| Identification | Back Directory | [Name]
(2S,4R)-1-((S)-2-amino-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide hydrochloride | [CAS]
1448189-80-7 | [Synonyms]
ULM-1
141003
CS-2718
ULM-1 HCl
MDK7526 HCl
VHL Ligand 1
MDK-7526;ULM-1
VH032 amine HCl
ULM-1(MDK7526HCL)
Protein degrader 1
PROTAC-VHL-Ligand 1
VHL Ligand 1 HCl salt
ULM-1HCl (MDK7526 HCl
Protein degrader 1 HCl)
VH032-NH2 hydrochloride
VHL ligand 1 hydrochlorid
(S,R,S)-AHPC hydrochloride
MDK7526(Protein degrader 1)
VHL Ligand 1 (hydrochloride)
VH032 desacetyl Hydrochloride
Degradation Inducing Moiety A
PROTAC-VHL-ligand hydrochloride
(S,R,S)-AHPC hydrochloride >=97%
Protein degrader 1 (hydrochloride)
(2S,4R)-1-((S)-2-Amino-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine
(4R)-3-Methyl-L-valyl-4-hydroxy-N-[[4-(4-methyl-5-thiazolyl)phenyl]methyl]-L-prolinamide hydrochloride
(2S,4R)-1-((S)-2-amino-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide hydrochloride
(2S,4R)-1-[(2S)-2-amino-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide hydrochloride
(2S,4R)-1-((S)-2-amino-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide hydrochloride ISO 9001：2015 REACH
PROTEIN DEGRADER 1 HYDROCHLORIDE; MDK7526 HCL; MDK7526; MDK-7526; MDK 7526; VHL LIGAND 1; ULM-1; VH032 DESACETYL HYDROCHLORIDE; VH032 AMINE HCL; DEGRADATION INDUCING MOIETY A; | [EINECS(EC#)]
604-604-1 | [Molecular Formula]
C22H31ClN4O3S | [MOL File]
1448189-80-7.mol | [Molecular Weight]
467.03 |
| Chemical Properties | Back Directory | [storage temp. ]
2-8°C | [solubility ]
DMF: 20 mg/ml; DMSO: 20 mg/ml; Ethanol: 20 mg/ml; PBS (pH 7.2): 10 mg/ml | [form ]
A crystalline solid | [color ]
White to yellow | [Appearance]
yellow-brown powder | [InChIKey]
JYRTWGCWUBURGU-XIMRXPCLNA-N | [SMILES]
C([C@@H]1C[C@@H](O)CN1C(=O)[C@@H](N)C(C)(C)C)(=O)NCC1C=CC(C2=C(N=CS2)C)=CC=1.Cl |&1:1,3,9,r| |
| Hazard Information | Back Directory | [Description]
VHL ligand 1 is a building block in the synthesis of proteolysis-targeting chimera technologies (PROTACs).1 It is the von Hippel-Lindau (VHL) E3 ligase binding portion of some VHL-based PROTACs, including BET PROTAC MZ1 (Item No. 21622).2 | [Uses]
(S,R,S)-AHPC (HCl salt) is a ligand used in the recruitment of the von Hippel-Lindau (VHL) protein for targeted protein degradation and PROTAC (proteolysis-targeting chimeras) technology. This (S,R,S) conformation is the active variant, and (S,S,S) is the inactive derivative (cat#901487) used as a negative control. | [reaction suitability]
reagent type: ligand | [Synthesis]
Step 4: Synthesis of (2S,4R)-1-((S)-2-amino-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide hydrochloride (ULM-1)
To a stirred solution of tert-butyl N-[(2S)-1-[(2S,4R)-4-hydroxy-2-({[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl}carbamoyl)pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]carbamate (12 g, 22.61 mmol) in dioxane (20 mL) at room temperature was added to a dioxane solution of hydrogen chloride (4N, 80 mL). The reaction mixture was stirred at room temperature for 2 h. LC-MS monitoring showed formation of the target product. The precipitated solid was collected by filtration to give ULM-1 in 48% yield as a yellow solid.
1H NMR (400 MHz, CD3OD): δ 9.84-9.82 (s, 1H), 7.58-7.54 (m, 4H), 4.71-4.41 (m, 4H), 4.13-4.08 (m, 1H), 3.86-3.71 (m, 2H), 3.36 (s, 1H), 2.60-2.58 (s, 3H), 2.35-2.07 (m, 2H), 1.19-1.12 (m, 9H).
LC-MS (ES+): m/z 431.11 [MH+], tR = 0.73 min (run time 2.0 min). | [IC 50]
VHL | [References]
[1] Patent: WO2016/118666, 2016, A1. Location in patent: Paragraph 0398; 0399; 0411; 0412
[2] Patent: US2017/8904, 2017, A1. Location in patent: Paragraph 0376; 0382
[3] Patent: US2017/281784, 2017, A1. Location in patent: Paragraph 0191; 0197
[4] Patent: US2018/125821, 2018, A1
[5] Patent: WO2014/108452, 2014, A1. Location in patent: Page/Page column 50 |
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