- Selenium-containing compounds and their use in treatment of neuro-degenerative diseases
-
The present invention relates to compounds of Formula I or pharmaceutically acceptable salts, solvates or pro-drugs thereof. The invention also relates to a preparation method of the compound or the pharmaceutically acceptable salt, solvate or prodrug thereof, a pharmaceutical composition containing the compound or the pharmaceutically acceptable salt, solvate or prodrug thereof and application ofthe compound or the pharmaceutically acceptable salt, solvate or prodrug thereof in preparation of drugs. The drugs are used for treating neuro-degenerative diseases.
- -
-
Paragraph 0089; 0097-0099
(2020/12/30)
-
- Structure-Activity Relationship of Hetarylpropylguanidines Aiming at the Development of Selective Histamine Receptor Ligands?
-
New classes of alkylated hetarylpropylguanidines with different functionality and variation in spacer length were synthesized to determine their behavior at the four histamine receptor (H1R, H2R, H3R, H4R) subtypes. Alkylated guanidines with different terminal functional groups and varied basicity, like amine, guanidine and urea were developed, based on the lead structure SK&F 91486 (2). Furthermore, heteroatomic exchange at the guanidine structure of 2 led to simple analogues of the lead compound. Radioassays at all histamine receptor subtypes were accomplished, as well as organ bath studies at the guinea pig (gp) ileum (gpH1R) and right atrium (gpH2R). Ligands with terminal functionalization led to, partially, highly affine and potent structures (two digit nanomolar), which showed up a bad selectivity profile within the histamine receptor family. While the benzoylurea derivative 144 demonstrated a preference towards the human (h) H3R, S-methylisothiourea analogue 143 obtained high affinity at the hH4R (pKi=8.14) with moderate selectivity. The molecular basis of the latter finding was supported by computational studies.
- Pockes, Steffen,Wifling, David,Buschauer, Armin,Elz, Sigurd
-
p. 285 - 297
(2019/04/04)
-
- A green one-pot synthesis of 3(5)-substituted 1,2,4-triazol-5(3)-amines as potential antimicrobial agents
-
Abstract: An efficient procedure was proposed for the synthesis of 3(5)-substituted 1,2,4-triazol-5(3)-amines via a one-pot reaction of thiourea, dimethyl sulfate and various hydrazides. 1,2,4-Triazole derivatives were prepared in aqueous media under mild conditions while adhering to some principles of green chemistry. The products were easily isolated in 83–95% yields without any need for further purification. Inhibitory activities of all synthetic compounds were assessed against a variety of Gram-positive and Gram-negative pathogenic bacteria as well as some fungal pathogens. The best antibacterial effects were observed with 3(5)-phenyl-1H-1,2,4-triazol-5(3)-amine according to its MIC values (4–8?μg?mL?1). All compounds were successful in blocking the growth of fungi. Acceptable antioxidant properties were observed only with 3(5)-(4-nitrophenyl)-1H-1,2,4-triazol-5(3)-amine. Graphic abstract: 3(5)-Substituted 1,2,4-triazol-5(3)-amines were efficiently prepared via a one-pot reaction of thiourea, dimethyl sulfate and various hydrazides in water as the solvent. Inhibitory activity of all synthesized derivatives was proved according to their MIC, MBC and MFC values. It is found that they are potential antifungal agents.[Figure not available: see fulltext.].
- Beyzaei, Hamid,Khosravi, Zahra,Aryan, Reza,Ghasemi, Behzad
-
p. 2565 - 2573
(2019/07/04)
-
- Application of the guanidine-acylguanidine bioisosteric approach to argininamide-type NPY Y2 receptor antagonists
-
Strongly basic groups such as guanidine moieties are crucial structural elements, but they compromise the drug-likeness of numerous biologically active compounds, including ligands of G-protein-coupled receptors (GPCRs). As part of a project focused on the search for guanidine bioisosteres, argininamide-type neuropeptideY (NPY) Y2 receptor (Y2R) antagonists related to BIIE0246 were synthesized. Starting from ornithine derivatives, NG-acylated argininamides were obtained by guanidinylation with tailor-made mono-Boc-protected N-acyl-S-methylisothioureas. The compounds were investigated for Y2R antagonism (calcium assays), Y2R affinity, and NPY receptor subtype selectivity (flow cytometric binding assays). Most of the NG-substituted (S)-argininamides showed Y2R antagonistic activities and binding affinities similar to those of the parent compound, whereas NG-acylated or -carbamoylated analogues with a terminal amine were superior (Y2R: Ki and KB values in the low nanomolar range). This demonstrates that the basicity of the compounds, although 4-5 orders of magnitude lower than that of guanidines, is sufficient to form key interactions with acidic amino acids of the Y2R. The acylguanidines bind with high affinity and selectivity to Y2R over the Y1, Y4, and Y5 receptors. As derivatization of the amino group is tolerated, these compounds can be considered building blocks for the preparation of versatile fluorescent and radiolabeled pharmacological tools for invitro studies of the Y2R. The results support the concept of bioisosteric guanidine-acylguanidine exchange as a broadly applicable approach to retain pharmacological activity despite decreased basicity.
- Pluym, Nikola,Brennauer, Albert,Keller, Max,Ziemek, Ralf,Pop, Nathalie,Bernhardt, Guenther,Buschauer, Armin
-
scheme or table
p. 1727 - 1738
(2012/01/14)
-
- Synthesis and cytotoxic activity of 2,5-disubstituted pyrimido[5,4-c] quinoline derivatives
-
A series of 2,5-disubstituted pyrimido[5,4-c]quinoline derivatives were synthesized and their cytotoxic activity against H460, HT-29 and MDA-MB-231 cell lines was evaluated in vitro. It was found that most of the tested compounds especially compound 17, s
- Zhang, Fan,Zhai, Xin,Chen, Li Juan,Qi, Jian Guo,Cui, Bo,Gu, Yu Cheng,Gong, Ping
-
scheme or table
p. 1277 - 1280
(2012/01/06)
-
- Antibiotic for methicillin resistant bacteria
-
The present invention is directed to anti-bacterial and anti-tumor agents and the synthesis thereof.
- -
-
-
- Antihypertensive cyanoguanidines
-
This invention relates to novel tri-substituted guanidines linked to a piperidine ring. More specifically, it relates to cyanoguanidines of formula I STR1 wherein R1, R2, R3, R4 are substituents n is an integer of zero to 1 n' is an integer of zero to 1 A and B are --CH2 --, CHOH, --CO-- or a single bond as well as the acid addition salts thereof with a mineral or organic acid. The compounds have interesting pharmacological properties which make them useful as active ingredient of medicines, e.g. antihypertensives.
- -
-
-
- SULPHOXIDES
-
The compounds are sulphoxides of heterocyclicthioalkylthioureas, ureas and guanidines which are useful to produce inhibition of histamine H-2 receptors.
- -
-
-
