18226-11-4Relevant articles and documents
MACROCYCLIC AMIDES ACTING AS PLASMEPSIN INHBITORS FOR THE TREATMENT OF MALARIA
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Paragraph 076-077; 078, (2021/06/26)
The present invention relates to medicine and in particular to the treatment of malarial infections, more particularly to inhibitors of malarial aspartic proteases - plasmepsins. Even more particularly, the invention relates to macrocyclic amides and pharmaceutical compositions thereof and their use as inhibitors for plasmepsins (Plm).
PH-Responsive near-infrared fluorescent cyanine dyes for molecular imaging based on pH sensing
Miki, Koji,Kojima, Kentaro,Oride, Kazuaki,Harada, Hiroshi,Morinibu, Akiyo,Ohe, Kouichi
supporting information, p. 7792 - 7795 (2017/07/15)
Indocyanine green (ICG) derivatives having nucleophilic substituents were synthesized as pH-responsive near-infrared dyes. pH-responsive dyes 1-C with closed-ring structures smoothly internalized and converted to emissive open-ring structures 1-O in respo
Carbazole compounds and therapeutic uses of the compounds
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, (2015/09/28)
Compounds of the general structural formula (I) and (II) and use of the compounds and salts and hydrates thereof, as therapeutic agents are disclosed. Treatable diseases and conditions include cancers, inflammatory diseases and conditions, and immunodeficiency diseases. (I), (II).
Improved Strategy for the Synthesis of the Anticancer Agent Culicinin D
Stach, Michaela,Weidkamp, Andreas J.,Yang, Sung-Hyun,Hung, Kuo-Yuan,Furkert, Daniel P.,Harris, Paul W. R.,Smaill, Jeff B.,Patterson, Adam V.,Brimble, Margaret A.
, p. 6341 - 6350 (2015/10/06)
The anticancer peptaibol culicinin D was synthesised via a newly developed pathway. This route included an improved attachment of a C-terminal amino acid alcohol building block to 2-chlorotrityl chloride resin. A model system utilising readily available Fmoc-alaninol as the substitute for the unusual APAE building block was developed to investigate the resin-loading by N-anchoring of the first C-terminal residue and an intramolecular O-N acyl shift. The use of both Fmoc SPPS and the crucial O-N acyl transfer afforded a C-terminal alcohol that enabled the synthesis of a library of five related peptaibols. This model system was then applied to the synthesis of culicinin D. The C-terminal APAE building block was anchored to 2-chlorotrityl chloride resin in 67 % loading yield using the optimised conditions, and culicinin D (6.31 mg, 4 %) was prepared by SPPS prior to peptide cleavage and O-N acyl shift. This synthetic strategy was also used to prepare a diastereomer of culicinin D containing the unnatural (S)-AHMOD amino acid. The anticancer agent Culicinin D, active against breast tumor cells, was synthesised on the solid phase. The resin loading was improved by attachment of first residue to solid-phase via the amine rather than the alcohol. After SPPS and cleavage, the peptide alcohol was formed via an intramolecular O-N transfer reaction. Successful synthesis of several culicinin D analogues demonstrated the feasibility of this new synthetic strategy.
A modular lead-oriented synthesis of diverse piperazine, 1,4-diazepane and 1,5-diazocane scaffolds
James, Thomas,Maclellan, Paul,Burslem, George M.,Simpson, Iain,Grant, J. Andrew,Warriner, Stuart,Sridharan, Visuvanathar,Nelson, Adam
supporting information, p. 2584 - 2591 (2014/04/17)
Piperazines are found widely in commercially-available compounds and bioactive molecules (including many drugs). However, in the vast majority of these molecules, the piperazine ring is isolated (i.e. not fused to another ring) and is not substituted on any of its carbon atoms. A modular synthetic approach is described in which combinations of cyclic sulfamidate and hydroxy sulfonamide building blocks may be converted into piperazines and related 1,4-diazepine and 1,5-diazocane scaffolds. By variation of the combinations of building blocks used, it was possible to vary the ring size, substitution and configuration of the resulting heterocyclic scaffolds. The approach was exemplified in the synthesis of a range of heterocyclic scaffolds that, on decoration, would target lead-like chemical space. It was demonstrated that lead-like small molecules based on these scaffolds would likely complement those found in large compound collections. This journal is the Partner Organisations 2014.
Scandium-catalyzed cascade cyclization to produce cyclobutane-fused tetrahydroquinoline, chromane, thiochromane, and tetrahydronaphthalene derivatives
Nakano, Shun-Ichi,Kakugawa, Kazumi,Nemoto, Tetsuhiro,Hamada, Yasumasa
supporting information, p. 2088 - 2096 (2014/07/07)
We have succeeded in the highly diastereoselective synthesis of cyclobutane-fused multi-cyclic compounds using a scandium-catalyzed cascade cyclization. Using 3-10 mol% of scandium(III) triflate [Sc(OTf)3], various cyclobutane-fused tetrahydroquinoline derivatives as well as its chromane, thiochromane, and tetrahydronaphthalene analogues were obtained in good to excellent yields. Derivatizations of the reaction products, as well as the plausible reaction mechanism, are also discussed.
Development of hypoxia-sensitive Gd3+-based MRI contrast agents
Iwaki, Shimpei,Hanaoka, Kenjiro,Piao, Wen,Komatsu, Toru,Ueno, Tasuku,Terai, Takuya,Nagano, Tetsuo
supporting information; experimental part, p. 2798 - 2802 (2012/06/01)
Hypoxia occurs in various diseases, including cancer, ischemia, and acute and chronic vascular diseases. Here we describe the design and synthesis of the first hypoxia-sensitive MRI contrast agents, SAGds. SAGds showed a pH-dependent r1 relaxivity change associated with intramolecular chelation of the nitrogen atom of the sulfonamide moiety to the Gd3+ center. There was a correlation between the pKa of the r1 relaxivity change and the sum of the Hammett σ constants of substituents on the aromatic ring. Among the synthesized compounds, 4NO22MeOSAGd was selectively reduced to the amine by rat liver microsomes under hypoxic conditions, resulting in a 1.8-fold increment of the r1 relaxivity owing to the change in pKa of the arylsulfonamide moiety. This enhancement of the r 1 relaxivity could be clearly detected in T1-weighted MR images. Thus, 4NO22MeOSAGd is a 'smart' MRI contrast agent for the detection of hypoxia under physiological conditions.
POTASSIUM ION CHANNEL MODULATORS AND USES THEREOF
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Page/Page column 17, (2012/03/27)
Compounds of formula (I) and pharmacologically acceptable salts and pro-drugs wherein: Ar1 and Ar2=aryl or heteroaryl; a=0 to 5; R1=alkyl, halogen, haloalkyl, alkoxy, alkoxycarbonyl, carboxyl, hydroxyl, amino, monalkylamin
POTASSIUM ION CHANNEL MODULATORS and USES THEREOF
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Page/Page column 55, (2009/07/17)
Compounds of formula (I) and pharmacologically acceptable salts and pro- drugs wherein: Ar1 and Ar 2 =aryl orheteroaryl; a = 0 to 5; R1 =alkyl, halogen, haloalkyl, alkoxy, alkoxycarbonyl, carboxyl, hydroxyl, amino, monalky
HSP90 FAMILY PROTEIN INHIBITORS
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Page/Page column 111, (2008/06/13)
The present invention provides Hsp90 family protein inhibitors comprising, as an active ingredient, a benzoyl compound represented by general formula (I): (wherein n represents an integer of 0 to 10; R1 represents substituted or unsubstituted lower alkoxy, substituted or unsubstituted lower alkoxycarbonyl, CONR7R8 or the like; R2 represents substituted or unsubstituted aryl, a substituted or unsubstituted aromatic heterocyclic group or the like; R3 and R5, which may be the same or different, each represent a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl or the like; and R4 and R6, which may be the same or different, each represent a hydrogen atom, halogen, substituted or unsubstituted lower alkyl, substituted or unsubstituted aryl or the like) or a prodrug thereof, or a pharmaceutically acceptable salt of said benzoyl compound or said prodrug.