Structure of 17573-94-3
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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.
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Rajapaksha, Ishanka N. ; Wang, Jing ; Leszczynski, Jerzy ; Scott, Colleen N. ;
Abstract: NIR dyes have become popular for many applications, including biosensing and imaging. For this reason, the mol. switch mechanism of the xanthene dyes makes them useful for in vivo detection and imaging of bioanalytes. Our group has been designing NIR xanthene-based dyes by the donor-acceptor-donor approach; however, the equilibrium between their opened and closed forms varies depending on the donors and spacer. We synthesized donor-acceptor-donor NIR xanthene-based dyes with an alkyne spacer via the Sonogashira coupling reaction to investigate the effects of the alkyne spacer and the donors on the maximum absorption wavelength and the mol. switching (ring opening) process of the dyes. We evaluated the strength and nature of the donors and the presence and absence of the alkyne spacer on the properties of the dyes. It was shown that the alkyne spacer extended the conjugation of the dyes, leading to absorption wavelengths of longer values compared with the dyes without the alkyne group. In addition, strong charge transfer donors shifted the absorption wavelength towards the NIR region, while donors with strong π-donation resulted in xanthene dyes with a smaller equilibrium constant DFT/TDDFT calculations corroborated the exptl. data in most of the cases. Dye 2 containing the N,N-dimethylaniline group gave contrary results and is being further investigated.
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Keywords: donor-acceptor-donor ; NIR dyes ; xanthene dyes ; amine donors ; alkyne spacers
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Purchased from AmBeed: 589-87-7 ; 768-60-5 ; 201802-67-7 ; 262861-81-4 ; 57102-42-8 ; 17573-94-3 ; 1066-54-2 ; 205877-26-5 ; 28611-39-4 ; 1195931-66-8
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CAS No. : | 17573-94-3 |
Formula : | C10H11N |
M.W : | 145.20 |
SMILES Code : | CN(C)C1=CC=C(C#C)C=C1 |
MDL No. : | MFCD00168816 |
InChI Key : | ZWMAYLMVFSCMMS-UHFFFAOYSA-N |
Pubchem ID : | 5191884 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H317-H319-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.2 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 48.58 |
TPSA ? Topological Polar Surface Area: Calculated from |
3.24 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.31 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.69 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.81 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.67 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.04 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.3 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.77 |
Solubility | 0.245 mg/ml ; 0.00169 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.41 |
Solubility | 0.564 mg/ml ; 0.00388 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.57 |
Solubility | 0.393 mg/ml ; 0.0027 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
No |
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 |
-5.28 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 |
2.0 |
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 |
1.0 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) |
1.45 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | n-BuLi (2.5 M in hexanes) (11.80mL, 29.4 mmol) was added portionwise via syringe to a cold (-70 C)stirred solution of 4-ethynyl-N,N-dimethylaniline (4.27 g, 29.4 mmol) inanhydrous THF (30 mL) under N2. The cold solution was stirred for 30min and then <strong>[4038-15-7](2,4-dimethoxyphenyl)(4-methoxyphenyl)methanone</strong>(4.00 g, 14.7 mmol) was added in a single portion. The cooling bath wasremoved and the mixture stirred for 20 h at room temperature under N2.The reaction mixture was diluted with water (150 mL) and extractedwith EtOAc (3 × 75 mL). The combined organic extracts were washedwith water (150 mL), dried with anhydrous sodium sulfate and evaporatedto afford a brown oil. Elution from silica with 20% EtOAc/petroleumether afforded the title compound as an orange powder (0.87 g,85%); m.p. = 49-50 C; νmax (neat) 3506, 2932, 2834, 2217, 1605,1503, 1245, 1206, 1156, 1028, 816, 586 and 523 cm 1; 1H NMR (400MHz, CDCl3) δH 2.95 (6H, s, NMe2), 3.78 (3H, s, OMe), 3.80 (3H, s,OMe), 3.81 (3H, s, OMe), 4.77 (1H, s, OH), 6.44 (1H, dd, J = 8.6, 2.4 Hz,Ar-H), 6.51 (1H, d, J = 2.4 Hz, Ar-H), 6.58-6.62 (2H, m, Ar-H),6.84-6.88 (2H, m, Ar-H), 7.30-7.35 (3H, m, Ar-H), 7.49-7.53 (2H, m,Ar-H); 13C{1H} NMR (100 MHz, CDCl3) δC 40.24, 55.27, 55.41, 55.93,74.27, 87.39, 89.35, 100.16, 103.97, 109.97, 111.69, 113.17, 126.25,127.71, 129.22, 132.82, 137.45, 150.12, 157.94, 158.78, 160.58; HRMS(ESI) found [M+H]+ = 418.2002. C26H27NO4 requires [M+H]+ =418.2018. |
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