- Selective CDK6 degradation mediated by cereblon, VHL, and novel IAP-recruiting PROTACs
-
Inhibitors of CDK4 and CDK6 have emerged as important FDA-approved treatment options for breast cancer patients. The properties and pharmacology of CDK4/6 inhibitor medicines have been extensively profiled, and investigations into the degradation of these
- Ahmed, Adil,Anderson, Niall A.,Benowitz, Andrew B.,Cryan, Jenni,Dai, Han,McGonagle, Grant A.,Rozier, Christine
-
-
Read Online
- CELL-PENETRATING GLYCOSAMINOGLYCAN MIMETICS
-
This invention relates to a glycosaminoglycan mimetic molecule comprising a polyproline backbone, an anionic pendant group and a fluorophore. The invention also relates to the use of the glycosaminoglycan mimetic molecule for internalizing a target molecule into a cell, a method for internalizing a target molecule into the cell, and a method for synthesizing a glycosaminoglycan mimetic molecule. [No suitable figure]
- -
-
Page/Page column 19
(2019/02/02)
-
- Reusable shuttles for exchangeable functional cargos: Reversibly assembled, magnetically powered organocatalysts for asymmetric aldol reactions
-
A supramolecular approach has been followed to support adamantyl substituted proline organocatalysts onto the surface of magnetite nanoparticles decorated with a β-cyclodextrin motif. The resulting magnetic nanoparticles (ca. ～10 nm diameter) were used as modular, magnetically recyclable catalysts in the asymmetric aldol reaction of aromatic aldehydes with cyclic ketones in water. The catalytic assemblies can be easily dismantled in organic media, and the recovered nanoparticles (magnetically powered chemical shuttles) re-complexed with another suitably substituted catalytic unit (replaceable functional cargo).
- Mendoza, Carolina,de la Croix, Augustin,Riente, Paola,Llorens, Lluís,de Mendoza, Javier,Pericàs, Miquel A.
-
supporting information
(2019/09/17)
-
- SPIRO-LACTAM AND BIS-SPIRO-LACTAM NMDA RECEPTOR MODULATORS AND USES THEREOF
-
Disclosed are compounds having potency in the modulation of NMDA receptor activity. Such compounds can be used in the treatment of conditions such as depression and related disorders. Orally delivered formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed.
- -
-
-
- Construction of Challenging Proline-Proline Junctions via Diselenide-Selenoester Ligation Chemistry
-
Polyproline sequences are highly abundant in prokaryotic and eukaryotic proteins, where they serve as key components of secondary structure. To date, construction of the proline-proline motif has not been possible owing to steric congestion at the ligatio
- Sayers, Jessica,Karpati, Phillip M. T.,Mitchell, Nicholas J.,Goldys, Anna M.,Kwong, Stephen M.,Firth, Neville,Chan, Bun,Payne, Richard J.
-
p. 13327 - 13334
(2018/10/20)
-
- PROLINE-BASED NEUROPEPTIDE FF RECEPTOR MODULATORS
-
Neuropeptide FF receptor modulators based on a proline scaffold are provided which offer NPFF receptor potencies in the nanomolar range and antagonistic selectivity for the NPFF 1 receptor. Methods, compounds and compositions for modulating the function o
- -
-
-
- Preparation method of antihypertensive medicine key intermediate of trans-4-cyclohexyl-L-proline
-
The invention discloses a preparation method of trans-4-cyclohexyl-L-proline. The method comprises the following steps of (1) under the effect of an acid-binding agent, 4S-hydroxy-N-Boc-L-proline ester 6 and sulfonyl chloride are subjected to condensation to generate sulphonate 5, wherein R is C1-4 alkyl; (2) under the effects of a copper catalyst, lithium salt and organic alkali, the sulphonate 5and cyclohexylmagnesium bromide take nucleophilic substitution to generate a compound 4; (3) the compound 4 is hydrolyzed by lithium hydroxide to obtain (4S)-N-Boc-4-cyclohexyl-L-proline (a compound3); (4) the compound 3 is subjected to Boc removal under the condition of hydrochloric acid or trifluoroacetic acid/methylene dichloride; a target product 2 is prepared. The preparation method has thebeneficial effects that the target product structure and chirality are introduced through sulphonate and Grignard reagent nucleophilic substitution; the defects of the existing noble metal reductionmethod are overcome; the operation of the method is simple; the conditions are mild; the yield is good; the chemical purity and the optical purity are very high; the preparation method is suitable forindustrial production.
- -
-
Paragraph 0032-0034
(2018/11/22)
-
- An ionic liquid containing L-proline moiety as highly efficient and recyclable chiral organocatalyst for Michael addition
-
A novel chiral ionic liquid containing proline moiety was synthesized. It can be used as a highly efficient and recyclable chiral organocatalyst for Michael addition of cyclohexanone with (E)-β-nitroalkenes in methanol at room temperature. The Michael add
- Li, Jiang,Li, Xia Bing,Ma, Sha Sha,Liu, Juan,Li, Ben Hao,Li, Bao Lin
-
p. 1259 - 1264
(2016/08/12)
-
- Exploration of labeling by near infrared dyes of the polyproline linker for bivalent-type CXCR4 ligands
-
We have previously used poly-l-proline linkers for the development of bivalent-type ligands for the chemokine receptor, CXCR4. The bivalent ligands with optimum linkers showed specific binding to CXCR4, suggesting the existence of CXCR4 possibly as a dime
- Nomura, Wataru,Aikawa, Haruo,Taketomi, Shohei,Tanabe, Miho,Mizuguchi, Takaaki,Tamamura, Hirokazu
-
p. 6967 - 6973
(2015/11/11)
-
- Efficient α-helix induction in a linear peptide chain by n-capping with a bridged-tricyclic diproline analogue
-
Secondary structure induction: The synthetic tricyclic amino acid ProM-5, which is formally created by stereoselective introduction of a vinylidene bridge into a di-proline unit, acts as a powerful scaffold to nucleate α-helix formation in a linear peptide chain. This might be exploited in the development of new proteomimetics for the modulation of protein interactions. Copyright
- Hack, Verena,Reuter, Cédric,Opitz, Robert,Schmieder, Peter,Beyermann, Michael,Neud?rfl, J?rg-Martin,Kühne, Ronald,Schmalz, Hans-Günther
-
supporting information
p. 9539 - 9543
(2013/09/23)
-
- HEPATITIS C VIRUS INHIBITORS
-
The invention provides compounds of formula (I): wherein the variables are defined in the specification, or a pharmaceutically-acceptable salt thereof, that are inhibitors of replication of the hepatitis C virus. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat hepatitis C viral infections, and processes and intermediates useful for preparing such compounds.
- -
-
-
- ANTIVIRAL COMPOUNDS
-
The present invention provides compounds of formula I, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the t
- -
-
Page/Page column 64; 65
(2013/09/12)
-
- Efficient SN2 fluorination of primary and secondary alkyl bromides by copper(I) fluoride complexes
-
Copper(I) fluoride complexes ligated by phenanthroline derivatives have been synthesized and structurally characterized by X-ray crystallography. These complexes adopt as either ionic or neutral forms in the solid state, depending on the steric bulkiness of the substituent groups on the phenanthroline ligands. These complexes react with primary and secondary alkyl bromides to produce the corresponding alkyl fluorides in modest to good yields. This new method is compatible with a variety of important functional groups such as ether, thioether, amide, nitrile, methoxyl, hydroxyl, ketone, ester, and heterocycle moieties.
- Liu, Yanpin,Chen, Chaohuang,Li, Huaifeng,Huang, Kuo-Wei,Tan, Jianwei,Weng, Zhiqiang
-
p. 6587 - 6592
(2013/12/04)
-
- ANTIBACTERIAL FLUOROQUINOLONE ANALOGS
-
Compounds having antibacterial activity are disclosed. The compunds have the following structure (I): including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein A, B, D, E, G, R1, R2, R3, R4, R5, R6 and R7 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.
- -
-
Page/Page column 182
(2010/01/29)
-
- PROCESS FOR PRODUCING ESTER OR ALCOHOL
-
Provided is a process for producing an ester or alcohol using a fluoroimidinium sulfonate derivative represented by the general formula (9) or a fluoroimidinium carboxylate derivative represented by the general formula (6) and using as a raw material alcohol involving inversion of steric configuration. Further provided are a fluoroimidinium sulfonate derivative represented by the general formula (9), and a process for producing the same.
- -
-
Page/Page column 46
(2009/04/23)
-
- PROLINAMIDE DERIVATIVES AS NK3 ANTAGONISTS
-
The present invention relates to a compound of formula I wherein R2 R3, R4, R5, X, n, and o are as defined herein and to a pharmaceutically acceptable acid addition salt thereof which are high potential NK-3 receptor antagonists for the treatment of depression, pain, psychosis, Parkinson's disease, schizophrenia, anxiety and attention deficit hyperactivity disorder (ADHD).
- -
-
Page/Page column 5-6; 15-16
(2009/01/20)
-
- N-type calcium channel blockers
-
The invention relates to novel 3-amino pyrrolidine derivatives, as well as methods for modulating calcium channel activity and for treating conditions associated with calcium channel function. In particular, the compounds generally contain at least one be
- -
-
Page/Page column 21
(2008/06/13)
-
- The synthesis and evaluation of [2.2.1]-bicycloazahydantoins as androgen receptor antagonists
-
A novel series of [2.2.1]-bicycloazahydantoins has been designed and synthesized in an enantiospecific manner. Several of these compounds were found to act as antagonists to the androgen receptor. A novel series of [2.2.1]-azahydantoins has been designed
- Balog, Aaron,Salvati, Mark E.,Shan, Weifang,Mathur, Arvind,Leith, Leslie W.,Wei, Donna D.,Attar, Ricardo M.,Geng, Jieping,Rizzo, Cheryl A.,Wang, Chihuei,Krystek, Stanley R.,Tokarski, John S.,Hunt, John T.,Gottardis, Marco,Weinmann, Roberto
-
p. 6107 - 6111
(2007/10/03)
-
- PROLINE DERIVATIVES AND USE THEREOF AS DRUGS
-
The present invention aims at providing compounds having therapeutic effects due to a DPP-IV inhibitory action, and satisfactory as pharmaceutical products. The present inventors have found that derivatives having a substituent introduced into the γ-position of proline represented by the formula (I) wherein each symbol is as defined in the specification, have a potent DPP-IV inhibitory activity, and completed the present invention by increasing the stability.
- -
-
-
- Synthesis of n.c.a. cis- and trans-4-[18F]fluoro-L-proline, radiotracers for PET-investigation of disordered matrix protein synthesis
-
A radiosynthesis of n.c.a. (2S,4R)-4-[18F]fluoroproline (trans-configuration) and its diastereomer (2S,4S)-4-[18F]fluoroproline (cis-configuration) has been developed. It allows the routine production of up to 18 GBq of product for c
- Hamacher, Kurt
-
p. 1135 - 1144
(2007/10/03)
-
- Amino acids bearing nucleobases for the synthesis of novel peptide nucleic acids
-
All of the four nucleobases found in DNA have been incorporated in their protected form into the 4-position of N-tert-butoxycarbonyl-L-proline methyl ester with cis-stereochemistry. An efficient route for the synthesis of N-tert-butoxycarbonyl-trans-4-hydroxy-D-proline methyl ester has been developed from which the enantiomers may be synthesized. In addition an efficient synthesis of N-tert-butoxycarbonyl-N-(2-hydroxyethyl)glycine methyl ester has been achieved and its hydroxy group replaced with protected nucleobases using the Mitsunobu reaction.
- Lowe, Gordon,Vilaivan, Tirayut
-
p. 539 - 546
(2007/10/03)
-
- CARBEPENEM DERIVATIVES
-
Carbapenem derivatives which may be utilized as antibiotics and which show strong antibacterial activity against various bacterial strains including Pseudomonas aeruginosa. The compounds containing the derivatives are quite safe and are also stable against hydrolases such as dehyropeptidase (DHP)
- -
-
-
