cas 126728-20-9, 2,4-DICHLOROPYRIDO[2,3-D]PYRIMIDINE

Articles about 126728-20-9Total 23 be found

Article title
Article abstract
Author
Journal number and time
Download

The discovery and optimisation of pyrido[2,3-d]pyrimidine-2,4-diamines as potent and selective inhibitors of mTOR kinase
We describe a novel series of potent inhibitors of the kinase activity of mTOR. The compounds display good selectivity relative to other PI3K-related kinase family members and, in cellular assays, inhibit both mTORC1 and mTORC2 complexes and exhibit good antiproliferative activity.
Malagu, Karine,Duggan, Heather,Menear, Keith,Hummersone, Marc,Gomez, Sylvie,Bailey, Christine,Edwards, Peter,Drzewiecki, Jan,Leroux, Frederic,Quesada, Mar Jimenez,Hermann, Gesine,Maine, Stephanie,Molyneaux, Carrie-Anne,Le Gall, Armelle,Pullen, James,Hickson, Ian,Smith, Lisa,Maguire, Sharon,Martin, Niall,Smith, Graeme,Pass, Martin
p. 5950 - 5953
(2009)
Read Online

Compounds containing pyrimidine heterocyclic structures and preparation methods and applications thereof
Compounds containing pyrimidine heterocyclic structures and preparation methods and applications thereof, belonging to the field of pharmaceutical technology, the present invention relates to compounds containing pyrimidine heterocyclic structures shown i
-
Paragraph 0177; 0180-0181

(2022/01/10)

ION CHANNEL INHIBITOR COMPOUNDS FOR CANCER TREATMENT
The present invention concerns a compound of following general formula (I): where: either R is an R1 group and R′ is an -A1-Cy1 group, or R is an -A1-Cy1 group and R′ is an R1 group, R1 particularly being H or (C1-C6)alkyl group;A1 being an —NH— radical or —NH—CH2— radical;Cy1 particularly being a phenyl group,A is a fused (hetero)aromatic ring having 5 to 7 atoms, for use for treating cancer.
-
(2021/01/25)

Synthesis and structure-activity relationship of: N 4-benzylamine- N 2-isopropyl-quinazoline-2,4-diamines derivatives as potential antibacterial agents
A series of N4-benzylamine-N2-isopropyl-quinazoline-2,4-diamine derivatives has been synthesized and tested for antibacterial activity against five bacterial strains. Twelve different substituents on the N4-benzylamine group have been investigated along with replacement of the quinazoline core (with either a benzothiophene or regioisomeric pyridopyrimidine ring systems). In order to develop structure activity relationships, all derivatives were tested for their antibacterial activities against Escherichia coli and Staphylococcus aureus via Kirby-Bauer assays and minimum inhibitory concentration assays. Eight of the most potent compounds against S. aureus and E. coli were also screened against one strain of methicillin-resistant S. aureus (MRSA), Staphylococcus epidermidis and Salmonella typhimurium to further examine their antibacterial activities. Lead compound A5 showed good activities with MICs of 3.9 μg mL-1 against E. coli, S. aureus and S. epidermidis and 7.8 μg mL-1 against MRSA. Selected front runners were also screened for their DMPK properties in vitro to assess their potential for further development.
Jiang, Zhengyun,Hong, W. David,Cui, Xiping,Gao, Hongcan,Wu, Panpan,Chen, Yingshan,Shen, Ding,Yang, Yang,Zhang, Bingjie,Taylor, Mark J.,Ward, Stephen A.,O'Neill, Paul M.,Zhao, Suqing,Zhang, Kun
p. 52227 - 52237
(2017/11/22)

2,4-quinazolinediamine derivatives, and preparation method and application thereof
The invention discloses 2,4-quinazolinediamine derivatives, and a preparation method and application thereof, belonging to the field of medicines and preparation and application thereof. The 2,4-quinazolinediamine derivatives comprises compounds as shown in a formula (I) which is described in the specification and a solvate, hydrate, tautomer and pharmaceutically acceptable salt thereof. Test results show that the 2,4-quinazolinediamine derivatives have strong Wolbachia resisting activity; and in the derivatives, 2-isopropylamido substitution has good effect, and compounds with better Wolbachia resisting activity can be obtained by changing a 4-amido group. The compounds have activity in resisting plasmodia, Wolbachia and bacteria.
-
Paragraph 0211; 0214; 0215

(2017/04/18)

PIPERAZINYL PYRIMIDINE DERIVATIVES, PREPARATION METHOD AND USE THEREOF
Provided are piperazinyl pyrimidine derivatives of formula I having CCR4 antagonism, and the preparation method, pharmaceutical composition and use thereof in the preparation of a medicament. The medicament is useful for the treatment and preve
-
(2015/05/13)

Novel quinazoline and pyrido[2,3-d]pyrimidine derivatives and their hydroselenite salts as antitumoral agents
A series of 22 quinazolines, pyrido[2,3-d]pyrimidines and their hydroselenite salts were synthesized with the aim of evaluating in vitro their cytotoxicity against PC-3 cell line and their antioxidant properties related to DPPH (1,1-diphenyl-2-picrylhydrazylradical) activity, showing some of them better profile than the respective controls. Three of these derivatives (5d, 6d and 7f) were selected in order to gain preliminary insights to establish the mechanism of action. Caspase-3 activity and cell cycle regulation studies revealed that compound 6d provoked an increase in caspase-3 level accompanied by cell cycle perturbation in a time-dependent manner.
Palop, Juan Antonio,Plano, Daniel,Moreno, Esther,Sanmartin, Carmen
p. 187 - 206
(2014/03/21)

Novel Hinge-Binding Motifs for Janus Kinase 3 Inhibitors: A Comprehensive Structure-Activity Relationship Study on Tofacitinib Bioisosteres
The Janus kinases (JAKs) are a family of cytosolic tyrosine kinases crucially involved in cytokine signaling. JAKs have been demonstrated to be valid targets in the treatment of inflammatory and myeloproliferative disorders, and two inhibitors, tofacitinib and ruxolitinib, recently received their marketing authorization. Despite this success, selectivity within the JAK family remains a major issue. Both approved compounds share a common 7H-pyrrolo[2,3-d]pyrimidine hinge binding motif, and little is known about modifications tolerated at this heterocyclic core. In the current study, a library of tofacitinib bioisosteres was prepared and tested against JAK3. The compounds possessed the tofacitinib piperidinyl side chain, whereas the hinge binding motif was replaced by a variety of heterocycles mimicking its pharmacophore. In view of the promising expectations obtained from molecular modeling, most of the compounds proved to be poorly active. However, strategies for restoring activity within this series of novel chemotypes were discovered and crucial structure-activity relationships were deduced. The compounds presented may serve as starting point for developing novel JAK inhibitors and as a valuable training set for in silico models.
Gehringer, Matthias,Forster, Michael,Pfaffenrot, Ellen,Bauer, Silke M.,Laufer, Stefan A.
supporting information
p. 2516 - 2527
(2015/08/24)

PIPERAZINYL PYRIMIDINE DERIVATIVES, PREPARATION METHOD AND USE THEREOF
Provided are piperazinyl pyrimidine derivatives of formula I having CCR4 antagonism, and the preparation method, pharmaceutical composition and use thereof in the preparation of a medicament. The medicament is useful for the treatment and preve
-
(2014/12/09)

Discovery of 1-methyl-1 H-imidazole derivatives as potent Jak2 inhibitors
Structure based design, synthesis, and biological evaluation of a novel series of 1-methyl-1H-imidazole, as potent Jak2 inhibitors to modulate the Jak/STAT pathway, are described. Using the C-ring fragment from our first clinical candidate AZD1480 (24), optimization of the series led to the discovery of compound 19a, a potent, orally bioavailable Jak2 inhibitor. Compound 19a displayed a high level of cellular activity in hematopoietic cell lines harboring the V617F mutation and in murine BaF3 TEL-Jak2 cells. Compound 19a demonstrated significant tumor growth inhibition in a UKE-1 xenograft model within a well-tolerated dose range.
Su, Qibin,Ioannidis, Stephanos,Chuaqui, Claudio,Almeida, Lynsie,Alimzhanov, Marat,Bebernitz, Geraldine,Bell, Kirsten,Block, Michael,Howard, Tina,Huang, Shan,Huszar, Dennis,Read, Jon A.,Rivard Costa, Caroline,Shi, Jie,Su, Mei,Ye, Minwei,Zinda, Michael
p. 144 - 158
(2014/02/14)

NOVEL MICROBICIDES
Compounds of formula (I) wherein G1 represents together with the two ring atoms of the pyrimidine ring to which it is attached, a 5- to 6-membered aromatic heterocyclic ring system which contains one or two heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, and the other substituents are as defined in claim 1, are suitable for use as micro-biocides.
-
Page/Page column 21

(2013/02/27)

Design and synthesis of a series of pyrido[2,3-d]pyrimidine derivatives as CCR4 antagonists
A series of pyrido[2,3-d]pyrimidine derivatives were designed and synthesized based on known CC chemokine receptor 4 (CCR4) antagonists. The activities of all the newly synthesized compounds were evaluated using a chemotaxis inhibition assay. Compound 6b
Gong, Hongwei,Qi, Hui,Sun, Wei,Zhang, Yang,Jiang, Dan,Xiao, Junhai,Yang, Xiaohong,Wang, Ying,Li, Song
p. 9961 - 9970
(2012/11/13)

Sulfur and selenium derivatives of quinazoline and pyrido[2,3-d]pyrimidine: Synthesis and study of their potential cytotoxic activity in vitro
The synthesis, cytotoxic activities and selectivities of 35 derivatives related to quinazoline and pyrido[2,3-d]pyrimidine are described. The synthesized compounds were screened in vitro against four tumoral cell lines - leukemia (CCRF-CEM), colon (HT-29), lung (HTB-54) and breast (MCF-7) - and two cell lines derived from non-malignant cell lines, one mammary (184B5) and one from bronchial epithelium (BEAS-2B). MCF-7 and HTB-54 were the most sensitive cell lines with GI50 values below 10 μM for eleven and ten compounds, respectively. Two compounds (2o and 3a) were identified that evoked a marked cytotoxic effect in all cell lines tested and one compound, 7h, was potent and selective against MCF-7. A preliminary study into the mechanism of the potent derivatives 2o, 3a and 7h indicated that the cytotoxic activities of these compounds might be mediated by inducing cell death without affecting cell cycle phases.
Moreno, Esther,Plano, Daniel,Lamberto, Iranzu,Font, María,Encío, Ignacio,Palop, Juan Antonio,Sanmartín, Carmen
scheme or table
p. 283 - 298
(2012/02/16)

NOVEL MICROBICIDES
Compounds of formula (I) wherein G1 represents together with the two ring atoms of the pyrimidine ring to which it is attached, a 5-to 6-membered aromatic heterocyclic ring system which contains one or two heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, and the other substituents are as defined in claim 1, are suitable for use as microbiocides.
-
Page/Page column 45

(2011/09/21)

New insights into the structural requirements for pro-apoptotic agents based on 2,4-diaminoquinazoline, 2,4-diaminopyrido[2,3-d]pyrimidine and 2,4-diaminopyrimidine derivatives
As a continuation of our work on new anti-tumoral derivatives with selective pro-apoptotic activity in cancer cells, we describe the synthesis and the preliminary evaluation of the cytotoxic and pro-apoptotic activities of a series of pyrimidin-2,4-diamine derivatives that are structurally related to quinazolin-2,4-diamine and pyrido[2,3-d]pyrimidin-2,4-diamine derivatives. We also describe the structure-activity relationship studies carried out on four series' of quinazolin-2,4-diamine, 2-(alkylsulfanyl)-N-alkyl- and 2-(alkylsulfanyl)-N-alkylarylpyrido[2,3-d]pyrimidine and pyrimidin-2,4-diamine derivatives. The proposed preliminary pharmacophore consists of a flat heterocyclic ring, preferably a pyrido[2,3-d]pyrimidine, with two equivalent alkylarylamine chains, preferably N-benzyl- or N-ethylphenylamine, located in positions 2 and 4 of the ring, and with a preferred ALogP in the range 4.5-5.5. The nitrogen present in the central ring can act as hydrogen bond acceptors (HBA) whereas the amino group in the 4-position can act as a donor (HBD) or an HBA and the amino group in the 2-position can act as an HBD. On the basis of the analyzed structural profiles, different mechanisms of action can be suggested for the quinazolin-2,4-diamine, the 2-(alkylsulfanyl)-N-alkylpyrido[2,3-d] pyrimidin-4-amine and the pyrido[2,3-d]pyrimidin-2,4-diamine derivatives.
Font, Maria,Gonzalez, Alvaro,Palop, Juan Antonio,Sanmartin, Carmen
supporting information; experimental part
p. 3887 - 3899
(2011/11/07)

Solvent-free or low-solvent large-scale preparation of chloropyrimidine and analogues
Chloropyrimidine or other N-containing aromatic heterocyclic analogues can be efficiently prepared from the corresponding hydroxylated precursors under solvent-free or low-solvent conditions with equimolar or less chlorinating reagents. This high-yielding protocol allows successful preparations of multigram and kilogram batches of these important synthetic intermediates.
Sun, Zhihua,Wang, Han,Wen, Kun,Li, Ya,Fan, Erkang
experimental part
p. 4149 - 4153
(2011/07/07)

Substituted pyrazolopyrimidines
The present invention is related to chemical compositions, processes for the preparation thereof and uses of the composition. Particularly, the present invention relates to compositions that include substituted heterobicyclic pyrimidines of Formula (I): wherein R1, R2, R3, R4, R5, X, W, and ring A are as defined herein; pharmaceutical compositions of substituted heterobicyclic pyrimidines of Formula (I); and their use in the treatment of chronic neurodegenerative diseases, neurotraumatic diseases, depression and/or diabetes. More particularly, the present invention relates to substituted pyrazolopyrimidines of Formula (I).
-
Page/Page column 100

(2008/06/13)

Compounds
Compounds of formula I: [in-line-formulae]A-B-C??(I)[/in-line-formulae] and isomers, salts, solvates, chemically protected forms, and prodrugs thereof wherein: B is selected from the group consisting of: ?where RN is H or Me; or B is a divalent C5 heterocyclic residue containing one or two ring heteroatoms; A is: RA3 and RA5 are independently selected from halo, ORO and RAC, where RO is H or Me, and RAC is H or C1-4 alkyl; XA is selected from N and CRA4, where RA4 is selected from H, ORO, CH2OH, CO2H, NHSO2Me and NHCOMe; RA2 and RA6 are independently selected from H, halo and ORO; or RA3 and RA4 together with the carbon atoms to which they are attached, or RA2 and RA3 together with the carbon atoms to which they are attached, may form a C5-6 heterocylic or heteroaromatic ring, containing at least one nitrogen ring atom; where if X is not N, 1, 2, or 3 of RA2 to RA6 are not H; C is: ?where X is selected from N and CH, Y is selected from N and CH, and Z is selected from N and CRC6; RC3 is selected from H, halo and an optionally substituted N-containing C5-7 heterocyclic group; RC5 is a group selected from: ?which group may be selected by one or two C1-4 alkyl groups or a carboxy group; RC6 is H; or, when X and Y are N, RC5 and RC6 (when Z is CRC6) together with the carbon atoms to which they are attached may form a fused C6 aromatic ring selected from the group consisting of:
-
Page/Page column 40

(2008/06/13)

Compounds
Compounds of formula l: and isomers, salts, solvates, chemically protected forms, and prodrugs thereof one of X1, X2 and X3 is N, and the others are CH; RN1 and RN2 together with the nitrogen atom to
-
Page/Page column 13

(2008/06/13)

Synthesis and biological evaluation of heteroaryldiamides and heteroaryldiamines as cytotoxic agents, apoptosis inducers and caspase-3 activators
The work described here involved the synthesis and biological evaluation of new heteroaryldiamides and heteroaryldiamines. A new general model in which the structures can be adjusted has been applied in this study. Three different structural units can be distinguished: a central nucleus and two symmetric terminal units. The central element is either an aliphatic chain of varying length and flexibility, piperazine, or a polyamine nucleus. However, the terminal units are pyridine, quinoline, indole, benzene or pyrido[2,3-d] pyrimidine with different substituents. The antitumoural activities of the compounds were evaluated in vitro by examining their cytotoxic effects against human breast, colon, and bladder cancer cell lines. Compounds that showed cytotoxic activity were subjected to both apoptosis and caspase-3 assays. With regard to selectivity, the cytotoxicity was also determined in cell cultures of two nontumoural lines. The most promising compounds are 4c, 5c and 7, which are amino-pyridinium, quinolyl-N-oxide, and pyridyl derivatives, respectively, and these reveal a significant in vitro cytotoxicity in at least two of the three cell lines tested. These compounds induced apoptosis and also produced a rapid dose-dependent increase in the caspase-3 level in HT-29 cells. Other encouraging profiles were found, such as those presented by 1k and 8d, which are cytotoxic and apoptotic but do not provoke an increase in the level of caspase-3, or those presented by 2f, 3c and 4a, which are slightly cytotoxic but do not show any other significant activity. The different types of behaviour of each compound are not necessarily parallel in the three cell lines tested.
Echeverria, Mikel,Mendivil, Beatriz,Cordeu, Lucia,Cubedo, Elena,Garcia-Foncillas, Jesus,Font, Maria,Sanmartin, Carmen,Palop, Juan Antonio
p. 182 - 192
(2007/10/03)

PYRAZOLE DERIVATIVES AS INHIBITORS OF RECEPTOR TYROSYNE KINASES
Compounds of formula (I): and their use in the inhibition of Trk activity are described.
-
Page/Page column 110

(2008/06/13)

Selective bifunctionalization of pyrido[2,3-d]pyrimidines in positions 2 and 4 by SNAr and palladium-catalyzed coupling reactions
Selective disubstitution of 2,4-dichloropyrido[2,3-d]pyrimidine with various nucleophiles was investigated. Suzuki and Stille cross-coupling reactions on monosubstituted compound 4-tert-butylamino-2-chloro-pyrido[2,3-d] pyrimidine were performed in high yields.
Lavecchia,Berteina-Raboin,Guillaumet
p. 5851 - 5855
(2007/10/03)

Synthesis and biological evaluation of new symmetrical derivatives as cytotoxic agents and apoptosis inducers
Based on the research of less toxic anticancer therapies, we have looked for novel compounds with anticancer activity based on a proapoptotic mechanism. The described compounds are derivatives of ether, carbamate, urea, amide, or amine. Some of the prepared compounds decreased cell viability of various tumor cell lines in a time- and dose-dependent manner, and also induced DNA fragmentation, which indicated cell apoptosis. The potential antitumoral activity of the compounds was evaluated in vitro by examining their cytotoxic effects against human mama, colon, and bladder cancer cell lines (MD-MBA-231, HT-29, and T-24). Compounds showing cytotoxic activity were subjected to an apoptosis assay. In addition, some of the synthesized compounds provoked a rapid and dose-dependent increase in the level of caspase-3, an enzyme, which is considered to be one of the principal executing caspases in which all of the biochemical routes involved in the apoptosis response converge. The most promising compounds, with respect to cytotoxicity and apoptosis induction capability, were the 4-nitrophenylcarbamate derivative of 2,2′- methylenebis(4-chlorophenyl) 3c, the naphthylurea derivative 4d, and the n-propylurea derivative 4c, from 4,4′-methylenebisphenyl, all of which displayed cytotoxic activity and showed very interesting levels of apoptosis. Furthermore, good levels of apoptosis induction were achieved for 3a and 4b in the T-24 cell line. Therefore, compounds such as 7b, a pyrido[2,3-d]pyrimidine derivative, show a significant in vitro cytotoxicity, with IC50 values between 3 and 8 μm in the three cell lines tested. This compound also produced a rapid and dose-dependent increase of the caspase-3 level and induced apoptosis in HT-29 cells. Other profiles have been found, such as those presented by 5c and 7c, which are cytotoxic and apoptotic but do not provoke an increase in the level of caspase-3, or those presented by 1c, 1d, and 2a, which are cytotoxic, without showing any other activity. The different types of behavior of each compound are not necessarily parallel in the three cell lines tested. A great number of these compounds of interest show no cytotoxicity in nontumoral human cells such as CRL-8799, a nontumoral line of mama. Subsequent modulation of these lead structures permits advances in the design of potent cytotoxic and proapoptotic anticancer drugs.
Sanmartin, Carmen,Echeverria, Mikel,Mendivil, Beatriz,Cordeu, Lucia,Cubedo, Elena,Garcia-Foncillas, Jesus,Font, Maria,Palop, Juan Antonio
p. 2031 - 2044
(2007/10/03)