- C-terminal 18F-fluoroethylamidation exemplified on [Gly-OH9] oxytocin
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The no-carrier-added (n.c.a.) 18F-fluoroethylamidation of the acid function of the protected nonapeptide Boc-Cys-Tyr(tBu)-Ile-Gln(Mtt)-Asn(Mtt)-Cys-Pro-Leu-Gly-OH forming the labelled peptide hormone derivative [Gly-(2-[18F]fluoroeth
- Jelinski,Hamacher,Coenen
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Read Online
- PH-responsive artesunate polymer prodrugs with enhanced ablation effect on rodent xenograft colon cancer
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Purpose: In this study, pH-sensitive poly(2-ethyl-2-oxazoline)-poly(lactic acid)-poly(β-amino ester) (PEOz-PLA-PBAE) triblock copolymers were synthesized and were conjugated with an antimalaria drug artesunate (ART), for inhibition of a colon cancer xenog
- Cai, Wei-Yan,Chen, Yan-Jun,De, Ge-Jing,Hao, Dan-Li,Liu, Li,Ma, Hai,Sui, Feng,Xie, Ran,Yang, Mi-Yi,Yi, Hong,Zang, Chen,Zhao, Qing-He
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Read Online
- High Stability of a Donor-Acceptor Type Oxazepine-Containing Fluorophore and Its Applications in Cellular Imaging and Two-Photon Deep Tissue Imaging
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A new donor (D)-acceptor (A) type naphthalene-based oxazepine-containing fluorophore, OXN-1, is reported, which shows unusually high stability in various environments. Its photophysical properties and structural stabilities under harsh conditions are thor
- Moon, Heejo,Jung, Yuna,Kim, Youngseo,Kim, Byeong Wook,Choi, Jin Gyu,Kim, Na Hee,Oh, Myung Sook,Park, Sungnam,Kim, B. Moon,Kim, Dokyoung
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Read Online
- Fluorescence-based active site probes for profiling deubiquitinating enzymes
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Novel ubiquitin-based active site probes including a fluorescent tag have been developed and evaluated. A new, functionalizable electrophilic trap is utilized allowing for late stage diversification of the probe. Attachment of fluorescent dyes allowed direct detection of endogenous deubiquitinating enzyme (DUB) activities in cell extracts by in-gel fluorescence imaging.
- McGouran, Joanna F.,Kramer, Holger B.,MacKeen, Mukram M.,Di Gleria, Katalin,Altun, Mikael,Kessler, Benedikt M.
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Read Online
- Design and Synthesis of New 9-Substituted Norharmane Derivatives as Potential Sirt5 Inhibitors
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Sirt5 is a potential new drug target for the treatment of cancer, Alzheimer's disease, and Parkinson's disease. Given that norharmane is an important chemical synthon for some biologically important compounds and 9-substituted norharmane derivatives containing a negatively charged carboxyl group may accord with the characteristic of potential Sirt5 inhibitors, a series of novel 9-substituted norharmane derivatives were synthesized. The chemical structures and purities of all the target compounds were characterized by 1H NMR, 13C NMR, MS, and HPLC. By in vitro SIRT5 inhibitory assays, three compounds (1a, 3a, and 3b) show over 30% inhibition ratios at concentration of 100 μM, and the most active compound 3b has 35% and 52% inhibition ratios at 30 μM and 100 μM, respectively. Docking analysis showed that compound 3b is likely to fit very well on the substrate binding site of Sirt5, and hence, we believe that compound 3b can serve as a lead compound for further efforts to develop specific Sirt5 inhibitors.
- Yang, Ling-Ling,He, Yan-Ying,Chen, Quan-Long,Qian, Shan,Wang, Zhou-Yu
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Read Online
- Preparation method of N-Boc-N-[2-(2-chloro-5-pyrimidinyl)ethyl] amine
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The present invention discloses a new N-Boc-N- [2- (2-chloro-5-pyrimidinyl)ethyl] amine preparation method, comprising the following steps: compound II (N-Boc-N- hydroxyethylamine) under the action of alkali reaction with compound III (p-toluenesulfonyl c
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Paragraph 0024-0027; 0032-0035
(2022/01/04)
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- Synthesis, radiolabeling, and preliminary in vivo evaluation of [68ga] ipcat-nota as an imaging agent for dopamine transporter
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Introduction: Novel radiotracer development for imaging dopamine transporters is a subject of interest because although [99mTc]TRODAT-1, [123I]β-CIT, and [123I]FP-CIT are commercially available;99Mo/99mTc generator is in short supply and123I production is highly dependent on compact cyclotron. Therefore, we designed a novel positron emission tomography (PET) tracer based on a tropane derivative through C-2 modification to conjugate NOTA for chelating68Ga, a radioisotope derived from a68Ge/68Ga generator. Methods: IPCAT-NOTA 22 was synthesized and labeled with [68Ga]GaCl4 ? at room tem-perature. Biological studies on serum stability, LogP, and in vitro autoradiography (binding assay and competitive assay) were performed. Furthermore, ex vivo autoradiography, biodis-tribution, and dynamic PET imaging studies were performed in Sprague Dawley rats. Results: [68Ga]IPCAT-NOTA 24 obtained had a radiochemical yield of ≥90% and a specific activity of 4.25 MBq/nmol. [68Ga]IPCAT-NOTA 24 of 85% radiochemical purity (RCP%) was stable at 37°C for up to 60 minutes in serum with a lipophilicity of 0.88. The specific binding ratio (SBR%) reached 15.8 ± 6.7 at 60 minutes, and the 85% specific uptake could be blocked through co-injection at 100-and 1000-fold of the cold precursor in in vitro binding studies. Tissue regional distribution studies in rats with [68Ga]IPCAT-NOTA 24 showed striatal uptake (0.02% at 5 minutes and 0.007% at 60 minutes) with SBR% of 6%, 25%, and 62% at 5–15, 30–40, and 60–70 minutes, respectively, in NanoPET studies. The RCP% of [68Ga]IPCAT-NOTA 24 at 30 minutes in vivo remained 67.65%. Conclusion: Data described here provide new information on the design of PET probe of conjugate/pendent approach for DAT imaging. Another chelator or another direct method of intracranial injection must be used to prove the relation between [68Ga]IPCAT-NOTA 24 uptake and transporter localization.
- Farn, Shiou-Shiow,Chang, Kang-Wei,Lin, Wan-Chi,Yu, Hung-Man,Lin, Kun-Liang,Tseng, Yu-Chin,Chang, Yu,Yu, Chung-Shan,Lin, Wuu-Jyh
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p. 2577 - 2591
(2021/07/06)
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- 3H-[1, 2, 3] triazolo [4, 5-d] pyrimidine-5-amine derivative and application thereof
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The invention discloses a 3H-[1, 2, 3] triazolo [4, 5-d] pyrimidine-5-amine derivative and application thereof and particularly relates to the novel 3H-[1, 2, 3] triazolo [4, 5-d] pyrimidine-5-amine derivative and a pharmaceutical composition containing the compound, and the derivative can be used as a selective adenosine A2A receptor antagonist. The invention also relates to a method for preparing the compound and the pharmaceutical composition and the application of the compound and the pharmaceutical composition in preparation of drugs for treating adenosine A2A receptor related diseases, especially Parkinson's disease.
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Paragraph 0220; 0221; 0226-0230
(2020/04/06)
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- Erratum: Efficient Targeted Degradation via Reversible and Irreversible Covalent PROTACs (Journal American Chemical Society (2020) DOI: 10.1021/jacs.9b13907)
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This addition corrects several errors in the chemical drawings in the article. The correction has no influence on the data or conclusions of the work. The configuration of the chiral carbon in Figure 1 in the main text was originally drawn as S. The corrected figure shown here depicts the R enantiomer used in this work. (Figure presented) In the Supporting Information PDF files, the configuration of the chiral carbon of the BTK binder in supplementary Table 1 (page S9), supplementary Figure 4 (page S13), and several of the synthetic schemes (pages S17-S42) was originally drawn and marked as S by error. The corrected supplementary file depicts the R enantiomer, which was the sole enantiomer used in the work. The linker in the right panel of supplementary Table 1 (page S9) was missing two carbons in the drawing, and the linker size written for compound PG15 (RC-0b) in the table was incorrect. The corrected supplementary file contains the correct drawings and linker sizes.
- Aharoni, Hila,Albeck, Shira,Avram, Liat,Brandis, Alexander,Gabizon, Ronen,Gehrtz, Paul,Gurwicz, Neta,Herishanu, Yair,Katz, Ben-Zion,Livnah, Ella,London, Nir,Shorer, Yamit,Shraga, Amit,Shulman, Ziv,Unger, Tamar
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supporting information
p. 11316 - 11316
(2020/07/28)
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- Efficient Targeted Degradation via Reversible and Irreversible Covalent PROTACs
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Proteolysis targeting chimeras (PROTACs) represent an exciting inhibitory modality with many advantages, including substoichiometric degradation of targets. Their scope, though, is still limited to date by the requirement for a sufficiently potent target binder. A solution that proved useful in tackling challenging targets is the use of electrophiles to allow irreversible binding to the target. However, such binding will negate the catalytic nature of PROTACs. Reversible covalent PROTACs potentially offer the best of both worlds. They possess the potency and selectivity associated with the formation of the covalent bond, while being able to dissociate and regenerate once the protein target is degraded. Using Bruton's tyrosine kinase (BTK) as a clinically relevant model system, we show efficient degradation by noncovalent, irreversible covalent, and reversible covalent PROTACs, with 85% degradation. Our data suggest that part of the degradation by our irreversible covalent PROTACs is driven by reversible binding prior to covalent bond formation, while the reversible covalent PROTACs drive degradation primarily by covalent engagement. The PROTACs showed enhanced inhibition of B cell activation compared to ibrutinib and exhibit potent degradation of BTK in patient-derived primary chronic lymphocytic leukemia cells. The most potent reversible covalent PROTAC, RC-3, exhibited enhanced selectivity toward BTK compared to noncovalent and irreversible covalent PROTACs. These compounds may pave the way for the design of covalent PROTACs for a wide variety of challenging targets.
- Gabizon, Ronen,Shraga, Amit,Gehrtz, Paul,Livnah, Ella,Shorer, Yamit,Gurwicz, Neta,Avram, Liat,Unger, Tamar,Aharoni, Hila,Albeck, Shira,Brandis, Alexander,Shulman, Ziv,Katz, Ben-Zion,Herishanu, Yair,London, Nir
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p. 11734 - 11742
(2020/07/21)
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- PROCESS FOR THE PREPARATION OF A SULFUR-AMINE
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The present invention relates to a process for the synthesis of cysteamine or a salt thereof.
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Paragraph 0036; 0037
(2018/05/03)
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- Modular One-Step Three-Component Synthesis of Tetrahydroisoquinolines Using a Catellani Strategy
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Reported is a modular one-step three-component synthesis of tetrahydroisoquinolines using a Catellani strategy. This process exploits aziridines as the alkylating reagents, through palladium/norbornene cooperative catalysis, to enable a Catellani/Heck/aza-Michael addition cascade. This mild, chemoselective, and scalable protocol has broad substrate scope (43 examples, up to 90 % yield). The most striking feature of this protocol is the excellent regioselectivity and diastereoselectivity observed for 2-alkyl- and 2-aryl-substituted aziridines to access 1,3-cis-substituted and 1,4-cis-substituted tetrahydroisoquinolines, respectively. Moreover, this is a versatile process with high step and atom economy.
- Qian, Guangyin,Bai, Miao,Gao, Shijun,Chen, Han,Zhou, Siwei,Cheng, Hong-Gang,Yan, Wei,Zhou, Qianghui
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supporting information
p. 10980 - 10984
(2018/07/30)
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- For the treatment of tumor macrocyclic derivatives (by machine translation)
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The invention discloses a method for modulating protein kinase activity, and is used for the treatment or prevention of protein kinase related disorders. Specifically, the invention relates to a method for the treatment of tumor of the macrocyclic derivatives, which belongs to the regulating Anaplastic lymphoma kinase (ALK) active compound, and provides the preparation method of the compound, and the compound used for the treatment or prevention of diseases associated with the ALK pharmaceutical use. (by machine translation)
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Paragraph 0103; 0107-0108
(2017/07/20)
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- Pyrido[3, 4-b]indole urea compound and use thereof as IDO inhibitor
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The invention discloses a pyrido[3, 4-b]indole urea compound. Specifically, the compound has substitution at the 9- position of pyrido[3, 4-b]indole, and the connection bridge is a urea structure. The invention also discloses a preparation method of the compound and use thereof as an IDO (indoleamine 2, 3-dioxygenase) inhibitor. The compound provided by the invention can be used for prevention and/or treatment of various diseases, like Alzheimer's disease, cataract, cell immune activation related infections, autoimmune diseases, AIDS, cancer, depression or tryptophan metabolic disorder, etc. (formula (I)).
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Paragraph 0050-0054
(2017/09/13)
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- C-3 NOVEL TRITERPENONE WITH C-28 UREA DERIVATIVES AS HIV INHIBITORS
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The present invention relates to C-3 novel triterpenone with C-28 urea derivatives of formula (I); or pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, tautomers, stereoisomers, prodrugs, compositions or combination thereof, wherein R1, R2, R3, W, J and X are as defined herein. The present invention also relates to pharmaceutical compositions comprising compounds of formula (I) useful for the treatment of viral diseases and particularly HIV mediated diseases.
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Page/Page column 40
(2017/05/02)
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- 9-substituted pyridino-[3,4-b]indole derivative, preparation method thereof and application thereof as SIRT protein inhibitor
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The invention discloses a 9-substituted pyridino-[3,4-b]indole derivative and further discloses a preparation method of the compound and application of the derivative as an SIRT protein inhibitor. The compound can be used for treating various diseases such as tumors, the neurodegenerative disease, the metabolic disease and the like.
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Paragraph 0117-0120
(2017/06/02)
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- HETEROARYL PYRIDONE AND AZA-PYRIDONE COMPOUNDS WITH ELECTROPHILIC FUNCTIONALITY
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Heteroaryl pyridone and aza-pyridone amide compounds with electrophilic functionality of Formula I are provided, including stereoisomers, tautomers, and pharmaceutically acceptable salts thereof, useful for inhibiting Btk, and for treating cancer and immune disorders such as inflammation mediated by Btk. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, and treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.
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Paragraph 0236
(2015/06/17)
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- SERINE/THREONINE KINASE INHIBITORS
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Compounds having the formula I wherein R1, R2, R3, R4, R5, Ra, Rb, Rc, Rd, Re, n, r, s and t are as defined herein and which compounds are inhibitors of PAK1. Also disclosed are compositions and methods for treating cancer and hyperproliferative disorders.
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Paragraph 0376
(2015/02/19)
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- Ring-fused bicyclic pyridyl derivatives as FGFR4 inhibitors
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The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof; a method for manufacturing said compound, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition comprising said compound.
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Paragraph 0839
(2015/05/05)
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- RING-FUSED BICYCLIC PYRIDYL DERIVATIVES AS FGFR4 INHIBITORS
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The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof; a method for manufacturing said compound, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition comprising said compound.
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Page/Page column 143
(2015/05/06)
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- Selective fluorescent nonpeptidic antagonists for vasopressin V2 GPCR: Application to ligand screening and oligomerization assays.
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A series of fluorescent benzazepine ligands for the arginine-vasopressin V2 receptor (AVP V2R) was synthesized using "Click" chemistry. Their in vitro pharmacological profile at AVP V2R, V1aR, V1bR, and oxytocin receptor was measured by binding assay and functional studies. Compound 9p, labeled with Lissamine Rhodamine B using novel solid-phase organic tagging (SPOrT) resin, exhibited a high affinity for V2R (4.0 nM), an excellent selectivity toward V2R and antagonist properties. By changing the nature of the dye, DY647 and Lumi4-Tb probes 44 and 47 still display a high affinity for V2R (5.6 and 5.8 nM, respectively). These antagonists constitute the first high-affinity selective nonpeptidic fluorescent ligands for V 2R. They enabled the development of V2R time-resolved FRET-based assay readily amenable to high-throughput screening. Taking advantage of their selectivity, these compounds were also successfully involved in the study of V1aR-V2R dimerization on cell surface.
- Loison, Stéphanie,Cottet, Martin,Orcel, Hélène,Adihou, Hélène,Rahmeh, Rita,Lamarque, Laurent,Trinquet, Eric,Kellenberger, Esther,Hibert, Marcel,Durroux, Thierry,Mouillac, Bernard,Bonnet, Dominique
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supporting information
p. 8588 - 8602
(2013/01/15)
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- Syntheis of new chiral 5,6,7,8-tetrahydrotetrazolo[1,5-a]pyrazines from α-amino acid derivatives following "click" chemistry
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An efficient and practical synthesis of new chiral fused tetrazoles have been synthesized following [3+2] cycloaddition reaction starting from α-amino acid derivatives.
- Mohapatra, Debendra K.,Maity, Pradip K.,Ghorpade, Ravindra V.,Gurjar, Mukund K.
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scheme or table
p. 865 - 872
(2010/09/16)
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- Alpha-helical mimetics
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Benzoyl urea derivatives that are alpha helical peptides mimetics that mimic BH3-only proteins, compositions containing them, their conjugation to cell-targeting-moieties, and their use in the regulation of cell death are disclosed. The benzoyl urea derivatives are capable of binding to and neutralizing pro-survival Bcl-2 proteins. Use of benzoyl urea derivatives in the treatment and/or prophylaxis of diseases or conditions associated with deregulation of cell death are also described.
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Page/Page column 86
(2011/05/18)
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- CYANOPYRIDINE DERIVATIVE AND USE THEREOF AS MEDICINE
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A therapeutic drug for cancer containing a substance selected from the group consisting of a novel cyanopyridine derivative, a pharmaceutically acceptable salt, a hydrate, a water adduct and a solvate as an active ingredient can be provided.
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Page/Page column 9-10
(2008/06/13)
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- THERAPEUTIC COMPOUNDS
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This invention relates to a novel class of substituted amino-ethoxy benzene derivatives of formula (I) which are inhibitors of serine proteases and to their use in treating aberrant serine protease activity in a mammal, contraception, anti-coagulant methods and methods for treating aberrant cell proliferation, tumours, cancer, angiogenesis, angiogenesis-based retinopathies, autoimmummune disease, inflammation, skin disease, arthritis, rheutmatoid arthritis, asthma, osteoarthritis and multiple sclerosis. (I), Wherein Rm, Rn, Rp, Rq, V, W, X, Y and R8 are as defined in the claims.
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Page/Page column 59
(2010/11/27)
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- ALPHA-HELICAL MIMETICS
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Benzoyl urea derivatives that are alpha helical peptide mimetics that mimic BH3-only proteins, compositions containing them, their conjugation to cell-targeting moieties, and their use in the regulation of cell death are disclosed. The benzoyl urea derivatives are capable of binding to and neutralising pro-survival Bcl-2 proteins. Use of the benzoyl urea derivatives in the treatment and/or prophylaxis of diseases or conditions associated with deregulation of cell death are also disclosed.
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Page/Page column 174
(2010/02/15)
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- Chemokine receptor binding heterocyclic compounds with enhanced efficacy
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The invention relates to heterocyclic compounds consisting of a core nitrogen atom surrounded by three pendant groups, wherein two of the three pendant groups are preferably benzimidazolyl methyl and tetrahydroquinolyl, and the third pendant group contains N and optionally contains additional rings. The compounds bind to chemokine receptors, including CXCR4 and CCR5, and demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).
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- Chemokine receptor binding heterocyclic compounds with enhanced efficacy
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The invention relates to heterocyclic compounds consisting of a core nitrogen atom surrounded by three pendant groups, wherein two of the three pendant groups are preferably benzimidazolyl methyl and tetrahydroquinolyl, and the third pendant group contains N and optionally contains additional rings. The compounds bind to chemokine receptors, including CXCR4 and CCR5, and demonstrate protective effects against infection of target cells by a human immunodeficiency virus (HIV).
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Page/Page column 17-19
(2010/02/03)
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- Synthesis, labelling and biological characteristics of derivatives of mercaptoacetyltriglycine with two amide functions
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Eight novel derivatives of MAG3, containing in their structure two instead of three amide functions, have been synthesized and evaluated. The synthesized ligands were labelled with 99mTc by exchange labelling at 100°C and/or by a dir
- Okarvi,Verbeke,Adriaens,Verbruggen
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p. 115 - 137
(2007/10/03)
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- Identification of a series of PPARγ/δ dual agonists via solid-Phase parallel synthesis
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We have developed a general solid-phase synthesis for identification of PPAR ligands. Synthesis of a 480-member library led to the identification of a potent PPARγ/δ dual agonist 23. Compound 23 showed good plasma exposure in rats and demonstrated antihyp
- Liu, Kevin G,Lambert, Millard H,Leesnitzer, Lisa M,Oliver Jr., William,Ott, Ronda J,Plunket, Kelli D,Stuart, Ludwig W,Brown, Peter J,Willson, Timothy M,Sternbach, Daniel D
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p. 2959 - 2962
(2007/10/03)
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- Synthesis of N-(2-[18F]fluoroethyl)-N'-methylthiourea: A hydrogen peroxide scavenger
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N-(2-[18F]fluoroethyl)-N'-methylthiourea ([18F]FEMTU), a fluorine- 18 labelled derivative of the hydrogen peroxide scavenger dimethylthiourea (DMTU), has been synthesized by reaction of 2-[18F]fluoroethylamine with methyli
- Gilissen,Bormans,De Groot,Verbruggen
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p. 491 - 502
(2007/10/03)
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- Substituted guanidine derivatives, process for production thereof, and pharmaceutical uses thereof
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A substituted guanidine derivative represented by the general formula: STR1 wherein R1, R2, R3 and R4 are independently a hydrogen atom, an unsubstituted alkyl group, a substituted alkyl group, a halogen atom or
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- Synthesis of a versatile purification handle for use with Boc chemistry solid phase peptide synthesis
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The synthesis of a versatile handle for the purification of synthetic peptides is described. The Boc-aminoethylsulfonylethyloxycarbonyl handle is coupled to the NH2-terminus of the resin-bound peptide. Removal of the Boc group affords a free amine which can be derivatized with any of a variety of functionalities. Cleavage from the resin gives a peptide functionalized for covalent chemoselective reaction with the column support. Desired full length peptide is eluted from the column by cleavage of the handle by treatment with base.
- Canne, Lynne E.,Winston, Rachel L.,Kent, Stephen B. H.
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p. 3361 - 3364
(2007/10/03)
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- Electrogenerated Superoxide-Activated Carbon Dioxide. A New Mild and Safe Approach to Organic Carbamates
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The electrochemical reduction of O2 (E = -1.0 V vs SCE) in dipolar aprotic solvents in the presence of CO2 gave a carboxylating reagent (O2·-/CO2) able to convert amines and different types of their derivatives into carbamates. Primary and secondary aliphatic and aromatic amines were converted into the corresponding ethyl carbamates by the addition of EtI to the carbamate anions generated in the first step of the reactions. The yields were dependent on the nucleophilicity of the nitrogen atom ω-Bromoethyl- and propylamine gave 2-oxazolidinone and tetrahydro-l,3-oxazm-2-one in moderate yields. N-Acyl or N-(alkoxycarbonyl)alkylamines bearing a leaving group at the β position of the alkyl substituent were converted into 3-substituted-2-oxazolidinones in high yields. By using chiral substrates, enantiopure 3-alkoxycarbonyl(or acyl)-4-substituted oxazolidin-2-ones (70-85% isolated yields) were obtained. This represents a new mild and safe route to these important auxiliaries for asymmetric synthesis. Some limitations of the process are also evidenced and accounted for.
- Casadei, Maria Antonietta,Moracci, Franco Micheletti,Zappia, Giovanni,Inesi, Achille,Rossi, Leucio
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p. 6754 - 6759
(2007/10/03)
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