Xue, Zhi-Yuan,Liang, Lu,Yu, Shu-Yi,Wen, Xin,Xi, Zhen
-
p. 9254 - 9264
(2019/08/26)
-
- p-diaminobenzene derivative as potassium channel regulator, preparation method and medical applications thereof
-
The invention relates to a p-diaminobenzene derivative as a potassium channel regulator, a preparation method and medical applications thereof, and specifically discloses a compound represented by a general formula A or a pharmaceutically acceptable salt
- -
-
Paragraph 0496-0500
(2019/12/09)
-
- Pyridine pyrimidine diketone containing benzoxazine ketone compound as well as preparation method and application thereof and herbicide composition
-
The invention relates to the field of herbicides, and discloses a pyridine pyrimidine diketone containing benzoxazine ketone compound as well as a preparation method and application thereof and a herbicide composition. The structure of the benzoxazine ket
- -
-
Paragraph 0138; 0142; 0143
(2018/11/22)
-
- Synthesis and biological evaluation of potential acetylcholinesterase inhibitors based on a benzoxazine core
-
With the purpose of expanding the structural variety of chemical compounds available as pharmacological tools for the treatment of Alzheimer's disease, we synthesized and evaluated a novel series of indole-benzoxazinones (Family I) and benzoxazine-arylpiperazine derivatives (Family II) for potential human acetylcholinesterase (hAChE) inhibitory properties. The most active compounds 7a and 7d demonstrated effective inhibitory profiles with Ki values of 20.3 ± 0.9 μM and 20.2 ± 0.9 μM, respectively. Kinetic inhibition assays showed non-competitive inhibition of AChE by the tested compounds. According to our docking studies, the most active compounds from both series (Families I and II) showed a binding mode similar to donepezil and interact with the same residues.
- Méndez-Rojas, Claudio,Quiroz, Gabriel,Faúndez, Mario,Gallardo-Garrido, Carlos,Pessoa-Mahana, C. David,Chung, Hery,Gallardo-Toledo, Eduardo,Saitz-Barría, Claudio,Araya-Maturana, Ramiro,Kogan, Marcelo J.,Zú?iga-López, María C.,Iturriaga-Vásquez, Patricio,Valenzuela-Gutiérrez, Carla,Pessoa-Mahana, Hernán
-
-
- Synthesis of 7 - fluoro - 6 - amino - 2 H - 1, 4 - benzoxazine - 3 (4 H) - one method (by machine translation)
-
The invention discloses a method for synthesizing 7 - fluoro - 6 - amino - 2 H - 1, 4 - benzoxazine - 3 (4 H) - one method, in order to 2, 4 - difluoroaniline as raw materials, through the substituted by hydroxyl, ether, nitration, hydrogenation reduction reaction to obtain the 7 - fluoro - 6 - amino - 2 H - 1, 4 - benzoxazine - 3 (4 H) - ketone (methylacetylene comprising diflufenican intermediate). Synthesis method of the invention, in order to 2, 4 - difluoroaniline as raw materials, cheap and easy to obtain, to a certain extent reduces the production cost; intermediate 1 without going through the high-pressure hydrogenation reaction can be with the chloroethyl acetate reaction ring, reduce the risk of the reaction; the nitration reaction is easy to control, decreasing the reaction, little impurity, raise the yield; hydrogenation reaction catalyst can be recovered, recycled, and reducing the cost; in addition the raw material is cheap, mild reaction, simple operation, facilitates large scale production. (by machine translation)
- -
-
Paragraph 0036; 0038; 0048; 0049
(2018/04/01)
-
- Synthesis and Herbicidal Activity of Pyrido[2,3-d]pyrimidine-2,4-dione-Benzoxazinone Hybrids as Protoporphyrinogen Oxidase Inhibitors
-
To search for new protoporphyrinogen oxidase (PPO, EC 1.3.3.4) inhibitors with improved bioactivity, a series of novel pyrido[2,3-d]pyrimidine-2,4-dione-benzoxazinone hybrids, 9-13, were designed and synthesized. Several compounds with improved tobacco PP
- Wang, Da-Wei,Li, Qian,Wen, Kai,Ismail, Ismail,Liu, Dan-Dan,Niu, Cong-Wei,Wen, Xin,Yang, Guang-Fu,Xi, Zhen
-
p. 5278 - 5286
(2017/07/12)
-
- Using gene expression database to uncover biology functions of 1,4-disubstituted 1,2,3-triazole analogues synthesized via a copper (I)-catalyzed reaction
-
We have synthesized bioactive 1,4-disubstituted 1,2,3-triazole analogues containing 2H-1,4-benzoxazin-3-(4H)-one derivatives via 1,3-dipolar cycloaddition in the presence of CuI. All the reactions proceeded smoothly and afforded its desired products in excellent yields. Among these analogues, 3y exhibited a better cytotoxic effect on human hepatocellular carcinoma (HCC) Hep 3B cells and displayed less cytotoxicity on normal human umbilical vein endothelial cells, compared with Sorafenib, a targeted therapy for advanced HCC. 3y also induced stronger apoptosis and autophagy. Addition of curcumin enhanced 3y-induced cytotoxicity by further induction of autophagy. Using gene expression signatures of 3y to query Connectivity Map, a glycogen synthase kinase-3 inhibitor (AR-A014418) was predicted to display similar molecular action of 3y. Experiments further demonstrate that AR-A014418 acted like 3y, and vice versa. Overall, our data suggest the chemotherapeutic potential of 3y on HCC.
- Su, Chun-Li,Tseng, Chia-Ling,Ramesh, Chintakunta,Liu, Hsiao-Sheng,Huang, Chi-Ying F.,Yao, Ching-Fa
-
-
- Tetrahydroquinoline analogues as muscarinic agonists
-
The present invention relates to tetrahydroquinoline compounds as muscarinic receptor agonists; compositions comprising the same; methods of inhibiting an activity of a muscarinic receptor with said compounds; methods of treating a disease condition associated with a muscarinic receptor using said compounds; and methods for identifying a subject suitable for treatment using said compounds.
- -
-
Page/Page column 32; 33
(2017/01/05)
-
- Discovery of selective and orally bioavailable protein kinase Cθ (PKCθ) inhibitors from a fragment hit
-
Protein kinase Cθ (PKCθ) regulates a key step in the activation of T cells. On the basis of its mechanism of action, inhibition of this kinase is hypothesized to serve as an effective therapy for autoimmune diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis. Herein, the discovery of a small molecule PKCθ inhibitor is described, starting from a fragment hit 1 and advancing to compound 41 through the use of structure-based drug design. Compound 41 demonstrates excellent in vitro activity, good oral pharmacokinetics, and efficacy in both an acute in vivo mechanistic model and a chronic in vivo disease model but suffers from tolerability issues upon chronic dosing.
- George, Dawn M.,Breinlinger, Eric C.,Friedman, Michael,Zhang, Yang,Wang, Jianfei,Argiriadi, Maria,Bansal-Pakala, Pratima,Barth, Martine,Duignan, David B.,Honore, Prisca,Lang, Qingyu,Mittelstadt, Scott,Potin, Dominique,Rundell, Lian,Edmunds, Jeremy J.
-
supporting information
p. 222 - 236
(2015/03/03)
-
- COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF PARASITIC DISEASES
-
The present invention provides compounds of formula I: [INSERT FORMULA HERE] or a pharmaceutically acceptable salt, tautomer, or stereoisomer, thereof, wherein the variables are as defined herein. The present invention further provides pharmaceutical compositions comprising such compounds and methods of using such compounds for treating, preventing, inhibiting, ameliorating, or eradicating the pathology and/or symptomology of a disease caused by a Plasmodium parasite, such as malaria.
- -
-
-
- PROCESS FOR PREPARATION OF DERIVATIVES OF TETRAHYDROPHTHALIMIDE
-
The present disclosure provides a process for preparation of a compound of formula 1, or isomers or its derivatives thereof, which show a high herbicidal activity against wide variety of weeds. (I) wherein R1 is a C3-C4 al
- -
-
Paragraph 00065
(2014/08/20)
-
- TRIAZINONE COMPOUNDS
-
The invention provides a compound of Formula (I) pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein the variable are defined herein. The compounds of the invention are useful for treati
- -
-
Paragraph 0977; 0978
(2014/08/06)
-
- TRICYCLIC COMPOUNDS AS TEC KINASE INHIBITORS
-
The present invention is directed to tricyclic compounds of formula (I) as Tec kinase inhibitors, in particular ITK (interleukin-2 inducible tyrosine kinase) inhibitors. Also provided herein are processes for preparing compounds described herein, intermed
- -
-
Page/Page column 47
(2013/11/05)
-
- NOVEL COMPOUNDS
-
The invention relates to tricyclic derivatives, and their use in treating diseases and conditions mediated by antagonism of the mGluR5 receptor, in particular substance related disorders. In addition, the invention relates to compositions containing the derivatives and processes for their preparation.
- -
-
Page/Page column 40-41
(2011/12/14)
-
- A simple and facile route for the synthesis of 2H-1,4-benzoxazin-3-(4H)- ones via reductive cyclization of 2-(2-nitrophenoxy)acetonitrile adducts in the presence of Fe/acetic acid
-
A simple route for the synthesis of 1,4-benzoxazin-3-(4H)-ones is described herein. This method involves the reductive cyclization of 2-(2-nitrophenoxy) acetonitrile adducts in the presence of Fe/acetic acid in good to excellent yields. This system was compatible with various other functional groups.
- Ramesh, Chintakunta,Raju, B. Rama,Kavala, Veerababurao,Kuo, Chun-Wei,Yao, Ching-Fa
-
p. 1187 - 1192
(2011/03/22)
-
- FUSED THIAZOLE AND THIOPHENE DERIVATIVES AS KINASE INHIBITORS
-
A series of fused bicyclic thiazole and thiophene derivatives which are substituted in the 2-position by an optionally substituted morpholin-4-yl moiety, and in the 4-position by hydroxy, oxo or an amine moiety, being selective inhibitors of PI3 kinase enzymes, are accordingly of benefit in medicine, for example in the treatment of inflammatory, autoimmune, cardiovascular, neurodegenerative, metabolic, oncological, nociceptive or ophthalmic conditions. (I)
- -
-
Page/Page column 96
(2009/07/17)
-
- Achieving multi-isoform PI3K inhibition in a series of substituted 3,4-dihydro-2H-benzo[1,4]oxazines
-
The SAR and pharmacokinetic profiles of a series of multi-isoform PI3K inhibitors based on a 3,4-dihydro-2H-benzo[1,4]oxazine scaffold are disclosed.
- Perry, Benjamin,Alexander, Rikki,Bennett, Gavin,Buckley, George,Ceska, Tom,Crabbe, Tom,Dale, Verity,Gowers, Lewis,Horsley, Helen,James, Lynwen,Jenkins, Kerry,Crepy, Karen,Kulisa, Claire,Lightfoot, Helen,Lock, Chris,Mack, Stephen,Morgan, Trevor,Nicolas, Anne-Lise,Pitt, Will,Sabin, Verity,Wright, Sara
-
scheme or table
p. 4700 - 4704
(2009/04/08)
-
- Tetrahydroquinoline analogues as muscarinic agonists
-
The present invention relates to tetrahydroquinoline compounds as muscarinic receptor agonists; compositions comprising the same; methods of inhibiting an activity of a muscarinic receptor with said compounds; methods of treating a disease condition associated with a muscarinic receptor using said compounds; and methods for identifying a subject suitable for treatment using said compounds.
- -
-
-
- Tetrahydroquinoline analogues as muscarinic agonists
-
The present invention relates to tetrahydroquinoline compounds as muscarinic receptor agonists; compositions comprising the same; methods of inhibiting an activity of a muscarinic receptor with said compounds; methods of treating a disease condition associated with a muscarinic receptor using said compounds; and methods for identifying a subject suitable for treatment using said compounds.
- -
-
-
- Heterocyclic herbicides
-
Compounds of Formula I, and their N-oxides and agriculturally suitable salts, are disclosed which are useful for controlling undesired vegetation wherein, Q is and W,X,R1-R7are as defined in the disclosure. Also disclosed are composi
- -
-
-
- Herbicidal tricyclic heterocycles
-
Compounds of Formula I having herbicidal utility are disclosed: STR1 wherein Q, R1, R2, V, m and p are defined in the text, including compositions containing such compounds, and a method for controlling weeds employing such compounds.
- -
-
-
- Herbicidal glutarimides
-
This invention relates to glutarimide compounds exhibiting herbicidal activity having the structure STR1 wherein A is carbonyl, thiocarbonyl or methylene, A1 is carbonyl or methylene, Q is O or (CH2)n where n is 0 or 1, D is CH or N and R, R1, R2, T, X, Y and Z are as defined within, compositions containing these compounds and methods of using these compounds as herbicides and algicides.
- -
-
-
- Herbicidal glutaramic acids and derivatives
-
This invention relates to glutaramic acids and derivatives exhibiting herbicidal activity having the structure STR1 wherein A is a carboxylic acid or a derivative thereof, D is CH or N, and R, R1, R2, T, X, Y, and Z are as defined within, compositions containing these compounds and methods of controlling weeds with these compounds.
- -
-
-
- Synergistic herbicidal composition
-
Disclosed are herbicidal compositions containing a combination of the compound 2-[1-(3-transchloroallyloxyimino)propyl]-5-(2-ethylthiopropyl)-3-hydroxy-2-cyclohexene-1-one (or a herbicidally effective salt thereof) and the compound 2-[7-fluoro-3,4-dihydro-3-oxo-4-(2-propynyl)-2H-1,4-benzoxazine-6-yl]-4,5,6,7-tetrahydro-1H-isoindole-1,3(2H)-dione. It has been found that this combination synergistically interacts so as to accelerate the post-emergent herbicidal activity of 2-[1-(3-trans-chloroallyloxyimino)propyl]-5-(2-ethylthiopropyl)-3-hydroxy-2-cyclohexen-1-one (or its salt) against grassy weeds.
- -
-
-
- Tetrazolinone herbicides
-
Herbicidal compounds of the formula STR1 in which R1 is H, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, alkoxyalkyl, alkoxyalkoxyalkyl, alkylsulfonyl, aralkyl, alkylthioalkyl, hydroxy or alkoxy; R2 and R3
- -
-
-
- Tetrahydrophthalimides and their herbicidal use
-
A compound of the formula: STR1 wherein R1 is a hydrogen atom, a C1 -C5 alkyl group, a C3 -C4 alkenyl group, a C3 -C4 alkynyl group, a C1 -C4 haloalkyl group, a C3 -C4 haloalkenyl group, a C3 -C4 haloalkynyl group, a C1 -C2 alkoxy(C1 -C2)alkyl group or a C1 -C2 alkoxy(C1 -C2)alkoxy(C1 -C2)alkyl group, R2 and R3 are, the same or different, each a hydrogen atom, a halogen atom, a C1 -C3 alkyl group or a phenyl group, X is a hydrogen atom, a chlorine atom or a fluorine atom and n is an integer of 0 or 1, which is useful as a herbicide.
- -
-
-