cas 5466-43-3, 2,4-DICHLORO-6,7-DIHYDRO-5H-CYCLOPENTAPYRIMIDINE

Articles about 5466-43-3Total 26 be found

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Discovery of novel pyrimidine molecules containing boronic acid as VCP/p97 Inhibitors
Valine-containing protein (VCP) is a member of the adenosine triphosphate family involved in a variety of cellular activities. VCP/p97 is capable of maintaining protein homeostasis and mediating the degradation of misfolded polypeptides by the ubiquitin–proteasome system (UPS). In this manuscript, a series of novel p97 inhibitors with pyrimidine as core structure were designed, synthesized and biologically evaluated. Based on the enzymatic results, a detailed structure–activity relationship discussion of the synthesized compounds was carried out. Furthermore, cellular activities of the compounds with enzymatic potency of less than 200 nM were investigated by using A549 and RPMI8226 cell lines. Among the screened inhibitors, compound 17 (IC50, 54.7 nM) showed good enzymatic activity. Investigation of cellular activities with non-small cell lung cancer A549 and multiple myeloma (MM) RPMI8226 further confirmed the potency of 17 with the IC50 values of 2.80 μM and 0.86 μM, respectively. Compound 17 is now being developed as a candidate. Finally, docking studies were carried out to explore the possible binding mode between the active inhibitor 17 and p97.
Zhang, Yonglei,Xie, Xiaomin,Wang, Xueyuan,Wen, Tiantian,Zhao, Chi,Liu, Hailong,Zhao, Bo,Zhu, Yongqiang
(2021/04/12)

Methylpyrazole derivatives as RET inhibitor
The invention relates to a methylpyrazole derivative as an RET inhibitor, in particular to a compound as shown in a formula (I), a stereoisomer and pharmaceutically acceptable salt thereof, a preparation method and a pharmaceutical composition thereof. The compound of the formula (I) can be used for preventing or treating diseases mediated by abnormal RET activity.
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Paragraph 0710-0712; 0716-0718

(2021/07/21)

METHODS OF USE FOR PYRIMIDINES AS FERROPORTIN INHIBITORS
The subject matter described herein is directed to ferroportin inhibitor compounds of Formula (I) and pharmaceutical salts thereof, methods of preparing the compounds, pharmaceutical compositions comprising the compounds, and methods of administering the compounds for prophylaxis and/or treatment of diseases caused by a lack of hepcidin or iron metabolism disorders, particularly iron overload states, such as thalassemia, sickle cell disease and hemochromatosis, and also kidney injuries.
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Paragraph 798-802

(2021/11/06)

Matrix Metalloproteinase 13 Inhibitors for Modulation of Osteoclastogenesis: Enhancement of Solubility and Stability
Matrix metalloproteinase 13 (MMP-13) activity has been correlated to breast cancer bone metastasis. It has been proposed that MMP-13 contributes to bone metastasis through the promotion of osteoclastogenesis. To explore the mechanisms of MMP-13 action, we previously described a highly efficacious and selective MMP-13 inhibitor, RF036. Unfortunately, further pursuit of RF036 as a probe of MMP-13 in vitro and in vivo activities was not practical due to the limited solubility and stability of the inhibitor. Our new study has explored replacing the RF036 backbone sulfur atom and terminal methyl group to create inhibitors with more favorable pharmacokinetic properties. One compound, designated inhibitor 3, in which the backbone sulfur and terminal methyl group of RF036 were replaced by nitrogen and oxetane, respectively, had comparable activity, selectivity, and membrane permeability to RF036, while exhibiting greatly enhanced solubility and stability. Inhibitor 3 effectively inhibited MMP-13-mediated osteoclastogenesis but spared collagenolysis, and thus represents a next-generation MMP-13 probe applicable for in vivo studies of breast cancer metastasis.
Knapinska, Anna M.,Singh, Chandani,Drotleff, Gary,Blanco, Daniela,Chai, Cedric,Schwab, Jason,Herd, Anu,Fields, Gregg B.
supporting information
p. 1133 - 1142
(2021/01/29)

Synthesis and evaluation of novel fused pyrimidine derivatives as GPR119 agonists
A novel series of fused pyrimidine derivatives were designed, synthesized and evaluated as GPR119 agonists. Among them, cyclohexene fused compounds (tetrahydroquinazolines) showed greater GPR119 agonistic activities than did dihydrocyclopentapyrimidine and tetrahydropyridopyrimidine scaffolds. Analogues (16, 19, 26, 28, 42) bearing endo-N-Boc-nortropane amine and fluoro-substituted aniline exhibited better EC50 values (0.27–1.2 μM) though they appeared to be partial agonists.
Fang, Yuanying,Xiong, Lijuan,Hu, Jianguo,Zhang, Shaokun,Xie, Saisai,Tu, Liangxing,Wan, Yang,Jin, Yi,Li, Xiang,Hu, Shaojie,Yang, Zunhua
p. 103 - 111
(2019/01/28)

Octahydropyrrolo[3,4-c]pyrrole derivatives and use thereof
The invention relates to octahydropyrrolo[3,4-c]pyrrole derivatives and a use thereof. The above compounds and a medicinal composition containing the compounds are used for suppressing an orexin receptor. The invention also relates to a method for preparing the compounds and the medicinal composition, and the use of the compounds and the medicinal composition in the treatment or prevention of orexin receptor related diseases.
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(2020/02/06)

Pyrimidine derivatives, preparation method therefor and application of pyrimidine derivatives
The invention belongs to the field of drug synthesis and relates to novel pyrimidine derivatives, pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereof, preparation methods of thenovel pyrimidine derivatives and the pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereof and use of the novel pyrimidine derivatives and the pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereof in preparation of therapeutic agents, particularly PAK inhibitors. The derivatives disclosed by the invention are represented by a general formula (I) or (II), wherein each substituent is as defined in claims.
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Paragraph 0150; 0151; 0155; 0156; 0174; 0175

(2018/03/26)

BIARYL DERIVATIVE AS GPR120 AGONIST
The present invention relates to a biaryl derivative expressed by the chemical formula 1, a method for producing the biaryl derivative, a pharmaceutical composition comprising same, and use of same, the biaryl derivative expressed by the chemical formula 1, as a GPR120 agonist, promoting GLP-1 generation in the gastro-intestinal tract, reducing insulin resistance in the liver, muscles and the like from anti-inflammatory activity in the macrophage, pancreatic cells and the like, and allowing effective use in prevention or treatment of inflammation or metabolic diseases such as diabetes, complications from diabetes, obesity, non-alcoholic fatty liver disease, fatty liver disease, and osteoporosis.
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Paragraph 0501

(2017/11/17)

Pyrimido-saturated fatty cyclodiamine compound and application thereof
The inventor of the invention designs and synthesizes a pyrimido-saturated fatty cyclodiamine compound of a brandnew structure. Tests show that most of compounds in the pyrimido-saturated fatty cyclodiamine compound disclosed by the invention have good inhibitory activity on three target spots, namely spleen tyrosine kinase (Syk), a stem cell receptor c-Kit and a platelet-derived growth factor (PDGFR-alpha); and a part of compounds show relatively good inhibitory activity in proliferation activity inhibitory experiments for synovial cells and mast cells related to inflammation and can effectively inhibit secretion of inflammatory cytokines IL-6, MMP-3 and TNF-alpha in corresponding cells and show relatively good anti-rheumatoid arthritis (RA) pharmaceutical effect. The pyrimido-saturated fat cyclodiamine compound lays a structure foundation for further design and development of a novel anti-RA medicine in future.
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Paragraph 0058; 0059; 0060; 0061; 0062

(2016/10/31)

BICYCLIC DERIVATIVE CONTAINING PYRIMIDINE RING, AND PREPARATION METHOD THEREFOR
The present invention provides: a bicyclic derivative comprising a pyrimidine ring, or a pharmaceutically acceptable salt thereof; a preparation method therefor, a pharmaceutical composition comprising the same; and a use therefor. According to the present invention, the bicyclic compound derivative comprising a pyrimidine ring, or a pharmaceutically acceptable salt thereof acts as a 5-HT4 receptor agonist, and thus can be usefully applied to the prevention or treatment of dysfunction in gastrointestinal motility, for example, gastrointestinal diseases such as gastroesophageal reflux disease (GERD), constipation, irritable bowel syndrome (IBS), dyspepsia, post-operative ileus, delayed gastric emptying, gastroparesis, intestinal pseudo-obstruction, drug-induced delayed transit, diabetic gastric atony and the like.
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Paragraph 0240; 0241

(2016/04/26)

Cyclopentyl-pyrimidine based analogues as novel and potent IGF-1R inhibitor
A series of novel 2-amino-4-pyrazolecyclopentylpyrimidines have been prepared and evaluated as IGF-1R tyrosin kinase inhibitors. The in vitro activity was found to depend strongly on the substitution pattern in the 2-amino ring, 4-pyrazolo moieties and size of fused saturated ring with the central pyrimidine core. A stepwise optimization by combination of active fragments led to discovery of compound 6f and 6k, two structures with IGF-1R IC50 of 20 nM and 10 nM, respectively. 6f was further profiled for its anti cancer activity across various cell lines and pharmacokinetic studies in Sprague Dawley rats.
Aware, Valmik,Gaikwad, Nitin,Chavan, Sambhaji,Manohar, Sonal,Bose, Julie,Khanna, Smriti,B-Rao, Chandrika,Dixit, Neeta,Singh, Kishori Sharan,Damre, Anagha,Sharma, Rajiv,Patil, Sambhaji,Roychowdhury, Abhijit
supporting information
p. 246 - 256
(2015/05/26)

BICYCLIC HETEROCYCLIC COMPOUNDS AS MULTI-KINASE INHIBITORS
The present invention provides bicyclic heterocyclic compounds (the compounds of formula I, or an isotopic form, a stereoisomer or a tautomer or a pharmaceutically acceptable salt, a solvate, a polymorph, a prodrug or N-oxide thereof and processes for their preparation. The invention further relates to pharmaceutical compositions containing said compounds and their use in the treatment of diseases or disorders associated with abnormal protein kinase activity.
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Page/Page column 38

(2015/03/16)

FUSED PYRIMIDINE COMPOUNDS AND USE THEREOF
Fused pyrimidine compounds as kinase inhibitors, such as multi-kinase inhibitors, are provided. Fused pyrimidine compounds as IGF-IR inhibitors are provided. The compounds may be used in a method of treating cancer. Pharmaceutical compositions containing a fused pyrimidine compound and a pharmaceutically acceptable carrier are also provided, as are kits containing a fused pyrimidine compound or salt thereof and instructions for use, e.g., in a method of treating cancer.
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Paragraph 0829

(2014/07/08)

FUSED PYRIMIDINES AS INHIBITORS OF p97 COMPLEX
Fused pyrimidine compounds having a saturated, unsaturated or aromatic A ring fused to a pyrimidine ring and having a complex substituents at the 2 position and a substituted amine at the 4 position of the pyrimidine ring as well as optional aliphatic, functional and/or aromatic components substituted at other positions of the pyrimidine ring and A ring are disclosed. These compounds are inhibitors of the AAA proteasome complex containing p97 and are effective medicinal agents for treatment of diseases associated with p97 bioactivity such as cancer.
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Page/Page column 170; 171

(2014/02/15)

Discovery and synthesis of N2,N4-substitued- cycloalkyl[d]pyrimidine-2,4-diamine analogs: The first examples of small-molecular FGFR-1 activator
A series of novel, cycloalkyl-modified pazopanib analogs 2 and 3 were designed and synthesized. Their kinase modulatory effects on FGFR-1, VEGFR-2, PDGFR-β, and c-KIT were evaluated by the caliper mobility shift assay. Introduction of cycloalkyl into the pyrimidine linker of pazopanib almost abolished the four kinases inhibitory potency of compounds 2 and 3, but surprisingly, resulted in good activation effects on FGFR-1. Compounds 3d and 3g showed double-digit, nanomolar, selective activation effects on FGFR-1, and could be classified as first-generation small molecular activators of FGFR-1 kinase.
Li, Bao-Li,Xiao, Fang,Lu, Wen-Chao,Sun, Yu-Yun,Zhu, Jin,Li, Jian
p. 989 - 994
(2014/08/18)

NOVEL SUBSTITUTED CONDENSED PYRIMIDINE COMPOUNDS
The invention relates to novel substituted condensed pyrimidine compounds of general formula (I) in which the chemical groupings, substituents and indices are as defined in the description, and to their use as medicaments, in particular as medicaments for the treatment of conditions and diseases that can be treated by inhibition of the PDE4 enzyme.
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(2014/08/19)

Identification of 2,4-diamino-6,7-dimethoxyquinoline derivatives as G9a inhibitors
G9a is a histone lysine methyltransferase (HKMT) involved in epigenetic regulation via the installation of histone methylation marks. 6,7-Dimethoxyquinazoline analogues, such as BIX-01294, are established as potent, substrate competitive inhibitors of G9a. With an objective to identify novel chemotypes for substrate competitive inhibitors of G9a, we have designed and synthesised a range of heterocyclic scaffolds, and investigated their ability to inhibit G9a. These studies have led to improved understanding of the key pharmacophoric features of BIX-01294 and the identification of a new core quinoline inhibitory scaffold, which retains excellent potency and high selectivity. Molecular docking was carried out to explain the observed in vitro data. This journal is
Srimongkolpithak, Nitipol,Sundriyal, Sandeep,Li, Fengling,Vedadi, Masoud,Fuchter, Matthew J.
p. 1821 - 1828
(2015/01/08)

Novel Biccyclic Compounds As GATA Modulators
Novel bicyclic compounds, stereoisomers, and/or pharmaceutically acceptable salts of the novel bicyclic compounds, and/or pharmaceutically acceptable salts of the stereoisomers of the novel bicyclic compounds are provided. Additionally, methods of forming novel bicyclic compounds, stereoisomers, and/or pharmaceutically acceptable salts of the novel bicyclic compounds, and/or pharmaceutically acceptable salts of the stereoisomers of the novel bicyclic compounds are provided.
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Page/Page column 22

(2010/06/19)

INHIBITORS OF THE HEDGEHOG PATHWAY
The present invention is directed to a compound of Formula (I) or a single isomer thereof; where the compound is optionally as a pharmaceutically acceptable salt, hydrate, solvate or combination thereof, in addition to methods of preparing a Compound of Formula I, and methods of using a Compound of Formula (I) to treat cancer.
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Page/Page column 207-208

(2008/12/07)

Substituted diazepan orexin receptor antagonists
The present invention is directed to substituted diazepan compounds which are antagonists of orexin receptors, and which are useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which orexin receptors are involved.
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Page/Page column 20-21

(2008/12/05)

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).
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Page/Page column 93-94

(2008/06/13)

Bicyclic pyrimidine compounds and therapeutic use thereof
A pyrimidine derivative of the formula (1) or a salt thereof; has an inhibitory activity of production of Th2 type cytokines such as IL-4, IL-5, etc., and is useful as an therapeutic agent for allergic diseases, autoimmune diseases such as systemic lupus erythemathosus, etc., and acquired immunodeficiecy syndrome (AIDS) and so on.
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(2008/06/13)

Cephalosporin compounds
The present invention relates to novel cephalosporin compounds, pharmaceutically acceptable non-toxic salts, physiologically hydrolyzable esters, hydrates and solvates and isomers thereof which possess potent and broad antibacterial activities. The compounds of the present invention have a (4-amino-1-substituted-alkapyrimidinium-4-yl)thiomethyl group in 3-position of the cephem nucleus and is specifically represented by the following formula(I): STR1 wherein: R 1 is a hydrogen atom or a C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl or --C(R A)(R B)COOH group wherein R A and R B are independently a hydrogen atom or a C 1-4 alkyl group, or form a C 3-7 cycloalkyl group together with the carbon atom to which they are attached;R 2 is an unsubstituted or substituted amino, C 1-4 alkyl or C 3-7 cycloalkyl group; andn is an integer ranging from 2 to 7.
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(2008/06/13)

Synthesis and antimicrobial activity of novel 3- [(aminopyrimidiniumyl)thio]methyl cephalosporins
A series of novel cephalosporin compounds which have 3- [(aminopyrimidiniumyl)thio]methyl substituents was synthesized. They show high antimicrobial activity against various bacterial species including Pseudomonas aeruginosa. Structure-activity relationships with various thiopyrimidines, thiopyrimidiniums, bicyclic thiotriazolopyrimidiniums, and bicyclic thioimidazolopyrimidiniums as 3'-substituents were also studied; cephalosporins with quarternized pyrimidinium moieties have better antimicrobial activities than neuteral pyrimidine cephalosporins, and stabilization of the positive charge on the pyrimidinium moieties is essential for better activity. According to semiempirical PM3 calculations, amino and alkylthio substituents on the pyrimidinium rings play a major role in charge stabilization and delocalization.
Kim,Lim,Yeo,Bang,Kim,Kim,Woo -,Yang,Oh,Nahm
p. 3828 - 3833
(2007/10/02)

Novel cephalosporin compounds
The present invention relates to novel cephalosporin compounds, pharmaceutically acceptable non-toxic salts, physiologically hydrolyzable esters, hydrates and solvates and isomers thereof which possess potent and broad antibacterial activities. The compounds of the present invention have a (4-amino-1-substituted-alkapyrimidinium-4-yl)thiomethyl group in 3-position of the cephem nucleus and is specifically represented by the following formula(I): wherein: R1 isa hydrogen atom or, a C1 4 alkyl, C2 4 alkenyl, C2 4 alkynyl or -C(RA)(RB)COOH group wherein RAand RBare independently a hydrogen atom or a C1 4 alkyl group, or form a C3 7 cycloalkyl group together with the carbon atom to which they are attached; R2 isan unsubstituted or substituted amino, C1 4 alkyl or C3 7 cycloalkyl group; and n isan integer ranging from 2 to 7.
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(2008/06/13)

Pyrimidine derivatives I. Synthesis of hypoglycemic 2-piperazino-5,6-polymethylenepyrimidines 5,6-polymethylenepyrimidines
Synthesis and hypoglycemic activity of 36 novel 2,4-diamino-5,6-polymethylenepyrimidine derivatives are described. Derivatives containing piperazino groups at position 2 showed a potent hypoglycemic activity and concomitantly inhibited platelet aggregation.
Sekiya,Hiranuma,Kanayama,Hata
p. 317 - 322
(2007/10/02)