- Optochemical control of transcription by the use of 7-deaza-adenosine-based diarylethenes
-
Out of nine different 7-deaza-adenosine diarylethenes, we identified a high-performance photoswitch, suitable for the synthesis of photochromic DNA. By using solid phase synthesis, a photoresponsive T7 promotor was generated which allowed reversibly modulating the rate of enzymatic RNA synthesisin vitro.
- Büllmann, Simon M.,Kolmar, Theresa,Slawetzky, Philip,Wald, Simon,J?schke, Andres
-
supporting information
p. 6596 - 6599
(2021/07/12)
-
- (1R, 4R, 7R) -7 - amino -2 - azabicyclo [2, 2, 1] heptane derivatives and preparation method thereof
-
The invention belongs to the field of medicines, and discloses (1R, 4R, 7R) -7 - amino -2 - azabicyclo [2, 2, 1] heptane derivatives and a preparation method thereof, which comprises: (S1) compound I - 1 and I - 2 carrying out nucleophilic aromatic substi
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Paragraph 0089-0093
(2021/11/27)
-
- IRREVERSIBLE INHIBITORS OF MENIN-MLL INTERACTION
-
Disclosed herein are heterocyclic compounds that inhibit the binding of menin and MLL or MLL fusion proteins. Also described are specific irreversible inhibitors of menin-MLL interaction. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the menin-MLL irreversible inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, leukemia and other diseases or conditions dependent on menin-MLL interaction.
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Paragraph 00522
(2020/07/21)
-
- N-(3-(7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)PHENYL)BENZAMIDE DERIVATIVES
-
The invention relates to compounds of the formula (I) (I) or a pharmaceutically acceptable salt thereof, wherein the substituents are as defined in the specification; to intermediates in the preparation of the compounds, to pharmaceutical compositions comprising the compounds and to use of the compounds in the treatment of disease.
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Page/Page column 78
(2019/10/23)
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- 3-HYDROXY-N-(3-(7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)PHENYL)PYRROLIDINE-1-CARBOXAMIDE DERIVATIVES
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The invention relates to compounds of the formula (I) or a pharmaceutically acceptable salt thereof, wherein the substituents are as defined in the specification; to intermediates in the preparation of the compounds, to pharmaceutical compositions compris
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Page/Page column 67-68
(2019/10/23)
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- The condensed heterocyclic compound such as Bruton kinase inhibitors (by machine translation)
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The invention relates to a fused heterocycle derivative and an application, which has a structure shown in a formula 1). The compound with the structure shown in the formula 1) has good inhibition effect to Bruton kinases activity, and median inhibitory concentration is lower than 10mol.L generally.
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-
Paragraph 0132-0134
(2018/04/20)
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- NOVEL PYRROLOPYRIMIDINE DERIVATIVES AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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The present invention relates to a compound represented by Chemical Formula 1 or a pharmaceutically acceptable salt thereof, and the compound according to the present invention can be usefully used for the prevention or treatment of diseases in which the
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Page/Page column 12; 13
(2018/05/27)
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- ATROPISOMERISM FOR ENHANCED KINASE INHIBITOR SELECTIVITY
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The invention provides a series of conformationally stable and selective kinase inhibitors, and methods of using the kinase inhibitors. The effect of atropisomerism on kinase selectivity was assessed, finding improved selectivity compared to rapidly inter
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Page/Page column 49
(2019/01/10)
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- Preparation method of baricitinib
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The invention discloses a preparation method of baricitinib. The method comprises the following steps: performing a substitution reaction on 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (II) serving as a raw material and benzene sulfonyl chloride in the presence of an alkali to obtain an intermediate III; then, performing a Suzuki coupling reaction on the intermediate III and 4-pyrazole-4-boronic acid pinacol ester in the presence of a palladium catalytic system and an alkali to obtain an intermediate V; then performing a Michael addition reaction on the intermediate V and 3-(cyanomethylene)azetidine-1-tert-butyl formate in the presence of a catalyst to obtain an intermediate VII; then removing Boc protection from the intermediate VII under the action of hydrochloric acid to obtain an intermediate VIII; then performing a sulfoamidate reaction on the intermediate VIII and ethyl sulfonyl chloride in an organic solvent in the presence of an alkali to obtain an intermediate IX; lastly, removing benzenesulfonyl protection from the intermediate IX under the action of tetramethylammonium fluoride or tetrabutylammonium fluoride or a trihydrate of the tetramethylammonium fluoride or the tetrabutylammonium fluoride to obtain baricitinib (I). Compared with the prior art, the method has the advantages of adoption of readily-available raw materials, low cost, high product yield and easiness for industrial production.
- -
-
Paragraph 0033; 0034; 0035
(2017/09/29)
-
- The role of alkyl substituents in deazaadenine-based diarylethene photoswitches
-
Diarylethenes are an important class of reversible photoswitches and often claimed to require two alkyl substituents at the carbon atoms between which the bond is formed or broken in the electrocyclic rearrangement. Here we probe this claim by the synthesis and characterization of four pairs of deazaadenine-based diarylethene photoswitches with either one or two methyl groups at these positions. Depending on the substitution pattern, diarylethenes with one alkyl group can exhibit significant photochromism, but they generally show poor stability towards extended UV irradiation, low thermal stability, and decreased fatigue resistance. The results obtained provide an important direction for the design of new efficient DNA photoswitches for the application in bionanotechnology and synthetic biology.
- Sarter, Christopher,Heimes, Michael,J?schke, Andres
-
supporting information
p. 1103 - 1110
(2016/07/06)
-
- 4-AMINO-6-ARYL[2,3-D]PYRIMIDINES FOR THE INHIBITION OF EGFR TYROSINE KINASE
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This invention relates to certain new pyrrolo-, thieno-, and furo-[2,3- d]pyrimidine compounds, such as of general formula (I) These compounds are epidermal growth factor receptor tyrosine kinase inhibitors and therefore offer potential in the treatment of cancer.
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-
-
- Identification of Purines and 7-Deazapurines as Potent and Selective Type i Inhibitors of Troponin I-Interacting Kinase (TNNI3K)
-
A series of cardiac troponin I-interacting kinase (TNNI3K) inhibitors arising from 3-((9H-purin-6-yl)amino)-N-methyl-benzenesulfonamide (1) is disclosed along with fundamental structure-function relationships that delineate the role of each element of 1 for TNNI3K recognition. An X-ray structure of 1 bound to TNNI3K confirmed its Type I binding mode and is used to rationalize the structure-activity relationship and employed to design potent, selective, and orally bioavailable TNNI3K inhibitors. Identification of the 7-deazapurine heterocycle as a superior template (vs purine) and its elaboration by introduction of C4-benzenesulfonamide and C7- and C8-7-deazapurine substituents produced compounds with substantial improvements in potency (>1000-fold), general kinase selectivity (10-fold improvement), and pharmacokinetic properties (>10-fold increase in poDNAUC). Optimal members of the series have properties suitable for use in in vitro and in vivo experiments aimed at elucidating the role of TNNI3K in cardiac biology and serve as leads for developing novel heart failure medicines.
- Lawhorn, Brian G.,Philp, Joanne,Zhao, Yongdong,Louer, Christopher,Hammond, Marlys,Cheung, Mui,Fries, Harvey,Graves, Alan P.,Shewchuk, Lisa,Wang, Liping,Cottom, Joshua E.,Qi, Hongwei,Zhao, Huizhen,Totoritis, Rachel,Zhang, Guofeng,Schwartz, Benjamin,Li, Hu,Sweitzer, Sharon,Holt, Dennis A.,Gatto, Gregory J.,Kallander, Lara S.
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p. 7431 - 7448
(2015/10/05)
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- SUBSTITUTED ETHYNYL HETEROBICYCLIC COMPOUNDS AS TYROSINE KINASE INHIBITORS
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The present disclosure provides a compound of formula (I) and the use thereof for the therapeutic treatment of human cancers including B-cell lymphoma and autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis.
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Paragraph 00140; 00141
(2015/12/11)
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- BIARYL COMPOUNDS USEFUL FOR THE TREATMENT OF HUMAN DISEASES IN ONCOLOGY, NEUROLOGY AND IMMUNOLOGY
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The present invention provides compounds and compositions thereof which are useful as inhibitors of Bruton's tyrosine kinase and which exhibit desirable characteristics for the same.
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Paragraph 0263
(2015/06/25)
-
- Identification of new 4-N-substituted 6-aryl-7H-pyrrolo[2,3-d]pyrimidine-4- amines as highly potent EGFR-TK inhibitors with Src-family activity
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The epidermal growth factor receptor is an important target in molecular cancer therapy. Herein, the enzymatic inhibition potential of a series of chiral and non chiral pyrrolopyrimidine based derivatives have been investigated and optimised. Overall, seven new compounds were identified having enzymatic IC 50 values comparable to or better than the commercial drug Erlotinib. High activity was also confirmed towards the epidermal growth factor receptor L858R and L861Q mutants. Based on calculated druglike properties, eight compounds were further evaluated towards a panel of 52 other kinases revealing interesting Src-family kinase and colony stimulating factor 1 receptor kinase inhibitory activity. Cell proliferation studies with the cell lines A431, C-33A, AU-565, K-562 and genetically engineered Ba/F3-EGFRL858R cells also showed several molecules to be more active than Erlotinib, and thus confirming these pyrrolopyrimidines as attractive drug candidates or lead structures.
- Kaspersen, Svein Jacob,Han, Jin,N?rsett, Kristin G.,Ryds?, Line,Kj?bli, Eli,Bugge, Steffen,Bj?rk?y, Geir,Sundby, Eirik,Hoff, B?rd Helge
-
-
- PYRROLO[2,3-D]PYRIMIDINE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND THEIR USE AS KINASE INHIBITORS
-
The present invention relates to 6-amino-7-deaza-purine derivatives which modulate the activity of protein kinases and are therefore useful in treating diseases caused by dysregulated protein kinase activity, in particular RET family kinases. The present
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Page/Page column 53; 54
(2014/12/12)
-
- TREATMENT OF DRY EYE
-
The present disclosure provides a method of treating dry eye by inhibition of Bruton's tyrosine kinase (hereinafter "BTK") inhibitors, pharmaceutical formulations comprising the same, and processes for preparing such compounds.
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Page/Page column 96
(2014/02/16)
-
- Tyrosine kinase inhibitors
-
The present disclosure provides compounds such as pyrazolpyrimidine compounds, and pharmaceutically acceptable salts thereof, that are tyrosine kinase inhibitors, in particular BLK, BMX, EGFR, HER2, HER4, ITK, TEC, BTK, and TXK and are therefore useful for the treatment of diseases treatable by inhibition of tyrosine kinases such as cancer and inflammatory diseases such as arthritis, and the like. Also provided are pharmaceutical compositions containing such compounds and pharmaceutically acceptable salts thereof and processes for preparing such compounds and pharmaceutically acceptable salts thereof.
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Page/Page column 241
(2014/03/26)
-
- REVERSIBLE COVALENT PYRROLO- OR PYRAZOLOPYRIMIDINES USEFUL FOR THE TREATMENT CANCER AND AUTOIMMUNE DISEASES
-
Oral pharmaceutical formulations comprising reversible covalent compounds having a Michael acceptor moiety, a process of their production, and use of these formulations for the treatment of diseases treatable by such compounds such as cancer and autoimmune diseases.
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Page/Page column 191
(2014/01/09)
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- Novel inhibitors of epidermal growth factor receptor: (4-(Arylamino)-7H- pyrrolo[2,3-d]pyrimidin-6-yl)(1H-indol-2-yl)methanones and (1H-indol-2-yl)(4- (phenylamino)thieno[2,3-d]pyrimidin-6-yl)methanones
-
Several members of the quinazoline class of known tyrosine kinase inhibitors are approved anticancer agents, often showing selectivity for receptors of the HER/ErbB-family. Combining structural elements of this class with the bisindolylmethanone-structure
- Beckers, Thomas,Sellmer, Andreas,Eichhorn, Emerich,Pongratz, Herwig,Sch?chtele, Christoph,Totzke, Frank,Kelter, Gerhard,Krumbach, Rebekka,Fiebig, Heinz-Herbert,B?hmer, Frank-D.,Mahboobi, Siavosh
-
scheme or table
p. 125 - 136
(2012/02/16)
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- PYRAZOLOPYRIMIDINE DERIVATIVES AS TYROSINE KINASE INHIBITORS
-
The present disclosure provides compounds and pharmaceutically acceptable salts that are tyrosine kinase inhibitors, in particular BLK, BMX, EGFR, HER2, HER4, ITK, Jak3, TEC, Btk, and TXK and are therefore useful for the treatment of diseases treatable by inhibition of tyrosine kinases such as cancer and inflammatory diseases such as arthritis, and the like. Also provided are pharmaceutical compositions containing such compounds and pharmaceutically acceptable salts and processes for preparing such compounds and pharmaceutically acceptable salts.
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Page/Page column 101
(2012/12/13)
-
- TYROSINE KINASE INHIBITORS
-
The present disclosure provides compounds and pharmaceutically acceptable salts thereof that are tyrosine kinase inhibitors, in particular BLK, BMX, EGFR, HER2, HER4, ITK, TEC, BTK, and TXK and are therefore useful for the treatment of diseases treatable by inhibition of tyrosine kinases such as cancer and inflammatory diseases such as arthritis, and the like. Also provided are pharmaceutical compositions containing such compounds and pharmaceutically acceptable salts thereof and processes for preparing such compounds and pharmaceutically acceptable salts thereof.
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Page/Page column 115
(2012/12/13)
-
- Efficient formation of 4,6-disubstituted pyrrolo[2,3-d]pyrimidines: A novel route to TWS119, a glycogen synthase kinase-3β inhibitor
-
A concise synthesis of 4,6-disubstituted pyrrolo[2,3-d]pyrimidines is described. The key step involves the formation of an ether or thioether linkage along with concurrent ring closure in one-pot to yield the desired product in only two steps from a common intermediate. The reaction is chemoselective to incorporate phenol, thiophenol, and thiol. This method enabled efficient production of TWS119, a glycogen synthase kinase-3β inhibitor.
- Mayasundari, Anand,Fujii, Naoaki
-
supporting information; scheme or table
p. 3597 - 3598
(2010/08/19)
-
- NEW CHEMICAL COMPOUNDS
-
The present invention encompasses compounds of general formula (1) while the groups R4 to R7 and the units W, L, Qa and QH are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and their use as medicaments having the above-mentioned properties.
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Page/Page column 77
(2010/04/03)
-
- NEW CHEMICAL COMPOUNDS
-
The present invention encompasses compounds of general formula (1) wherein the units W, A, L, Q1 and QH are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and their use as medicaments having the above-mentioned properties.
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Page/Page column 111
(2010/04/03)
-
- Heterocyclic Compounds Useful as RAF Kinase Inhibitors
-
The present invention provides compounds useful as inhibitors of Raf protein kinase. The present invention also provides compositions thereof, and methods of treating Raf-mediated diseases.
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Page/Page column 26
(2009/01/24)
-
- ARYL-AMINO SUBSTITUTED PYRROLOPYRIMIDINE MULTI-KINASE INHIBITING COMPOUNDS
-
Compounds represented by Formula (I): or stereoisomers or pharmaceutically acceptable salts thereof, are inhibitors of least two of the Abl, Aurora-A, Blk, c-Raf, cSRC, Src, PRK2, FGFR3, Flt3, Lck, Mekl, PDK-1, GSK3?, EGFR, p70S6K, BMX, SGK, CaMKII, Tie-2
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Page/Page column 55-56
(2008/06/13)
-
- Monocyclic-7H-pyrrolo[2,3-d]pyrimidine compounds, compositions, and methods of use
-
Novel pyrrolo[2,3-d]pyrimidine compounds useful as inhibitors of the enzyme protein tyrosine kinases such as Janus Kinase 3 as well as immunosuppressive agents for organ transplants, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, Leukemia and other autoimmune diseases are described.
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Page/Page column 22
(2008/06/13)
-
- Pyrrolo[2,3-d]pyrimidine compounds
-
A compound of the formula wherein R1, R2 and R3 are as defined above, which are inhibitors of the enzyme protein tyrosine kinases such as Janus Kinase 3 and as such are useful therapy as immunosuppressive agents for organ transplants, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, Leukemia and other autoimmune diseases.
- -
-
-
- Selective N-alkylation of pyrrolopyrimidines and indoles by 'transfer of activation'
-
The benzene sulfonyl group is used as a 'transfer of activation' reagent to alkylate selectively the NH of both pyrrolopyrimidines and 5-aminoindoles substituted on thienopyrimidines. A variety of primary and secondary alcohols are utilized as alkylating
- Sobolov, Susan B.,Sun, Jianmin,Cooper, Beth A.
-
p. 5685 - 5688
(2007/10/03)
-