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Chemical Structure| 1028252-13-2 Chemical Structure| 1028252-13-2

Structure of 1028252-13-2

Chemical Structure| 1028252-13-2

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Product Details of [ 1028252-13-2 ]

CAS No. :1028252-13-2
Formula : C9H5BrClNO
M.W : 258.50
SMILES Code : ClC1=CC2=C(C=C1)C(Br)=CNC2=O
English Name :4-Bromo-7-chloroisoquinolin-1(2H)-one
MDL No. :MFCD13193317
InChI Key :DNIKNSRKTYSIMS-UHFFFAOYSA-N
Pubchem ID :59423588

Safety of [ 1028252-13-2 ]

Computational Chemistry of [ 1028252-13-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 10
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 57.28
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

32.86 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.98
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

2.37
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

2.94
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

2.92
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

3.87
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.82

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-3.51
Solubility 0.0808 mg/ml ; 0.000313 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.7
Solubility 0.515 mg/ml ; 0.00199 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-5.08
Solubility 0.00216 mg/ml ; 0.00000834 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately soluble

Pharmacokinetics

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)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

Yes
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.19 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

0.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<0.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.7

Application In Synthesis of [ 1028252-13-2 ]

* 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.

  • Downstream synthetic route of [ 1028252-13-2 ]

[ 1028252-13-2 ] Synthesis Path-Downstream   1~14

  • 1
  • [ 24188-74-7 ]
  • [ 1028252-13-2 ]
YieldReaction ConditionsOperation in experiment
90% With N-Bromosuccinimide In acetonitrile for 3.5h; Reflux; Inert atmosphere;
With N-Bromosuccinimide In acetonitrile for 3.5h; Reflux; 6.1.5 A slurry of the product of Step 4 and NBS (39.747 g, 223.3 mmol) in MeCN (500 mL, anhydrous) was slowly heated to a gentle reflux over a period of approximately 2 h and maintained at a gentle reflux for 1.5 h. (This reaction can be monitored by LC/MS). The reaction mixture was then slowly cooled to room temperature over a period of 3 h and the observed solid was removed by simple filtration. The collected solid was washed with MeCN (100 mL×3) to provide 47 g of the desired product. This material was used in the next step without further purification.1H NMR (400 MHz, CD3OD) δ ppm 7.46(s, 1H), 7.81 (dd, J=8.40, 2.00 Hz, 1H), 7.88 (d, J=8.8 Hz, 1H), 8.27(d, J=2.00 Hz, 1H); 13C NMR (100 MHz, DMSO-D6) δ ppm 96.68, 126.34, 127.58, 127.71, 130.73, 132.20, 133.47, 134.46, 159.88; LC-MS, MS m/z 258 (M++H).
With N-Bromosuccinimide In acetonitrile at 20℃; Reflux; 2.5 Step 5: A slurry of the product of Step 4, Example 2 and NBS (39.747 g, 223.3 mmol) in MeCN (500 mL, anhydrous) was slowly heated to a gentle reflux over a period of approximately 2 h and maintained at a gentle reflux for 1.5 h. (This reaction can be monitored by LC/MS). The reaction mixture was then slowly cooled to room temperature over a period of 3 h and the observed solid was removed by simple filtration. The collected solid was washed with MeCN (100 mL×3) to provide 47 g of the desired product. This material was used in the next step without further purification. 1H NMR (400 MHz, CD3OD) δ ppm 7.46(s, 1H), 7.81 (dd, J=8.40, 2.00 Hz, 1H), 7.88 (d, J=8.8 Hz, 1H), 8.27(d, J=2.00 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ ppm 96.68, 126.34, 127.58, 127.71, 130.73, 132.20, 133.47, 134.46, 159.88; LC-MS, MS m/z 258.
With N-Bromosuccinimide In acetonitrile at 20℃; for 6.5h; Heating / reflux; 22.5 Step 5:; A slurry of the product of Step 4 and NBS (39.747 g, 223.3 mmol) in MeCN (500 mL, anhydrous) was slowly heated to a gentle reflux over a period of approximately 2 h and maintained at a gentle reflux for 1.5 h (This reaction can be monitored by LC/MS). The reaction mixture was then slowly cooled to room temperature over a period of 3 h and the observed solid was removed by simple filtration. The collected solid was washed with MeCN (100 mL×3) to provide 47 g of the desired product. This material was used in the next step without further purification.1H NMR (400 MHz, CD3OD) δ ppm 7.46 (s, 1H), 7.81 (dd, J=8.40, 2.00 Hz, 1H), 7.88 (d, J=8.8 Hz, 1H), 8.27 (d, J=2.00 Hz, 1H); 13C NMR (100 MHz, DMSO-D6) δ ppm 96.68, 126.34, 127.58, 127.71, 130.73, 132.20, 133.47, 134.46, 159.88; LC-MS, MS m/z 258.

  • 2
  • [ 1028252-13-2 ]
  • [ 953421-74-4 ]
YieldReaction ConditionsOperation in experiment
73% With trichlorophosphate for 5h; Reflux; Inert atmosphere;
Stage #1: 4-bromo-7-chloroisoquinolin-1-ol With trichlorophosphate for 5h; Reflux; Stage #2: With sodium hydroxide In dichloromethane; water at -35℃; 6.1.6 A heterogeneous solution of the product of Step 5 (47 g, 182 mmol) in POCl3 (200 mL, 2.15 mol) was slowly heated to reflux over a period of 1 h. The reaction mixture was maintained at reflux for 4 h. The reaction mixture was then cooled to room temperature and concentrated in vacuo to remove excess POCl3. The resulting residue was then taken up into 600 mL of CH2Cl2, cooled to at -35° C., then slowly treated with 1 N NaOH (400 mL) until the mixture was slightly basic (pH=8). The resulting organic layer was separated, washed with water, dried over MgSO4, filtered, and concentrated in vacuo. The resulting residue was crystallized from EtOAc (approximately 50 mL) to give 32 g of desired product. The collected solid was washed with 10% EtOAc/Hexanes (3×50 mL).The mother liquors were concentrated and purified by flash column chromatography (SiO2, eluted with 16% EtOAc in hexanes) to give 4 g of the desired product as a solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.80 (dd, J=8.81, 2.01 Hz, 1H), 8.14 (d, J=9.06 Hz, 1H), 8.34 (d, J=1.76 Hz, 1H), 8.48 (s, 1H); 13C NMR (100 MHz, DMSO-D6) δ ppm 118.39, 125.06, 127.59, 128.71, 133.89, 134.14, 134.93, 143.18, 148.98; LC-MS, MS m/z 275 (M++H).
Stage #1: 4-bromo-7-chloroisoquinolin-1-ol With trichlorophosphate for 5h; Reflux; Stage #2: With sodium hydroxide In dichloromethane; water 2.6 Step 6:A heterogeneous solution of the product of Step 5, Example 2 (47 g, 182 mmol) in POCl3 (200 mL, 2.15 mol) slowly heated to reflux over a period of 1 h. The reaction mixture was maintained at reflux for 4 h. The reaction mixture was then cooled to room temperature and concentrated in vacuo to remove excess POCl3. The resulting residue was then taken-up into 600 mL of CH2Cl2, cooled to at -35° C., then neutralized carefully with 1 N NaOH (400 mL) until the mixture was slightly basic (pH=8). The resulting organic layer was separated, washed with water, dried over MgSO4 and concentrated in vacuo. The resulting residue was crystallized from EtOAc (approximately 50 mL) to give 32 g of desired product. The collected solid was washed with 10% EtOAc/Hexanes (3×50 ml). The mother liquid was concentrated and purified by Biotage (elution with 16% EtOAc in hexanes) to give 4 g of the desired product as a solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.80 (dd, J=8.81, 2.01 Hz, 1H), 8.14 (d, J=9.06 Hz, 1H), 8.34 (d, J=1.76 Hz, 1H), 8.48 (s, 1H); 13C NMR (100 MHz, DMSO-d6) δ ppm 118.39, 125.06, 127.59, 128.71, 133.89, 134.14, 134.93, 143.18, 148.98; LC-MS, MS m/z 275.
Stage #1: 4-bromo-7-chloroisoquinolin-1-ol With trichlorophosphate for 5h; Heating / reflux; Stage #2: With sodium hydroxide In dichloromethane; water at -35℃; 22.6 Step 6:; A heterogeneous solution of the product of Step 5 (47 g, 182 mmol) in POCl3 (200 mL, 2.15 mol) slowly heated to reflux over a period of 1 h. The reaction mixture was maintained at reflux for 4 h. The reaction mixture was then cooled to room temperature and concentrated in vacuo to remove excess POCl3. The resulting residue was then taken-up into 600 mL of CH2Cl2, cooled to at -35° C., then neutralized carefully with 1 N NaOH (400 mL) until the mixture was slightly basic (pH=8). The resulting organic layer was separated, washed with water, dried over MgSO4 and concentrated in vacuo. The resulting residue was crystallized from EtOAc (approximately 50 mL) to give 32 g of desired product. The collected solid was washed with 10% EtOAc/Hexanes (3×50 ml).The mother liquid was concentrated and purified by Biotage (elution with 16% EtOAc in hexanes) to give 4 g of the desired product as a solid.1H NMR (400 MHz, CDCl3) δ ppm 7.80 (dd, J=8.81, 2.01 Hz, 1H), 8.14 (d, J=9.06 Hz, 1H), 8.34 (d, J=1.76 Hz, 1H), 8.48 (s, 1H); 13C NMR (100 MHz, DMSO-D6) δ ppm 118.39, 125.06, 127.59, 128.71, 133.89, 134.14, 134.93, 143.18, 148.98; LC-MS, MS m/z 275.

  • 3
  • [ 24188-74-7 ]
  • [ 1028252-13-2 ]
YieldReaction ConditionsOperation in experiment
With N-Bromosuccinimide In acetonitrile Reflux; 1001.2 Step 2A slurry of the product of Step 1, Example 1001, 7-chloroisoquinolin-l(2H)- one (36.33 g, 203 mmol) and N-bromosuccinimide (39.74 g, 223.3 mmol) in anhydrous CH3CN (500 mL) was slowly heated to a gentle reflux over a period of approximately 2 h and maintained at a gentle reflux for 1.5 h. The reaction was monitored by LC/MS and, when complete, the slurry, was slowly cooled to room temperature over a period of 3 h. The precipitated solid was collected by filtration and washed with CH3CN (100 mL x 3) to provide 47 g (90%) of 4-bromo-7- chloroisoquinolin-l(2H)-one. This material was used in the next step without further purification. ¾ NMR (400 MHz, CD3OD) δ ppm 7.46(s, 1H), 7.81 (dd, J=8.40, 2.00 Hz, 1 H), 7.88 (d, J=8.8 Hz, 1 H), 8.27(d, J=2.00 Hz, 1 H); 13C NMR (101 MHz, DMSO-D6) δ ppm 96.68, 126.34, 127.58, 127.71, 130.73, 132.20, 133.47, 134.46, 159.88; LC/MS, MS m/z (M+H)+ 258.
With N-Bromosuccinimide In N,N-dimethyl-formamide at 20℃;
  • 4
  • [ 1028252-13-2 ]
  • [ 630423-36-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: trichlorophosphate / 5 h / Reflux 1.2: -35 °C / pH 8 2.1: n-butyllithium; Triisopropyl borate / hexane; tetrahydrofuran / 0.75 h / -78 - -65 °C 2.2: 1.17 h / -60 - 20 °C 2.3: 0 °C / pH 6 3.1: diazomethyl-trimethyl-silane / hexane; acetonitrile / 14 h / 0 - 20 °C
  • 5
  • [ 1028252-13-2 ]
  • [ 953421-74-4 ]
YieldReaction ConditionsOperation in experiment
Stage #1: 4-bromo-7-chloro-2H-isoquinolin-1-one With trichlorophosphate for 5h; Reflux; Stage #2: With sodium hydroxide In dichloromethane at -35℃; 1001.3 Step 3A heterogeneous solution of the product of Step 2, Example 1001, 4-bromo-7- chloroisoquinolin-l(2H)-one (47 g, 182 mmol) in POCl3 (200 mL, 2.15 mol) was slowly heated to reflux over a period of 1 h. It should be noted that during this heating process, the reaction mixture became homogeneous. The reaction mixture was maintained at reflux for 4 h before being cooled to room temperature and concentrated in vacuo to remove excess POCl3. To ensure complete removal of residual POCl3, the residue was dissolved in CH2CI2 or, alternatively, toluene and concentrated in vacuo. This process was repeated as necessary. (Note that POCl3 was properly disposed of in glass bottles which were labeled accordingly). The residue was taken-up into 600 mL of CH2CI2, cooled to -35 °C, neutralized and subsequently basified carefully with IN NaOH (400 mL) until the mixture was slightly basic (pH = 8). The organic layer was separated, washed with H20, dried over MgS04 and concentrated in vacuo. The residual solid was crystallized from EtOAc (approximately 50 mL) to give 32 g of 4-bromo-l,7-dichloroisoquinoline. The mother liquor from the crystallization process was concentrated and purified by Biotage (16% EtOAc in hexanes) to provide an additional 4 g of 4-bromo-l,7- dichloroisoquinoline as a solid. In total 36 g (73 %) of 4-bromo-l,7- dichloroisoquinoline was obtained. XH NMR (400 MHz, CDC13) δ ppm 7.80 (dd, J=8.81, 2.01 Hz, 1 H), 8.14 (d, J=9.06 Hz, 1 H), 8.34 (d, J=1.76 Hz, 1 H), 8.48 (s, 1 H); 13C NMR (101 MHz, DMSO-D6) δ ppm 1 18.39, 125.06, 127.59, 128.71, 133.89, 134.14, 134.93, 143.18, 148.98; LC/MS, MS m/z (M+H)+ 275.
  • 8
  • [ 1028252-13-2 ]
  • [ 630420-16-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: trichlorophosphate / 5 h / Reflux; Inert atmosphere 2.1: n-butyllithium / hexane; tetrahydrofuran / 0.75 h / 65 °C / Inert atmosphere 2.2: 0.75 h / 65 °C / Inert atmosphere 2.3: 0.5 h / -60 - -40 °C 3.1: diazomethyl-trimethyl-silane / hexane; acetonitrile / 14 h / 0 - 20 °C / Inert atmosphere 4.1: potassium <i>tert</i>-butylate / dimethyl sulfoxide / 3.5 h / 10 - 20 °C / Sonication; Inert atmosphere 5.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h / Inert atmosphere 6.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h / 20 °C / Inert atmosphere
Multi-step reaction with 6 steps 1.1: trichlorophosphate / 5 h / Reflux; Inert atmosphere 2.1: n-butyllithium / hexane; tetrahydrofuran / 0.75 h / 65 °C / Inert atmosphere 2.2: 0.75 h / 65 °C / Inert atmosphere 2.3: 0.5 h / -60 - -40 °C 3.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 1 h / 4 °C / Inert atmosphere 4.1: potassium <i>tert</i>-butylate / dimethyl sulfoxide / 3.5 h / 10 - 20 °C / Sonication; Inert atmosphere 5.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h / Inert atmosphere 6.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h / 20 °C / Inert atmosphere
References: [1]Scola, Paul M.; Sun, Li-Qiang; Wang, Alan Xiangdong; Chen, Jie; Sin, Ny; Venables, Brian L.; Sit, Sing-Yuen; Chen, Yan; Cocuzza, Anthony; Bilder, Donna M.; D'Andrea, Stanley V.; Zheng, Barbara; Hewawasam, Piyasena; Tu, Yong; Friborg, Jacques; Falk, Paul; Hernandez, Dennis; Levine, Steven; Chen, Chaoqun; Yu, Fei; Sheaffer, Amy K.; Zhai, Guangzhi; Barry, Diana; Knipe, Jay O.; Han, Yong-Hae; Schartman, Richard; Donoso, Maria; Mosure, Kathy; Sinz, Michael W.; Zvyaga, Tatyana; Good, Andrew C.; Rajamani, Ramkumar; Kish, Kevin; Tredup, Jeffrey; Klei, Herbert E.; Gao, Qi; Mueller, Luciano; Colonno, Richard J.; Grasela, Dennis M.; Adams, Stephen P.; Loy, James; Levesque, Paul C.; Sun, Huabin; Shi, Hong; Sun, Lucy; Warner, William; Li, Danshi; Zhu, Jialong; Meanwell, Nicholas A.; McPhee, Fiona [Journal of Medicinal Chemistry, 2014, vol. 57, # 5, p. 1730 - 1752].
[2]Scola, Paul M.; Sun, Li-Qiang; Wang, Alan Xiangdong; Chen, Jie; Sin, Ny; Venables, Brian L.; Sit, Sing-Yuen; Chen, Yan; Cocuzza, Anthony; Bilder, Donna M.; D'Andrea, Stanley V.; Zheng, Barbara; Hewawasam, Piyasena; Tu, Yong; Friborg, Jacques; Falk, Paul; Hernandez, Dennis; Levine, Steven; Chen, Chaoqun; Yu, Fei; Sheaffer, Amy K.; Zhai, Guangzhi; Barry, Diana; Knipe, Jay O.; Han, Yong-Hae; Schartman, Richard; Donoso, Maria; Mosure, Kathy; Sinz, Michael W.; Zvyaga, Tatyana; Good, Andrew C.; Rajamani, Ramkumar; Kish, Kevin; Tredup, Jeffrey; Klei, Herbert E.; Gao, Qi; Mueller, Luciano; Colonno, Richard J.; Grasela, Dennis M.; Adams, Stephen P.; Loy, James; Levesque, Paul C.; Sun, Huabin; Shi, Hong; Sun, Lucy; Warner, William; Li, Danshi; Zhu, Jialong; Meanwell, Nicholas A.; McPhee, Fiona [Journal of Medicinal Chemistry, 2014, vol. 57, # 5, p. 1730 - 1752].
  • 9
  • [ 1028252-13-2 ]
  • [ 1574537-76-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1.1: trichlorophosphate / 5 h / Reflux; Inert atmosphere 2.1: n-butyllithium / hexane; tetrahydrofuran / 0.75 h / 65 °C / Inert atmosphere 2.2: 0.75 h / 65 °C / Inert atmosphere 2.3: 0.5 h / -60 - -40 °C 3.1: diazomethyl-trimethyl-silane / hexane; acetonitrile / 14 h / 0 - 20 °C / Inert atmosphere 4.1: potassium <i>tert</i>-butylate / dimethyl sulfoxide / 3.5 h / 10 - 20 °C / Sonication; Inert atmosphere 5.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h / Inert atmosphere 6.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h / 20 °C / Inert atmosphere 7.1: hydrogen; platinum on carbon / ethyl acetate / 0.5 h / 1551.49 Torr / Inert atmosphere
Multi-step reaction with 7 steps 1.1: trichlorophosphate / 5 h / Reflux; Inert atmosphere 2.1: n-butyllithium / hexane; tetrahydrofuran / 0.75 h / 65 °C / Inert atmosphere 2.2: 0.75 h / 65 °C / Inert atmosphere 2.3: 0.5 h / -60 - -40 °C 3.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 1 h / 4 °C / Inert atmosphere 4.1: potassium <i>tert</i>-butylate / dimethyl sulfoxide / 3.5 h / 10 - 20 °C / Sonication; Inert atmosphere 5.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h / Inert atmosphere 6.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h / 20 °C / Inert atmosphere 7.1: hydrogen; platinum on carbon / ethyl acetate / 0.5 h / 1551.49 Torr / Inert atmosphere
References: [1]Scola, Paul M.; Sun, Li-Qiang; Wang, Alan Xiangdong; Chen, Jie; Sin, Ny; Venables, Brian L.; Sit, Sing-Yuen; Chen, Yan; Cocuzza, Anthony; Bilder, Donna M.; D'Andrea, Stanley V.; Zheng, Barbara; Hewawasam, Piyasena; Tu, Yong; Friborg, Jacques; Falk, Paul; Hernandez, Dennis; Levine, Steven; Chen, Chaoqun; Yu, Fei; Sheaffer, Amy K.; Zhai, Guangzhi; Barry, Diana; Knipe, Jay O.; Han, Yong-Hae; Schartman, Richard; Donoso, Maria; Mosure, Kathy; Sinz, Michael W.; Zvyaga, Tatyana; Good, Andrew C.; Rajamani, Ramkumar; Kish, Kevin; Tredup, Jeffrey; Klei, Herbert E.; Gao, Qi; Mueller, Luciano; Colonno, Richard J.; Grasela, Dennis M.; Adams, Stephen P.; Loy, James; Levesque, Paul C.; Sun, Huabin; Shi, Hong; Sun, Lucy; Warner, William; Li, Danshi; Zhu, Jialong; Meanwell, Nicholas A.; McPhee, Fiona [Journal of Medicinal Chemistry, 2014, vol. 57, # 5, p. 1730 - 1752].
[2]Scola, Paul M.; Sun, Li-Qiang; Wang, Alan Xiangdong; Chen, Jie; Sin, Ny; Venables, Brian L.; Sit, Sing-Yuen; Chen, Yan; Cocuzza, Anthony; Bilder, Donna M.; D'Andrea, Stanley V.; Zheng, Barbara; Hewawasam, Piyasena; Tu, Yong; Friborg, Jacques; Falk, Paul; Hernandez, Dennis; Levine, Steven; Chen, Chaoqun; Yu, Fei; Sheaffer, Amy K.; Zhai, Guangzhi; Barry, Diana; Knipe, Jay O.; Han, Yong-Hae; Schartman, Richard; Donoso, Maria; Mosure, Kathy; Sinz, Michael W.; Zvyaga, Tatyana; Good, Andrew C.; Rajamani, Ramkumar; Kish, Kevin; Tredup, Jeffrey; Klei, Herbert E.; Gao, Qi; Mueller, Luciano; Colonno, Richard J.; Grasela, Dennis M.; Adams, Stephen P.; Loy, James; Levesque, Paul C.; Sun, Huabin; Shi, Hong; Sun, Lucy; Warner, William; Li, Danshi; Zhu, Jialong; Meanwell, Nicholas A.; McPhee, Fiona [Journal of Medicinal Chemistry, 2014, vol. 57, # 5, p. 1730 - 1752].
  • 10
  • [ 1028252-13-2 ]
  • [ 1574537-77-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1.1: trichlorophosphate / 5 h / Reflux; Inert atmosphere 2.1: n-butyllithium / hexane; tetrahydrofuran / 0.75 h / 65 °C / Inert atmosphere 2.2: 0.75 h / 65 °C / Inert atmosphere 2.3: 0.5 h / -60 - -40 °C 3.1: diazomethyl-trimethyl-silane / hexane; acetonitrile / 14 h / 0 - 20 °C / Inert atmosphere 4.1: potassium <i>tert</i>-butylate / dimethyl sulfoxide / 3.5 h / 10 - 20 °C / Sonication; Inert atmosphere 5.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h / Inert atmosphere 6.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h / 20 °C / Inert atmosphere 7.1: hydrogenchloride / methanol / 1 h / Reflux; Inert atmosphere 7.2: 2 h / 50 °C / Inert atmosphere 8.1: hydrogen; platinum on carbon / ethyl acetate / 0.6 h / 1551.49 Torr / Inert atmosphere
Multi-step reaction with 8 steps 1.1: trichlorophosphate / 5 h / Reflux; Inert atmosphere 2.1: n-butyllithium / hexane; tetrahydrofuran / 0.75 h / 65 °C / Inert atmosphere 2.2: 0.75 h / 65 °C / Inert atmosphere 2.3: 0.5 h / -60 - -40 °C 3.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 1 h / 4 °C / Inert atmosphere 4.1: potassium <i>tert</i>-butylate / dimethyl sulfoxide / 3.5 h / 10 - 20 °C / Sonication; Inert atmosphere 5.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h / Inert atmosphere 6.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h / 20 °C / Inert atmosphere 7.1: hydrogenchloride / methanol / 1 h / Reflux; Inert atmosphere 7.2: 2 h / 50 °C / Inert atmosphere 8.1: hydrogen; platinum on carbon / ethyl acetate / 0.6 h / 1551.49 Torr / Inert atmosphere
References: [1]Scola, Paul M.; Sun, Li-Qiang; Wang, Alan Xiangdong; Chen, Jie; Sin, Ny; Venables, Brian L.; Sit, Sing-Yuen; Chen, Yan; Cocuzza, Anthony; Bilder, Donna M.; D'Andrea, Stanley V.; Zheng, Barbara; Hewawasam, Piyasena; Tu, Yong; Friborg, Jacques; Falk, Paul; Hernandez, Dennis; Levine, Steven; Chen, Chaoqun; Yu, Fei; Sheaffer, Amy K.; Zhai, Guangzhi; Barry, Diana; Knipe, Jay O.; Han, Yong-Hae; Schartman, Richard; Donoso, Maria; Mosure, Kathy; Sinz, Michael W.; Zvyaga, Tatyana; Good, Andrew C.; Rajamani, Ramkumar; Kish, Kevin; Tredup, Jeffrey; Klei, Herbert E.; Gao, Qi; Mueller, Luciano; Colonno, Richard J.; Grasela, Dennis M.; Adams, Stephen P.; Loy, James; Levesque, Paul C.; Sun, Huabin; Shi, Hong; Sun, Lucy; Warner, William; Li, Danshi; Zhu, Jialong; Meanwell, Nicholas A.; McPhee, Fiona [Journal of Medicinal Chemistry, 2014, vol. 57, # 5, p. 1730 - 1752].
[2]Scola, Paul M.; Sun, Li-Qiang; Wang, Alan Xiangdong; Chen, Jie; Sin, Ny; Venables, Brian L.; Sit, Sing-Yuen; Chen, Yan; Cocuzza, Anthony; Bilder, Donna M.; D'Andrea, Stanley V.; Zheng, Barbara; Hewawasam, Piyasena; Tu, Yong; Friborg, Jacques; Falk, Paul; Hernandez, Dennis; Levine, Steven; Chen, Chaoqun; Yu, Fei; Sheaffer, Amy K.; Zhai, Guangzhi; Barry, Diana; Knipe, Jay O.; Han, Yong-Hae; Schartman, Richard; Donoso, Maria; Mosure, Kathy; Sinz, Michael W.; Zvyaga, Tatyana; Good, Andrew C.; Rajamani, Ramkumar; Kish, Kevin; Tredup, Jeffrey; Klei, Herbert E.; Gao, Qi; Mueller, Luciano; Colonno, Richard J.; Grasela, Dennis M.; Adams, Stephen P.; Loy, James; Levesque, Paul C.; Sun, Huabin; Shi, Hong; Sun, Lucy; Warner, William; Li, Danshi; Zhu, Jialong; Meanwell, Nicholas A.; McPhee, Fiona [Journal of Medicinal Chemistry, 2014, vol. 57, # 5, p. 1730 - 1752].
  • 11
  • [ 1028252-13-2 ]
  • [ 1028252-15-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: trichlorophosphate / 5 h / Reflux; Inert atmosphere 2.1: n-butyllithium / hexane; tetrahydrofuran / 0.75 h / 65 °C / Inert atmosphere 2.2: 0.75 h / 65 °C / Inert atmosphere 2.3: 0.5 h / -60 - -40 °C 3.1: diazomethyl-trimethyl-silane / hexane; acetonitrile / 14 h / 0 - 20 °C / Inert atmosphere 4.1: potassium <i>tert</i>-butylate / dimethyl sulfoxide / 3.5 h / 10 - 20 °C / Sonication; Inert atmosphere
Multi-step reaction with 4 steps 1.1: trichlorophosphate / 5 h / Reflux; Inert atmosphere 2.1: n-butyllithium / hexane; tetrahydrofuran / 0.75 h / 65 °C / Inert atmosphere 2.2: 0.75 h / 65 °C / Inert atmosphere 2.3: 0.5 h / -60 - -40 °C 3.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 1 h / 4 °C / Inert atmosphere 4.1: potassium <i>tert</i>-butylate / dimethyl sulfoxide / 3.5 h / 10 - 20 °C / Sonication; Inert atmosphere
References: [1]Scola, Paul M.; Sun, Li-Qiang; Wang, Alan Xiangdong; Chen, Jie; Sin, Ny; Venables, Brian L.; Sit, Sing-Yuen; Chen, Yan; Cocuzza, Anthony; Bilder, Donna M.; D'Andrea, Stanley V.; Zheng, Barbara; Hewawasam, Piyasena; Tu, Yong; Friborg, Jacques; Falk, Paul; Hernandez, Dennis; Levine, Steven; Chen, Chaoqun; Yu, Fei; Sheaffer, Amy K.; Zhai, Guangzhi; Barry, Diana; Knipe, Jay O.; Han, Yong-Hae; Schartman, Richard; Donoso, Maria; Mosure, Kathy; Sinz, Michael W.; Zvyaga, Tatyana; Good, Andrew C.; Rajamani, Ramkumar; Kish, Kevin; Tredup, Jeffrey; Klei, Herbert E.; Gao, Qi; Mueller, Luciano; Colonno, Richard J.; Grasela, Dennis M.; Adams, Stephen P.; Loy, James; Levesque, Paul C.; Sun, Huabin; Shi, Hong; Sun, Lucy; Warner, William; Li, Danshi; Zhu, Jialong; Meanwell, Nicholas A.; McPhee, Fiona [Journal of Medicinal Chemistry, 2014, vol. 57, # 5, p. 1730 - 1752].
[2]Scola, Paul M.; Sun, Li-Qiang; Wang, Alan Xiangdong; Chen, Jie; Sin, Ny; Venables, Brian L.; Sit, Sing-Yuen; Chen, Yan; Cocuzza, Anthony; Bilder, Donna M.; D'Andrea, Stanley V.; Zheng, Barbara; Hewawasam, Piyasena; Tu, Yong; Friborg, Jacques; Falk, Paul; Hernandez, Dennis; Levine, Steven; Chen, Chaoqun; Yu, Fei; Sheaffer, Amy K.; Zhai, Guangzhi; Barry, Diana; Knipe, Jay O.; Han, Yong-Hae; Schartman, Richard; Donoso, Maria; Mosure, Kathy; Sinz, Michael W.; Zvyaga, Tatyana; Good, Andrew C.; Rajamani, Ramkumar; Kish, Kevin; Tredup, Jeffrey; Klei, Herbert E.; Gao, Qi; Mueller, Luciano; Colonno, Richard J.; Grasela, Dennis M.; Adams, Stephen P.; Loy, James; Levesque, Paul C.; Sun, Huabin; Shi, Hong; Sun, Lucy; Warner, William; Li, Danshi; Zhu, Jialong; Meanwell, Nicholas A.; McPhee, Fiona [Journal of Medicinal Chemistry, 2014, vol. 57, # 5, p. 1730 - 1752].
  • 13
  • [ 1028252-13-2 ]
  • [ 630423-36-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: trichlorophosphate / 5 h / Reflux; Inert atmosphere 2.1: n-butyllithium / hexane; tetrahydrofuran / 0.75 h / 65 °C / Inert atmosphere 2.2: 0.75 h / 65 °C / Inert atmosphere 2.3: 0.5 h / -60 - -40 °C 3.1: diazomethyl-trimethyl-silane / hexane; acetonitrile / 14 h / 0 - 20 °C / Inert atmosphere
Multi-step reaction with 3 steps 1.1: trichlorophosphate / 5 h / Reflux; Inert atmosphere 2.1: n-butyllithium / hexane; tetrahydrofuran / 0.75 h / 65 °C / Inert atmosphere 2.2: 0.75 h / 65 °C / Inert atmosphere 2.3: 0.5 h / -60 - -40 °C 3.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 1 h / 4 °C / Inert atmosphere
Multi-step reaction with 3 steps 1.1: trichlorophosphate / 5 h / Heating / reflux 1.2: -35 °C / pH 8 2.1: n-butyllithium / tetrahydrofuran; hexanes / 0.75 h / -78 - -65 °C 2.2: 0.67 h / -78 - -65 °C 3.1: methanol; hexanes; acetonitrile / 14 h / 0 - 20 °C
References: [1]Scola, Paul M.; Sun, Li-Qiang; Wang, Alan Xiangdong; Chen, Jie; Sin, Ny; Venables, Brian L.; Sit, Sing-Yuen; Chen, Yan; Cocuzza, Anthony; Bilder, Donna M.; D'Andrea, Stanley V.; Zheng, Barbara; Hewawasam, Piyasena; Tu, Yong; Friborg, Jacques; Falk, Paul; Hernandez, Dennis; Levine, Steven; Chen, Chaoqun; Yu, Fei; Sheaffer, Amy K.; Zhai, Guangzhi; Barry, Diana; Knipe, Jay O.; Han, Yong-Hae; Schartman, Richard; Donoso, Maria; Mosure, Kathy; Sinz, Michael W.; Zvyaga, Tatyana; Good, Andrew C.; Rajamani, Ramkumar; Kish, Kevin; Tredup, Jeffrey; Klei, Herbert E.; Gao, Qi; Mueller, Luciano; Colonno, Richard J.; Grasela, Dennis M.; Adams, Stephen P.; Loy, James; Levesque, Paul C.; Sun, Huabin; Shi, Hong; Sun, Lucy; Warner, William; Li, Danshi; Zhu, Jialong; Meanwell, Nicholas A.; McPhee, Fiona [Journal of Medicinal Chemistry, 2014, vol. 57, # 5, p. 1730 - 1752].
[2]Scola, Paul M.; Sun, Li-Qiang; Wang, Alan Xiangdong; Chen, Jie; Sin, Ny; Venables, Brian L.; Sit, Sing-Yuen; Chen, Yan; Cocuzza, Anthony; Bilder, Donna M.; D'Andrea, Stanley V.; Zheng, Barbara; Hewawasam, Piyasena; Tu, Yong; Friborg, Jacques; Falk, Paul; Hernandez, Dennis; Levine, Steven; Chen, Chaoqun; Yu, Fei; Sheaffer, Amy K.; Zhai, Guangzhi; Barry, Diana; Knipe, Jay O.; Han, Yong-Hae; Schartman, Richard; Donoso, Maria; Mosure, Kathy; Sinz, Michael W.; Zvyaga, Tatyana; Good, Andrew C.; Rajamani, Ramkumar; Kish, Kevin; Tredup, Jeffrey; Klei, Herbert E.; Gao, Qi; Mueller, Luciano; Colonno, Richard J.; Grasela, Dennis M.; Adams, Stephen P.; Loy, James; Levesque, Paul C.; Sun, Huabin; Shi, Hong; Sun, Lucy; Warner, William; Li, Danshi; Zhu, Jialong; Meanwell, Nicholas A.; McPhee, Fiona [Journal of Medicinal Chemistry, 2014, vol. 57, # 5, p. 1730 - 1752].
[3]Current Patent Assignee: BRISTOL MYERS SQUIBB - US2008/119461, 2008, A1.
  • 14
  • [ 1028252-13-2 ]
  • [ 1028252-17-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: trichlorophosphate / 5 h / Reflux; Inert atmosphere 2.1: n-butyllithium / hexane; tetrahydrofuran / 0.75 h / 65 °C / Inert atmosphere 2.2: 0.75 h / 65 °C / Inert atmosphere 2.3: 0.5 h / -60 - -40 °C 3.1: diazomethyl-trimethyl-silane / hexane; acetonitrile / 14 h / 0 - 20 °C / Inert atmosphere 4.1: potassium <i>tert</i>-butylate / dimethyl sulfoxide / 3.5 h / 10 - 20 °C / Sonication; Inert atmosphere 5.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h / Inert atmosphere
Multi-step reaction with 5 steps 1.1: trichlorophosphate / 5 h / Reflux; Inert atmosphere 2.1: n-butyllithium / hexane; tetrahydrofuran / 0.75 h / 65 °C / Inert atmosphere 2.2: 0.75 h / 65 °C / Inert atmosphere 2.3: 0.5 h / -60 - -40 °C 3.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 1 h / 4 °C / Inert atmosphere 4.1: potassium <i>tert</i>-butylate / dimethyl sulfoxide / 3.5 h / 10 - 20 °C / Sonication; Inert atmosphere 5.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / dichloromethane / 16 h / Inert atmosphere
References: [1]Scola, Paul M.; Sun, Li-Qiang; Wang, Alan Xiangdong; Chen, Jie; Sin, Ny; Venables, Brian L.; Sit, Sing-Yuen; Chen, Yan; Cocuzza, Anthony; Bilder, Donna M.; D'Andrea, Stanley V.; Zheng, Barbara; Hewawasam, Piyasena; Tu, Yong; Friborg, Jacques; Falk, Paul; Hernandez, Dennis; Levine, Steven; Chen, Chaoqun; Yu, Fei; Sheaffer, Amy K.; Zhai, Guangzhi; Barry, Diana; Knipe, Jay O.; Han, Yong-Hae; Schartman, Richard; Donoso, Maria; Mosure, Kathy; Sinz, Michael W.; Zvyaga, Tatyana; Good, Andrew C.; Rajamani, Ramkumar; Kish, Kevin; Tredup, Jeffrey; Klei, Herbert E.; Gao, Qi; Mueller, Luciano; Colonno, Richard J.; Grasela, Dennis M.; Adams, Stephen P.; Loy, James; Levesque, Paul C.; Sun, Huabin; Shi, Hong; Sun, Lucy; Warner, William; Li, Danshi; Zhu, Jialong; Meanwell, Nicholas A.; McPhee, Fiona [Journal of Medicinal Chemistry, 2014, vol. 57, # 5, p. 1730 - 1752].
[2]Scola, Paul M.; Sun, Li-Qiang; Wang, Alan Xiangdong; Chen, Jie; Sin, Ny; Venables, Brian L.; Sit, Sing-Yuen; Chen, Yan; Cocuzza, Anthony; Bilder, Donna M.; D'Andrea, Stanley V.; Zheng, Barbara; Hewawasam, Piyasena; Tu, Yong; Friborg, Jacques; Falk, Paul; Hernandez, Dennis; Levine, Steven; Chen, Chaoqun; Yu, Fei; Sheaffer, Amy K.; Zhai, Guangzhi; Barry, Diana; Knipe, Jay O.; Han, Yong-Hae; Schartman, Richard; Donoso, Maria; Mosure, Kathy; Sinz, Michael W.; Zvyaga, Tatyana; Good, Andrew C.; Rajamani, Ramkumar; Kish, Kevin; Tredup, Jeffrey; Klei, Herbert E.; Gao, Qi; Mueller, Luciano; Colonno, Richard J.; Grasela, Dennis M.; Adams, Stephen P.; Loy, James; Levesque, Paul C.; Sun, Huabin; Shi, Hong; Sun, Lucy; Warner, William; Li, Danshi; Zhu, Jialong; Meanwell, Nicholas A.; McPhee, Fiona [Journal of Medicinal Chemistry, 2014, vol. 57, # 5, p. 1730 - 1752].
 

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