Structure of 4916-57-8
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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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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Purchased from AmBeed: 106685-40-9 ; 828-51-3 ; 14670-94-1 ; 2632-99-7 ; 4916-57-8 ; 15291-66-4
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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 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
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 |
25.78 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.96 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.0 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.26 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.49 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.17 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.18 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.68 |
Solubility | 0.386 mg/ml ; 0.0021 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.17 |
Solubility | 1.25 mg/ml ; 0.00679 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.98 |
Solubility | 0.00193 mg/ml ; 0.0000105 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
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) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.0 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.35 |
* 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.
Yield | Reaction Conditions | Operation 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 |
Yield | Reaction Conditions | Operation 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%. |
Yield | Reaction Conditions | Operation 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%. |
Yield | Reaction Conditions | Operation 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. |
Yield | Reaction Conditions | Operation 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). |
A139358 [30532-36-6]
3-(Pyridin-4-yl)propan-1-amine
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