Structure of 4570-41-6
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
4.5
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Ru(ii)–arene azole complexes as anti-amyloid-β agents
Ryan M. Hacker ; Daniela M. Grimard ; Katie A. Morgan ; Eaman Saleh ; Morgan M. Wrublik ; Cade J. Meiss , et al.
Abstract: With the recent clinical success of anti-amyloid-β (Aβ) monoclonal antibodies, there is a renewed interest in agents which target the Aβ peptide of Alzheimer's disease (AD). Metal complexes are particularly well-suited for this development, given their structural versatility and ability to form stabile interactions with soluble Aβ. In this report, a small series of ruthenium–arene complexes were evaluated for their respective ability to modulate both the aggregation and cytotoxicity of Aβ. First, the stability of the complexes was evaluated in a variety of aqueous media where the complexes demonstrated exceptional stability. Next, the ability to coordinate and modulate the Aβ peptide was evaluated using several spectroscopic methods, including thioflavin T (ThT) fluorescence, dynamic light scattering (DLS), and transmission electron microscopy (TEM). Overall, the complex RuBO consistently gave the greatest inhibitory action towards Aβ aggregation, which correlated with its ability to coordinate to Aβ in solution. Furthermore, RuBO also had the lowest affinity for serum albumin, which is a key consideration for a neurotherapeutic, as this protein does not cross the blood brain barrier. Lastly, RuBO also displayed promising neuroprotective properties, as it had the greatest inhibition of Aβ-inducted cytotoxicity.
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Novel amides of mycophenolic acid and some heterocyclic derivatives as immunosuppressive agents
Walczak, Juliusz Maksymilian ; Iwaszkiewicz-Grzes, Dorota ; Ziomkowska, Michalina ; Sliwka-Kaszynska, Magdalena ; Dasko, Mateusz ; Trzonkowski, Piotr , et al.
Abstract: The group of 18 new amide derivatives of mycophenolic acid (MPA) and selected heterocyclic amines was synthesised as potential immunosuppressive agents functioning as inosine-5′-monophosphate dehydrogenase (IMPDH) uncompetitive inhibitors. The synthesis of 14 of them employed uronium-type activating system (TBTU/HOBt/DIPEA) while 4 of them concerned phosphonic acid anhydride method (T3P/Py) facilitating amides to be obtained in moderate to excellent yields without the need of phenolic group protection. Most of optimised protocols did not require complicated reaction work-ups, including chromatographic, solvent-consuming methods. The biological activity assay was performed on the T-Jurkat cell line and peripheral mononuclear blood cells (PBMCs) which are both dedicated for antiproliferative activity determination. Each of designed derivatives was characterised by reduced cytotoxicity and benzoxazole analogue (A2) revealed the most promising activity. Subsequently, an observed structure-activity relationship was discussed.
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Keywords: Mycophenolic acid ; amide derivatives ; heterocycles ; benzoxazole ; IMPDH inhibition
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Purchased from AmBeed: 934-32-7 ; 1477-42-5 ; 5464-79-9 ; 5464-79-9 ; 136-95-8 ; 95-24-9 ; 533-30-2 ; 1123-93-9 ; 6285-57-0 ; 15864-32-1 ; 29927-08-0 ; 348-40-3 ; 58-63-9 ; 4570-41-6 ; 75985-45-4 ; 24280-93-1 ; 2536-91-6 ; 19952-47-7 ; 1747-60-0 ; 777-12-8 ; 63837-12-7 ; 58-63-9
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CAS No. : | 4570-41-6 |
Formula : | C7H6N2O |
M.W : | 134.14 |
SMILES Code : | NC1=NC2=CC=CC=C2O1 |
MDL No. : | MFCD00182850 |
InChI Key : | JPBLHOJFMBOCAF-UHFFFAOYSA-N |
Pubchem ID : | 20707 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 38.41 |
TPSA ? Topological Polar Surface Area: Calculated from |
52.05 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.47 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.53 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.42 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.78 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.23 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.28 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.3 |
Solubility | 0.67 mg/ml ; 0.00499 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.23 |
Solubility | 0.786 mg/ml ; 0.00586 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.52 |
Solubility | 0.403 mg/ml ; 0.00301 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.03 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.27 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.