Structure of 2-Imino-4-thiobiuret
CAS No.: 2114-02-5
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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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Keyes, Robert F. ; McAllister, Donna ; Dwinell, Michael B. ; Smith, Brian C. ;
Abstract: Triphenylphosphonium (TPP+) compounds like mito-metformin (MMe) target cancer cells by exploiting their hyperpolarized mitochondrial membrane potential. Here, we present a protocol for synthesizing TPP+ analogs with selectivity for mammalian cancer cells, reduced toxicity, and quantifiability using fluorine-19 NMR (19F-NMR). We describe steps for treating mammalian cells with mitochondria-targeted compounds, treating and preparing mouse tissue with these compounds, and 19F-NMR detection of MMe analogs in cells and tissue. TPP+-conjugated metformin analogs include para-methoxy (pMeO-MMe) and para-trifluoromethyl MMe (pCF3-MMe) and meta-trifluoromethyl MMe (mCF3-MMe).
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CAS No. : | 2114-02-5 |
Formula : | C2H6N4S |
M.W : | 118.16 |
SMILES Code : | S=C(N)NC(N)=N |
MDL No. : | MFCD00014472 |
InChI Key : | OKGXJRGLYVRVNE-UHFFFAOYSA-N |
Pubchem ID : | 2724563 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P301+P312-P302+P352-P304+P340-P305+P351+P338 |
Num. heavy atoms | 7 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 4.0 |
Molar Refractivity | 31.33 |
TPSA ? Topological Polar Surface Area: Calculated from |
120.01 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
-0.09 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-1.13 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-1.29 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-1.51 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.36 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.88 |
Log S (ESOL):? ESOL: Topological method implemented from |
0.27 |
Solubility | 221.0 mg/ml ; 1.87 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.9 |
Solubility | 14.9 mg/ml ; 0.126 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
0.59 |
Solubility | 462.0 mg/ml ; 3.91 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 |
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) |
No |
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 |
-7.82 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 |
3.0 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) |
2.25 |
* 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 |
---|---|---|
In ethanol; acetone; | (A) Ethyl 2-Guanidino-5-thiazolecarboxylate Hydrochloride A solution of amidinothiourea (117 g; 0.99 mole) and ethyl chloro-alpha-formylacetate (150 g; 1.0 mole) in 3.5 liters of absolute ethanol was stirred at ambient temperature for 18 hours and then heated at reflux temperature for 1 hour. At this time additional ethyl chloro-alpha-formylacetate (20.0 g; 0.13 mole) was added and 1 hour later another 20.0 g of ethyl chloro-alpha-formylacetate was added. After 2 hours of additional heating at reflux temperature, the reaction mixture was evaporated under reduced pressure and the residue triturated with 1.5 liters of acetone and filtered to give 103 g of product. Recrystallization from 2-propanol yielded the title compound, mp 204-206. Anal. Calcd for C7 H11 ClN4 O2 S: C, 33.53; H, 4.43; N, 22.35; Cl, 14.14; S, 12.79. Found: C, 33.38; H, 4.40; N, 22.54; Cl, 13.97; S, 12.92. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen bromide; bromine; In ethanol; chloroform; acetic acid; | The 2-guanidino-4-(3-aminophenyl)-5-methylthiazole dihydrochloride used as starting material may be prepared as follows: To a stirred mixture of <strong>[17408-16-1]m-nitropropiophenone</strong> (3.6 g.) in chloroform (50 ml.) was added 3 drops of a solution of hydrogen bromide in acetic acid (45% w/v). Bromine (3.2 g.) in chloroform (10 ml.) was then added dropwise. After addition the mixture was stirred until colourless, evaporated to dryness, the residue dissolved in ethanol (50 ml.) and this solution added to amidinothiourea (2.4 g.) in ethanol (150 ml.) at reflux. The mixture was heated under reflux for 30 minutes and then evaporated to approximately 50 ml. On standing overnight at room temperature a crystalline solid was produced. This was filtered off, washed with ethanol and air-dried to give 6.05 g. of 2-guanidino-4-(3-nitrophenyl)-5-methylthiazole hydrobromide, m.p. 217-222 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen bromide; bromine; In ethanol; chloroform; acetic acid; | The 2-guanidino-4-(3-amino-4-fluorophenyl)thiazole used as starting material may be prepared as follows: To a solution of <strong>[72802-25-6]3-fluoro-4-nitroacetophenone</strong> (6 g.) in chloroform (40 ml.) was added 2 drops of hydrogen bromide in acetic acid (45% w/v) followed by bromine (1.75 ml.) added dropwise. After the bromine colour had disappeared the clear yellow solution was evaporated to dryness and the residue, dissolved in hot ethanol (40 ml.), was added to amidinothiourea (4.0 g.) in ethanol (100 ml.) under reflux. The mixture was heated under reflux for 15 minutes and then cooled to room temperature. The crystalline solid was filtered off to give 8.8 g. of 2-guanidino4-(3-fluoro-4-nitrophenyl)thiazole hydrobromide, m.p. 248-252 C. |
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