Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C19H17F3N8 |
| Molecular Weight | 414.3871 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CN1N=CC(C2=C3N(N=CN=C3N4CCC4)C(C)=N2)=C1C5=NC=C(C=C5)C(F)(F)F
InChI
InChIKey=CLGCHUKGBICQTE-UHFFFAOYSA-N
InChI=1S/C19H17F3N8/c1-11-27-15(17-18(29-6-3-7-29)24-10-26-30(11)17)13-9-25-28(2)16(13)14-5-4-12(8-23-14)19(20,21)22/h4-5,8-10H,3,6-7H2,1-2H3
| Molecular Formula | C19H17F3N8 |
| Molecular Weight | 414.3871 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
Approval Year
| Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 01:31:19 GMT 2023
by
admin
on
Sat Dec 16 01:31:19 GMT 2023
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| Record UNII |
5L84K4IEN9
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| Record Status |
Validated (UNII)
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| Record Version |
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5L84K4IEN9
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DB14885
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100000178396
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60143346
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TARGET -> INHIBITOR |
IC50
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ACTIVE MOIETY |
Coincidently, a similar structural change was incorporated onto the initial pyrazolopyrimidine which led to a ninefold increase in potency, as exemplified by compound 14 (PDE2a IC50 = 0.009 .MU.M) and compound 15 (PDE2a IC50 = 0.001 .MU.M).42 It was proposed that the nitrogen from the imidazolotriazine (labeled N1, compound 15) interacts more efficiently with the water molecules present in the catalytic domain. Using free energy calculations the researchers determined that the hydrogen bond intereactions were energetically stronger by 1.4 kcal/mol for the imidazolotriazine (15) compared to the pyrazolopyrimidine (14).43 After further profiling of compound 15, Pfizer advanced this analog as their clinical compound (PF-999). This analog displayed good PDE selectivity (2000-fold selective over PDE10) and reasonable free brain/plasma ratio in rat (0.5). This compound increased cGMP levels in the cerebrospinal fluid of rats. Pharmacological evaluation of PF-999 in rat showed efficacy in models of working memory (attenuate ketamine-induced disruption) and spatial learning and memory (reverse effects of scopolamine in water maze). Pfizer was developing PF-999 for the treatment of schizophrenia and no further development has been reported since mid 2012.
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ACTIVE MOIETY |
Originator: Pfizer; Class: Anti-migraine, Antipsychotic, Small molecule; Mechanism of Action: Type 2 cyclic nucleotide phosphordiesterase inhibitor; Orphan Drug Status: No; On Fast track: No; New Molecular Entity: Yes; Highest Development Phases: Discontinued for Migraine, Schizophrenia; Most Recent Events: 07 Aug 2014 Discontinued for Phase-I for Migraine (In volunteers) in USA (PO), 01 Dec 2013 Phase-I clinical trials in Migraine (in volunteers) in USA (PO), 28 Feb 2013 Discontinued for Phase-I for Schizophrenia in USA (PO)
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