27631-29-4Relevant articles and documents
2,4- Dichloro -6,7-dimethoxyquinazoline solvate and preparation method thereof (by machine translation)
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Paragraph 0039-0041, (2020/06/02)
The invention provides 2,4 - dichloro - 66667-dimethoxyquinazoline solvate, and the solvate has the chemical structure: shown in the formula I. A specific preparation method is: dichloro - 666627-dimethoxyquinazoline solvate 2,4 - obtained by adding first kinds of solvent, stirring crystallization; to the quinazoline concentrate second of - 5 5 5 5 5-dimethoxyquinazoline solvate by stirring, through filtration, drying, to obtain a pale yellow crystalline solid powder, which is a, dichloro - 666627-dimethoxyquinazolinazolinazolinazolinazolinone chemical unstable. 2,4 - 2,4 - in drying and, storage. The present invention relates to a method for preparing the intermediate 2,4 - in a dry state. (by machine translation)
One-pot cascade ring enlargement of isatin-3-oximes to 2,4-dichloroquinazolines mediated by bis(trichloromethyl)carbonate and triarylphosphine oxide
Qin, Jinjing,Li, Zhenhua,Ma, Shengzhe,Ye, Lixian,Jin, Guoqiang,Su, Weike
supporting information, p. 1007 - 1012 (2020/07/10)
An efficient and convenient one-pot cascade synthesis of 2,4-dichloroquinazolines directly from isatin-3-oximes with the addition of bis(trichloromethyl)carbonate and triarylphosphine oxide was developed, leading to substituted quinazolines in moderate to excellent yields. The efficiency of this transformation was demonstrated by compatibility with a range of functional groups. Thus, the method represents a convenient and practical strategy for the synthesis of substituted 2,4-dichloroquinazolines.
Combining Isocyanides with Carbon Dioxide in Palladium-Catalyzed Heterocycle Synthesis: N3-Substituted Quinazoline-2,4(1H,3H)-diones via a Three-Component Reaction
Mampuys, Pieter,Neumann, Helfried,Sergeyev, Sergey,Orru, Romano V. A.,Jiao, Haijun,Spannenberg, Anke,Maes, Bert U. W.,Beller, Matthias
, p. 5549 - 5556 (2017/08/17)
We report a Pd-catalyzed three-component reaction of 2-bromoanilines, carbon dioxide, and isocyanides. The combination of these two readily available C1-reactants, featuring a huge difference in kinetic and thermodynamic stability, is hitherto unprecedented in transition-metal catalysis. With this one-pot three-component reaction, N3-substituted quinazoline-2,4(1H,3H)-diones are obtained in moderate to high yields in a completely regio- and chemoselective manner. Our approach easily allows variation of the arene and N3-substitution pattern of the desired heterocycle. The formal synthesis of different APIs illustrates its practical applicability. In addition, the methodology also allows for a convenient and selective 13C-labeling through the use of 13CO2. This is illustrated for [2-13C]-2,4-dichloro-6,7-dimethoxyquinazoline synthesis, a key intermediate for several APIs.
SUBSTITUTED QUINAZOLINE COMPOUNDS AND PREPARATION AND USES THEREOF
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Page/Page column 52; 71; 72, (2017/03/08)
The present invention relates quinazolinone compounds of Formula (I), as well as their preparation and uses, and further relates pharmaceutical compositions comprising these compounds and their uses； wherein the compounds or pharmaceutical compositions disclosed herein can be used for antagonizing the orexin receptor. The present invention also relates to uses of the compounds or pharmaceutical compositions in treating or preventing neurological and psychiatric disorders and diseases of the central nervous system in mammals, especially in humans.
Function-oriented development of CXCR4 antagonists as selective human immunodeficiency virus (HIV)-1 entry inhibitors
Wu, Chien-Huang,Wang, Chuan-Jen,Chang, Chun-Ping,Cheng, Yung-Chi,Song, Jen-Shin,Jan, Jiing-Jyh,Chou, Ming-Chen,Ke, Yi-Yu,Ma, Jing,Wong, Ying-Chieh,Hsieh, Tsung-Chih,Tien, Yun-Chen,Gullen, Elizabeth A.,Lo, Chen-Fu,Cheng, Chia-Yi,Liu, Yu-Wei,Sadani, Amit A.,Tsai, Chia-Hua,Hsieh, Hsin-Pang,Tsou, Lun K.,Shia, Kak-Shan
, p. 1452 - 1465 (2015/03/04)
Motivated by the pivotal role of CXCR4 as an HIV entry co-receptor, we herein report a de novo hit-to-lead effort on the identification of subnanomolar purine-based CXCR4 antagonists against HIV-1 infection. Compound 24, with an EC50 of 0.5 nM against HIV-1 entry into host cells and an IC50 of 16.4 nM for inhibition of radioligand stromal-derived factor-1α (SDF-1α) binding to CXCR4, was also found to be highly selective against closely related chemokine receptors. We rationalized that compound 24 complementarily interacted with the critical CXCR4 residues that are essential for binding to HIV-1 gp120 V3 loop and subsequent viral entry. Compound 24 showed a 130-fold increase in anti-HIV activity compared to that of the marketed CXCR4 antagonist, AMD3100 (Plerixafor), whereas both compounds exhibited similar potency in mobilization of CXCR4+/CD34+ stem cells at a high dose. Our study offers insight into the design of anti-HIV therapeutics devoid of major interference with SDF-1α function.
Novel 2-chloro-4-anilino-quinazoline derivatives as EGFR and VEGFR-2 dual inhibitors
Barbosa, Maria Letícia De Castro,Lima, Lídia Moreira,Tesch, Roberta,Sant'Anna, Carlos Mauricio R.,Totzke, Frank,Kubbutat, Michael H.G.,Sch?chtele, Christoph,Laufer, Stefan A.,Barreiro, Eliezer J.
, p. 1 - 14 (2013/12/04)
Novel 2-chloro-4-anilino-quinazolines designed as EGFR and VEGFR-2 dual inhibitors were synthesized and evaluated for inhibitory effects. EGFR and VEGFR-2 are validated targets in cancer therapy and combined inhibition might be synergistic for both antitumor activity and resistance prevention. The biological data obtained proved the potential of 2-chloro-4-anilino-quinazoline derivatives as EGFR and VEGFR-2 dual inhibitors, highlighting compound 8o, which was approximately 7-fold more potent on VEGFR-2 and approximately 11-fold more potent on EGFR compared to the prototype 7. SAR and docking studies allowed the identification of pharmacophoric groups for both kinases and demonstrated the importance of a hydrogen bond donor at the para position of the aniline moiety for interaction with conserved Glu and Asp amino acids in EGFR and VEGFR-2 binding sites.
Design and synthesis of 6,7-dimethoxyquinazoline analogs as multi-targeted ligands for α1- and AII-receptors antagonism
Yadav,Naik,Gandhi,Chauhan,Giridhar
, p. 3959 - 3966 (2013/07/27)
Multiple-targeted ligands can have certain advantages for the management of hypertension which has multiple controls. Molecules with dual bioactivities are available in literature for treating metabolic disorders like diabetes, hypertension and hypercholesterolemia. After scrutinizing the SAR of prazosin-type α1-blockers and AII-antagonists it was planned to develop dual α1- and AII-antagonists. Five series of quinazoline derivatives were synthesized and evaluated as dual α1- and AII-antagonists on rat aortic strips for the blockade of known α1- and AII-agonist mediated contractions. Many compounds showed balanced activity on both the receptors but compound (22) was found to be the most active derivative having higher antagonistic activity on both the receptors. In the in vivo experiments the chosen compound (22) was slightly less active than prazosin but was found to be equipotent to losartan. These findings shed a new light on the structural requirements for both α1- as well as AII-receptor antagonists.
Synthesis and anti-proliferative activity of substituted- anilinoquinazolines and its relation to EGFR inhibition
El Ella,Saleh,Hassan,Hamdy,El-Araby,Abouzid
, p. 360 - 366 (2012/10/29)
4-Anilinoquinazoline is a privileged scaffold in developing small molecule inhibitors of tyrosine kinases (TK) especially epidermal growth factor receptor (EGFR). 2 series belonging to 3'-substituted-4-anilinoquinazoline scaffold were synthesized and screened in vitro on isolated and a breast cancer cell line. The research aims at exploring the activity of compounds having diverse substituents at 3' position of the aniline moiety. Generally, the meta-substituted-anilinoquinazolines exhibited significant inhibitory activity against isolated enzyme as well as MCF-7 cancer cell line. For instance, compound 10b inhibited >99% of EGFR activities at 10 M concentration. 6 of the tested compounds exhibited range of anti-proliferative activity below 10 M potency. In particular, compounds 6e and 10b displayed the highest activity among the tested compounds with IC50 values equal to 8.6 and 4.84 M, respectively. Structure-based tools were utilized to rationalize EGFR-TK binding of compound 10b since it is the most active compound in the enzyme inhibition test. Georg Thieme Verlag KG Stuttgart.New York.
Facile and efficient cyclization of anthranilonitrile to 2,4-dichloroquinazoline by bis(trichloromethyl) carbonate and catalytic amount triphenylphosphine oxide
Li, Zhenhua,Wu, Danli,Zhong, Weihui
experimental part, p. 1417 - 1426 (2012/08/28)
2,4-Dichloroquinazolines were synthesized by the cyclization of anthranilonitrile using bis(trichloromethyl) carbonate (BTC) with the aid of catalytic amount of triphenylphosphine oxide (Ph3PO) at 120 °C. This method was also applied to the syn
Structure-based design of potent and selective 2-(quinazolin-2-yl)phenol inhibitors of checkpoint kinase 2
Caldwell, John J.,Welsh, Emma J.,Matijssen, Cornelis,Anderson, Victoria E.,Antoni, Laurent,Boxall, Kathy,Urban, Frederique,Hayes, Angela,Raynaud, Florence I.,Rigoreau, Laurent J. M.,Raynham, Tony,Aherne, G. Wynne,Pearl, Laurence H.,Oliver, Antony W.,Garrett, Michelle D.,Collins, Ian
supporting information; experimental part, p. 580 - 590 (2011/03/21)
Structure-based design was applied to the optimization of a series of 2-(quinazolin-2-yl)phenols to generate potent and selective ATP-competitive inhibitors of the DNA damage response signaling enzyme checkpoint kinase 2 (CHK2). Structure-activity relationships for multiple substituent positions were optimized separately and in combination leading to the 2-(quinazolin-2-yl) phenol 46 (IC50 3 nM) with good selectivity for CHK2 against CHK1 and a wider panel of kinases and with promising in vitro ADMET properties. Off-target activity at hERG ion channels shown by the core scaffold was successfully reduced by the addition of peripheral polar substitution. In addition to showing mechanistic inhibition of CHK2 in HT29 human colon cancer cells, a concentration dependent radioprotective effect in mouse thymocytes was demonstrated for the potent inhibitor 46 (CCT241533).
