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Chemical Structure| 38362-15-1 Chemical Structure| 38362-15-1

Structure of 38362-15-1

Chemical Structure| 38362-15-1

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Product Details of [ 38362-15-1 ]

CAS No. :38362-15-1
Formula : C2HClN2S
M.W : 120.56
SMILES Code : ClC1=NC=NS1
MDL No. :MFCD09743974
InChI Key :RZKVGQCJNANFDR-UHFFFAOYSA-N
Pubchem ID :548032

Safety of [ 38362-15-1 ]

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

Computational Chemistry of [ 38362-15-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 6
Num. arom. heavy atoms 5
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 24.92
TPSA ?

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

54.02 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.46
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

1.72
Log Po/w (WLOGP)?

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

1.19
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.

-0.65
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

2.97
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.

-2.29
Solubility 0.622 mg/ml ; 0.00516 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.

-2.47
Solubility 0.408 mg/ml ; 0.00338 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

-1.49
Solubility 3.91 mg/ml ; 0.0324 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.

-5.81 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

2.0
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<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)

2.48

Application In Synthesis of [ 38362-15-1 ]

* 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 [ 38362-15-1 ]

[ 38362-15-1 ] Synthesis Path-Downstream   1~15

  • 1
  • [ 7552-07-0 ]
  • [ 38362-15-1 ]
  • 2
  • [ 110-89-4 ]
  • [ 38362-15-1 ]
  • [ 90008-96-1 ]
  • 3
  • [ 38362-15-1 ]
  • [ 624-78-2 ]
  • [ 89211-53-0 ]
  • 4
  • [ 38362-15-1 ]
  • [ 75-04-7 ]
  • [ 89125-06-4 ]
  • 5
  • [ 38362-15-1 ]
  • [ 124-40-3 ]
  • [ 53147-88-9 ]
  • 6
  • [ 38362-15-1 ]
  • [ 122684-38-2 ]
  • Sodium; 3-[1,2,4]thiadiazol-5-yl-1-aza-bicyclo[2.2.1]heptane-3-carboxylate [ No CAS ]
  • 7
  • [ 38362-15-1 ]
  • [ 38206-86-9 ]
  • (S)-3-[1,2,4]Thiadiazol-5-yl-1-aza-bicyclo[2.2.2]octane-3-carboxylic acid methyl ester [ No CAS ]
  • 9
  • [ 6313-33-3 ]
  • [ 594-42-3 ]
  • [ 38362-15-1 ]
YieldReaction ConditionsOperation in experiment
EXAMPLE 7 (R,R,)-2-(tert-Butyloxycarbonyl-5-(1,2,4-thiadiazol-5-yl)-2,5-diazabicyclo[2.2.1]heptane The title compound is prepared by the procedure of Example 5 using the product from Example 1, 5-chloro-1,2,4-thiadiazole prepared by the procedure of J. Goerdeler, Chim. Ber., 1957, 90, 182, and potassium carbonate to give 0.94 g of the desired product: [alpha26°D =+175° (c=1.3percent), methyl alcohol.
YieldReaction ConditionsOperation in experiment
EXAMPLE 8 (S,S)-2-(tert-Butyloxycarbonyl)-5-(1,2,4-thiadiazol-5-yl)-2,5-diazabicyclo[2.2.1]heptane The title compound is prepared by the procedure of Example 5 using the product from Example 2, 5-chloro-1,2,4-thiadiazole prepared as above, and potassium carbonate to give 2.4 g of the desired product: [alpha26°D =-190° (c=1.0percent), methyl alcohol.
  • 13
  • [ 38362-15-1 ]
  • [ 57260-71-6 ]
  • [ 1019637-88-7 ]
  • 14
  • [ 38362-15-1 ]
  • C25H36N6O2Si [ No CAS ]
  • C21H22N8OS [ No CAS ]
YieldReaction ConditionsOperation in experiment
Parallel preparation of Examples 145-148: To a set of vials individually containing requisite aryl chloride or bromide (0.063 mmol) and Cs2C03 (51 mg, 0.16 mmol) was added a solution of the piperazine from Scheme C (25 mg, 0.052 mmol) in THF (1 mL). The vials were capped and transferred to a glove box under an atmosphere of nitrogen. To each vial was added chloro(2-dicyclohexylphosphino-2',6'-di-i-propoxy-l,l '- biphenyl)[2-(2-aminoethylphenyl)]palladium(II), methyl-t-butylether adduct (Strem) (2.1 mg, 0.0026 mmol). The vials were capped and heated at 80°C overnight. The vials were cooled to RT and removed from the glove box. To each vial was added water. The mixtures were extracted with CH2C12 and the organic layers were transferred into a new set of vials. The organic layers were dried in vacuo. To each vial was then added THF:MeOH (1 :3, 1 mL) followed by HC1 (4 N in dioxane, 0.20 mL, 0.80 mmol). The vials were capped and the solutions were heated to 70°C for 0.5 h. The solutions were allowed to cool to RT and the solvent was then removed in vacuo. Each crude product was redissolved in 1 mL of DMSO and filtered. The crude products were purified by mass triggered HPLC. Examples 145-146 were purified using the following conditions: [Waters Sunfire C18 column, 5muetaiota, 19x100 mm, gradient 10percent to 60percent MeCN (0.1percent formic acid) in water (0.1 percent formic acid) 50 mL/min, 8 min run time] Examples 147-148 were purified using the following conditions: [Waters XBridge CI 8 column, 5muiotaeta, 19x100 mm, gradient ranges from 10percent initial to 70-76percent MeCN (0.1percent NH4OH) in water (0.1percent NH4OH) 50 mL/min, 8 min run time].
  • 15
  • [ 38362-15-1 ]
  • [ 75-05-8 ]
  • 2-(1,2,4-thiadiazol-5-yl)acetonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
60% With lithium hexamethyldisilazane; In tetrahydrofuran; at 0 - 20℃; A solution of dry MeCN (226 mg, 11 mmol) in dry THF (25 ml) was added LiHIVIDS (5.5 mmol, 5.5 mL) at 0 °C, then the mixture was stirred at 0 °C for 30 mi 5-chloro-1,2,4- thiadiazole (691 mg, 5.5 mmol) in dry THF (5 mL) was added to the mixture at 0 °C, then stirred at rt overnight. The reaction mixture was quenched by H20 (1 mL), and extracted by EA (30 mL X 3), dried with Na2SO4, filtered and dried in vacuo to afford the crude product. Further purification by column chromatography (Si02, 100 g, 200-3 00 m, eluted by PE/EA = 5:1) gave the desired product (410 mg, 60percent) as yellow solid. MS [M+H] calcd for C4H3N35126.0, found 126.0.
 

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