- Histamine H3 receptor antagonists with peptidomimetic (keto)piperazine structures to inhibit Aβ oligomerisation
-
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.
- Falkenstein, Markus,Reiner-Link, David,Zivkovic, Aleksandra,Gering, Ian,Willbold, Dieter,Stark, Holger
-
-
- INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE AND METHODS OF THEIR USE
-
The present invention provides compounds of formula (I): wherein all of the variables are as defined herein. These compounds are inhibitors of indoleamine 2,3-dioxygenase (IDO), which may be used as medicaments for the treatment of proliferative disorders, such as cancer, viral infections and/or autoimmune diseases.
- -
-
-
- Discovery of DA-1229: A potent, long acting dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes
-
A series of β-amino amide containing substituted piperazine-2-one derivatives was synthesized and evaluated as inhibitors of dipeptidyl pepdidase-4 (DPP-4) for the treatment of type 2 diabetes. As results of intensive SAR study of the series, (R)-4-[(R)-3-amino-4-(2,4,5-trifluorophenyl)- butanoyl]-3-(t-butoxymethyl)-piperazin-2-one (DA-1229) displayed potent DPP-4 inhibition pattern in several animal models, was selected for clinical development.
- Kim, Heung Jae,Kwak, Woo Young,Min, Jong Pil,Lee, Jae Young,Yoon, Tae Hyun,Kim, Ha Dong,Shin, Chang Yell,Kim, Mi Kyung,Choi, Song Hyen,Kim, Hae Sun,Yang, Eun Kyoung,Cheong, Ye Hwang,Chae, Yu Na,Park, Kyung Jin,Jang, Ji Myun,Choi, Soo Jung,Son, Moon Ho,Kim, Soon Hoe,Yoo, Moohi,Lee, Bong Jin
-
p. 3809 - 3812
(2011/07/31)
-
- Arylpiperazine derivatives and uses thereof
-
Compounds of the formula: or pharmaceutically acceptable salts thereof, wherein Ar, R1, R2, R3 and R4 are as defined herein. Also provided are pharmaceutical compositions, methods of using, and methods of preparing the compounds.
- -
-
Page/Page column 15
(2009/09/05)
-
- Design, synthesis and preliminary pharmacological evaluation of new piperidine and piperazine derivatives as cognition-enhancers
-
A series of 2-oxopiperazine, 4-aminomethyl-, 3-amino- and 3-aminomethylpiperidine analogues of DM235 (sunifiram) and MN19 (sapunifiram), two previously reported potent cognition-enhancers, have been synthesized and tested in the mouse passive-avoidance test. The compounds display minimal effective doses in the range 0.3-10 mg/kg. Although the new substances do not show improved activity when compared to the parent compounds, some useful information has been obtained to understand structure-activity relationships. In addition, the 3-aminopiperidine moiety appears to be a promising scaffold to synthesize new drugs endowed with cognition-enhancing activity.
- Martini, Elisabetta,Ghelardini, Carla,Dei, Silvia,Guandalini, Luca,Manetti, Dina,Melchiorre, Michele,Norcini, Monica,Scapecchi, Serena,Teodori, Elisabetta,Romanelli, Maria Novella
-
p. 1431 - 1443
(2008/09/18)
-
- PHENOXYACETIC ACID DERIVATIVES USEFUL FOR TREATING RESPIRATORY DISEASES
-
The invention relates to substituted phenoxyacetic acids as useful pharmaceutical compounds for treating respiratory disorders, pharmaceutical compositions containing them, and processes for their preparation.Formula (I)
- -
-
Page/Page column 116-117
(2008/06/13)
-
- PHOSPHAGEN SYNTHESIS
-
Cyclocreatine phosphate can be prepared in large quantities from inexpensive starting materials to afford a stable product.
- -
-
Page/Page column 16, 17
(2008/06/13)
-
- Diastereoselectivity in the cycloaddition of 1-benzyl-2-piperazinone nitrone with alkenes
-
The diastereoselectivity of the [2 + 3]-cycloaddition of 1-benzyl-2-piperazinone nitrone with several alkenes has been examined. exo-Type cycloadducts predominated for most substrates. Georg Thieme Verlag Stuttgart.
- Bernotas, Ronald C.,Sing, Lily,Friedrich, Dirk
-
p. 465 - 469
(2007/10/03)
-
- Selective reduction of secondary amides to amines in the presence of tertiary amides
-
Secondary amides activated with a Cbz group can be reduced to their corresponding hemiaminals using lithium borohydride. Hydrogenation then removes the Cbz and hydroxyl groups to produce the related amine. Tertiary amides are not affected.
- Lee, Byung H.,Clothier, Michael F.
-
p. 643 - 644
(2007/10/03)
-
- Synthesis of a 1-benzylpiperazin-2-one nitrone and its reaction with alkynes and alkenes
-
A novel 1-benzylpiperazin-2-one nitrone has been synthesized. It readily undergoes [3 + 2] cycloadditions with alkynes and alkenes to give Δ4-isoxazolines and isoxazolidines, respectively, which can be reductively opened to 3-substituted piperazin-2-ones and 1,3-amino alcohols.
- Bernotas, Ronald C.,Adams, Ginette
-
p. 7339 - 7342
(2007/10/03)
-