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Chemical Structure| 6708-37-8 Chemical Structure| 6708-37-8

Structure of 6708-37-8

Chemical Structure| 6708-37-8

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Product Details of [ 6708-37-8 ]

CAS No. :6708-37-8
Formula : C10H10O3
M.W : 178.18
SMILES Code : O=C1OC(C2C3C=CC(CC3)C21)=O
MDL No. :MFCD06796361
InChI Key :YIHKILSPWGDWPR-UHFFFAOYSA-N
Pubchem ID :220977

Safety of [ 6708-37-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 6708-37-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 0
Fraction Csp3 0.6
Num. rotatable bonds 0
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 44.85
TPSA ?

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

43.37 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.5
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

1.2
Log Po/w (WLOGP)?

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

0.9
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.

1.92
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

1.2
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.34

Water Solubility

Log S (ESOL):?

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

-1.7
Solubility 3.55 mg/ml ; 0.0199 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-1.71
Solubility 3.5 mg/ml ; 0.0196 mol/l
Class?

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

Very 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

-0.78
Solubility 29.9 mg/ml ; 0.168 mol/l
Class?

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

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

No
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.

-6.53 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

1.0
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

3.0 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<1.0
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)

3.64

Application In Synthesis of [ 6708-37-8 ]

* 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.

  • Upstream synthesis route of [ 6708-37-8 ]

[ 6708-37-8 ] Synthesis Path-Upstream   1~2

  • 1
  • [ 108-31-6 ]
  • [ 1165952-91-9 ]
  • [ 6708-37-8 ]
YieldReaction ConditionsOperation in experiment
88% at 60℃; for 3 h; Schlenk technique; Inert atmosphere; Reflux 1,3-Cyclohexadiene (36.40 g, 0.4543 mol) and maleic anhydride (29.10 g, 0.2968 mol) were charged to a 250 mL Schlenk flask containing a magnetic stir bar. The Schlenk flask was then fitted with a condenser and placed under dynamic nitrogen after which the flask was heated to 60° C. Within five minutes of heating all of the maleic anhydride had dissolved to form a bright yellow colored solution with concomitant refluxing of 1,3-cyclohexadiene followed by subsequent solidification of the charge to light yellow colored crystals within 25 minutes following the beginning of heating. The reaction was allowed to continue for a total of three hours after which unreacted 1,3-cyclohexadiene was removed via reduced pressure. Crystalline yellow solid was then recrystallized from 200 proof ethanol and the Diels Alder adduct 5 was obtained as a crystalline white solid 46.54 g (88percent yield). 1H NMR (700 MHz, CDCl3, 25° C.): δ=1.43 (d, J=7.7 Hz, 2H, CH2 cyclohexene), 1.62 (d, J=7.7 Hz, 2H, CH2 cyclohexene), 3.15 (t, 2H, —CH—CO)), 3.25 (m, 2H, methine cyclohexene), 6.33 (dd, J=7.7 Hz, 4.2 Hz, 3.5 Hz, 2H, —CH═CH—). 13C NMR (700 MHz, CDCl3, 25° C.): δ=22.98 (CH2, cyclohexene), 31.63 (methine cyclohexene), 44.77 (—CH—CO), 133.05 (—C═C—), 172.83 (CO). IR: 3055 cm−1 (═C—H stretching), 2980-2870 cm−1 (CH stretching), 1867-1766 cm−1 (C═O stretching), 1462-1322 cm−1 (CH bending), 1238-1177 cm−1 (C—O stretching), 1075-684 cm−1 (CH out of plane bending). LC-MS: m/z 179.07 (M+), 151.07, 147, 133, 123, 105, 79, 73.
References: [1] Patent: US2013/324688, 2013, A1, . Location in patent: Paragraph 0039; 0041; 0085-0087.
[2] Heterocycles, 2006, vol. 68, # 11, p. 2259 - 2267.
[3] Journal of the Chemical Society, 1929, p. 906.
[4] Justus Liebigs Annalen der Chemie, 1928, vol. 460, p. 98[5] Justus Liebigs Annalen der Chemie, 1930, vol. 478, p. 141.
[6] Chemische Berichte, 1980, vol. 113, # 5, p. 1663 - 1690.
[7] Chemische Berichte, 1980, vol. 113, # 5, p. 1663 - 1690.
[8] Patent: US2018/272325, 2018, A1, . Location in patent: Paragraph 0139-0141.
[9] Patent: US2018/273561, 2018, A1, . Location in patent: Paragraph 0137; 0138; 0147; 0148.
  • 2
  • [ 108-30-5 ]
  • [ 1165952-91-9 ]
  • [ 6708-37-8 ]
References: [1] Australian Journal of Chemistry, 1981, vol. 34, # 8, p. 1719 - 1727.
 

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