Synonym
PF-06442609; PF 06442609; PF06442609; PF-6442609; PF 6442609; PF6442609.
IUPAC/Chemical Name
2-((S)-1-(4-fluoro-2-((R)-1,1,1-trifluoropropan-2-yl)phenoxy)propan-2-yl)-7-(4-methyl-1H-imidazol-1-yl)-3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,6-dione
InChi Key
XZFBQMFLEPCQCW-JKSUJKDBSA-N
InChi Code
InChI=1S/C24H24F4N4O3/c1-14-11-30(13-29-14)19-5-6-20-23(34)31(8-9-32(20)22(19)33)15(2)12-35-21-7-4-17(25)10-18(21)16(3)24(26,27)28/h4-7,10-11,13,15-16H,8-9,12H2,1-3H3/t15-,16+/m0/s1
SMILES Code
O=C1C(N2CCN1[C@@H](C)COC3=CC=C(F)C=C3[C@@H](C)C(F)(F)F)=CC=C(N4C=C(C)N=C4)C2=O
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
PF-06442609 is a potent, metabolic stable γ-secretase modulators (GSMs) for Alzheimer's disease (AD).
In vivo activity:
In vivo efficacy of 21 (PF-06442609) was evaluated in a guinea pig time-course experiment. Compound 21 was administered orally at a dose of 60 mg/kg, and Aβ42, Aβ40, Aβ38, and Aβ-total were measured along with compound exposure at time-points ranging from 1 to 24 h. Sustained reductions of both Aβ42 and Aβ40 were achieved, while Aβ-total remained relatively unchanged (Figure (Figure1).1). A 41% reduction of brain Aβ42 was observed at the 3 h time-point for the 60 mg/kg dose, whereas Aβ38 was increased 46% in accordance with the typical profile of a GSM.
Reference: ACS Med Chem Lett. 2015 Apr 3;6(5):596-601. https://pubmed.ncbi.nlm.nih.gov/26005540/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
492.47
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
Pettersson M, Johnson DS, Humphrey JM, Butler TW, Am Ende CW, Fish BA, Green ME, Kauffman GW, Mullins PB, O'Donnell CJ, Stepan AF, Stiff CM, Subramanyam C, Tran TP, Vetelino BC, Yang E, Xie L, Bales KR, Pustilnik LR, Steyn SJ, Wood KM, Verhoest PR. Design of Pyridopyrazine-1,6-dione γ-Secretase Modulators that Align Potency, MDR Efflux Ratio, and Metabolic Stability. ACS Med Chem Lett. 2015 Apr 3;6(5):596-601. doi: 10.1021/acsmedchemlett.5b00070. PMID: 26005540; PMCID: PMC4434474.
In vivo protocol:
Pettersson M, Johnson DS, Humphrey JM, Butler TW, Am Ende CW, Fish BA, Green ME, Kauffman GW, Mullins PB, O'Donnell CJ, Stepan AF, Stiff CM, Subramanyam C, Tran TP, Vetelino BC, Yang E, Xie L, Bales KR, Pustilnik LR, Steyn SJ, Wood KM, Verhoest PR. Design of Pyridopyrazine-1,6-dione γ-Secretase Modulators that Align Potency, MDR Efflux Ratio, and Metabolic Stability. ACS Med Chem Lett. 2015 Apr 3;6(5):596-601. doi: 10.1021/acsmedchemlett.5b00070. PMID: 26005540; PMCID: PMC4434474.
1: Pettersson M, Johnson DS, Humphrey JM, Butler TW, Am Ende CW, Fish BA, Green
ME, Kauffman GW, Mullins PB, O'Donnell CJ, Stepan AF, Stiff CM, Subramanyam C,
Tran TP, Vetelino BC, Yang E, Xie L, Bales KR, Pustilnik LR, Steyn SJ, Wood KM,
Verhoest PR. Design of Pyridopyrazine-1,6-dione γ-Secretase Modulators that Align
Potency, MDR Efflux Ratio, and Metabolic Stability. ACS Med Chem Lett. 2015 Apr
3;6(5):596-601. doi: 10.1021/acsmedchemlett.5b00070. eCollection 2015 May 14.
PubMed PMID: 26005540; PubMed Central PMCID: PMC4434474.
2: Johnson, D. S., & Pettersson, M. (2017). γ-secretase modulators as Aβ42-lowering pharmacological agents to treat Alzheimer’s disease. Alzheimer’s Disease II, 87-118.
