- Preparation method 2 - chloro -3 - bromoaniline
-
The invention discloses a preparation method of 2 - chloro -3 - bromoaniline, and the specific steps of the preparation method are as follows: (1) the compound II and the bromosuccinimide are subjected to electrophilic substitution reaction to generate the compound III. (2) The sulfonic acid group of the compound III was removed to give compound IV. (3) Compound IV is reduced to compound I with a safety powder, i.e. said 2 - chloro -3 - bromoaniline. To the invention, 4 - chlorine -3 - nitrobenzene sulfonic acid is used as a starting raw material in a full synthetic route process, reagents with large toxicity and large pollution are avoided, and meanwhile, the raw materials are low in price and higher in yield.
- -
-
Paragraph 0022; 0026-0027; 0032; 0036-0037; 0040; 0044-0045
(2021/10/05)
-
- SUBSTITUTED QUINAZOLINE COMPOUNDS AND THEIR USE AS INHIBITORS OF G12C MUTANT KRAS, HRAS AND/OR NRAS PROTEINS
-
Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I) or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein R, R1, R2a, R2b, R2c, A, B, L1 and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.
- -
-
Page/Page column 100
(2017/02/09)
-
- Design, synthesis and herbicidal activity study of aryl 2,6-disubstituted sulfonylureas as potent acetohydroxyacid synthase inhibitors
-
A series of sulfonylurea derivatives containing a 2,6-disubstituted aryl moiety were designed, synthesized and evaluated for their herbicidal activities. Most of these compounds showed excellent inhibitory rates against both monocotyledonous and dicotyledonous weeds, especially 10a, 10h and 10i. They exhibited equivalent or superior herbicidal efficiency than commercial chlorsulfuron at the dosage of 15?g/ha and the preliminary SAR was summarized. In order to illuminate the molecular mechanism of several potent compounds, their apparent inhibition constant (Kiapp) of Arabidopsis thaliana acetohydroxyacid synthase (AHAS) were determined and the results confirmed that these compounds were all potent AHAS inhibitors. 10i have a Kiapp of 11.5?nM, which is about 4 times as potent as chlorsulfuron (52.4?nM).
- Wei, Wei,Zhou, Shaa,Cheng, Dandan,Li, Yuxin,Liu, Jingbo,Xie, Yongtao,Li, Yonghong,Li, Zhengming
-
supporting information
p. 3365 - 3369
(2017/07/07)
-
- INHIBITORS OF KRAS G12C
-
Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein R1, R2a, R3a, R3b, R4a, R4b, G1, G2, L1, L2, m1, m2, A, B, W, X, Y, Z and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.
- -
-
Page/Page column 271
(2015/04/28)
-
- Compounds and Compositions as Protein Kinase Inhibitors
-
The present invention provides compounds of Formula I or II: wherein R1, R1b, R2, R3, R4, R5, R6 and R7 are defined herein. The compounds of Formula (I) or (II) and pharmaceutical compositions thereof are useful for the treatment of B-Raf-associated diseases.
- -
-
-
- DIKETOPIPERAZINE DERIVATIVES AS P2X7 MODULATORS
-
The invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof: (I) wherein: A represents an aryl, heteroaryl or heterocyclyl group; and any ring or ring system of said aryl or heteroaryl is optionally substituted with 1 to 3 substituents, which may be the same or different, selected from the group consisting of halogen, C1-6 alkyl, -CF3, - OCF3, cyano, C1-6 alkoxy, -NR10R11, -X-aryl, -X-heteroaryl and -X-heterocyclyl; R1, R2, R3, R4 and R5 independently represent hydrogen, fluorine, chlorine, -CF3, cyano or C1-6 alkyl, such that at least one of R1, R2, R3, R4 and R5 is other than hydrogen; R6, R7, R8, R9, R10 and R11 independently represent hydrogen or C1-6 alkyl; X represents a linker selected from a bond, -(CH2)n- and -O-(CH2)n-; and n represents an integer from 1 to 3. The compounds or salts modulate P2X7 receptor function and are capable of antagonizing the effects of ATP at the P2X7 receptor ("P2X7 receptor antagonists").
- -
-
Page/Page column 78
(2010/11/17)
-
- IMIDAZOLINYLMETHYL ARYL SULFONAMIDE
-
This invention relates to an alpha-1A receptor partial agonist, which is represented by Formula I: and pharmaceutically acceptable salts or solvates thereof. The invention further relates to pharmaceutical compositions containing formula I, methods for their use as therapeutic agents, and methods of preparation thereof.
- -
-
Page/Page column 5
(2009/08/16)
-
- Synthesis and potent antifungal activity against Candida species of some novel 1H-benzimidazoles
-
(Chemical Equation Presented) A series of 47 novel N1-alkylated- 2-aryl-5(6)-substituted-1H-benzimidazoles and their three novel indole analogues were synthesized and evaluated for in vitro antifungal activities against Candida species by the tube dilution method. The results showed that compounds 79 and 80, having pyridine at the position C-2, of benzimidazoles exhibited the greatest activity with MIC values of 6.25-3.12 μg/mL. Indole analogues 108-110 have no inhibitory activity.
- Goeker, Hakan,Alp, Mehmet,Ates-Alagoez, Zeynep,Yildiz, Sulhiye
-
scheme or table
p. 936 - 948
(2009/12/05)
-
- BENZIMIDAZOLYL COMPOUNDS AS POTENTIATORS OF MGLUR2 SUBTYPE OF GLUTAMATE RECEPTOR
-
Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula (I) as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.
- -
-
Page/Page column 61
(2010/11/30)
-
- FUSED PYRIMIDINE DERIVATIVE AND USES THEREOF
-
A compound represented by the formula (I) wherein ring A is a 5-membered aromatic heterocycle optionally having substituent(s), R1 is a hydrogen atom or a hydrocarbon group optionally having substituent(s), W is an oxygen atom or a sulfur atom, X1 and X2 may be the same or different and each is a hydrogen atom, a hydrocarbon group optionally having substituent(s) or a heterocyclic group, or, X1 and X2 in combination optionally form an oxygen atom, a sulfur atom or =NR2, ring B is an aromatic ring optionally further having substituent(s), Y is a bond, C1-6 alkylene C2-6 alkenylene or C2-6 alkynylene, optionally having substituent(s), and Z is a group represented by formula: -SOnR3, or a group represented by formula: -COR4, or a salt thereof, is useful as a pharmaceutical agent having GnRH antagonistic action.
- -
-
Page/Page column 71-72
(2008/06/13)
-
- Synthesis and structure-activity studies of novel benzocycloheptanone oxazolidinone antibacterial agents
-
We describe a novel class of benzocycloheptanone derived oxazolidinone antibacterial agents. The synthesis and antibacterial activities with structure variation is discussed.
- Vara Prasad,Boyer, Frederick E.,Chupak, Lou,Dermyer, Michael,Ding, Qizhu,Gavardinas,Hagen, Susan E.,Huband, Michael D.,Jiao, Wenhua,Kaneko, Takushi,Maiti, Samarendra N.,Melnick, Michael,Romero, Karina,Patterson,Wu, Xiujuan
-
p. 5392 - 5397
(2007/10/03)
-
- ANTIBACTERIAL AGENTS
-
Compounds of formula I and methods for their preparation are disclosed. Further disclosed are methods of making biologically active compounds of formula I as well as pharmaceutically acceptable compositions comprising compounds of formula I. Compounds of formula I as disclosed herein can be used in a variety of applications including use as antibacterial agents.
- -
-
Page 126-127
(2010/02/08)
-
- High-affinity α-aminobutyric acid A/benzodiazepine ligands: Synthesis and structure - Activity relationship studies of a new series of tetracyclic imidazoquinoxalines
-
A series of tetracyclic imidazoquinoxaline analogs was developed which constrain the carbonyl group of the partial agonist 3-(5-cyclopropyl-1,2,4- oxadiazol-3-yl)-5-[(dimethylamino)carbonyl]4,5-dihydroimidazo[1,5- a]quinoxaline (2, U-91571) away from the benzene ring. These analogs orient the carbonyl group in the opposite direction of the previously reported full agonist 1-(5-cyclopropyl- 1,2,4-oxadiazol-3-yl)- 12,12a-dihydroimidazo[1,5- a]pyrrolo[2,1-c]quinoxalin- 10(11H)one (3, U-89267). A number of approaches were utilized to form the 'bottom' ring of this tetracyclic ring system including intramolecular cyclizations promoted by Lewis acids or base, as well as metal-carbenoid conditions. The size and substitution pattern of the additional ring was widely varied. Analogs within this series had high affinity for the benzodiazepine receptor on the α-aminobutyric acid A chloride ion channel complex. From TBPS shift and Cl- current assays, the in vitro efficacy of compounds within this class ranged from antagonists to partial agonists with only 18a identified as a full agonist. Additionally, several analogs were quite potent at antagonizing metrazole-induced seizures indicating possible anticonvulsant or anxiolytic activity. Unlike 3, analogs in this series did not have high affinity for the diazepam insensitive α6β2δ2 subtype. These results suggest that either constraining the carbonyl group away from the benzene ring or the greater planarity that results from the additional cyclic structure provides analogs with partial agonist properties and prevents effective interaction with the α6β2δ2 subtype.
- Mickelson, John W.,Jacobsen, E. Jon,Carter, Donald B.,Im, Haesook K.,Im, Wha Bin,Schreur, Peggy J. K. D.,Sethy, Vimala H.,Tang, Andy H.,McGee, James E.,Petke, James D.
-
p. 4654 - 4666
(2007/10/03)
-
- The Exchange Reaction of 3-Bromo-2-iodonitrobenzene with Tetrabutylammonium Bromochlorocuprate(I) in Chlorobenzene
-
In the halogen exchange reaction of 3-bromo-2-iodonitrobenzene with tetrabutylammonium bromochlorocuprate, Br as well as Cl of the bromochlorocuprate(I) ion are available for exchange with I of the aryl halide.Simulated values of the rate constants for the formation of the end product, 3-bromo-2-chloronitrobenzene, are given.
- Liedholm, Brita
-
p. 237 - 241
(2007/10/02)
-
- Solvent Effects in the Halogen Exchange Reaction of 2,3-Dibromonitrobenzene and Tetrabutylammonium Dichlorocuprate(I)
-
The copper(I) catalyzed halogen exchange reaction of 2,3-dibromonitrobenzene with tetrabutylammonium dichlorocuprate(I) has been studied kinetically in dimethyl sulfoxide and in aqueous dimethyl sulfoxide, where reactions are faster than in chlorobenzene or toluene.The enhancement of the reaction rate observed in aqueous dimethyl sulfoxide compared to dry dimethyl sulfoxide is primarily due to stronger solvation of the initial state, mainly of the large CuCl2- anion, by DMSO than by water.
- Liedholm, Brita,Nilsson, Martin
-
p. 289 - 293
(2007/10/02)
-