- Scaffold hopping of the SYK inhibitor entospletinib leads to broader targeting of the BCR signalosome
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Spleen tyrosine kinase (SYK) and Bruton's tyrosine kinase (BTK) are attractive targets in human haematological malignancies with excessively activated B-cell receptor (BCR) signalling pathways. Entospletinib is a SYK inhibitor that has been evaluated as a
- Jorda, Radek,Kraj?ovi?ová, Soňa,Králová, Petra,Soural, Miroslav,Kry?tof, Vladimír
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Read Online
- Development of a Commercial Manufacturing Route to 2-Fluoroadenine, the Key Unnatural Nucleobase of Islatravir
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We report the practical synthesis of a key fragment of islatravir (MK-8591), a novel nucleoside reverse transcriptase translocation inhibitor (NRTTI) currently under investigation for treatment and pre-exposure prophylaxis (PrEP) against HIV infection. The fragment, the unnatural nucleobase 2-fluoroadenine, is incorporated into MK-8591 via a biocatalytic aldol-glycosylation cascade, which imposes stringent requirements for its synthesis and isolation. Presented herein is the development work leading to a practical, scalable route from guanine, featuring a dual fluorination approach to a novel 9-THP-2,6-difluoropurine intermediate that enables a mild, highly selective, direct amination. This one-pot fluorination/amination sequence utilizes a direct isolation to deliver high purity 9-THP-2-fluoroadenine, which features ideal properties with respect to reactivity, solubility, and crystallinity. An acid-catalyzed liberation of 2-fluoroadenine in aqueous buffer delivers the appropriate purity profile to facilitate the enzymatic cascade to access MK-8591.
- Hong, Cynthia M.,Xu, Yingju,Chung, John Y. L.,Schultz, Danielle M.,Weisel, Mark,Varsolona, Richard J.,Zhong, Yong-Li,Purohit, Akasha K.,He, Cyndi Q.,Gauthier, Donald R.,Humphrey, Guy R.,Maloney, Kevin M.,Lévesque, Fran?ois,Wang, Zhixun,Whittaker, Aaron M.,Sirota, Eric,McMullen, Jonathan P.
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Read Online
- Copper-catalyzed N-alkoxyalkylation of nucleobases involving direct functionalization of sp3 CeH bonds adjacent to oxygen atoms
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N-Alkoxyalkylation of nucleobases was realized by the copper-catalyzed peroxide-promoted coupling of nucleobases with readily available saturated ethers. Both purines and pyrimidines could be N-alkoxyalkylated through this method in moderate to good yields. 2D-NMR revealed that N9-alkoxyalkylation preferentially occurred when purines were used in this reaction. Crown Copyright
- Huang, Rui,Xie, Chunsong,Huang, Lin,Liu, Jinhua
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Read Online
- Structure-activity relationship studies of QS11, a small molecule Wnt synergistic agonist
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Both the Wnt/β-catenin signaling pathway and small GTPases of the ADP-ribosylation factors (ARF) family play important roles in regulating cell development, homeostasis and fate. The previous report of QS11, a small molecule Wnt synergist that binds to AR
- Singh, Manish K.,Gao, Huanyao,Sun, Wei,Song, Zhiquan,Schmalzigaug, Robert,Premont, Richard T.,Zhang, Qisheng
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Read Online
- L-ProT catalyzed highly regioselective N-alkoxyalkylation of purine rings with vinyl ethers
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An efficient and regioselective synthesis of N-9 alkoxyalkylated purine nucleoside derivatives was achieved via the N-alkoxyalkylation of purine rings with vinyl ethers catalyzed by l-ProT. The advantages of this protocol include good to excellent yield,
- Li, Jian-Jun,Gui, Xing-Xing
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Read Online
- N-9 Alkylation of purines via light-promoted and metal-free radical relay
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A metal-free and light-promoted approach to the synthesis of N-9 alkylated purine nucleoside derivatives, via a CF3 radical triggered radical relay pathway, has been developed. Purine nucleoside derivatives were prepared regioselectively in good to high yields. Photosensitizers and metals are free in this transformation. Visible light or even sunlight can be used as the source of light for the reactions.
- Mao, Runze,Sun, Lifeng,Wang, Yong-Shi,Zhou, Min-Min,Xiong, De-Cai,Li, Qin,Ye, Xin-Shan
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Read Online
- Synthesis and photophysical properties of 2-azolyl-6-piperidinylpurines
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[Figure not available: see fulltext.] A synthesis of novel fluorescent 2-azolyl-6-piperidinylpurine derivatives was designed. Azolyl substituent at purine C-2 atom was introduced via nucleophilic aromatic substitution or in the case of tetrazolyl and 1,2,3-triazolyl substituents via a ring formation on a preinstalled amine or azide moiety, respectively. The obtained purine intermediates were functionalized at N-9 position using Mitsunobu reaction conditions to achieve amorphous compounds, which form thin-layer films of good quality. The synthesized push-pull systems exhibited fluorescence with emission in range of 360–400 nm and quantum yields up to 66% in CH2Cl2 solution and up to 45% in the thin-layer film.
- Novosjolova, Irina,Sebris, Armands,Traskovskis, Kaspars,Turks, Māris
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p. 560 - 567
(2021/06/14)
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- COMPOSITIONS CONTAINING, METHODS AND USES OF ANTIBODY-TLR AGONIST CONJUGATES
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Disclosed herein are Trastuzumab-linked TLR-agonist derivative analogs that include at least one non-natural amino acid, and methods for making such non-natural amino acids and polypeptides. The Trastuzumab-linked TLR-agonist derivative analogs can includ
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Paragraph 00636; 00646
(2020/08/28)
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- Purine-aminomethyl-pyridone derivative, preparation method and applications thereof
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The invention relates to a purine-aminomethyl-pyridone derivative, a preparation method and applications thereof, and belongs to the field of medicines, and provides a compound represented by a formula I or a pharmaceutically acceptable salt thereof. According to the invention, the pharmacodynamic experiment results prove that the purine-aminomethyl-pyridone derivative can significantly inhibit the proliferation of multiple tumor cells such as colorectal cancer, breast cancer, liver cancer, lung cancer and the like, and has broad-spectrum antitumor effect, and the IC50 values of part of the compounds can reach the nano-mole level wide and are equivalent to the effect of the anti-cancer drug doxorubicin, so that the new choice is provided for development and application of antitumor drugs.
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Paragraph 0276-0280
(2020/04/02)
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- Design, synthesis and biological evaluation of a novel tubulin inhibitor SKLB0565 targeting the colchicine binding site
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A series of 3-(((9H-purin-6-yl) amino) methyl) pyridin-2(1H)-one derivatives were designed, synthesized and confirmed as tubulin polymerization inhibitors. All compounds were evaluated for their anti-proliferative activities on three colorectal carcinoma (CRC) cell lines. Among these compounds, SKLB0565 displayed noteworthy potency against eight CRC cell lines with IC50 values ranging from 0.012 μM and 0.081 μM. Besides, SKLB0565 inhibited tubulin polymerization, caused G2/M phase cell cycle arrest, depolarized mitochondria and induced cell apoptosis in CRC cells. Furthermore, SKLB0565 suppressed cell migration and disrupted the capillary tube formation of human umbilical vein endothelial cells (HUVECs). Our data clarified that SKLB0565 is a promising anti-tubulin agent for CRC therapy which is worthy of further evaluation.
- Feng, Zhanzhan,Hu, Xi,Li, Lu,Wang, Qianqian,Xia, Yong,Xu, Ying,Yu, Luoting,Zhang, Qiangsheng
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- PROCESS FOR THE PREPARATION OF 2-FLUOROADENINE
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The present invention provides processes for the preparation of 2-fluoroadenine, as well as certain intermediates useful in the preparation of 2'-deoxy-4'-C-ethynyl-2-fluoroadenosine (EFdA): EFdA.
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Page/Page column 13; 14
(2021/01/23)
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- COMPOUNDS AS INHIBITORS OF MACROPHAGE MIGRATION INHIBITORY FACTOR
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The present invention provides compounds of Formula (I) shown above and their pharmaceutically acceptable salt, solvates, isomers, or prodrugs, as well as pharmaceutical compositions containing these compounds. Also provided by the invention is a method for treating a disorder mediated by macrophage migration inhibitory factor in a subject, comprising administering to the subject in need thereof a compound or a pharmaceutical composition of this invention.
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Paragraph 0375
(2020/09/27)
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- Purine derivative as well as preparation method and medical application thereof
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The invention provides a novel purine derivative, a preparation method thereof, a pharmaceutical composition containing the same, and application of the same in medicine. Particularly, the invention relates to a compound shown as a formula (I), a preparat
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Paragraph 0164-0169
(2020/07/24)
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- Discovery of 3-(((9H-purin-6-yl)amino)methyl)-4,6-dimethylpyridin-2(1H)-one derivatives as novel tubulin polymerization inhibitors for treatment of cancer
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A new series of 3-(((9H-purin-6-yl)amino)methyl)-4,6-dimethylpyridin-2(1H)-one derivatives were designed, synthesized and demonstrated to act as tubulin polymerization inhibitors. These new derivatives showed significant antitumor activities, among which
- Zhang, Qiangsheng,Hu, Xi,Wan, Guoquan,Wang, Jia,Li, Lu,Wu, Xiuli,Liu, Zhihao,Yu, Luoting
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- CRYSTALS OF [2-(1-METHYL-1H-PYRAZOL-4-YL)-6(MORPHOLIN-4-YL)-9H-PURIN-8-YL][4-(MORPHOLIN-4-YL)PIPERIDIN-1-YL]METHANONE AND PHARMACEUTICALLY ACCEPTABLE SALT THEREOF
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Provided are novel crystals of [2-(1-methyl-1H-pyrazol-4-yl)-6-(morpholin-4-yl)-9H-purin-8-yl][4-(morpholin-4-yl)piperidin-1-yl]methanone and a pharmaceutically acceptable salt thereof having advantageous characteristics. [2-(1-Methyl-1H-pyrazol-4-yl)-6-(
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Paragraph 0124; 0125; 0126
(2019/08/02)
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- PURINE AND 3-DEAZAPURINE ANALOGUES AS CHOLINE KINASE INHIBITORS
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There are provided substituted purine and 3-deazapurine analogues, which modulate the activity of Choline Kinase (ChoK). The compounds of this invention are therefore useful in treating diseases caused by an altered choline metabolism, such as cancer, cell proliferative disorders, infectious diseases of different origin, immune-related disorders and neurodegenerative disorders. The present invention also provides methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and methods of treating diseases utilizing pharmaceutical compositions comprising these compounds.
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Page/Page column 116; 117
(2018/02/28)
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- HETEROCYCLIC COMPOUNDS AND USE THEREOF
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Heterocyclic compounds of Formula (I) shown herein. Also disclosed is a pharmaceutical composition containing one of the heterocyclic compounds. Further disclosed are methods of using one of the heterocyclic compounds for mobilizing hematopoietic stem cells and endothelial progenitor cells into the peripheral circulation, and for treating tissue injury, cancer, inflammatory disease, and autoimmune disease.
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Page/Page column 54; 55
(2018/08/03)
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- 9-(2-OXACYCLOALKYL)-9H-PURINE-2,6-DIAMINE DERIVATIVES AND THEIR USE FOR THE TREATMENT OF SKIN DISORDERS
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The invention relates to N22,N66-disubstituted-9-(2-oxacycloalkyl)-9H-purine-2,6-diamine derivatives and their use as drugs and cosmetics. The compounds of the present invention exhibit a number of biological activities associated with oxidative stress inhibition, especially anti-aging, anti-inflammatory and anti-neurodegenerative biological activities. The invention also relates to cosmetic and pharmaceutical compositions containing such derivatives as active agents.
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Page/Page column 21
(2018/12/13)
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- Fused-pyrimidine derivatives, preparation method thereof, and pharmaceutical composition for use in preventing or treating Bruton's tyrosine kinase activity related diseases containing the same as an active ingredient
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The present invention relates to a conjugated pyrimidine derivative, a method for manufacturing the same, and a pharmaceutical composition for preventing or treating Bruton′s tyrosine kinase activity-related diseases containing the same as an active ingredient. The conjugated pyrimidine derivative according to the present invention is excellent in the ability to inhibit the activity of Bruton′s tyrosine kinase or TMD80, and thus can be usefully used for prevention or treatment of diseases related to Bruton′s tyrosine kinase activity, particularly cancer or autoimmune diseases.COPYRIGHT KIPO 2019
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Paragraph 0678-0682
(2019/02/02)
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- PYRROLOPYRIMIDINE COMPOUNDS, USE AS INHIBITORS OF THE KINASE LRRK2, AND METHODS FOR PREPARATION THEREOF
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The present disclosure is concerned with certain pyrrolopyrimidine compounds that are capable of inhibiting certain protein kinases, and especially the leucine-rich repeat kinase 2 (LRRK2) protein. Compounds of the present disclosure can be used to treat
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Paragraph 00536
(2017/07/06)
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- 2, 6-Di-Nitrogen-Containing Substituted Purine Derivative, And Preparation Method, Pharmaceutical Composition And Use Thereof
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The present invention provides a 2, 6-di-nitrogen-containing substituted purine derivative having a formula (I) structure, or pharmaceutical salt or hydrate thereof, and preparation method and use thereof. The compound is broad spectrum anticancer, low to
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Paragraph 0109; 0115
(2016/08/17)
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- HETEROCYCLIC COMPOUNDS AND USE THEREOF
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Heterocyclic compounds of Formula (I) shown herein. Also disclosed are pharmaceutical compositions containing the heterocyclic compounds and methods of using the heterocyclic compounds to mobilize hematopoietic stem cells and endothelial progenitor cells into the peripheral circulation. Further provided are methods for treating tissue injury, cancer, inflammatory disease, and autoimmune disease with the heterocyclic compounds.
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Paragraph 0234; 0235
(2016/04/19)
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- COMPOUNDS FOR TREATING CYSTIC FIBROSIS
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The present invention relates to compounds of Formula (I) or pharmaceutically acceptable enantiomers, salts, solvates or prodrugs thereof. The invention further relates to the use of the compounds of Formula (I) for the treatment of cystic fibrosis. The invention also relates to a process for manufacturing compounds of Formula (I).
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Page/Page column 86
(2016/06/28)
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- Development of an Efficient, Safe, and Environmentally Friendly Process for the Manufacture of GDC-0084
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An improved, efficient process with a significantly reduced process mass intensity (PMI) led to the multikilogram synthesis of a brain penetrant PI3K inhibitor GDC-0084. Highlights of the synthesis include a phase transfer catalyzed annulation in water, an efficient Suzuki-Miyaura cross-coupling of a chloropyrimidine with an arylboronic acid using a low palladium catalyst loading, and the development of a controlled crystallization to provide the API. The process delivered GDC-0084 with low levels of both impurities and residual metals.
- Stumpf, Andreas,McClory, Andrew,Yajima, Herbert,Segraves, Nathaniel,Angelaud, Remy,Gosselin, Francis
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supporting information
p. 751 - 759
(2016/05/19)
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- TRICYCLIC DLK INHIBITORS AND USES THEREOF
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The invention relates to compounds of formula (I) and salts thereof, wherein ring A and R1-R2 have any of the values defined in the specification. The compounds and salts are useful for treating DLK mediated disorders. The invention also provides pharmaceutical compositions comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, as well as methods of using said compounds, salts, or compositions as DLK inhibitors and for treating neurodegeneration diseases and disorders.
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Page/Page column 88
(2016/09/26)
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- COMPOUNDS FOR IMPROVING MRNA SPLICING
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Provided herein are compounds useful for improving mRNA splicing in a cell. Exemplary compounds provided herein are useful for improving mRNA splicing in genes comprising at least one exon ending in the nucleotide sequence CAA. Methods for preparing the compounds and methods of treating diseases of the central nervous system are also provided.
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Page/Page column 228; 229
(2016/08/10)
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- ADENINE DERIVATIVES WHICH ARE USEFUL IN THE TREATMENT OF ALLERGIC DISEASES OR OTHER INFLAMMATORY CONDITIONS
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Compounds of formula (I).
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Page/Page column 32; 34
(2016/06/13)
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- Function-oriented development of CXCR4 antagonists as selective human immunodeficiency virus (HIV)-1 entry inhibitors
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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.
- 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
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supporting information
p. 1452 - 1465
(2015/03/04)
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- Structural requirements for TLR7-selective signaling by 9-(4-piperidinylalkyl)-8-oxoadenine derivatives
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We report the synthesis and biological evaluation of a new series of 8-oxoadenines substituted at the 9-position with a 4-piperidinylalkyl moiety. In vitro evaluation of the piperidinyl-substituted oxoadenines 3a-g in human TLR7- or TLR8-transfected HEK293 cells and in human PBMCs indicated that TLR7/8 selectivity/potency and cytokine induction can be modulated by varying the length of the alkyl linker. Oxoadenine 3f containing a 5-carbon linker was found to be the most potent TLR7 agonist and IFNα inducer in the series whereas 3b possessing a 1-carbon linker was the most potent TLR8 agonist.
- Bazin, Hélène G.,Li, Yufeng,Khalaf, Juhienah K.,Mwakwari, Sandra,Livesay, Mark T.,Evans, Jay T.,Johnson, David A.
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p. 1318 - 1323
(2015/04/14)
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- SUBSTITUTED PURINE COMPOUNDS AS BTK INHIBITORS
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The present invention relates to the compound of Formula (I) wherein the substituents are as described herein, and their use in a medicine for the treatment of diseases, disorders associated with the inhibition of Bruton's tyrosine kinase (BTK). It furthe
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Page/Page column 38; 43
(2015/11/17)
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- Purine derivatives as potent Bruton's tyrosine kinase (BTK) inhibitors for autoimmune diseases
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Investigation of various heterocyclic core isosteres of imidazopyrazines 1 & 2 yielded purine derivatives 3 & 8 as potent and selective BTK inhibitors. Subsequent SAR studies of the purine series led to the discovery of 20 as a leading compound. Compound
- Shi, Qing,Tebben, Andrew,Dyckman, Alaric J.,Li, Hedy,Liu, Chunjian,Lin, James,Spergel, Steve,Burke, James R.,McIntyre, Kim W.,Olini, Gilbert C.,Strnad, Joann,Surti, Neha,Muckelbauer, Jodi K.,Chang, Chiehying,An, Yongmi,Cheng, Lin,Ruan, Qian,Leftheris, Katerina,Carter, Percy H.,Tino, Joseph,De Lucca, George V.
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p. 2206 - 2211
(2014/05/06)
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- Synthesis and evaluation of 18F-labeled ATP competitive inhibitors of topoisomerase II as probes for imaging topoisomerase II expression
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Type II topoisomerase (Topo-II) is an ATP-dependent enzyme that is essential in the transcription, replication, and chromosome segregation processes and, as such, represents an attractive target for cancer therapy. Numerous studies indicate that the respo
- Daumar, Pierre,Zeglis, Brian M.,Ramos, Nicholas,Divilov, Vadim,Sevak, Kuntal Kumar,Pillarsetty, Nagavarakishore,Lewis, Jason S.
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p. 769 - 781
(2015/01/16)
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- HETEROCYCLIC COMPOUNDS AND USES AS ANTICANCER AGENTS.
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The present disclosure provides pharmaceutical compounds, compositions and methods, especially as they are related to compositions and methods for the treatment of tumors and related diseases related to the dysregulation of kinase (such as EGFR (including
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Paragraph 00201
(2013/07/25)
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- Targeting conserved water molecules: Design of 4-aryl-5-cyanopyrrolo[2,3-d] pyrimidine Hsp90 inhibitors using fragment-based screening and structure-based optimization
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Inhibitors of the Hsp90 molecular chaperone are showing promise as anti-cancer agents. Here we describe a series of 4-aryl-5-cyanopyrrolo[2,3-d] pyrimidine ATP competitive Hsp90 inhibitors that were identified following structure-driven optimization of purine hits revealed by NMR based screening of a proprietary fragment library. Ligand-Hsp90 X-ray structures combined with molecular modeling led to the rational displacement of a conserved water molecule leading to enhanced affinity for Hsp90 as measured by fluorescence polarization, isothermal titration calorimetry and surface plasmon resonance assays. This displacement was achieved with a nitrile group, presenting an example of efficient gain in binding affinity with minimal increase in molecular weight. Some compounds in this chemical series inhibit the proliferation of human cancer cell lines in vitro and cause depletion of oncogenic Hsp90 client proteins and concomitant elevation of the co-chaperone Hsp70. In addition, one compound was demonstrated to be orally bioavailable in the mouse. This work demonstrates the power of structure-based design for the rapid evolution of potent Hsp90 inhibitors and the importance of considering conserved water molecules in drug design.
- Davies, Nicholas G.M.,Browne, Helen,Davis, Ben,Drysdale, Martin J.,Foloppe, Nicolas,Geoffrey, Stephanie,Gibbons, Ben,Hart, Terance,Hubbard, Roderick,Jensen, Michael Rugaard,Mansell, Howard,Massey, Andrew,Matassova, Natalia,Moore, Jonathan D.,Murray, James,Pratt, Robert,Ray, Stuart,Robertson, Alan,Roughley, Stephen D.,Schoepfer, Joseph,Scriven, Kirsten,Simmonite, Heather,Stokes, Stephen,Surgenor, Allan,Webb, Paul,Wood, Mike,Wright, Lisa,Brough, Paul
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p. 6770 - 6789
(2013/01/15)
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- Lead optimization of purine based orally bioavailable Mps1 (TTK) inhibitors
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Efforts to optimize biological activity, novelty, selectivity and oral bioavailability of Mps1 inhibitors, from a purine based lead MPI-0479605, are described in this Letter. Mps1 biochemical activity and cytotoxicity in HCT-116 cell line were improved. On-target activity confirmation via mechanism based G2/M escape assay was demonstrated. Physico-chemical and ADME properties were optimized to improve oral bioavailability in mouse.
- Kumar, D. Vijay,Hoarau, Christophe,Bursavich, Matthew,Slattum, Paul,Gerrish, David,Yager, Kraig,Saunders, Michael,Shenderovich, Mark,Roth, Bruce L.,McKinnon, Rena,Chan, Ashley,Cimbora, Daniel M.,Bradford, Chad,Reeves, Leslie,Patton, Scott,Papac, Damon I.,Williams, Brandi L.,Carlson, Robert O.
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scheme or table
p. 4377 - 4385
(2012/08/07)
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- TRICYCLIC PI3K INHIBITOR COMPOUNDS AND METHODS OF USE
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Tricyclic PI3k inhibitor compounds of Formula I with anti-cancer activity, anti- inflammatory activity, or immunoregulatory properties, and more specifically with PI3 kinase modulating or inhibitory activity are described. Methods are described for using the tricyclic PI3K inhibitor compounds of Formula I for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, organisms, or associated pathological conditions. Formula I compounds include stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof. The dashed lines indicate an optional double bond, and at least one dashed line is a double bond. The substituents are as described.
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Page/Page column 136
(2012/06/30)
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- Intermolecular hydrogen abstraction reaction between nitrogen radicals in purine rings and alkyl ethers: A highly selective method for the synthesis of N-9 alkylated purine nucleoside derivatives
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A highly selective method for the synthesis of N-9 alkylated purine nucleoside derivatives via an intermolecular hydrogen abstraction reaction between nitrogen radicals in purine rings and alkyl ethers was developed. Novel purine nucleoside derivatives we
- Guo, Hai-Ming,Xia, Chao,Niu, Hong-Ying,Zhang, Xiao-Ting,Kong, Si-Nan,Wang, Dong-Chao,Qu, Gui-Rong
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supporting information; experimental part
p. 53 - 56
(2011/03/22)
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- PURINE DERIVATIVES AND THEIR PHARMACEUTICAL USES
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Compounds of formula (I), wherein; R1 represents hydrogen or C1-3alkyl; n is an integer having a value of 1 to 5; X represents O or NH; Y represents C or N; or a pharmaceutically acceptable salt thereof, have been shown to be inducers of human interferon
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Page/Page column 20; 26; 27
(2011/09/15)
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- PI3K (DELTA) SELECTIVE INHIBITORS
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Novel PI3K, especially PI3K delta isoform, selective inhibitors are disclosed. The compounds are useful in treating disorders related to abnormal PI3K or PI3Kδ activities such as cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine disorders and neurological disorders.
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Page/Page column 45
(2011/04/25)
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- Discovery of selective irreversible inhibitors for EGFR-T790M
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Targeting the epidermal growth factor receptor kinase (EGFR) with ATP-competitive kinase inhibitors results in dramatic but short-lived responses in patients with EGFR mutant non small cell lung cancer. A series of novel covalent EGFR kinase inhibitors with selectivity for the clinically relevant T790M 'gatekeeper' resistance mutation relative to wild-type EGFR were discovered by library screening. A representative compound 3i was obtained through a systematic SAR study guided by mutant EGFR-dependent cellular proliferation assays.
- Zhou, Wenjun,Ercan, Dalia,Jaenne, Pasi A.,Gray, Nathanael S.
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scheme or table
p. 638 - 643
(2011/03/18)
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- 6-AMINO-2-{ [ (1S)-1-METHYLBUTYL] OXY}-9-[5-(1-PIPERIDINYL)-7,9-DIHYDRO-8H-PURIN-8-ONE MALEATE
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A compound which is 6-amino-2-{[(1S)-1-methylbutyl]oxy}-9-[5-(1-piperidinyl)pentyl]-7,9-dihydro-8H-purin-8-one: Formula (I) in the form of a maleate salt, may be useful in the treatment of various disorders, for example the treatment of allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, the treatment of infectious diseases and cancer, and may also be useful as vaccine adjuvants.
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Page/Page column 22
(2011/09/15)
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- PURINE DERIVATIVES FOR USE IN THE TREATMENT OF ALLERGIC, INFLAMMATORY AND INFECTIOUS DISEASES
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Compounds of formula (I): wherein R1 is C1-6alkylamino, C1-6alkoxy, or C3-7cycloalkyloxy; m is an integer having a value of 3 to 6; n is an integer having a value of 0 to 4; and salts thereof are inducers of human interferon. Compounds which induce human interferon may be useful in the treatment of various disorders, for example the treatment of allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, the treatment of infectious diseases and cancer, and may also be useful as vaccine adjuvants.
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Page/Page column 42-43
(2010/04/03)
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- NOVEL ADENINE DERIVATIVES
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Compounds of formula (I) wherein R1 is C1-6alkylamino, or C1-6alkoxy; R2 is a group having the structure (II): n is an integer having a value of 1 to 6; Het is a 6-membered saturated heterocycle containing one nitrogen atom wherein Het is attached to the -(CH2)n- moiety at any carbon atom of the heterocycle; R3 is hydrogen, C1-8alkyl, or C3-7cycloalkylC0-6alkyl; and salts thereof are inducers of human interferon. Compounds which induce human interferon may be useful in the treatment of various disorders, for example the treatment of allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, the treatment of infectious diseases and cancer, and may also be useful as vaccine adjuvants.
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Page/Page column 50
(2010/04/03)
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- A class of novel conjugates of substituted purine and Gly-AA-OBzl: Synthesis and evaluation of orally analgesic activity
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Aimed at the chemotherapy of chronic pain two kinds of analgesic pharmacophores, substituted purine and Gly-AA-OBzl, were coupled via a five-step-reaction procedure and 19 novel conjugates N-[2-chloro-9- (tetrahydropyran-2-yl)-9H-purin-6-yl]-N-cyclopropylglycylamino acid benzylesters were provided. On mouse-tail flick model their in vivo analgesic activities were assayed. The results indicate that introducing Gly-OC2H 5 into the 6-position of the substituted purine leads to ambiguous increase of the analgesic activity, while introducing Gly-AA-OBzl into this position leads to significant increase of the analgesic activity.
- Kang, Guifeng,Zhao, Ming,Zhang, Xiaoyi,Peng, Li,Li, Chunbo,Mao, Wei,Ye, Weidong,Peng, Shiqi
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supporting information; experimental part
p. 6157 - 6160
(2010/12/19)
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- PI3K ISOFORM SELECTIVE INHIBITORS
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2-Morpholin-4-yl-9H-purine and 5-Morpholin-4-yl-3H-[1,2,3]triazolo[4,5-d] pyrimidine derivatives, especially those substituted by 6-heteroaryl, are unexpected PI3 kinase isoform selective inhibitors with good drug properties and are useful in treating disorders related to abnormal PI3K activities such as cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine disorders and neurological disorders
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Page/Page column 78
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- PURINE DERIVATIVES FOR USE IN THE TREATMENT OF ALLERGIC, INFLAMMATORY AND INFECTIOUS DISEASES
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Compounds of formula (I): wherein R1 is C1-6alkylamino, or C1-6alkoxy; m is an integer having a value of 3, 4, or 5; n is an integer having a value of 0 to 3; p is an integer having a value of 1 or 2 and salts thereof are inducers of human interferon. Compounds which induce human interferon may be useful in the treatment of various disorders, for example the treatment of allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, the treatment of infectious diseases and cancer, and may also be useful as vaccine adjuvants.
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Page/Page column 40-41
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- PURINE DERIVATIVES FOR USE IN THE TREATMENT OF ALLERGIC, INFLAMMATORY AND INFECTIOUS DISEASES
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Compounds of Formula (I): wherein R1 is C1-6alkylamino, C1-6alkoxy, or C3-7cycloalkyloxy; m is an integer having a value of 2 to 6; R2 is hydrogen, C1-6alkyl, or C3-7cycloalkylC0-6alkyl; and salts thereof are inducers of human interferon. Compounds which induce human interferon may be useful in the treatment of various disorders, for example the treatment of allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, the treatment of infectious diseases and cancer, and may also be useful as vaccine adjuvants.
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Page/Page column 42-43
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- COMPOUNDS
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Compounds of formula (I): wherein R1 is C1-6alkylamino, or C1-6alkoxy; m is an integer having a value of 2 or 3; n is an integer having a value of 0 to 3; p is an integer having a value of 1 or 2; and salts thereof are inducers of human interferon. Compounds which induce human interferon may be useful in the treatment of various disorders, for example the treatment of allergic diseases and other inflammatory conditions for example allergic rhinitis and asthma, the treatment of infectious diseases and cancer, and may also be useful as vaccine adjuvants.
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Page/Page column 38-39
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- COMPOUNDS AND THERAPEUTIC USES THEREOF
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The invention relates to compounds, pharmaceutical compositions, and uses thereof, including therapeutic uses thereof, such as methods useful for treating cancer.
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Page/Page column 124-125
(2010/11/03)
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- EGFR INHIBITORS AND METHODS OF TREATING DISORDERS
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The present invention relates to novel pyrimidine, pyrrolo-pyrimidine, pyrrolo-pyridine, pyridine, purine and triazine compounds which are able to modulate epidermal growth factor receptor (EGFR), including Her-kinases, and the use of such compounds in the treatment of various diseases, disorders or conditions.
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Page/Page column 114
(2010/11/18)
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