30166-29-1Relevant academic research and scientific papers
Histamine H3 receptor antagonists with peptidomimetic (keto)piperazine structures to inhibit Aβ oligomerisation
Falkenstein, Markus,Reiner-Link, David,Zivkovic, Aleksandra,Gering, Ian,Willbold, Dieter,Stark, Holger
, (2021/10/29)
Alzheime?s disease (AD) is the most prominent neurodegenerative disorder with high medical need. Protein-protein-interactions (PPI) interactions have a critical role in AD where β-amyloid structures (Aβ) build toxic oligomers. Design of disease modifying multi target directed ligand (MTDL) has been performed, which disable PPI on the one hand and on the other hand, act as procognitive antagonists at the histamine H3 receptor (H3R). The synthetized compounds are structurally based on peptidomimetic amino acid-like structures mainly as keto, diketo-, or acyl variations of a piperazine moiety connected to an H3R pharmacophore. Most of them showed low nanomolar affinities at H3R and some with promising affinity to Aβ-monomers. The structure–activity relationships (SAR) described offer new possibilities for MTDL with an optimized profile combining symptomatic and potential causal therapeutic approaches in AD.
Site selective synthesis of cytotoxic 1,3,6-trisubstituted 3,6-diunsaturated (3Z,6Z)-2,5-diketopiperazines via a one-pot multicomponent method
Liao, Sheng-Rong,Du, Li-Juan,Qin, Xiao-Chu,Xu, Liang,Wang, Jun-Feng,Zhou, Xue-Feng,Tu, Zheng-Chao,Li, Juan,Liu, Yong-Hong
, p. 1051 - 1057 (2016/02/09)
A one-pot multicomponent approach was established for site selective synthesis of novel 1,3,6-trisubstituted 3,6-diunsaturated (3Z,6Z)-2,5-diketopiperazine derivatives with high stereoselectivity. The computational studies revealed that the steric hindran
Novel approach to the synthesis of aliphatic and aromatic α-keto acids
Balducci, Daniele,Conway, Philip A.,Sapuppo, Giulia,Müller-Bunz, Helge,Paradisi, Francesca
experimental part, p. 7374 - 7379 (2012/09/10)
A new practical and efficient synthesis of α-keto acids was accomplished starting from the synthon 1,4-diacetylpiperazine-2,5-dione. The synthesis encompasses both aromatic and aliphatic substrates proving to be versatile and innovative with excellent carbon economy and recycling of the glycine by-product.
Synthesis and structure-activity relationship study of antimicrotubule agents phenylahistin derivatives with a didehydropiperazine-2,5-dione structure
Yamazaki, Yuri,Tanaka, Koji,Nicholson, Benjamin,Deyanat-Yazdi, Gordafaried,Potts, Barbara,Yoshida, Tomoko,Oda, Akiko,Kitagawa, Takayoshi,Orikasa, Sumie,Kiso, Yoshiaki,Yasui, Hiroyuki,Akamatsu, Miki,Chinen, Takumi,Usui, Takeo,Shinozaki, Yuki,Yakushiji, Fumika,Miller, Brian R.,Neuteboom, Saskia,Palladino, Michael,Kanoh, Kaneo,Lloyd, George Kenneth,Hayashi, Yoshio
experimental part, p. 1056 - 1071 (2012/04/04)
Plinabulin (11, NPI-2358) is a potent microtubule-targeting agent derived from the natural diketopiperazine "phenylahistin" (1) with a colchicine-like tubulin depolymerization activity. Compound 11 was recently developed as VDA and is now under phase II clinical trials as an anticancer drug. To develop more potent antimicrotubule and cytotoxic derivatives based on the didehydro-DKP skeleton, we performed further modification on the tert-butyl or phenyl groups of 11, and evaluated their cytotoxic and tubulin-binding activities. In the SAR study, we developed more potent derivatives 33 with 2,5-difluorophenyl and 50 with a benzophenone in place of the phenyl group. The anti-HuVEC activity of 33 and 50 exhibited a lowest effective concentration of 2 and 1 nM for microtubule depolymerization, respectively. The values of 33 and 50 were 5 and 10 times more potent than that of CA-4, respectively. These derivatives could be a valuable second-generation derivative with both vascular disrupting and cytotoxic activities.
Synthesis and phytotoxicity of structural analogues of thaxtomin natural products
Molesworth, Peter P.,Gardiner, Michael G.,Jones, Roderick C.,Smith, Jason A.,Tegg, Robert S.,Wilson, Calum
experimental part, p. 813 - 820 (2011/08/03)
Structural analogues of the phytotoxic thaxtomin natural products have been synthesized by building upon a piperazinedione core and from l-phenylalanine. The compounds were evaluated for their phytotoxic activity against Arabidopsis thaliana seedlings and some of the key features for activity have been identified. CSIRO 2010.
ANALOGS OF DEHYDROPHENYLAHISTINS AND THEIR THEAPEUTIC USE
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Page/Page column 20, (2008/12/08)
Compounds represented by the following structure (II) are disclosed: as are methods for making such compounds. Compositions and methods for treating various disease conditions including cancer and non-cancer diseases associated with vascular proliferation are also disclosed.
Dehydrophenylahistins and analogs thereof and the synthesis of dehydrophenylahistins and analogs thereof
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, (2008/06/13)
Compounds represented by the following structure (I) are disclosed: as are methods for making such compounds, wherein said methods comprise reacting a diacyldiketopiperazine with a first aldehyde to produce an intermediate compound; and reacting the intermediate compound with a second aldehyde to produce the class of compounds with the generic structure, where the first aldehyde and the second aldehydes are selected from the group consisting of an oxazolecarboxaldeyhyde, imidazolecarboxaldehyde, a benzaldehyde, imidazolecarboxaldehyde derivatives, and benzaldehyde derivatives, thereby forming the above compound wherein R1, R1′, R1″, R2, R3, R4, R5, and R6, X1 and X2, Y, Z, Z1, Z2, Z3, and Z4 may each be separately defined in a manner consistent with the accompanying description. Compositions and methods for treating vascular proliferation are also disclosed.
Improvements in aldol reactions with diketopiperazines
Gonzalez, Juan Francisco,De La Cuesta, Elena,Avendano, Carmen
, p. 1589 - 1597 (2007/10/03)
Precipitation of products by using dichloromethane as solvent permits an efficient aidol-type reaction between 1,4-diacetyl-2,5-piperazinedione and aromatic aldehydes catalyzed by KtBuO/tBuOH independently of the electrophilic character of the aryl ring. A simple method to obtain 3-methyl-2,4,5-trimethoxybenzaldehyde is also reported.
Pharmaceutical compounds
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, (2008/06/13)
Diketopiperazines of the formula STR1 where one or both of R1 and R2, which are different, are chosen from X and a phenyl group substituted by X, C(O)X, OC(O)CH2 X, OCH2 CH2 X, CH2 X, CONH(CH2)n X, O(CH2)n CH(OH)(CH2)n X STR2 and, where appropriate, the other of R1 and R2 is a phenyl group optionally substituted by one or more groups selected from halogen, nitro, methoxy, NHC(O)R12, CO2 H, O(CH2)n N(R12 R13), C1 -C4 alkyl and (CH2)n C(O)OR12 ; X is a five- or six-membered heterocyclic ring selected from the group consisting of pyridyl, imidazolyl, furyl, pyrrolyl, pyrrolidinyl, thienyl, piperazinyl, piperidinyl, morpholinyl, quinolyl, isoquinotyl and indolyl, the heteroatom(s) of the said heterocyclic ring, when nitrogen, being optionally substituted by hydrogen, methyl, oxygen, tertiary-butyloxycarbonyl, or SO2 Me, the heterocyclic ring being optionally substituted by halogen ?hydrogen!, methyl, MeS, phenyl, O(CH2)n N(R12 R13) or optionally containing one or more carbonyl groups and being optionally fused to a benzene ring; Y is O or S; R12 and R13, which may be the same or different, are hydrogen or C1 -C6 alkyl; and n is 0 or an integer having the value 1, 2, 3 or 4; a pharmaceutically acceptable salts or esters having activity as inhibitors of plasminogen activator inhibitor.
Pharmaceutical piperazine compounds
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, (2008/06/13)
Diketopiperazines of formula (A): STR1 wherein each of R1 to R8 is H or an organic radical as described herein and the pharmaceutically acceptable salts thereof have activity as inhibitors of plasminogen activator inhibitor.
