| Identification | Back Directory | [Name]
JH-II-127 | [CAS]
1700693-08-8 | [Synonyms]
JH-II-127
2-anilino-4-methylamino-5-chloropyrrolopyrimidine
2-ANILINO-4-METHYLAMINO-5-CHLOROPYRROLOPYRIMIDINE;JH-II127;JH-II 127
(4-((5-Chloro-4-(methylamino)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholi
(4-((5-chloro-4-(methylamino)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-methoxyphenyl)(morpholino)methanone
[4-[[5-Chloro-4-(methylamino)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-3-methoxyphenyl]-4-morpholinyl-methanone
Methanone, [4-[[5-chloro-4-(methylamino)-7H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-3-methoxyphenyl]-4-morpholinyl- | [Molecular Formula]
C19H21ClN6O3 | [MDL Number]
MFCD28975160 | [MOL File]
1700693-08-8.mol | [Molecular Weight]
416.86 |
| Chemical Properties | Back Directory | [Melting point ]
>166°C (dec.) | [density ]
1.458±0.06 g/cm3(Predicted) | [storage temp. ]
Refrigerator | [solubility ]
DMSO (Slightly), Methanol (Slightly) | [form ]
Solid | [pka]
12.49±0.50(Predicted) | [color ]
White to Pale Beige | [InChI]
1S/C19H21ClN6O3/c1-21-16-15-12(20)10-22-17(15)25-19(24-16)23-13-4-3-11(9-14(13)28-2)18(27)26-5-7-29-8-6-26/h3-4,9-10H,5-8H2,1-2H3,(H3,21,22,23,24,25) | [InChIKey]
HUEKBQXFNHWTQQ-UHFFFAOYSA-N | [SMILES]
Clc1c2c(nc([nH]c2NC)Nc3c(cc(cc3)C(=O)N4CCOCC4)OC)nc1 |
| Hazard Information | Back Directory | [Description]
JH-II-127 is an orally bioavailable inhibitor of wild-type (WT) and mutant forms of leucine-rich repeat kinase 2 (LRRK2). It inhibits WT LRRK2, as well as LRRK2 containing the G2019S and A2016T substitution mutations (IC50s = 6.6, 2.2, and 47.7 nM, respectively), which are present in certain patients with Parkinson’s disease, but not LRRK2 containing both mutations (IC50 = 3,080 nM). JH-II-127 (0.1-0.3 μM) inhibits phosphorylation of the serines at positions 910 and 935 of WT LRRK2 and LRRK2G2019S in vitro. It also inhibits Ser935 phosphorylation in vivo in mouse brain, spleen, and kidney when administered at a dose of 30 mg/kg. | [Uses]
JH-II-127 is a highly potent, selective, and brain penetrant LRRK2 inhibitor. | [in vivo]
JH-II-127 (100 mg/kg; i.p.; single) results in near complete dephosphorylation of Ser935 of LRRK2 in all tissues including brain[1].
1.19 Pharmacokinetic Parameters of JH-II-127 in Wild type male C57BL/6 mice[1]. | matrix | route | Tmax (h) | C0/Cmax (ng/mL) | AUCLast (h?ng/mL) | AUGINF (h?ng/mL) | T1/2 (h) | CL (mL/min/kg) | Vss (L/kg) | | plasma | IV (2 mg/kg) | - | 1604.47 | 532.67 | 535.57 | 0.66 | 62.24 | 1.73 | | plasma | PO (10 mg/kg) | 1 | 802.72 | 3094.58 | 3867.07 | - | - | - | | brain | IV (2 mg/kg) | - | 1343.6 | 239.31 | 246.47 | 0.23 | 135.24 | 1.7 | | brain | PO (10 mg/kg) | 1 | 247.35 | 688.21 | 762.38 | - | - | - | |
| Animal Model: | Wild type male C57BL/6 mice[1]. | | Dosage: | 2 mg/kg (for i.v.); 10 mg/kg (for p.o.); 10, 30, 100 mg/kg (for i.p.) | | Administration: | Intravenous and intraperitoneal injection; oral administration; single. | | Result: | Led to near complete dephosphorylation of Ser935 of LRRK2 in all tissues including brain when at 100 mg/kg of i.p. and near complete inhibition in all tissues at 30 mg/kg but only partial inhibition in brain at the 10 mg/kg dose.
Demonstrated good oral bioavailability.
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| [storage]
Store at -20°C | [References]
[1] JOHN M. HATCHER. Discovery of a Pyrrolopyrimidine (JH-II-127), a Highly Potent, Selective, and Brain Penetrant LRRK2 Inhibitor[J]. ACS Medicinal Chemistry Letters, 2015, 6 5: 584-589. DOI: 10.1021/acsmedchemlett.5b00064 |
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