Structure of L-Tyrosinamide
CAS No.: 4985-46-0
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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.
Synonyms: H-Tyr-NH2
4.5
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CAS No. : | 4985-46-0 |
Formula : | C9H12N2O2 |
M.W : | 180.20 |
SMILES Code : | O=C(N)[C@@H](N)CC1=CC=C(O)C=C1 |
Synonyms : |
H-Tyr-NH2
|
MDL No. : | MFCD00069935 |
InChI Key : | PQFMNVGMJJMLAE-QMMMGPOBSA-N |
Pubchem ID : | 151243 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.22 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 3.0 |
Molar Refractivity | 48.66 |
TPSA ? Topological Polar Surface Area: Calculated from |
89.34 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.94 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.63 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-0.25 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.11 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.15 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.06 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.7 |
Solubility | 35.6 mg/ml ; 0.198 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.77 |
Solubility | 30.4 mg/ml ; 0.168 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.5 |
Solubility | 5.63 mg/ml ; 0.0313 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 |
-7.85 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) |
1.58 |
* 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 |
---|---|---|
86% | With ammonium hydroxide; at 20℃; for 4h; | L-tyrosine methyl ester hydrochloride (1.16 g, 5 mmol) and concentrated aqueous ammonia (40 mL) were added to a 50 ml reaction vessel and stirred for 4 h at room temperature. Rotary evaporation of ammonia, spin dry, with anhydrous ethanol (20mL × 2) with water, column chromatography (silica gel, 200-300 mesh; exhibition Preparative, ethyl acetate: methanol: aqueous ammonia = 300: 10: 15) gave L-tyrosinamide in 86% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | Solid GdCl3 (100.3 mg, 0.27 mmol) was added to a solution of DOTA-tyramide (110 mg, 0.18 mmol) in triethylammonium acetate (2 mL, pH=5). The mixture was stirred at room temperature for 8 hours and the product was crystallized at 4 C. in trimethylammonium acetate. The precipitate was washed with cold water to provide 101.3 mg (75% yield) of crystalline compound. LRMS (MALDI-TOF) calculated for C27H39N6O9Gd (M+H)+ 748.89, found 749.96. The resultant crystalline product was determined to be pure by HPLC. | |
Potassium hydroxide, 0.3 g, was added thereto, followed by the same procedures as in Example 18, and 4.2 g (dry mass) of the mixture of D- and L-p-hydroxy-phenylalanine amide was obtained (yield from separated mother liquor: 72%). | ||
EXAMPLE 31 L-Tyrosinamide, N-acetyl-O-phosphono-L-tyrosyl-N-(3-phenylpropyl)-O-phosphono- or Ac-(O-phosphono)-L-Tyr-(O-phosphono)-L-Tyr-NH(3-phenylpropyl) STR64 The title compound was synthesised in a manner similar to that described for Example 1. The product was obtained as a colorless solid (64 mg). HPLC 96%, rt=14.5 minutes, C18, eluding with a gradient of 0% to 66% acetonitrile containing 0.1% TFA and water containing 0.1% TFA over 22 minutes. Electrospray Mass Spectrum (50/50 acetonitrile/water+0.1% ammonium hydroxide) m/z 663.3 (M-H). |
With ammonia; at 20℃; | General procedure: The amino acid (4 mmol) was dissolved in methanol (10 ml), the solution was cooled to 0 C and thionyl chloride (8 mmol) was added drop wise. The reaction mixture was heated to reflux, stirred for 6 h-12 h and cooled to room temperature. Solvents were evaporated under reduced pressure, and the resulting product was used in the next step without further purification (95% yield). The amino acid ester hydrochloride (4 mmol) was dissolved in ammonia solution (2 ml) and the reaction mixture was stirred at room temperature for 2-4 h. Solvents were evaporated under reduced pressure and resulting in amino acid amide 1. NMR (500 MHz, D20) delta 3.75 (d, / = 7.5 Hz, 1H) ppm. 13C NMR (125 MHz, D20) delta 169.3, 40.0 ppm. MS (ESI) [M+H]+ calcd. C2H6N20 75.0, found 75.1. |
A1193497 [2442565-30-0]
(S)-2-Amino-3-(4-hydroxyphenyl)propanamide dihydrochloride
Reason: Free-salt