cas 123148-78-7, 4-Chloro-5-iodo-7H-pyrrol[2,3-d]pyrimidine

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Study on the synthesis and PKA-I binding activities of 5-alkynyl tubercidin analogues
5-Alkynyl tubercidin analogues were synthesized and their biologica activities were evaluated. It was found that protein kinase A could be activated by 5-alkynyl tubercidin (9a) and cAMP- binding ability to PKA-I was selectively inhibited by it. Molecular
Zhang, Liangren,Zhang, Yunlong,Li, Xianghui,Zhang, Lihe
p. 907 - 912
(2002)
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Identification of fused pyrimidines as interleukin 17 secretion inhibitors
Inhibiting the interleukin 17 pathway is of interest in a number of autoimmune diseases. Herein, 42 fused pyrimidines have been evaluated as interleukin 17 secretion inhibitors using a phenotypic assay with peripheral blood mononuclear cells. 7H-Pyrrolo [
Reiers?lmoen, Ann Christin,Han, Jin,Sundby, Eirik,Hoff, B?rd Helge
p. 562 - 578
(2018)
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Synthesis of responsive fluorescent nucleobases 7-(benzofuran-2-yl)-7-deazahypoxanthine and 7-(benzofuran-2-yl)-7-deazaguanine using cross-coupling reaction
In order to develop fluorescent guanine analogs having substitutions at the 7-positions, 7-(benzofuran-2-yl)-7-deaza-hypoxanthine (1a) and 7-(benzofuran-2-yl)-7-deazaguanine (1b), were synthesized from 7-deaza-7-iodohypoxanthine and 7-deaza-7-iodo-2-N-pivaloylguanine via a Suzuki-Miyaura cross-coupling, respectively. Compound 1b showed strong fluorescence, with higher fluorescent quantum yields in less polar solvents; meanwhile, 1a showed higher activity in more polar solvents. It is expected that the guanine analogs can be incorporated into nucleosides to develop new fluorescent oligonucleotides.
Tokugawa, Munefumi,Kaneko, Kazuhei,Saito, Masanori,Masaki, Yoshiaki,Ohkubo, Akihiro,Sekine, Mitsuo,Seio, Kohji,Kanamori, Takashi
p. 64 - 66
(2015)
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Pre-steady state kinetic analysis of cyclobutyl derivatives of 2′-deoxyadenosine 5′-triphosphate as inhibitors of HIV-1 reverse transcriptase
Pre-steady state kinetic analysis was utilized for biochemical evaluation of a series of cyclobutyl adenosine nucleotide analogs with HIV-1 RT WT. The phosphonyl-diphosphate form of the cyclobutyl nucleotide, 5, was the most efficiently incorporated of the series. Nucleotide 5 was fourfold more efficiently incorporated than the FDA approved TFV-DP by RTWT. The kinetics of incorporation for 5 using the drug resistant mutant enzyme K65R was also determined. Compound 5 was threefold more efficiently incorporated compared to TFV-DP with RTK65R. These results demonstrate cyclobutyl adenosine analogs can act as substrates for incorporation by HIV-1 RT and be a potential scaffold for HIV inhibitors.
Kim, Jiae,Wang, Ligong,Li, Yongfeng,Becnel, Kimberlynne D.,Frey, Kathleen M.,Garforth, Scott J.,Prasad, Vinayaka R.,Schinazi, Raymond F.,Liotta, Dennis C.,Anderson, Karen S.
p. 4064 - 4067
(2012)
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Potent and selective EGFR inhibitors based on 5-aryl-7H-pyrrolopyrimidin-4-amines
The epidermal growth factor receptor represents an important target in cancer therapy, and low molecular weight inhibitors based on quinazolines have reached the marked. Herein we report on a new scaffold, 5-aryl-7H-pyrrolo[2,3-d]pyrimidin-4-amines, and show that when employing (S)-phenylglycinol as C-4 substituent, potent inhibitors can be made. The two most active inhibitors have suitable druglike properties, were equipotent with Erlotinib in Ba/F3 cell studies, and showed lower cross reactivity than Erlotinib in a panel of 50 kinases.
Reiers?lmoen, Ann Christin,Aarhus, Thomas Ihle,Eckelt, Sarah,N?rsett, Kristin Gabestad,Sundby, Eirik,Hoff, B?rd Helge
(2019)
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Inhibition of osimertinib-resistant epidermal growth factor receptor EGFR-T790M/C797S
Precision medicine has revolutionized the treatment of patients in EGFR driven non-small cell lung cancer (NSCLC). Targeted drugs show high response rates in genetically defined subsets of cancer patients and markedly increase their progression-free survival as compared to conventional chemotherapy. However, recurrent acquired drug resistance limits the success of targeted drugs in long-term treatment and requires the constant development of novel efficient inhibitors of drug resistant cancer subtypes. Herein, we present covalent inhibitors of the drug resistant gatekeeper mutant EGFR-L858R/T790M based on the pyrrolopyrimidine scaffold. Biochemical and cellular characterization, as well as kinase selectivity profiling and western blot analysis, substantiate our approach. Moreover, the developed compounds possess high activity against multi drug resistant EGFR-L858R/T790M/C797S in biochemical assays due to their highly reversible binding character, that was revealed by characterization of the binding kinetics. In addition, we present the first X-ray crystal structures of covalent inhibitors in complex with C797S-mutated EGFR which provide detailed insight into their binding mode.
Lategahn, Jonas,Keul, Marina,Kl?vekorn, Philip,Tumbrink, Hannah L.,Niggenaber, Janina,Müller, Matthias P.,Hodson, Luke,Fla?hoff, Maren,Hardick, Julia,Grabe, Tobias,Engel, Julian,Schultz-Fademrecht, Carsten,Baumann, Matthias,Ketzer, Julia,Mühlenberg, Thomas,Hiller, Wolf,Günther, Georgia,Unger, Anke,Müller, Heiko,Heimsoeth, Alena,Golz, Christopher,Blank-Landeshammer, Bernhard,Kollipara, Laxmikanth,Zahedi, René P.,Strohmann, Carsten,Hengstler, Jan G.,Van Otterlo, Willem A. L.,Bauer, Sebastian,Rauh, Daniel
p. 10789 - 10801
(2019)
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Synthesis and photophysical evaluation of new fluorescent 7-arylethynyl-7-deazaadenosine analogs
Three new fluorescent 7-deaza-2′-deoxyadenosine analogs were synthesized via the Sonogashira cross-coupling reaction of 7-iodo-7-deaza-2′-deoxyadenosine with 1-ethynylpyrene, 2-ethynyl-6-methoxynaphthalene, and 9-ethynylphenanthrene. The spectral properties of these analogs were evaluated in dioxane, EtOH, and H2O to determine their potential for use as environmentally sensitive fluorescent probes. All three analogs displayed large solvatofluorochromicity in H2O, relative to their emission wavelengths in dioxane or EtOH. Moreover, all three analogs exhibited microenvironmental sensitivity of their fluorescence emission intensity, being moderate to high quantum yields in dioxane and EtOH and significantly lower in H2O. Various attempts to perform domino cross-coupling and annuation reactions on 7-deaza-7-alkynyladenine derivatives to form a new fused tricyclic adenine analog were unsuccessful.
Matarazzo, Augusto,Brow, Justin,Hudson, Robert H.E.
p. 1093 - 1100
(2018)
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Novel HPK1 inhibitor as well as preparation method and application thereof
The present invention provides an HPK1 kinase inhibitor, the preparation thereof and use thereof. Specifically, the present invention provides a compound as represented by formula I. The definitions on groups are as stated in the description. The compound has excellent HPK1 inhibitory activity, and therefore can be used for preparing a pharmaceutical composition for treating cancer and other diseases related to HPK1 activity.
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(2021/09/08)

Inhibitors of NEK7 kinase
Compounds having activity as inhibitors of NEK7 are provided. The compounds have Structure (I):or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein, A, X, Y, R1, R2, R3, R4 and R5 are as defined herein. Methods associated with p
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Page/Page column 91

(2021/11/03)

Selective C-H Iodination of (Hetero)arenes
Iodoarenes are versatile intermediates and common synthetic targets in organic synthesis. Here, we present a strategy for selective C-H iodination of (hetero)arenes with a broad functional group tolerance. We demonstrate the utility and differentiation to other iodination methods of supposed sulfonyl hypoiodites for a set of carboarenes and heteroarenes.
Tanwar, Lalita,B?rgel, Jonas,Lehmann, Johannes,Ritter, Tobias
supporting information
p. 5024 - 5027
(2021/06/30)

CYCLOALKYLIDENE CARBOXYLIC ACIDS AND DERIVATIVES AS BTK INHIBITORS
The present invention relates to novel cycloalkylidene carboxylic acids and derivatives thereof useful as Bruton tyrosine kinase (BTK) inhibitors. The present disclosure also relates to processes for their preparation, pharmaceutical compositions containing one or more such compounds, and to the use of such compounds and pharmaceutical compositions for the treatment of disorders involving mediation of BTK in humans (Formula I).
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Page/Page column 125-126

(2021/03/05)

Nitrogen-containing heterocyclic ring derivative or pharmaceutically acceptable salt and application thereof
The invention discloses a nitrogen-containing heterocyclic ring derivative or a pharmaceutically acceptable salt thereof. The general formula of the nitrogen-containing heterocyclic ring derivative is shown as a formula I. The invention also provides appl
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Paragraph 0052-0058

(2021/07/09)

Bruton's tyrosine protein kinase inhibitor
The invention discloses a compound capable of reversibly inhibiting Bruton's tyrosine protein kinase (BTK) and a pharmaceutically acceptable salt thereof, and containing the compound or a pharmaceutical composition thereof. The invention further discloses the compound or a salt and thereof, and the pharmaceutical composition is used for treating tumors caused BTK abnormity. Use of an autoimmune disease and inflammatory disease or the like.
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Paragraph 0314; 0317-0318

(2021/10/27)

Synthesis of 7-trifluoromethyl-7-deazapurine ribonucleoside analogs and their monophosphate prodrugs
Novel 7-trifluoromethyl-7-deazapurine ribonucleoside analogs (13a-c) and their Protides (15a-c) were successfully synthesized from ribolactol or 1-α-bromo-ribose derivatives using Silyl-Hilbert-Johnson or nucleobase-anion substitution reactions followed by key aromatic trifluoromethyl substitution. Newly prepared compounds were evaluated against a panel of RNA viruses, including HCV, Ebola or Zika viruses.
Cho, Jong Hyun,Bassit, Leda C.,Amblard, Franck,Schinazi, Raymond F.
p. 671 - 687
(2019/11/03)

Targeting Her2-insYVMA with Covalent Inhibitors - A Focused Compound Screening and Structure-Based Design Approach
Mutated or amplified Her2 serves as a driver of non-small cell lung cancer or mediates resistance toward the inhibition of its family member epidermal growth factor receptor with small-molecule inhibitors. To date, small-molecule inhibitors targeting Her2 which can be used in clinical routine are lacking, and therefore, the development of novel inhibitors was undertaken. In this study, the well-established pyrrolopyrimidine scaffold was modified with structural motifs identified from a screening campaign with more than 1600 compounds, which were applied against wild-type Her2 and its mutant variant Her2-A775_G776insYVMA. The resulting inhibitors were designed to covalently target a reactive cysteine in the binding site of Her2 and were further optimized by means of structure-based drug design utilizing a set of obtained complex crystal structures. In addition, the analysis of binding kinetics and absorption, distribution, metabolism, and excretion parameters as well as mass spectrometry experiments and western blot analysis substantiated our approach.
Lategahn, Jonas,Hardick, Julia,Grabe, Tobias,Niggenaber, Janina,Jeyakumar, Kirujan,Keul, Marina,Tumbrink, Hannah L.,Becker, Christian,Hodson, Luke,Kirschner, Tonia,Kl?vekorn, Philip,Ketzer, Julia,Baumann, Matthias,Terheyden, Susanne,Unger, Anke,Weisner, J?rn,Müller, Matthias P.,Van Otterlo, Willem A. L.,Bauer, Sebastian,Rauh, Daniel
p. 11725 - 11755
(2020/11/26)

Synthesis and anti-HBV activity of carbocyclic nucleoside hybrids with salient features of entecavir and aristeromycin
Modified carbocyclic nucleosides (4a-g) constituting 7-deazapurine, 4′-methyl, exocyclic double bond and 2′,3′-hydroxy were synthesized. NOE and X-ray studies of4cconfirmed the α-configuration of 4′-methyl. The anti-HBV assay demonstrated4e(IC50/sub
Baba, Masanori,Bal, Chandralata,Jha, Ashok Kumar,Neeladri, Seshubabu,Pallaka, Renuka Sivasankar,Samunuri, Ramakrishnamraju,Toyama, Masaaki
p. 597 - 601
(2020/06/08)

Design, synthesis and evaluation of novel 7H-pyrrolo[2,3-d]pyrimidin-4-amine derivatives as potent, selective and reversible Bruton's tyrosine kinase (BTK) inhibitors for the treatment of rheumatoid arthritis
A series of 7H-pyrrolo[2,3-d]pyrimidine derivatives were designed and synthesized as reversible BTK inhibitors, and evaluated their kinase selectivity, anti-proliferation against the B-cell lymphoma cell lines (Ramos, Jeko-1) and cell line BTK enhanced (Daudi) in vitro. Among them, compound 28a exhibited the most excellent potency (IC50 = 3.0 nM against BTK enzyme, 8.52 μM, 11.10 μM and 7.04 μM against Ramos, Jeko-1, Daudi cells, respectively), good kinase selectivity and inhibited BTK Y223 auto-phosphorylation and PLCγ2 Tyr1217 phosphorylation. Importantly, 28a showed efficacy anti-arthritic effect on collagen-induced arthritis (CIA) model in vivo. 28a 60 mg/kg dose level once a day group displayed markedly reduced joint damage and cellular infiltration without any bone and cartilage morphology change.
Zhang, Chufeng,Pei, Heying,He, Jun,Zhu, Jiali,Li, Weimin,Niu, Ting,Xiang, Mingli,Chen, Lijuan
p. 121 - 143
(2019/03/13)

INHIBITORS OF THE BCL6 BTB DOMAIN PROTEIN-PROTEIN INTERACTION AND USES THEREOF
The present application relates to compounds of Formula I (I) or pharmaceutically acceptable salts, solvates and/or prodrugs thereof, to compositions comprising these compounds or pharmaceutically acceptable salts, solvates and/or prodrugs thereof, and various uses in the treatment of diseases, disorders or conditions that are treatable by inhibiting interactions with BCL6 BTB, such as cancer.
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Page/Page column 00193

(2019/08/29)

NEW COMPOUND HAVING FGFR INHIBITORY ACTIVITY AND PREPARATION AND APPLICATION THEREOF
The present invention relates to a new compound having an FGFR inhibitory activity and preparation and application thereof. In particular, the compound according to the present invention has a structure as shown in formula I, wherein each group and substituent are as defined in the description. Also disclosed in the present invention are a preparation method for the compound and a use thereof in preparation of a drug for treating and/or preventing a tumor-related disease and/or an FGFR-related disease.
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Paragraph 0125; 0126

(2019/05/30)

4 - Amino - pyrimidine and nitrogen heterocyclic derivatives and its preparation and use (by machine translation)
The invention belongs to the field of biological chemistry, and in particular relates to 4 - amino - pyrimidine and nitrogen heterocyclic derivatives and its preparation and use. The present invention provides a 4 - amino - pyrimidine and nitrogen heteroc
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Paragraph 0151-0155

(2019/10/02)

Pd/PTABS: An Efficient Catalytic System for the Aminocarbonylation of a Sugar-Protected Nucleoside
A highly efficient and mild protocol for the aminocarbonylation of a nucleoside is developed by employing palladium/(1,3,5-Triaza-7-phosphaadamantan-1-ium-1-yl)butane-1-sulfonate (Pd/PTABS) as the catalytic system. The developed aminocarbonylation methodology employs CO gas at a relatively low temperature of 60? °C and is suitable for a wide range of amines, including (heteroaryl)benzylic, aliphatic acyclic, alicyclic and secondary amines. This protocol is also utilized for the synthesis of a sangivamycin precursor by carrying out the Pd-catalyzed amination and aminocarbonylation simultaneously. The utility of this protocol is further demonstrated by the synthesis of the drugs moclobemide and nikethamide.
Bhanage, Bhalchandra M.,Bhilare, Shatrughn,Gaikwad, Vinayak,Gupta, Gaurav,Kapdi, Anant R.,Sanghvi, Yogesh S.,Shah, Jagrut
supporting information
p. 4239 - 4248
(2019/11/14)

Enantioselective Synthesis of Pyrrolopyrimidine Scaffolds through Cation-Directed Nucleophilic Aromatic Substitution
The catalytic enantioselective synthesis of 3-aryl-substituted pyrrolopyrimidines (PPYs), a common motif in drug discovery, is achieved through a kinetic resolution via quaternary ammonium salt-catalyzed nucleophilic aromatic substitution (SNAr). Both enantioenriched products and starting materials can be functionalized with no observed racemization to give enantiodivergent access to diverse chiral analogues of an important class of kinase inhibitor. One of the compounds was found to be a potent and selective inhibitor of breast tumor kinase.
Cardenas, Mariel M.,Toenjes, Sean T.,Nalbandian, Christopher J.,Gustafson, Jeffrey L.
supporting information
p. 2037 - 2041
(2018/04/12)

PHARMACEUTICAL COMPOSITION AND APPLICATION REPLACING QUINOLONE DERIVATIVE, PHARMACEUTICAL ACCEPTABLE SALT, OR STEREOISOMER
Provided are a substituted quinolone derivative as shown by formula (I), or a pharmaceutically acceptable salt and a prodrug molecule thereof, and a pharmaceutical composition thereof, as well as the use of same in preparing drugs for the prevention and treatment of a tumor. The quinolone derivative, salt, prodrug molecule, and pharmaceutical composition thereof can be used as a protein kinase inhibitor, which is effective in inhibiting the activity of AXL protein kinase, and is capable of inhibiting the proliferation, migration and invasion of various tumor cells; and can be used in the preparation of anti-tumor drugs, especially drugs for treating hyperproliferative diseases such as a tumor in human beings and other mammals.
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Paragraph 0208; 0209

(2018/07/06)

PYRROLOPYRIMIDINES AS CFTR POTENTIATORS
The present invention relates to compounds of Formula I, wherein R1a, R1b, R2, R3, R4, W, Y, and Z are as described herein, and pharmaceutically acceptable salts thereof. The compounds are potentiator
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Paragraph 0418; 0419

(2018/06/04)

Discovery of 7-Oxo-2,4,5,7-tetrahydro-6 H -pyrazolo[3,4- c] pyridine Derivatives as Potent, Orally Available, and Brain-Penetrating Receptor Interacting Protein 1 (RIP1) Kinase Inhibitors: Analysis of Structure-Kinetic Relationships
We report the discovery of 7-oxo-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridine derivatives as a novel class of receptor interacting protein 1 (RIP1) kinase inhibitors. On the basis of the overlay study between HTS hit 10 and GSK2982772 (6) in RIP1 kinase, we designed and synthesized a novel class of RIP1 kinase inhibitor 11 possessing moderate RIP1 kinase inhibitory activity and P-gp mediated efflux. The optimization of the core structure and the exploration of appropriate substituents utilizing SBDD approach led to the discovery of 22, a highly potent, orally available, and brain-penetrating RIP1 kinase inhibitor with excellent PK profiles. Compound 22 significantly suppressed necroptotic cell death both in mouse and human cells. Oral administration of 22 (10 mg/kg, bid) attenuated disease progression in the mouse experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). Moreover, analysis of structure-kinetic relationship (SKR) for our novel chemical series was also discussed.
Yoshikawa, Masato,Saitoh, Morihisa,Katoh, Taisuke,Seki, Tomohiro,Bigi, Simone V.,Shimizu, Yuji,Ishii, Tsuyoshi,Okai, Takuro,Kuno, Masako,Hattori, Harumi,Watanabe, Etsuro,Saikatendu, Kumar S.,Zou, Hua,Nakakariya, Masanori,Tatamiya, Takayuki,Nakada, Yoshihisa,Yogo, Takatoshi
supporting information
p. 2384 - 2409
(2018/03/26)

6-methyl 7-position-denitrified purine nucleoside compounds and application thereof
The invention discloses6-methyl 7-position-denitrified purine nucleoside compounds and an application thereof and belongs to the field of medicinal chemistry. The 6-methyl 7-position-denitrified purine nucleoside compounds or pharmaceutically acceptable salts of the compounds having characteristics of a structure shown as formula I are a kind of novel-structured compounds designed and synthesized according to protein structure characteristics of RNA virus polymerase, and the compounds can inhibit RNA viruses, thereby being capable of serving as potential drugs for preventing and treating infection of RNA viruses such as HCV (hepatitis c virus), influenza virus, HRV (rhinovirus), RSV, Ebola virus, DENV (Dengue virus), enterovirus and the like.
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(2017/09/02)

Identification of pyrrolo[2,3-d]pyrimidines as potent HCK and FLT3-ITD dual inhibitors
A series of novel pyrrolo[2,3-d]pyrimidines were synthesized by introducing 15 different amino acids to 7-cyclohexyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidine-4-amine. Compounds with potent activities against HCK and FLT3-ITD were evaluated in viabi
Koda, Yasuko,Kikuzato, Ko,Mikuni, Junko,Tanaka, Akiko,Yuki, Hitomi,Honma, Teruki,Tomabechi, Yuri,Kukimoto-Niino, Mutsuko,Shirouzu, Mikako,Shirai, Fumiyuki,Koyama, Hiroo
p. 4994 - 4998
(2017/10/20)

Synthesis and evaluation of analogs of 5′-(((Z)-4-amino-2-butenyl)methylamino)-5′-deoxyadenosine (MDL 73811, or AbeAdo) – An inhibitor of S-adenosylmethionine decarboxylase with antitrypanosomal activity
We describe our efforts to improve the pharmacokinetic properties of a mechanism-based suicide inhibitor of the polyamine biosynthetic enzyme S-adenosylmethionine decarboxylase (AdoMetDC), essential for the survival of the eukaryotic parasite Trypanosoma brucei responsible for Human African Trypanosomiasis (HAT). The lead compound, 5′-(((Z)-4-amino-2-butenyl)methylamino)-5′-deoxyadenosine (1, also known as MDL 73811, or AbeAdo), has curative efficacy at a low dosage in a hemolymphatic model of HAT but displayed no demonstrable effect in a mouse model of the CNS stage of HAT due to poor blood–brain barrier permeation. Therefore, we prepared and evaluated an extensive set of analogs with modifications in the aminobutenyl side chain, the 5′-amine, the ribose, and the purine fragments. Although we gained valuable structure–activity insights from this comprehensive dataset, we did not gain traction on improving the prospects for CNS penetration while retaining the potent antiparasitic activity and metabolic stability of the lead compound 1.
Brockway, Anthony J.,Volkov, Oleg A.,Cosner, Casey C.,MacMillan, Karen S.,Wring, Stephen A.,Richardson, Thomas E.,Peel, Michael,Phillips, Margaret A.,De Brabander, Jef K.
supporting information
p. 5433 - 5440
(2017/10/06)

COMBINATION THERAPIES FOR TREATMENT OF CANCER
Combination therapies for treatment of cancers associated with mutations in the KRAS gene are provided. Compositions comprising therapeutic agents for treatment of cancers associated with mutations in the KRAS gene are also provided.
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(2016/04/09)

INHIBITORS OF KRAS G12C
Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein R1, R2a, R3a, R3b, R4a, R4b, G1, G2, L1, L2, m1, m2, A, B, W, X, Y, Z and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.
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(2015/04/28)

Benzothiazole Kinase Inhibitors and Methods of Use
The present invention provides chemical entities or compounds and pharmaceutical compositions thereof that are capable of modulating lipid kinases such PI3 kinases, tryosine kinases and protein kinases such as mTOR. Also provided in the present invention are methods of using these compositions to modulate these kinases especially for therapeutic applications.
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Paragraph 0396

(2015/09/22)

Design and synthesis of fluorescent 7-deazaadenosine nucleosides containing π-extended diarylacetylene motifs
C-modified 7-deazaadenosines containing a diphenylacetylene moiety have been synthesised using cross-coupling approaches. The C-modified nucleosides exhibit remarkable fluorescence properties, including high quantum yields. Solvatochromic studies show a n
De Ornellas, Sara,Slattery, John M.,Edkins, Robert M.,Beeby, Andrew,Baumann, Christoph G.,Fairlamb, Ian J. S.
supporting information
p. 68 - 72
(2015/02/02)

Nucleotides and nucleosides and methods for their use in DNA sequencing
The present invention relates generally to labeled and unlabled cleavable terminating groups and methods for DNA sequencing and other types of DNA analysis. More particularly, the invention relates in part to nucleotides and nucleosides with chemically cleavable, photocleavable, enzymatically cleavable, or non-photocleavable groups and methods for their use in DNA sequencing and its application in biomedical research.
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Page/Page column 110; 111; 112

(2015/12/18)

HETEROCYCLIC COMPOUNDS AND METHODS OF USE
The present application discloses compounds that are inhibitors of Btk, compounds that are inhibitors of ΡΒΚδ, and compounds that are dual inhibitors of both Btk and PI3Kδ. Also described are methods for synthesizing such inhibitors and methods for using such inhibitors for the treatment of diseases wherein inhibition of Btk and PI3Kδ provides a therapeutic benefit to a patient having the disease.
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Paragraph 0342

(2015/05/05)

4'-SUBSTITUTED NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
Provided is 4'-substituted nucleoside derivatives of Formula I and their use in the inhibition of HIV reverse transcriptase, the prophylaxis of infection by HIV, the treatment of infection by HIV, and the prophylaxis, treatment, and delay in the onset or progression of AIDS and/or ARC.
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Page/Page column 54; 55

(2015/12/08)

Discovery of a 4-aryloxy-1H-pyrrolo[3,2-c]pyridine and a 1-aryloxyisoquinoline series of TRPA1 antagonists
A series of TRPA1 antagonists is described having a 4-aryloxy-1H-pyrrolo[3,2-c]pyridine or a 1-aryloxyisoquinoline scaffold. These compounds have high ligand efficiency and favorable physical properties and may thus serve as scaffolds for further optimization.
Hu, Yun-Jin,St.-Onge, Miguel,Laliberté, Sébastien,Vallée, Frédéric,Jin, Shujuan,Bedard, Leanne,Labrecque, Jean,Albert, Jeffrey S.
supporting information
p. 3199 - 3203
(2015/02/19)

Method and reagent for gene sequence analysis
Provided is a nucleic acid substrate which has nucleic acid substrate characteristics equivalent to those of dATP, has a low substrate specificity for luciferase, exerts no negative effect on enzymatic reactions such as a complementary-strand synthesis, and therefore is particularly suitable for the pyrosequencing method. As a nucleic acid substrate complementary to nucleotide T, a 7-substituted deoxyribonucleotide triphosphate whose 7-position of a purine group is modified by a substituent is used as a substitute for a nucleotide α-thiotriphosphate analog.
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Page/Page column 16

(2014/10/16)

Facile methods for the synthesis of 5-aryl and 5-iodo pyrrolo[2,3-d] pyrimidines
An efficient and environmentally benign one-pot method has been developed for the synthesis of 4-amino-5-arylpyrrolo[2,3-d]pyrimidines. Phthalimido acetophenones were reacted with cyanoacetamide to give 2-amino-4-phenyl-1H- pyrrole-3-carboxamides, which were further converted to 5-aryl-3H-pyrrolo[2,3-d] pyrimidin-4-ones. A novel method is also developed for the synthesis of 4-amino-5-iodopyrrolo[2,3-d]pyrimidines.
Venkata Rao,Raghu Prasad,Raghuram Rao
p. E380-E383
(2014/11/07)

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 94

(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 239

(2014/03/26)

QUINOLYL PYRROLO PYRIMIDYL CONDENSED-RING COMPOUND AND SALT THEREOF
The present invention provides a new compound that has an inhibitory action against EGFR and that has cell growth inhibitory effects. The present invention further provides a pharmaceutical preparation useful for preventing and/or treating cancer, based o
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Paragraph 0237-0240

(2014/03/24)

5'-SUBSTITUTED NUCLEOSIDE DERIVATIVES AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES
The present invention relates to 5'-Substituted Nucleoside Derivatives of Formula (I): (I) and pharmaceutically acceptable salts thereof, wherein B, X, Y, Z, R1, R2, R3 and R3' are as defined herein. The present
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Page/Page column 49

(2013/03/26)

First total synthesis of a naturally occurring iodinated 5′-deoxyxylofuranosyl marine nucleoside
4-Amino-7-(5′-deoxy-β-D-xylofuranosyl)-5-iodo-pyrrolo[2,3-d] pyrimidine 1, an unusual naturally occurring marine nucleoside isolated from an ascidan, Diplosoma sp., was synthesized from D-xylose in seven steps with 28% overall yield on 10 g scale. The key step was Vorbrueggen glycosylation of 5-iodo-pyrrolo[2,3-d]pyrimidine with 5-deoxy-1, 2-O-diacetyl-3-O-benzoyl-D- xylofuranose. Its absolute configuration was confirmed.
Sun, Jianyun,Dou, Yanhui,Ding, Haixin,Yang, Ruchun,Sun, Qi,Xiao, Qiang
p. 881 - 889
(2012/07/14)

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 100

(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 213

(2012/12/13)

HETEROCYCLIC COMPOUNDS AND METHODS OF USE
Formula I compounds, including stereoisomers, geometric isomers, tautomers, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting the delta isoform of PI3K, and for treating disorders mediated by lipid kinases such as inflammation, immunological disorders, and cancer. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.
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Page/Page column 258

(2012/08/27)

Synthesis and antiviral properties of novel tetracyclic nucleoside inhibitors of hepatitis C NS5B polymerase
As part of an ongoing medicinal chemistry effort to identify novel nucleoside inhibitors of HCV NS5B polymerase, we report the discovery of a novel series of 2-C-Methyl-ribose nucleoside derivatives bearing a 7-aryl and 7-heteroaryl- substituted 7-deaza-adenine nucleobase. A reliable platform for the synthesis and simplified purification of the corresponding nucleoside triphosphates (NTPs) was established, enabling a solid understanding of the SAR relationship within the series. By this approach, we identified the novel analogs 13a and 13b that demonstrated micromolar levels of cellular activity, and the NTPs of which, 16a and 16b, are excellent inhibitors of NS5B with IC50 = 0.1M, a level of intrinsic potency similar to that of previous and current clinical candidates.
Francesco, M. Emilia Di,Avolio, Salvatore,Dessole, Gabriella,Koch, Uwe,Pompei, Marco,Pucci, Vincenzo,Rowley, Michael,Summa, Vincenzo
p. 592 - 607
(2012/11/07)

Efficient and practical synthesis of 5′-deoxytubercidin and its analogues via Vorbrggen glycosylation
An efficient and practical synthesis of naturally occurring marine nucleosides 5′-deoxytubercidins on a 10 gram scale in good overall yield is reported. The key step was the Vorbrggen glycosylation of pyrrolo[2,3-d]pyrimidines with 5-deoxy-1,2,3-tri-O-ace
Song, Yang,Ding, Haixin,Dou, Yanhui,Yang, Ruchun,Sun, Qi,Xiao, Qiang,Ju, Yong
supporting information; experimental part
p. 1442 - 1446
(2011/06/21)

Discovery of selective irreversible inhibitors for EGFR-T790M
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.
scheme or table
p. 638 - 643
(2011/03/18)

ETHER DERIVATIVES OF BICYCLIC HETEROARYLS
The invention relates to compounds of formula (I), wherein the substituents are as defined in the specification; to processes for the preparation of such compounds; pharmaceutical compositions comprising such compounds; such compounds as a medicament; such compounds for the treatment of a proliferative disease
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Page/Page column 75

(2011/04/18)

COMPOUNDS AND METHODS FOR KINASE MODULATION, AND INDICATIONS THEREFOR
Compounds and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described. In certain aspects and embodiments, the described compounds or salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof are active on at least one Raf protein kinase. In certain aspects and embodiments, the described compounds are active in inhibiting proliferation of a Ras mutant cell line. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of B-Raf V600E mutant protein kinase, including melanoma, glioma, glioblastoma multiforme, pilocytic astrocytoma, colorectal cancer, thyroid cancer, lung cancer, ovarian cancer, prostate cancer, liver cancer, gallbladder cancer, gastrointestinal stromal tumors, biliary tract cancer, and cholangiocarcinoma. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of c-Raf-1 protein kinase, including acute pain, chronic pain or polycystic kidney disease.
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Page/Page column 186-187

(2011/06/19)