N-Succinimidyl iodoacetate | SIA Crosslinker | Pyrrolidines

CAS No. :	39028-27-8
Formula :	C₆H₆INO₄
M.W :	283.02
SMILES Code :	O=C(ON1C(CCC1=O)=O)CI
Synonyms :	SIA Crosslinker; Iodoacetic acid N-hydroxysuccinimide ester
MDL No. :	MFCD00058451
InChI Key :	VRDGQQTWSGDXCU-UHFFFAOYSA-N
Pubchem ID :	3299230

Safety of [ 39028-27-8 ]

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

Computational Chemistry of [ 39028-27-8 ] Show Less

Physicochemical Properties

Num. heavy atoms	12
Num. arom. heavy atoms	0
Fraction Csp3	0.5
Num. rotatable bonds	3
Num. H-bond acceptors	4.0
Num. H-bond donors	0.0
Molar Refractivity	50.3
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	63.68 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.32
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	-0.09
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	-0.35
Log P_o/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.	0.43
Log P_o/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	0.78
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	0.42

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.34
Solubility	12.9 mg/ml ; 0.0457 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.	-0.8
Solubility	45.4 mg/ml ; 0.16 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	-1.14
Solubility	20.3 mg/ml ; 0.0718 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	No
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.	-8.09 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	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<0.0
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)	2.39

Application In Synthesis of [ 39028-27-8 ]

* 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 [ 39028-27-8 ]

[ 39028-27-8 ] Synthesis Path-Downstream 1~54

1
[ 6066-82-6 ]
[ 64-69-7 ]
[ 39028-27-8 ]

Yield	Reaction Conditions	Operation in experiment
60%	With diisopropyl-carbodiimide; In ethyl acetate; at 20℃; for 24h;Sealed tube;	A 100-mL flask sealed with a sleeve stopper was charged with N- hydroxysuccinimide (1.15 g, 10 mmol) and iodoacetic acid (1.86 g, 10 mmol). 50 mL of ethyl acetate was added and diisopropylcarbodiimide (1.55 mL, 10 mmol) was added dropwise.The reaction was left stirring at room temperature for 24 h. The mixture was then filtered, the precipitate was washed with a minimum amount of ethyl acetate and dried in vacuo. The solids were dissolved in -50 mL of boiling isopropanol and the solution was transferred into a beaker to initiate crystallization. The crystals were filtered, washed with isopropanol and dried in vacuo to give 1.72 g (60%) of pure product as white crystals. The compound is indefinitely stable at -20 C and should be stored at this temperature. 'H NMR (500 MHz, CDCb) d 4.02 (s, 2H), 2.95 - 2.85 (m, 4H).
30%	With dicyclohexyl-carbodiimide; at 0 - 20℃; for 4h;	On a solution of N-hydroxysuccinimide (12.6 mmol) and dicyclohexylcarbodiimide (20.3 mmol) at 0 C., corresponding acid (6 mmol) was added and allowed to react for 4 hours at room temperature. In the case of compound VIa, a solution of maleic anhydride (10 mmol) and beta-alanine was added in N,N-dimethylformamide, which has been previously made react for 1 hour. After 4 hours, mixture was evaporated at reduced pressure and the crude was dissolved in dichloromethane and washed with water. Organic extracts were dried with anhydrous magnesium sulfate, filtered and evaporated to dryness. Resulting residue was recrystallized to give desired compound. [0112] Using this methodology, and corresponding acid, the following compounds were prepared: Succinimidyl iodoacetate (VIb, 30% yield). 1H NMR (CDCl3) delta ppm: 2.87 (2H, s), 3.96 (1H, s); 13C NMR (CDCl3) delta ppm: -12.47 (1C, s) 25.85 (2C, s) 164.78 (1C, s) 168.78 (2C, s).

References: [1]Organic and Biomolecular Chemistry,2016,vol. 14,p. 7777 - 7791.
[2]Patent: WO2019/168654,2019,A2 .Location in patent: Paragraph 00232; 00234.
[3]Patent: US2013/273581,2013,A1 .Location in patent: Page/Page column 0092; 0111-0112; 0114.
[4]Il Farmaco,1992,vol. 47,p. 1367 - 1383.

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[ 76387-70-7 ]
[ 129365-01-1 ]

References: [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 2755 - 2759.

3
[ 39028-27-8 ]
[ 72198-35-7 ]
[ 74252-23-6 ]

References: [1]Liebigs Annalen der Chemie,1980,p. 416 - 424.

4
[ 39028-27-8 ]
[ 142182-02-3 ]
[ 142182-11-4 ]

References: [1]Il Farmaco,1991,vol. 46,p. 1497 - 1516.

5
[ 39028-27-8 ]
[ 79677-63-7 ]
1-(N-benzyloxycarbonyl-3-iodo-L-tyrosyl)-2-iodoacetylhydrazine [ No CAS ]

References: [1]European Journal of Medicinal Chemistry,1993,vol. 28,p. 297 - 311.

6
[ 39028-27-8 ]
[ 13724-90-8 ]
3-<(2''-iodoacetoamido)ethylthio>-rifamycin [ No CAS ]

References: [1]Il Farmaco,1992,vol. 47,p. 1367 - 1383.

7
[ 39028-27-8 ]
[ 87876-22-0 ]
[ 87876-25-3 ]

References: [1]Liebigs Annalen der Chemie,1983,vol. NO. 9,p. 1533 - 1540.

8
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[ 81035-22-5 ]
[ 81034-80-2 ]