D-Cysteine HCl hydrate | Carboxylic Acids

CAS No. :	207121-46-8
Formula :	C₃H₁₀ClNO₃S
M.W :	175.63
SMILES Code :	O=C(O)[C@H](N)CS.[H]Cl.[H]O[H]
Synonyms :	D-Cysteine hydrochloride hydrate
MDL No. :	MFCD00150051
InChI Key :	QIJRTFXNRTXDIP-YBBRRFGFSA-N
Pubchem ID :	10176341

Safety of [ 207121-46-8 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H315-H319
Precautionary Statements:	P264-P280-P337+P313-P305+P351+P338-P302+P352-P332+P313-P362

Computational Chemistry of [ 207121-46-8 ] Show Less

Physicochemical Properties

Num. heavy atoms	9
Num. arom. heavy atoms	0
Fraction Csp3	0.67
Num. rotatable bonds	2
Num. H-bond acceptors	4.0
Num. H-bond donors	3.0
Molar Refractivity	38.96
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	111.35 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	0.0
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	-2.16
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	0.07
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.	-3.46
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	-0.69
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	-1.25

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	0.56
Solubility	643.0 mg/ml ; 3.66 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Highly soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	0.35
Solubility	395.0 mg/ml ; 2.25 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	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	0.59
Solubility	682.0 mg/ml ; 3.88 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	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.	-8.9 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	3.0
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<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)	1.94

Application In Synthesis of [ 207121-46-8 ]

* 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 [ 207121-46-8 ]

[ 207121-46-8 ] Synthesis Path-Downstream 1~25

1
[ 207121-46-8 ]
[ 1493-27-2 ]
acetyl agent [ No CAS ]
(S)-2-acetylamino-3-(2-nitrophenyl)thiopropionic acid [ No CAS ]

References: [1]Chemical and Pharmaceutical Bulletin,1986,vol. 34,p. 3747 - 3761.

2
[ 64419-24-5 ]
[ 207121-46-8 ]
[ 220541-94-6 ]

Yield	Reaction Conditions	Operation in experiment
66%	In methanol; sodium hydrogencarbonate;	<strong>[207121-46-8]D-cysteine hydrochloride monohydrate</strong> (6.8 g, 38.7 mmol) was added to a solution of 2,4-dihydroxybenzonitrile (3.5 g, 25.9 mmol), prepared as described above, in a mixture of degassed methanol (105 ml) and 0.1 M phosphate buffer, pH 5.95 (70 ml). NaHCO3 (3.25 g, 38.7 mmol) was carefully added and the mixture was stirred at 70 C. under Argon for 54 hours. Volatile components were removed under reduced pressure and the solution was acidified with 1 N HCl to pH 2. The resulting brown precipitate was vacuum filtered and the solid was washed with water (40 ml) and ethanol (20 ml). The crude product was dissolved in saturated NaHCO3 (700 ml) and the aqueous solution washed with ethyl acetate (2200 ml). The aqueous layer was filtered through a fine frit and acidified with 1 N HCl to pH 2. The precipitated product was vacuum filtered. The aqueous layer was extracted with ethyl acetate (4400 ml), the combined organic extracts were dried (Na2SO4) and the solvent was removed in vacuo. The remaining solid was combined with the precipitated product and dried under high vacuum at 40 C. for 12 hours to give 4,5-dihydro-2-(2,4-dihydroxyphenyl)-thiazole-4(S)-carboxylic acid (4.08 g, 66%), mp 266-268 C. (dec) (Ind. J. Chem., Vol. 15B, Kishore et al, pages 255-257 (1977) for (L)-isomer: 261-262 C.). 1H NMR (300 MHz, DMSO-d6) delta3.61 (m, 2 H), 5.38 (dd, 1 H, J=7.2/9.4 Hz), 6.31 (d, 1 H, J=2.3 Hz), 6.38 (dd, 1 H, J=2.3/8.6 Hz), 7.25 (d, 1 H, J=8.6 Hz), 10.25 (br s, 1 H), 12.60 (br s, 1 H), 13.15 (br s, 1 H). Anal. Calc. For C10H9NO4S: C, 50.20; H, 3.79; N, 5.85. Found: C, 50.13; H, 3.82; N, 5.85.

References: [1]Patent: US2003/83349,2003,A1 .

3
[ 250234-86-7 ]
[ 207121-46-8 ]
(3S)-8-(3-methylbutylidene)-1-thia-4-azaspiro[4.5]decane-3-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium acetate; In ethanol; water;	Referential Example 3 In a mixture of 3.5 ml of ethanol and 1.5 ml of water are dissolved 1.0 g of 4-(3-methylbutylidene)-1-cyclohexanone, 1.1 g of <strong>[207121-46-8]D-cysteine hydrochloride monohydrate</strong> and 0.52 g of sodium acetate. The resulting solution is stirred at ambient temperature for 2 hours. Water is added to the reaction mixture and the deposited crystal is collected by filtration. Thus, 0.81 g of (3S)-8-(3-methylbutylidene)-1-thia-4-azaspiro[4.5]decane-3-carboxylic acid is obtained as a colorless crystalline product. NMR (CDCl3) delta: 0.87 (6H,d,J=6.1Hz), 1.2-2.8 (11H,m),3.1-3.6 (2H,m), 4.34 (1H,t,J=7.8Hz), 5.19 (1H,t,J=7.1Hz), 6.9-7.5 (2H,bs)

References: [1]Patent: EP1127869,2001,A1 .

4
[ 932-35-4 ]
[ 207121-46-8 ]
2-(3'-hydroxypyrid-2'-yl)-2-thiazoline-4-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 7 The isomeric 2-(3'-hydroxy-pyrid-2'-yl)-2-thiazoline-4-carboxylic acid is obtained by reacting 0.526 g (4.4 mmol) of 3-hydroxy-picolinic acid nitrile with 1.0 g (5.7 mmol) of <strong>[207121-46-8]D-cysteine hydrochloride monohydrate</strong> (FLUKA puriss.) in a manner analogous to that described in Example 6.

References: [1]Patent: US4406905,1983,A .

5
[ 272792-00-4 ]
[ 207121-46-8 ]
[ 1254475-18-7 ]