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Chemical Structure| 315203-39-5 Chemical Structure| 315203-39-5

Structure of 315203-39-5

Chemical Structure| 315203-39-5

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Product Details of [ 315203-39-5 ]

CAS No. :315203-39-5
Formula : C19H20Cl2N4
M.W : 375.30
SMILES Code : NC1=CC2=C(C=C1)C(CN3CCCC3)=NN2CC4=C(Cl)C=CC=C4Cl
MDL No. :MFCD03093364
InChI Key :RPIVQHHCHQAMGO-UHFFFAOYSA-N
Pubchem ID :10499688

Safety of [ 315203-39-5 ]

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

Computational Chemistry of [ 315203-39-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 25
Num. arom. heavy atoms 15
Fraction Csp3 0.32
Num. rotatable bonds 4
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 108.8
TPSA ?

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

47.08 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.02
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

4.1
Log Po/w (WLOGP)?

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

4.04
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.

3.69
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

4.05
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.78

Water Solubility

Log S (ESOL):?

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

-4.93
Solubility 0.00441 mg/ml ; 0.0000118 mol/l
Class?

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

Moderately soluble
Log S (Ali)?

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

-4.79
Solubility 0.00602 mg/ml ; 0.0000161 mol/l
Class?

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

Moderately 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

-6.67
Solubility 0.0000797 mg/ml ; 0.000000212 mol/l
Class?

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

Poorly 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

Yes
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

Yes
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

Yes
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

Yes
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

Yes
Log Kp (skin permeation)?

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

-5.68 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

1.0 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<2.0
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)

2.73

Application In Synthesis of [ 315203-39-5 ]

* 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 [ 315203-39-5 ]

[ 315203-39-5 ] Synthesis Path-Downstream   1~14

  • 1
  • [ 372963-38-7 ]
  • [ 315203-39-5 ]
YieldReaction ConditionsOperation in experiment
69% With iron(III) chloride hexahydrate; pyrographite; hydrazine hydrate; In methanol; at 100℃; for 2h;Sealed tube; To an oven dried pressure tube with stir bar was added indazole8 (18 mg, 0.044 mmol) and MeOH (5 mL). FeCl36H2O (25 mol%,2.6 mg), hydrazine monohydrate solution (65% active hydrazine,0.05 mL, 0.7 mmol), and activated charcoal (20 mg) were added,the tube was capped tightly, and the reaction was stirred at 100C for 2 h. A sample aliquot was taken from the reaction, concentratedunder reduced pressure, dissolved in a minimal amount ofHPLC grade MeCN, and analyzed with LCMS to confirm reactioncompletion. The reaction was filtered, the charcoal and filteredsolids were washed with MeOH (10 mL), and the filtrate was concentratedunder reduced pressure to give crude material that wasdry loaded using silica onto a 5 g silica column and purified withflash chromatography (0-20% MeOH/DCM) to give 9 (11.5 mg) asa white solid in 69% yield. LC-MS tR = 1.44 min (CharacterizationMethod A); m/z = 374.95 (M+H+); 1H NMR (300 MHz, CDCl3) d =7.57 (d, J = 8.5 Hz, 1H), 7.37 (d, J = 8.2 Hz, 2H), 7.31-7.20 (s, 1H),6.63 (d, J = 8.8 Hz, 1H), 6.58 (s, 1H), 5.63 (s, 2H), 4.29 (s, 2H), 3.96(br. s., 2H), 3.13 (br. s., 4H), 1.84 (br. s., 4H); 13C NMR (75 MHz,CDCl3) d = 146.5, 142.5, 137.0, 131.6, 130.3, 128.8, 121.0, 117.7,113.7, 92.2, 52.3, 48.5, 48.2, 23.9.
  • 2
  • [ 7693-46-1 ]
  • [ 315203-39-5 ]
  • [1-(2,6-dichloro-benzyl)-3-pyrrolidin-1-ylmethyl-1<i>H</i>-indazol-6-yl]-carbamic acid 4-nitro-phenyl ester [ No CAS ]
  • 6
  • [ 315203-39-5 ]
  • RWJ 58259 [ No CAS ]
  • 7
  • [ 315203-39-5 ]
  • {3-benzylcarbamoyl-3-[2-{3-[1-(2,6-dichloro-benzyl)-3-pyrrolidin-1-ylmethyl-1<i>H</i>-indazol-6-yl]-ureido}-3-(3,4-difluoro-phenyl)-propionylamino]-propyl}-carbamic acid <i>tert</i>-butyl ester [ No CAS ]
  • 8
  • [ 315203-39-5 ]
  • [ 1416442-76-6 ]
  • 9
  • [ 315203-39-5 ]
  • [ 1416442-78-8 ]
  • 10
  • [ 315203-39-5 ]
  • Nα-[(2S)-1-(3-(1-(2,6-dichlorobenzyl)-3-(pyrrolidin-1-ylmethyl)-1H-indazol-6-yl)ureido)-3-phenylpropan-2-yl]lysine benzyl amide trihydrochloride [ No CAS ]
  • 11
  • [ 32315-10-9 ]
  • [ 315203-39-5 ]
  • C20H18Cl2N4O [ No CAS ]
  • 12
  • [ 32315-10-9 ]
  • [ 315203-39-5 ]
  • [ 315203-40-8 ]
  • {3-benzylcarbamoyl-3-[2-{3-[1-(2,6-dichloro-benzyl)-3-pyrrolidin-1-ylmethyl-1<i>H</i>-indazol-6-yl]-ureido}-3-(3,4-difluoro-phenyl)-propionylamino]-propyl}-carbamic acid <i>tert</i>-butyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
Part 1: Coupling reaction. Aniline 9 (40 mg, 0.11 mmol) wasadded to an oven-dried round bottom flask with stir bar and sealedunder nitrogen, then anhydrous THF (16 mL) was added. The solutionwas cooled in a NaCl/H2O bath (5 C) for 15 min., and thenboth DMAP (34.6 mg, 0.282 mmol) and triphosgene (12 mg, 0.04mmol) were added consecutively. Immediately the reactionbecame a light orange suspension. The reaction was stirred at -5C for 8 min., and then amine 4 (35 mg, 0.071 mmol) was addedand the reaction was stirred at 5 C for 1 h, then for an additional1 h while warming to room temperature. A sample aliquot wastaken from the reaction, concentrated under reduced pressure, dissolvedin a minimal amount of HPLC grade MeCN, and analyzedwith LC-MS to confirm reaction completion. The reaction was concentratedunder reduced pressure to give crude material 10 thatcould be either carried onto the next reaction without purification,or triturated with DCM/hexanes (1:1) to provide purer material.
  • 13
  • [ 315203-39-5 ]
  • N-((S)-4-(benzylamino)-3-((S)-2-(3-(1-(2,6-dichlorobenzyl)-3-(pyrrolidin-1-ylmethyl)-1H-indazol-6-yl)ureido)-3-(3,4-difluorophenyl)propanamido)-4-oxobutyl)pent-4-ynamide [ No CAS ]
  • 14
  • [ 315203-39-5 ]
  • RWJ-58259 [ No CAS ]
 

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