US8623901, 257

ID: ALA3693850

PubChem CID: 135912148

Max Phase: Preclinical

Molecular Formula: C21H19F3N6O2

Molecular Weight: 444.42

Molecule Type: Small molecule

This compound is available for customization.

Associated Items:

Bioactivity Summary Target Summary Assay Summary

Names and Identifiers

Canonical SMILES: O=c1[nH]c(Cc2cc(C(F)(F)F)ccc2-n2cccn2)nc2c1cnn2C1CCOCC1

Standard InChI: InChI=1S/C21H19F3N6O2/c22-21(23,24)14-2-3-17(29-7-1-6-25-29)13(10-14)11-18-27-19-16(20(31)28-18)12-26-30(19)15-4-8-32-9-5-15/h1-3,6-7,10,12,15H,4-5,8-9,11H2,(H,27,28,31)

Standard InChI Key: DKGXBMGHVFVBEI-UHFFFAOYSA-N

Molfile:

     RDKit          2D

 32 36  0  0  0  0  0  0  0  0999 V2000
   -0.0190   -7.1954    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0140   -5.9954    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0510   -5.3915    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0556   -6.5913    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    1.2883   -5.2495    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5847   -6.0040    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.8864   -5.2585    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.8915   -3.7585    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5951   -3.0039    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.5973   -1.5031    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2990   -0.7500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2990    0.7500    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.0000    1.5000    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2990    0.7500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.4133    1.7530    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8032    3.1233    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3115    2.9665    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.6928    4.0817    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.3384    5.5341    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.4233    6.5700    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.8628    6.1485    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.2175    4.6910    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1327    3.6551    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2990   -0.7500    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3383   -1.3500    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.0000   -1.5000    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.2935   -3.7495    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.1938   -3.0126    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.3392   -1.5325    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.8080   -1.2280    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.5514   -2.5308    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.5421   -3.6405    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  2  4  1  0
  2  5  1  0
  5  6  2  0
  6  7  1  0
  7  8  2  0
  8  9  1  0
  9 10  1  0
 10 11  1  0
 11 12  2  0
 12 13  1  0
 13 14  2  0
 14 15  1  0
 15 16  2  0
 16 17  1  0
 17 13  1  0
 17 18  1  0
 18 19  1  0
 19 20  1  0
 20 21  1  0
 21 22  1  0
 22 23  1  0
 23 18  1  0
 14 24  1  0
 24 25  2  0
 24 26  1  0
 26 11  1  0
  9 27  2  0
 27  5  1  0
  8 28  1  0
 28 29  1  0
 29 30  2  0
 30 31  1  0
 31 32  2  0
 32 28  1  0
M  END

Natural Product: No	Oral: No	Chemical Probe: No	Parenteral: No
Molecule Type: Small molecule	Topical: No	First In Class: No	Black Box: No
Chirality: No	Availability: No	Prodrug: No

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 444.42	Molecular Weight (Monoisotopic): 444.1522	AlogP: 3.27	#Rotatable Bonds: 4
Polar Surface Area: 90.62	Molecular Species: NEUTRAL	HBA: 7	HBD: 1
#RO5 Violations: ┄	HBA (Lipinski): 8	HBD (Lipinski): 1	#RO5 Violations (Lipinski): ┄
CX Acidic pKa: 9.16	CX Basic pKa: 1.61	CX LogP: 2.05	CX LogD: 2.04
Aromatic Rings: 4	Heavy Atoms: 32	QED Weighted: 0.52	Np Likeness Score: -2.04

References

1. (2014) Compounds for the treatment of CNS disorders,
2. Fisher, D A DA, Smith, J F JF, Pillar, J S JS, St Denis, S H SH and Cheng, J B JB. 1998-06-19 Isolation and characterization of PDE9A, a novel human cGMP-specific phosphodiesterase. [PMID:9624146]
3. Boyle, Craig D CD and 20 more authors. 2005-05-02 Optimization of purine based PDE1/PDE5 inhibitors to a potent and selective PDE5 inhibitor for the treatment of male ED. [PMID:15837326]
4. Wang, Huanchen H and 5 more authors. 2010-02-25 Insight into binding of phosphodiesterase-9A selective inhibitors by crystal structures and mutagenesis. [PMID:20121115]
5. Verhoest, Patrick R PR and 15 more authors. 2012-11-08 Design and discovery of 6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (PF-04447943), a selective brain penetrant PDE9A inhibitor for the treatment of cognitive disorders. [PMID:22780914]
6. Meng, Fei and 12 more authors. 2012-10-11 Structure-based discovery of highly selective phosphodiesterase-9A inhibitors and implications for inhibitor design. [PMID:22985069]
7. Claffey, Michelle M MM and 23 more authors. 2012-11-08 Application of structure-based drug design and parallel chemistry to identify selective, brain penetrant, in vivo active phosphodiesterase 9A inhibitors. [PMID:23025719]
8. Fiorito, Jole J and 10 more authors. 2013-02 Synthesis of quinoline derivatives: discovery of a potent and selective phosphodiesterase 5 inhibitor for the treatment of Alzheimer's disease. [PMID:23313637]
9. Shao, Yong-xian YX and 11 more authors. 2014-12-26 Discovery of a phosphodiesterase 9A inhibitor as a potential hypoglycemic agent. [PMID:25432025]
10. Cheng, Zhong-Bin ZB and 8 more authors. 2014-12-26 (±)-Torreyunlignans A-D, rare 8-9' linked neolignan enantiomers as phosphodiesterase-9A inhibitors from Torreya yunnanensis. [PMID:25495612]
11. Guo, Yan-Qiong YQ and 6 more authors. 2018-01-20 Prenylated flavonoids as potent phosphodiesterase-4 inhibitors from Morus alba: Isolation, modification, and structure-activity relationship study. [PMID:29291443]
12. Wu, Yinuo Y and 13 more authors. 2019-04-25 Discovery of Potent, Selective, and Orally Bioavailable Inhibitors against Phosphodiesterase-9, a Novel Target for the Treatment of Vascular Dementia. [PMID:30916555]
13. Zhang, Pei and 7 more authors. 2020-07-15 Design, synthesis and evaluation of pyrazolopyrimidinone derivatives as novel PDE9A inhibitors for treatment of Alzheimer's disease. [PMID:32527553]
14. Wu, Yinuo and 8 more authors. 2020-07-23 Discovery of Novel Selective and Orally Bioavailable Phosphodiesterase-1 Inhibitors for the Efficient Treatment of Idiopathic Pulmonary Fibrosis. [PMID:32603117]

US8623901, 257

Names and Identifiers

Alternative Forms

Associated Targets(Human)

Molecule Features

Drug Indications

Mechanisms of Action

Calculated Properties

References

Source