24164-06-5Relevant academic research and scientific papers
On the selective N-methylation of BOC-protected amino acids
Malkov, Andrei V.,Vrankova, Kvetoslava,Cerny, Miloslav,Kocovsky, Pavel
, p. 8425 - 8427 (2009)
(Chemical Equation Presented) The selective N-methylation of BOC-protected valine 1a with MeI and NaH in THF (i.e., in the presence of a free carboxyl group) has been attributed to the protection of the carboxylate by chelation to Na+. An alternative mechanism, involving the formation of the carbene intermediate generated from MeI and its insertion into the N-H bond, has been ruled out by isotopic labeling. 2009 American Chemical Society.
Design and Synthesis of 2-(1-Alkylaminoalkyl)pyrazolo[1,5-a]pyrimidines as New Respiratory Syncytial Virus Fusion Protein Inhibitors
Abe-Kumasaka, Tomoko,Busujima, Tsuyoshi,Iwakiri, Kanako,Kanuma, Kosuke,Kawaguchi, Takanori,Kurosaka, Jun,Ogata, Yuya,Sugaya, Yutaka,Sugiyama, Hiroyuki,Takahashi, Ryo,Tamura, Yunoshin,Tanigawa, Eiji,Ueda-Yonemoto, Naoko,Yamaguchi-Sasaki, Toru
, p. 345 - 362 (2020/05/14)
Respiratory syncytial virus (RSV) is one of the most common causes of lower respiratory tract infections and a significant pathogen for both adults and children. Although two drugs have been approved for the treatment of RSV infections, the low therapeutic index of these drugs have led pharmaceutical companies to develop safe and effective small-molecule anti-RSV drugs. The pyrazolo[1,5-a]pyrimidine series of compounds containing a piperidine ring at the 2-position of the pyrazolo[1,5-a]pyrimidine scaffold are known as candidate RSV fusion (F) protein inhibitor drugs, such as presatovir and P3. The piperidine ring has been revealed to facilitate the formation of an appropriate dihedral angle between the pyrazolo[1,5-a]pyrimidine scaffold and the plane of the amide bond for exertion of anti-RSV activity. A molecular-dynamic study on newly designed compounds with an acyclic chain instead of the piperidine ring proposed and demonstrated a new series of pyrazolo[1,5-a]pyrimidine derivatives, such as 9c with a 1-methyaminopropyl moiety, showing similar dihedral angle distributions to those in presatovir. Compound 9c exhibited potent anti-RSV activity with an EC50 value of below 1nM, which was similar to that of presatovir. A subsequent optimization study on the benzene ring of 9c led to the potent RSV F protein inhibitor 14f with an EC50 value of 0.15nM. The possibility of improving the biological properties of anti-RSV agents by modification at the 7-position of pyrazolo[1,5-a]pyrimidine is also discussed.
Benzoazepine-Fused Isoindolines via Intramolecular (3 + 2)-Cycloadditions of Azomethine Ylides with Dinitroarenes
Wales, Steven M.,Rivinoja, Daniel J.,Gardiner, Michael G.,Bird, Melissa J.,Meyer, Adam G.,Ryan, John H.,Hyland, Christopher J. T.
, p. 4703 - 4708 (2019/06/27)
Aminobenzaldehydes bearing a pendant 3,5-dinitrophenyl group react thermally with N-substituted α-amino acids to form unprecedented benzoazepine-fused isoindolines. The reaction proceeds via a dearomatization/rearomatization sequence involving an intramolecular (3 + 2)-cycloaddition between the in situ formed azomethine ylide and the dinitroarene. Various glycine derivatives are tolerated as well as branched substrates based on cyclic, α-mono-, and α,α-disubstituted amino acids, giving single diastereomers in many cases. The method is scalable and gives products with a nitro group ready for further manipulation.
TUBULYSIN ANALOGUES AS ANTICANCER AGENTS AND PAYLOADS FOR ANTIBODY-DRUG CONJUGATES AND METHODS OF TREATMENT THEREWITH
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Page/Page column 59-60; 108, (2019/06/17)
In one aspect, the present disclosure provides tubulysin analogs of the formula (I) wherein the variables are as defined herein. In another aspect, the present disclosure also provides methods of preparing the compounds disclosed herein. In another aspect
Improved Total Synthesis of Tubulysins and Design, Synthesis, and Biological Evaluation of New Tubulysins with Highly Potent Cytotoxicities against Cancer Cells as Potential Payloads for Antibody-Drug Conjugates
Nicolaou,Erande, Rohan D.,Yin, Jun,Vourloumis, Dionisios,Aujay, Monette,Sandoval, Joseph,Munneke, Stefan,Gavrilyuk, Julia
supporting information, p. 3690 - 3711 (2018/03/21)
Improved, streamlined total syntheses of natural tubulysins such as V (Tb45) and U (Tb46) and pretubulysin D (PTb-D43), and their application to the synthesis of designed tubulysin analogues (Tb44, PTb-D42, PTb-D47-PTb-D49, and Tb50-Tb120), are described.
HEMIASTERLIN DERIVATIVES AND USES THEREOF IN THE TREATMENT OF CANCER
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Paragraph 0112; 0113, (2016/08/17)
The present invention provides compounds having formula (I): and additionally provides methods for the synthesis thereof and methods for the use thereof in the treatment of cancer, wherein R 1 -R 7 , X 1 , X 2 , R, Q, and n are as defined herein.
NOVEL PYRAZOLO PYRIMIDINE DERIVATIVES AND THEIR USE AS MALT1 INHIBITORS
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Page/Page column 56, (2015/12/31)
The present invention describes new pyrazolo-pyrimidine derivatives of formula (I) or a pharmaceutically acceptable salt thereof; (I) wherein, R1 is halogen, cyano, or C1-C3alkyl optionally substituted by halogen; R2 is C1-C6alkyl optionally substituted one or more times by C1-C6alkyl, C2-C6alkenyl, hydroxyl, N,N-di-C1-C6alkyl amino, N-mono-C1-C6alkyl amino, O-Rg, Rg, phenyl, or by C1-C6alkoxy wherein said alkoxy again may optionally be substituted by C1-C6alkoxy, N,N-di-C1-C6alkyl amino, Rg or phenyl; C3-C6cycloalkyl optionally substituted by C1-C6alkyl, N,N-di-C1-C6alkyl amino or C1-C6alkoxy-C1-C6alkyl, and/or two of said optional substituents together with the atoms to which they are bound may form an annulated or spirocyclic 4 - 6 membered saturated heterocyclic ring comprising 1 - 2 O atoms; phenyl optionally substituted by C1-C6alkoxy; a 5 - 6 membered heteroaryl ring having 1 to 3 heteroatoms selected from N and O said ring being optionally substituted by C1-C6alkyl which may be optionally substituted by amino or hydroxy; Rg; or N,N-di-C1-C6alkyl amino carbonyl; and R is phenyl independently substituted two or more times by Ra, 2-pyridyl independently substituted one or more times by Rb, 3-pyridyl independently substituted one or more times by Rc, or 4-pyridyl independently substituted one or more times by Rd; which are generally interacting with MALT1 proteolytic and/or autoproteolytic activity, and in particular which may inhibit said activity. The present invention further describes the synthesis of said new pyrazolo-pyrimidine derivatives, their use as a medicament, especially by interacting with MALT1 proteolytic and/or autoproteolytic activity.
Deprotection/reprotection of the amino group in α-amino acids and peptides. A one-pot procedure in [Bmim][BF4] ionic liquid
Di Gioia,Barattucci,Bonaccorsi,Leggio,Minuti,Romio,Temperini,Siciliano
, p. 2678 - 2686 (2014/01/06)
This paper presents an efficient one-pot protocol for the sequential deprotection/reprotection of the α-amino group in α-amino acid and dipeptide methyl esters. [Bmim][BF4] is used as the solvent in the entire process. In particular, the use of the ionic liquid allows for rapid and clean removal of the 4-nitrobenzenesulfonyl (nosyl) group and for facile subsequent tert-butyloxycarbonylation of the free α-amino function under very mild conditions. N-Boc-α-amino acid as well as peptide derivatives are isolated in excellent yields, and do not require any further purification. Absolute configurations of the precursors are totally preserved during the process.
A flexible asymmetric approach to methyl 5-alkyltetramates and its application in the synthesis of cytotoxic marine natural product belamide A
Lan, Hong-Qiao,Ye, Jian-Liang,Wang, Ai-E,Ruan, Yuan-Ping,Huang, Pei-Qiang
experimental part, p. 958 - 968 (2011/03/20)
By using a methyl tetramate derivative (R)- or (S)-9 as a novel chiral building block, a direct, flexible, and highly enantioselective approach to methyl (R)- or (S)-5-alkyltetramates (2) is disclosed. Among the synthesized methyl 5-alkyltetramates 2, met
Synthesis of Microcolin B, a Potent New Immunosuppressant Using an Efficient Mixed Imide Formation Reaction
Andrus, Merritt B.,Li, Wenke,Keyes, Robert F.
, p. 5542 - 5549 (2007/10/03)
Microcolin B, a potent new immunosuppressant isolated from blue-green alga Lyngbya majuscula off the Venezuelan coast, has been made using a methyl-directed asymmetric hydrogenation reaction with rhodium on alumina catalyst on lactone 4 for the synthesis of the key (R,R)-2,4-dimethyl-octanoic acid fragment 1. A new, direct mixed imide formation reaction was also developed for the production of the unusual prolylpyrrolen-2-one 2 portion of microcolin. The pentafluorophenyl ester of CBZ-proline 5 was reacted with the lithium imidate of lactam 6, providing the mixed imide in 80% yield. Coupling of acid 1 with the N-terminus of the tripeptide, followed by coupling with pyrrolylproline 2, gave microcolin B. The new mixed-imide forming reaction was also applied to a formal total synthesis of microcolin A. The pentafluorophenyl ester of TBS-protected cis-hydroxyproline was coupled with lactam 6, and the resultant imide was converted to the key pyrrolylproline made previously for microcolin A.
