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Chemical Structure| 4916-57-8

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Product Citations

Product Citations

Josephine Bicknell ; Sidhaesh A. Agarwal ; Kyle J. Petersen ; Jesus Daniel Loya ; Nicholas Lutz ; Paulina M. Sittinger , et al.

Abstract: Lipophilic aggregation using adamantanes is a widely exploited molecular property in medicinal and materials chemistry. Adamantanes are traditionally installed to molecular units via covalent bonds. However, the noncovalent installation of adamantanes has been relatively underexplored and presents the potential to bring properties associated with adamantanes to molecules without affecting their intrinsic properties (e.g., pharmacophores). Here, we systematically study a series of adamantanecarboxylic acids with varying substitution levels of methyl groups and their cocrystals with bipyridines. Specifically, single-crystal X-ray diffraction shows that while the directionality of single-component adamantanes is notably sensitive to changes in methyl substitution, hydrogen-bonded cocrystals with bipyridines show consistent and robust packing due to π-stacking predominance. Our observations are supported by Hirshfeld surface and energy framework analyses. The applicability of cocrystal formation of adamantanes bearing carboxylic acids was used to generate the first cocrystals of adapalene, an adamantane-bearing retinoid used for treating acne vulgaris. We envisage our study to inspire noncovalent (i.e., cocrystal) installation of adamantanes to generate lipophilic aggregation in multicomponent systems.

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Product Details of [ 4916-57-8 ]

CAS No. :4916-57-8
Formula : C12H12N2
M.W : 184.24
SMILES Code : C1(CCC2=CC=NC=C2)=CC=NC=C1
MDL No. :MFCD00006451
InChI Key :DQRKTVIJNCVZAX-UHFFFAOYSA-N
Pubchem ID :78630

Safety of [ 4916-57-8 ]

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

Computational Chemistry of [ 4916-57-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 12
Fraction Csp3 0.17
Num. rotatable bonds 3
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 56.29
TPSA ?

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

25.78 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.96
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

2.0
Log Po/w (WLOGP)?

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

2.26
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.

1.49
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

3.17
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.18

Water Solubility

Log S (ESOL):?

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

-2.68
Solubility 0.386 mg/ml ; 0.0021 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.

-2.17
Solubility 1.25 mg/ml ; 0.00679 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

-4.98
Solubility 0.00193 mg/ml ; 0.0000105 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.

-6.0 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

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)

1.35

Application In Synthesis of [ 4916-57-8 ]

* 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.

  • Downstream synthetic route of [ 4916-57-8 ]

[ 4916-57-8 ] Synthesis Path-Downstream   1~21

  • 1
  • [ 108-89-4 ]
  • [ 94-36-0 ]
  • [ 1620-55-9 ]
  • [ 4916-57-8 ]
  • [ 3337-46-0 ]
  • 2
  • [ 108-89-4 ]
  • [ 1620-55-9 ]
  • [ 4916-57-8 ]
  • [ 3337-46-0 ]
  • 3
  • [ 4916-57-8 ]
  • zinc hydroxide hydrate [ No CAS ]
  • [ 99-14-9 ]
  • [ 7732-18-5 ]
  • [Zn(tricarballylic acid-2H)(1,2-bis(4-pyridine)ethane)](n)*4nH2O [ No CAS ]
  • 4
  • iron(II) nitrate [ No CAS ]
  • [ 4916-57-8 ]
  • [ 7732-18-5 ]
  • [ 68-04-2 ]
  • [ 1005007-95-3 ]
  • 5
  • [ 4916-57-8 ]
  • [ 940-07-8 ]
  • copper(II) acetate dihydrate [ No CAS ]
  • [ 7732-18-5 ]
  • [ 937021-46-0 ]
  • 6
  • [ 4916-57-8 ]
  • [ 940-07-8 ]
  • [ 5970-45-6 ]
  • [(Zn(pyrazine-2,6-dicarboxylate)(H2O)2)2(μ-1,2-bis(4-pyridyl)ethane]*1.75H2O [ No CAS ]
  • 7
  • [ 67-56-1 ]
  • [ 4916-57-8 ]
  • [ 940-07-8 ]
  • [ 7732-18-5 ]
  • [ 6147-53-1 ]
  • [Co2(pyrazine-2,6-dicarboxylic acid(-2H))2(1,2-bis(4-pyridyl)ethane)(H2O)4]*0.5CH3OH*H2O [ No CAS ]
  • 8
  • [ 4916-57-8 ]
  • [ 940-07-8 ]
  • [ 7732-18-5 ]
  • [ 6147-53-1 ]
  • [Co(pyrazine-2,6-dicarboxylic acid(-2H))(1,2-bis(4-pyridyl)ethane)]*0.125(1,2-bis(4-pyridyl)ethane)*1.75H2O [ No CAS ]
  • 9
  • [ 4916-57-8 ]
  • copper(II) nitrate hexahydrate [ No CAS ]
  • [ 499-49-0 ]
  • Cu(II)(5-methylisophthalate)(1,2-bis(4-pyridyl)ethane)0.5 [ No CAS ]
  • 10
  • [ 4916-57-8 ]
  • zinc(II) nitrate hexahydrate [ No CAS ]
  • [ 610-09-3 ]
  • [Zn2(e,a-cis-1,2-cyclohexanedicarboxylate)2(H2O)(μ-1,2-bis(4-pyridyl)ethane)]*4H2O [ No CAS ]
  • 11
  • [ 4916-57-8 ]
  • [ 499-49-0 ]
  • [ 6046-93-1 ]
  • Cu2(5-methylisophthalic acid(2-))2(1,2-bis(4-pyridyl)-ethane) [ No CAS ]
  • 12
  • [ 4916-57-8 ]
  • [ 23351-91-9 ]
  • [ 6156-78-1 ]
  • [ 1333488-51-9 ]
  • 13
  • [ 4916-57-8 ]
  • cadmium(II) nitrate tetrhydrate [ No CAS ]
  • [ 23351-91-9 ]
  • Cd(1,2-bis(4-pyridyl)ethane)1.5(5-bromoisophthalate) [ No CAS ]
  • 14
  • [ 4916-57-8 ]
  • zinc(II) nitrate hexahydrate [ No CAS ]
  • [ 499-49-0 ]
  • [ 68-12-2 ]
  • [ 1430420-06-6 ]
  • 15
  • [ 4916-57-8 ]
  • [ 499-49-0 ]
  • 3NO3(1-)*Zn(2+)*6H2O [ No CAS ]
  • [ 1198077-38-1 ]
YieldReaction ConditionsOperation in experiment
42% With sodium hydroxide; In ethanol; water; at 130℃; for 72h;pH 5.5;Autoclave; A mixture of Zn(NO3)36H2O (0.2 mmol) and H2mip (0.2 mmol)and bpe (0.2 mmol) were added to 10 ml H2O/EtOH (1:1 volumeratio). The pH value was adjusted to 5.5 with 1.0 mmol L1 NaOHsolution. It was then sealed in a 25 mL Teflon-lined stainless steelautoclave and heated at 130 C for 3 days and then slowly cooled toroom temperature. Colorless block crystals were collected by filtrationand washed with distilled water in 42percent yield based on bpe.Anal. Calcd. for C21H18N2O4Zn (percent): C, 58.96; H, 4.24; N, 6.55. Found(percent): C, 59.12; H, 4.39; N, 6.38. IR (KBr, cm1): 3392(s), 1612(s),1550(s), 1432(s), 1370(s), 1106(w), 726
  • 16
  • zinc perchlorate [ No CAS ]
  • [ 5928-51-8 ]
  • [ 4916-57-8 ]
  • [Zn(1,2-bis(4-pyridyl)ethane)1.5(2-thiophenepropionate)]*ClO4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
A mixture of zinc perchlorate hexahydrate (0.1169 g, 0.3139 mmol), 2-thiophenepropionic acid (0.200 g, 1.2820 mmol), bpa (0.1031 g, 0.5603 mmol) water (30 mL) and ethanol (30 mL). This mixture was stirred for 30 min and stoichiometrically neutralized with sodium hydroxide. This solution was sealed in a polyfluoroethylene-lined stainless steel bomb, heated to 90 C in 6 h and kept at 90 C under autogenous pressure for 72 h. After cooling at a ramp of 0.77 C/h to room temperature, the solution was transferred to a beaker and then suitable single crystals were obtained after a few days and separated by filtration. Elemental analysis for compound 2: Anal. Calc: C25H25ClN3O6SZn: C, 50.35%; H, 4.23%; N, 7.05%. Found: C, 51.93%; H, 4.33%; N, 6.93%.
  • 17
  • zinc perchlorate [ No CAS ]
  • [ 5928-51-8 ]
  • [ 4916-57-8 ]
  • [Zn3(1,2-bis(4-pyridyl)ethane)4(2-thiophenepropionate)4]*(ClO4)2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
A mixture of 2-thiophenepropionic acid (0.0118 g,0.0756 mmol), bpa (0.0135 g, 0.0733 mmol) and of KOH (0.0029 g, 0.0517 mmol) was dissolved in ethanol (10 mL) and stirredfor 30 min resulting in a homogeneous colorless solution; tothis solution was added by slow diffusion 5 mL of an aqueous solutioncontaining zinc perchlorate hexahydrate (0.026 g,0.0698 mmol). Suitable single crystals were obtained after a fewdays and separated by filtration. Elemental analysis for compound3: Anal. Calc. C76H77Cl2N8O16S4Zn3: C, 52.05%; H, 4.43%; N, 6.39%.Found C, 52.01%; H, 4.35% N, 7.07%.
  • 18
  • [ 4916-57-8 ]
  • zinc(II) nitrate hexahydrate [ No CAS ]
  • [ 130-85-8 ]
  • Zn(pamoate)(1,2-bis(4-pyridyl)ethane) [ No CAS ]
  • 19
  • [ 4916-57-8 ]
  • cadmium(II) sulfate octahydrate [ No CAS ]
  • [ 99-14-9 ]
  • [Cd2(hydro(tricarballylate))2(1,2-di(4-pyridyl)ethane)2]n [ No CAS ]
YieldReaction ConditionsOperation in experiment
78% In water; at 80℃; for 72h;High pressure; Sealed tube; CdSO4·8H2O (63 mg, 0.18 mmol), dpe (68 mg, 0.37 mmol) and tricarballylicacid (33 mg, 0.19 mmol) were placed into 5 mL distilled H2Oin a 15 mL screw-cap glass vial. The vial was sealed and heated in an oilbath at 80 C for 72 hrs, whereupon it was cooled slowly to 25 C.Colorless blocks of 1 (66 mg, 78% yield based on Cd) were isolated afterwashing with distilled water and acetone, and drying in air. Anal. Calc.for C36H36Cd2N4O12 1: C, 45.92; H, 3.85; N, 5.95% Found: C, 45.77; H,3.73; N, 5.89%. IR ( ): 3251 (w, br), 1702 (m), 1612 (m), 1579 (s),1426 (w), 1397 (s), 1312 (w), 1258 (w), 1226 (w), 1098 (w), 1018 (w),832 (m), 808 (w), 722 (w), 675 (w) cm-1.
  • 20
  • [ 4916-57-8 ]
  • [ 1071125-59-1 ]
  • C27H18O9*C12H12N2 [ No CAS ]
  • 21
  • [ 4916-57-8 ]
  • cadmium(II) nitrate tetrhydrate [ No CAS ]
  • [ 1050912-62-3 ]
  • [ 7732-18-5 ]
  • [ 33513-42-7 ]
  • [Cd(HL)(1,2-di(4-pyridyl)ethane)•H2O]•H2O•DMF}n [ No CAS ]
YieldReaction ConditionsOperation in experiment
48.5% at 80℃; for 72h;Autoclave; For the complex 1, we mixed 0.1 mmol and 0.0315 g H3L with 0.1 mmol and 0.0308 g Cd(NO3)2•4H2O and 0.1 mmol and 0.0156 g bpy to generate a mixture, and dissolved the obtained mixture into the 6 mL H2O and DMF solution (with the volume rate of 3:3), the above mixed solutions were then kept into the 25 mL stainless steel vessel lined with Teflon. After reaction for 72 hours under the pressure of autogenous at 80C, the above mixtures were cooled slowly to the ambient temperature. Thus, the crystals with block were filtrated, cleaned through utilizing the water and then dried, with 48.5% yield on the basis of H3L. Anal. calcd for the C31H34N3O10Cd, calcd.: N, 5.83 %; H, 4.75 and C, 51.64. Found: N 5.49%, H 4.37 and C 12.54. IR (KBr pellet: cm-1): 439(w), 492(w), 632(m), 696(w), 729(m), 779(m), 812(m), 1009(w), 1070(w), 1092(w), 1254(s), 1372(m), 1414(m), 1552(s), 1605(m), 1672(s), 3400(m).
 

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