cas 5466-00-2, 6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diol

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Formation of 5,6-cyclopentano-uracil by cyclization of the bisamide of adipic acid induced by oxalyl chloride
Cyclization of the bisamide of adipic acid induced by oxalyl chloride will eventually yield a product of the composition C9H8N2O5, which upon hydrolysis gave 5,6-cyclo-pentanouracil. The structures of both compounds were established by X-ray crystallography.
Bergman, Jan,Svensson, Per H.
p. 4601 - 4603
(2010)
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Synthesis of new 6,7-dihydro-1H-cyclopenta[d]pyrimidine-2,4(3H,5H)-dione derivatives containing the substituted aliphatic ring
The bromination of 6,7-dihydro-1H-cyclopenta[d]pyrimidine-2,4(3H,5H)-dione (1) resulted in the substitution in the aliphatic ring. The reaction of this product with different N-nucleophiles gives new derivatives of the starting compound. The direction of
Papoyan,Khachatryan,Panosyan,Kochikyan
(2012)
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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 0710-0715

(2021/07/21)

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)

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)

Synthetic method of medical intermediate cycloalkanopyrimidinedione compound
The invention provides a synthetic method of a cycloalkanopyrimidinedione compound, and belongs to the technical field of organic synthesis. The method provided by the invention comprises the following steps of: taking a 2-methoxycarbonyl naphthenone comp
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(2020/12/15)

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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Paragraph 0256; 0262-0265

(2020/02/06)

Development of matrix metalloproteinase-13 inhibitors – A structure-activity/structure-property relationship study
A structure-activity/structure-property relationship study based on the physicochemical as well as in vitro pharmacokinetic properties of a first generation matrix metalloproteinase (MMP)-13 inhibitor (2) was undertaken. After systematic variation of inhi
Fuerst, Rita,Yong Choi, Jun,Knapinska, Anna M.,Smith, Lyndsay,Cameron, Michael D.,Ruiz, Claudia,Fields, Gregg B.,Roush, William R.
supporting information
p. 4984 - 4995
(2018/09/27)

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 0239

(2016/04/26)

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 0053; 0054; 0055; 0056; 0057

(2016/10/31)

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)

1-(Arylmethyl)-5,6,7,8-tetrahydroquinazolline-2,4-diones and Analogs and the Use Thereof
Disclosed are novel 1-(arylmethyl)-5,6,7,8-tetrahydroquinazoline-2,4-diones and analogs thereof, represented by the Formula I, wherein Ar, A, B, R3-R6 are defined herein. Compounds having Formula I are PARP inhibitors. Therefore, compounds of the invention may be used to treat clinical conditions that are responsive to the inhibition of PARP activity, such as cancer.
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Paragraph 0152; 0200

(2014/09/30)

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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Page/Page column 59

(2014/08/19)

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

(2014/02/15)

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 0828

(2014/07/08)

Outstanding effects on antithrombin activity of modified TBA diastereomers containing an optically pure acyclic nucleotide analogue
Herein, we report optically pure modified acyclic nucleosides as ideal probes for aptamer modification. These new monomers offer unique advantages in exploring the role played in thrombin inhibition by a single residue modification at key positions of the TBA structure.
Scuotto,Persico,Bucci,Vellecco,Borbone,Morelli,Oliviero,Novellino,Piccialli,Cirino,Varra,Fattorusso,Mayol
p. 5235 - 5242
(2014/07/08)

1-(ARYLMETHYL)-5,6,7,8-TETRAHYDROQUINAZOLINE-2,4-DIONES AND ANALOGS AND THE USE THEREOF
Disclosed are novel 1-(arylmethyl)-5,6,7,8-tetrahydroquinazoline-2,4-diones and analogs thereof, represented by the Formula I, wherein Ar, A, B, R3-R6 are defined herein. Compounds having Formula I are PARP inhibitors. Therefore, compounds of the invention may be used to treat clinical conditions that are responsive to the inhibition of PARP activity, such as cancer.
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Page/Page column 23; 24; 33

(2013/05/22)

Synthesis of modified uracil and cytosine nucleobases using a microwave-assisted method
Modified nucleobases and nucleic acids have found many biological and pharmaceutical applications. Here we report a microwave-directed synthesis of a variety of modified uracil and cytosine nucleobases with high yields under solvent-free conditions. The reaction yields were further improved by addition of Lewis acid. The crystal structures of 5-isopropyl-6-methyluracil and 6-phenyluracil were also determined.
Burgula, Laxmi Narayana,Radhakrishnan,Kundu, Lal Mohan
supporting information; experimental part
p. 2639 - 2642
(2012/06/30)

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 21-22

(2010/06/19)

SYNTHESIS OF DIHYDROTHIENO[3,2-d]PYRIMIDINE DIOLS AND SIMILAR PYRIMIDINE DIOLS
The present invention relates to an improved process for the preparation of dihydrothieno[3,2-d]pyrimidine diols, and similar pyrimidine diols, that is efficient, high-yielding, and does not require expensive and potentially unstable intermediates. The di
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Page/Page column 33

(2009/12/23)

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 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

(2008/06/13)

Characterization of the 1H-cyclopentapyrimidine-2,4(1H,3H)-dione derivative (S)-CPW399 as a novel, potent, and subtype-selective AMPA receptor full agonist with partial desensitization properties
(S)-CPW399 (2b) is a novel, potent, and subtype-selective AMPA receptor full agonist that, unlike (S)-willardiine and related compounds, in mouse cerebellar granule cells, stimulated an increase in [Ca2+]i, and induced neuronal cell death in a time- and concentration-dependent manner. Compound 2b appears to be a weakly desensitizing, full agonist at AMPA receptors and therefore represents a new pharmacological tool to investigate the role of AMPA receptors in excitotoxicity and their molecular mechanisms of desensitization.
Campiani,Morelli,Nacci,Fattorusso,Ramunno,Novellino,Greenwood,Liljefors,Griffiths,Sinclair,Reavy,Kristensen,Pickering,Schousboe,Cagnotto,Fumagalli,Mennini
p. 4501 - 4504
(2007/10/03)

New procedures for the synthesis of heterocyclic substituted and 2,4-difunctionalized pyrimidines
N-Tosyl-2-and -3-acetylpyrrols 1 or N-tosyl-2-pyrrolidone 5 were condensed with cyano compounds in the presence of triflic anhydride (Tf2O) to yield heteroarylpyrimidines. 2,4-Difunctionalized pyrimidines were obtained by reaction of the corresponding 2,4-bis(methylsulfonyl)pyrimidines with nucleophiles.
Garcia Martinez, Antonio,Herrera Fernandez, Antonio,Moreno Jimenez, Florencio,Munoz Martinez, Pablo J.,Alonso Martin, Cristina,Subramanian, Laksminarayanapuran R.
p. 7973 - 7982
(2007/10/03)

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)

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)

Synthesis and antiviral study of cyclopentano [d] pyrimidine-2,4-diones and octahydroquinazoline-2,4-diones acyclic nucleosides as potential anti- HIV agents
The Vorbruggen and Niedballa's method afforded new cyclopentano [d] pyrimidine-2,4-dione and octahydroquinazoline-2,4-dione nucleosides. Various modifications of these new derivatives enabled us to obtain HEPT related compounds which were tested against H
Renault,Laduree,Robba
p. 891 - 901
(2007/10/02)

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)

SIDE-REACTIONS IN THE INDUSTRIAL METHOD FOR THE PREPARATION OF BUTYL 5-(CYCLOHEXYLUREIDO)CYCLOPENT-1-ENE-1-CARBOXYLATE
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Danilov, V. A.,Barysheva, N. A.,Postylyakov, A. B.,Rybina, E. A.,Sapozhnikov, Yu. E.
p. 130 - 133
(2007/10/02)

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)