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Details

Stereochemistry ACHIRAL
Molecular Formula C23H22ClN7O3
Molecular Weight 479.919
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PF-06273340

SMILES

CC(C)(CO)N1C=C(C(=O)C2=CN=CC(NC(=O)CC3=NC=C(Cl)C=C3)=C2)C4=CN=C(N)N=C14

InChI

InChIKey=BPIWZDNVMQQBQX-UHFFFAOYSA-N
InChI=1S/C23H22ClN7O3/c1-23(2,12-32)31-11-18(17-10-28-22(25)30-21(17)31)20(34)13-5-16(9-26-7-13)29-19(33)6-15-4-3-14(24)8-27-15/h3-5,7-11,32H,6,12H2,1-2H3,(H,29,33)(H2,25,28,30)

HIDE SMILES / InChI

Description
Curator's Comment: The description was created based on several sources, including https://www.drugbank.ca/drugs/DB12269 | https://clinicaltrials.gov/ct2/show/record/NCT01601834 | https://clinicaltrials.gov/ct2/show/NCT02260947 | https://clinicaltrials.gov/ct2/show/NCT01934738

PF-06273340 is a brain penetrant, orally available and potent tropomyosin-related kinase (Trk) inhibitor. PF-06273340 has a low metabolic turnover in Human liver microsomes and hepatocytes is a good substrate for efflux transporters P-glycoprotein and Breast cancer resistance protein (BCRP) and have moderate passive permeability. PF-06273340 was investigated in Phase I clinical trials for the treatment acute and chronic pain. However clinical development has been discontinued.

Originator

Curator's Comment: # Pfizer Limited

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
6.0 nM [IC50]
4.0 nM [IC50]
3.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1396 ng/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PF-06273340 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
3630 ng × h/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PF-06273340 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
PubMed

PubMed

TitleDatePubMed
The Discovery of a Potent, Selective, and Peripherally Restricted Pan-Trk Inhibitor (PF-06273340) for the Treatment of Pain.
2016 Nov 23
Patents

Patents

Sample Use Guides

Tablets, 100 mg TID, 14 days
Route of Administration: Oral
Primary pharmacological activity was assessed using stably transfected U2OS cells expressing human TrkA, TrkB or TrkC (DiscoverX PathHunter system) in the presence of p75. 4 mM stock solutions of test compounds (PF-06273340) are prepared and serially diluted in 100% DMSO. A standard curve using the compound of Example 135, WO2005/116035 at a maximum concentration of 150 μM is also prepared on each test plate. High percentage effect (HPE) is defined by 150 μM of the compound of Example 135, WO2005/116035 and 0% effect (ZPE) is defined by 100% DMSO. Plates containing 1 ul of serially diluted compound, standard and HPE/ZPE were diluted 1/66 in assay buffer (PBS minus Ca2+, minus Mg2+ with 0.05% pluronic F127) using a Wellmate. Using a Platemate Plus, 5 μl of 1/66 diluted test compounds were then transferred to the cell plate and allowed to reach equilibrium by incubating for 30 min at room temperature before addition of agonist stimulus: 10 μl/well of 2nM (0.571nM FAC) of the cognate neurotrophin (Peprotech) diluted in agonist buffer (HBSS with 0.25% BSA). Final assay concentration of the test compounds was 8.66 M. The plates were left at room temperature for a further 2 hours before addition of 10 μl of the DiscoveRx PathHunter detection reagent. After reagent addition, plates were covered and incubated at room temperature for 60 minutes. Luminescence signal was read using an Envision plate reader. Test compound data were expressed as percentage inhibition defined by HPE and ZPE values for each plate.
Name Type Language
PF-06273340
Common Name English
2-PYRIDINEACETAMIDE, N-(5-((2-AMINO-7-(2-HYDROXY-1,1-DIMETHYLETHYL)-7H-PYRROLO(2,3-D)PYRIMIDIN-5-YL)CARBONYL)-3-PYRIDINYL)-5-CHLORO-
Systematic Name English
PF06273340
Code English
N-(5-((2-AMINO-7-(2-HYDROXY-1,1-DIMETHYLETHYL)-7H-PYRROLO(2,3-D)PYRIMIDIN-5-YL)CARBONYL)PYRIDIN-3-YL)-2-(5-CHLOROPYRIDIN-2-YL)ACETAMIDE
Systematic Name English
Code System Code Type Description
DRUG BANK
DB12269
Created by admin on Sat Dec 16 11:52:09 GMT 2023 , Edited by admin on Sat Dec 16 11:52:09 GMT 2023
PRIMARY
FDA UNII
I136775ABW
Created by admin on Sat Dec 16 11:52:09 GMT 2023 , Edited by admin on Sat Dec 16 11:52:09 GMT 2023
PRIMARY
CAS
1402438-74-7
Created by admin on Sat Dec 16 11:52:09 GMT 2023 , Edited by admin on Sat Dec 16 11:52:09 GMT 2023
PRIMARY
PUBCHEM
66571548
Created by admin on Sat Dec 16 11:52:09 GMT 2023 , Edited by admin on Sat Dec 16 11:52:09 GMT 2023
PRIMARY