104-58-5Relevant articles and documents
Mild LIBF4-Promoted Aminolysis of Oxetanes
Chini, Marco,Crotti, Paolo,Favero, Lucilla,Macchia, Franco
, p. 761 - 764 (1994)
LiBF4 in acetonitrile efficiently catalyzes the aminolysis of trimethylene oxide and 2-octyl oxetane under mild conditions (r.t. or 80 deg C) to give the corresponding γ-amino alcohols in very good yields.
Formation of 3-hydroxyalkyl carbamates from carbon dioxide, amines and oxetanes
Ishii, Shigeru,Zhou, Ming,Yoshida, Yasuhiko,Noguchi, Hiromichi
, p. 3207 - 3214 (1999)
The reactions of carbon dioxide, primary or secondary aliphatic amines and oxetanes at a CO2 pressure of 40 atm at 100-120°C without any catalysts afforded new monocarbamates of 1,3-propanediols, with concomitant formation of amino alcohols from oxetanes and amines.
Studies on molecular properties prediction and histamine H3 receptor affinities of novel ligands with uracil-based motifs
Lipani, Luca,Odadzic, Dalibor,Weizel, Lilia,Schwed, Johannes-Stephan,Sadek, Bassem,Stark, Holger
, p. 578 - 588 (2014)
The histamine H3 receptor (H3R) plays a role in cognitive and memory processes and is involved in different neurological disorders, including Alzheimer's disease, schizophrenia, and narcolepsy. Therefore, several hH3R antagonists/inverse agonists entered clinical phases for a broad spectrum of mainly centrally occurring diseases. However, many other promising candidates failed due to their pharmacokinetic profile, mostly because of their strong lipophilicity accompanied with low solubility. Analysis of previous potential H3R selective antagonists/inverse agonists, e.g. pitolisant, revealed promising results concerning physicochemical properties and drug-likeness. Herein, a series of new hH3R ligands 8-20 consisting of piperidin-1-yl or piperidin-1-yl-propoxyphenyl coupled to different uracil, thymine, and 5,6-dimethyluracil related moieties, were synthesized, evaluated on their binding properties at the hH3R and the estimation of different physicochemical and drug-likeness properties. Due to the coupling to various positions at pyrimidine-2,4-(1H,3H)-dione, affinity at hH3Rs and drug-likeness parameters have been improved. For instance, compound 9 showed in addition to high affinity at the hH3R (pKi (hH3R) Combining double low line 8.14) clog S, clog P, LE, LipE, and drug-likeness score values of -'4.36, 3.47, 0.34, 4.63, and 1.54, respectively. Also, the methyl substituted analog 17 (pKi (hH3R) Combining double low line 8.15) revealed LE, LipE and drug-likeness score values of -'3.29, 2.47, 0.49, 5.52, and 1.76, respectively.
Intramolecular Quenching of Iminium Ions Generated by Photooxidation of Aminoalcohols with Ketones. A New Synthesis of Oxazines and Oxazoles
Cossy, Janine,Guha, Madhumita
, p. 1715 - 1718 (1994)
The irradiation of tertiary amines in the presence of ketones leads to a regioselective and stereoselective formation of iminium salts which then react to afford the corresponding oxazines or oxazoles. - Key words : Ammoniumyl ions, iminium ions, electron transfer, amines, ketones, tetrahydrooxazine tetrahydrooxazoles.
Novel indanone derivatives as MAO B/H3R dual-targeting ligands for treatment of Parkinson's disease
Affini, Anna,Hagenow, Stefanie,Zivkovic, Aleksandra,Marco-Contelles, Jose,Stark, Holger
, p. 487 - 497 (2018)
The design of multi-targeting ligands was developed in the last decades as an innovative therapeutic concept for Parkinson's disease (PD) and other neurodegenerative disorders. As the monoamine oxidase B (MAO B) and the histamine H3 receptor (H3R) are promising targets for dopaminergic regulation, we synthetized dual-targeting ligands (DTLs) as non-dopaminergic receptor approach for the treatment of PD. Three series of compounds were developed by attaching the H3R pharmacophore to indanone-related MAO B motifs, leading to development of MAO B/H3R DTLs. Among synthesized indanone DTLs, compounds bearing the 2-benzylidene-1-indanone core structure showed MAO B preferring inhibition capabilities along with nanomolar hH3R affinity. Substitution of C5 and C6 position of the 2-benzylidene-1-indanones with lipophilic substituents revealed three promising candidates exhibiting inhibitory potencies for MAO B with IC50 values ranging from 1931 nM to 276 nM and high affinities at hH3R (Ki 50 = 276 nM, hH3R Ki = 6.5 nM) showed highest preference for MAO B over MAO A (SI > 36). Interestingly, IC50 determinations after preincubation of enzyme and DTLs revealed also nanomolar MAO B potency for 3e (MAO B IC50 = 232 nM), a structural isomer of 3f, and 3d (MAO B IC50 = 541 nM), suggesting time-dependent inhibition modes. Reversibility of inhibition for all three compounds were confirmed by dilution studies in excess of substrate. Thus, indanone-substituted derivatives are promising lead structures for the design of MAO B/hH3R DTLs as novel therapeutic approach of PD therapy.
Ether derivatives of 3-piperidinopropan-1-ol as non-imidazole histamine H3 receptor antagonists
Lazewska, Dorota,Ligneau, Xavier,Schwartz, Jean-Charles,Schunack, Walter,Stark, Holger,Kiec-Kononowicz, Katarzyna
, p. 3522 - 3529 (2006)
A series of aliphatic and aromatic ether derivatives of 3-piperidinopropan-1-ol has been prepared by four different methods. The ethers obtained were evaluated for their affinities at recombinant human histamine H3 receptor, stably expressed in CHO-K1 or HEK 293 cells. All compounds investigated show from moderate to high in vitro affinities in the nanomolar concentration range. Selected compounds were investigated under in vivo conditions after oral administration to mice. Some proved to be highly potent and orally available histamine H3 receptor antagonists. The most potent antagonists in this series have been in vitro the 4-(1,1-dimethylpropyl)phenyl ether 19 (hH3R Ki = 8.4 nM) and in vivo the simple ethyl ether 2 (ED50 = 1.0 mg/kg).
QUINOLINO-PYRROLIDIN-2-ONE DERIVATIVE AND APPLICATION THEREOF
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Paragraph 0098-0100; 0140-0142, (2021/07/08)
Disclosed are a series of quinolino-pyrrolidin-2-one compounds, and application thereof in preparation of drugs for ATM inhibitor-related diseases. The present disclosure specifically relates to a derivative compound represented by formula (I), tautomers thereof or pharmaceutically acceptable compositions thereof.
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.
Manganese-Catalyzed Anti-Markovnikov Hydroamination of Allyl Alcohols via Hydrogen-Borrowing Catalysis
Das, Kuhali,Sarkar, Koushik,Maji, Biplab
, p. 7060 - 7069 (2021/06/30)
Controlling the selectivity in a hydroamination reaction is an extremely challenging yet highly desirable task for the diversification of amines. In this article, a selective formal anti-Markovnikov hydroamination of allyl alcohols is presented. It enables the versatile synthesis of valuable γ-amino alcohol building blocks. A phosphine-free Earth's abundant manganese(I) complex catalyzed the reaction under hydrogen-borrowing conditions. A vast range of aliphatic, aromatic amines, drug molecules, and natural product derivatives underwent successful hydroamination with primary and secondary allylic alcohols with excellent functional group tolerance (57 examples). The catalysis could be performed on a gram scale and has been applied for the synthesis of drug molecules. The mechanistic studies revealed the metal-ligand bifunctionality as well as hemilability of the ligand backbone as the key design principle for the success of this catalysis.
QUINAZOLINE DERIVATIVE
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, (2017/07/04)
Provided are a quinazoline derivative, a pharmaceutical composition containing the same, a method for preparation of said derivative, and an application of same as an anti-cancer drug.
