4-(3-Chloro-4-methoxy-benzylamino)-1-ethyl-4,5-dihydro-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid (pyridin-4-ylmethyl)-amide

ID: ALA7868

Cas Number: 261769-44-2

PubChem CID: 9933503

Max Phase: Preclinical

Molecular Formula: C23H23ClN6O2

Molecular Weight: 450.93

Molecule Type: Small molecule

This compound is available for customization.

Associated Items:

Names and Identifiers

Canonical SMILES:  CCn1ncc2c(NCc3ccc(OC)c(Cl)c3)c(C(=O)NCc3ccncc3)cnc21

Standard InChI:  InChI=1S/C23H23ClN6O2/c1-3-30-22-17(14-29-30)21(26-12-16-4-5-20(32-2)19(24)10-16)18(13-27-22)23(31)28-11-15-6-8-25-9-7-15/h4-10,13-14H,3,11-12H2,1-2H3,(H,26,27)(H,28,31)

Standard InChI Key:  NJAQIMZSDVLFQH-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 32 35  0  0  0  0  0  0  0  0999 V2000
    3.9042   -7.2167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.9042   -8.0292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6292   -6.7917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.3417   -7.2042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.6500   -7.6292    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    4.6292   -8.4417    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.1292   -8.2792    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.1292   -6.9542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.0542   -6.7917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.3417   -8.0292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6417   -5.9667    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.7625   -7.2167    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.0917   -3.4792    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.3667   -3.0667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.0750   -5.9667    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    6.0792   -4.3167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.8250   -9.3542    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    4.6417   -3.4917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.3625   -5.5667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.3667   -4.7292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.7292   -8.0417    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.7917   -3.0542    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
    4.6417   -4.3167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.8542   -9.0667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.3625   -2.2417    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    7.4292   -8.4917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.0917   -9.7417    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.8417   -8.5292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.1500   -8.1042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.4000   -9.3042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.0667   -1.8167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.4042   -9.6917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  1  2  0
  3  1  1  0
  4  3  2  0
  5  8  2  0
  6  2  1  0
  7  2  1  0
  8  1  1  0
  9  4  1  0
 10  4  1  0
 11  3  1  0
 12  9  1  0
 13 16  1  0
 14 18  1  0
 15  9  2  0
 16 20  2  0
 17 27  2  0
 18 23  2  0
 19 11  1  0
 20 19  1  0
 21 12  1  0
 22 13  1  0
 23 20  1  0
 24  7  1  0
 25 14  1  0
 26 21  1  0
 27 30  1  0
 28 29  2  0
 29 26  1  0
 30 26  2  0
 31 25  1  0
 32 24  1  0
  5  7  1  0
  6 10  2  0
 13 14  2  0
 28 17  1  0
M  END

Associated Targets(Human)

PDE5A Tclin Phosphodiesterase 5A (5113 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
PDE5A Tclin Phosphodiesterase 3 and 5 (PDE3 and PDE5) (91 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Associated Targets(non-human)

Rattus norvegicus (775804 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Canis familiaris (36305 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Molecule Features

Natural Product: NoOral: NoChemical Probe: NoParenteral: No
Molecule Type: Small moleculeTopical: NoFirst In Class: NoBlack Box: No
Chirality: NoAvailability: NoProdrug: No

Biocomponents

Calculated Properties

Molecular Weight: 450.93Molecular Weight (Monoisotopic): 450.1571AlogP: 4.05#Rotatable Bonds: 8
Polar Surface Area: 93.96Molecular Species: NEUTRALHBA: 7HBD: 2
#RO5 Violations: HBA (Lipinski): 8HBD (Lipinski): 2#RO5 Violations (Lipinski):
CX Acidic pKa: CX Basic pKa: 5.02CX LogP: 2.80CX LogD: 2.80
Aromatic Rings: 4Heavy Atoms: 32QED Weighted: 0.42Np Likeness Score: -1.81

References

1. Yu G, Mason HJ, Wu X, Wang J, Chong S, Dorough G, Henwood A, Pongrac R, Seliger L, He B, Normandin D, Adam L, Krupinski J, Macor JE..  (2001)  Substituted pyrazolopyridines as potent and selective PDE5 inhibitors: potential agents for treatment of erectile dysfunction.,  44  (7): [PMID:11297448] [10.1021/jm0155042]
2. Yu G, Mason H, Wu X, Wang J, Chong S, Beyer B, Henwood A, Pongrac R, Seliger L, He B, Normandin D, Ferrer P, Zhang R, Adam L, Humphrey WG, Krupinski J, Macor JE..  (2003)  Substituted pyrazolopyridopyridazines as orally bioavailable potent and selective PDE5 inhibitors: potential agents for treatment of erectile dysfunction.,  46  (4): [PMID:12570368] [10.1021/jm0256068]
3. Rotella, D P DP and 7 more authors.  2000-04-06  N-3-substituted imidazoquinazolinones: potent and selective PDE5 inhibitors as potential agents for treatment of erectile dysfunction.  [PMID:10753463]
4. Yu, G G and 13 more authors.  2001-03-29  Substituted pyrazolopyridines as potent and selective PDE5 inhibitors: potential agents for treatment of erectile dysfunction.  [PMID:11297448]
5. Ukita, T T and 10 more authors.  2001-06-21  Novel, potent, and selective phosphodiesterase 5 inhibitors: synthesis and biological activities of a series of 4-aryl-1-isoquinolinone derivatives.  [PMID:11405657]
6. Haning, Helmut H and 6 more authors.  2002-03-25  Imidazo[5,1-f]triazin-4(3H)-ones, a new class of potent PDE 5 inhibitors.  [PMID:11958981]
7. Arnold, Ruth R and 20 more authors.  2002-09-16  8-Aryl xanthines potent inhibitors of phosphodiesterase 5.  [PMID:12182866]
8. Sui, Zhihua Z and 10 more authors.  2002-09-12  Pyrimidinylpyrroloquinolones as highly potent and selective PDE5 inhibitors for treatment of erectile dysfunction.  [PMID:12213052]
9. Jiang, Weiqin W and 13 more authors.  2003-01-30  Furoyl and benzofuroyl pyrroloquinolones as potent and selective PDE5 inhibitors for treatment of erectile dysfunction.  [PMID:12540243]
10. Yu, Guixue G and 16 more authors.  2003-02-13  Substituted pyrazolopyridopyridazines as orally bioavailable potent and selective PDE5 inhibitors: potential agents for treatment of erectile dysfunction.  [PMID:12570368]
11. Pissarnitski, Dmitri A DA and 16 more authors.  2004-03-08  SAR development of polycyclic guanine derivatives targeted to the discovery of a selective PDE5 inhibitor for treatment of erectile dysfunction.  [PMID:14980684]
12. Bi, Yingzhi Y and 9 more authors.  2004-03-22  Quinolines as extremely potent and selective PDE5 inhibitors as potential agents for treatment of erectile dysfunction.  [PMID:15006407]
13. 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]
14. Xia, Guangxin G and 8 more authors.  2005-06-02  Synthesis and phosphodiesterase 5 inhibitory activity of novel pyrido[1,2-e]purin-4(3H)-one derivatives.  [PMID:15878277]
15. Allerton, Charlotte M N CM and 12 more authors.  2006-06-15  A novel series of potent and selective PDE5 inhibitors with potential for high and dose-independent oral bioavailability.  [PMID:16759100]
16. Giovannoni, Maria Paola MP and 8 more authors.  2006-08-24  Novel pyrazolopyrimidopyridazinones with potent and selective phosphodiesterase 5 (PDE5) inhibitory activity as potential agents for treatment of erectile dysfunction.  [PMID:16913726]
17. Arnold, Nichola J NJ and 28 more authors.  2007-04-15  Potent and selective xanthine-based inhibitors of phosphodiesterase 5.  [PMID:17337182]
18. Flores Toque, Haroldo A HA and 12 more authors.  2008-05-08  Synthesis and pharmacological evaluations of sildenafil analogues for treatment of erectile dysfunction.  [PMID:18393409]
19. Antunes, João E JE, Freitas, Matheus P MP, da Cunha, Elaine F F EF, Ramalho, Teodorico C TC and Rittner, Roberto R.  2008-08-15  In silico prediction of novel phosphodiesterase type-5 inhibitors derived from Sildenafil, Vardenafil and Tadalafil.  [PMID:18656371]
20. Owen, Dafydd R DR and 28 more authors.  2009-08-01  Identification, synthesis and SAR of amino substituted pyrido[3,2b]pyrazinones as potent and selective PDE5 inhibitors.  [PMID:19540112]
21. Hughes, Robert O RO and 25 more authors.  2010-03-25  Design, synthesis, and biological evaluation of 3-[4-(2-hydroxyethyl)piperazin-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one, a potent, orally active, brain penetrant inhibitor of phosphodiesterase 5 (PDE5).  [PMID:20196613]
22. Abadi, Ashraf H; Gary, Bernard D; Tinsley, Heather N; Piazza, Gary A and Abdel-Halim, Mohammad.  2010-04  Synthesis, molecular modeling and biological evaluation of novel tadalafil analogues as phosphodiesterase 5 and colon tumor cell growth inhibitors, new stereochemical perspective.  [PMID:20206015]
23. Höfgen, Norbert N and 14 more authors.  2010-06-10  Discovery of imidazo[1,5-a]pyrido[3,2-e]pyrazines as a new class of phosphodiesterase 10A inhibitiors.  [PMID:20450197]
24. Mohamed, Heba A and 8 more authors.  2011-01-27  Synthesis and molecular modeling of novel tetrahydro-β-carboline derivatives with phosphodiesterase 5 inhibitory and anticancer properties.  [PMID:21189023]
25. Allcock, Robert W RW and 8 more authors.  2011-06-01  Phosphodiesterase inhibitors. Part 1: Synthesis and structure-activity relationships of pyrazolopyridine-pyridazinone PDE inhibitors developed from ibudilast.  [PMID:21530250]
26. 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]
27. Bartolomé-Nebreda, José Manuel JM and 13 more authors.  2014-05-22  Discovery of a potent, selective, and orally active phosphodiesterase 10A inhibitor for the potential treatment of schizophrenia.  [PMID:24758746]
28. Mittal, Anupama A and 5 more authors.  2014-07-15  Pharmacophore based virtual screening, molecular docking and biological evaluation to identify novel PDE5 inhibitors with vasodilatory activity.  [PMID:24856068]
29. Shao, Yong-xian YX and 11 more authors.  2014-12-26  Discovery of a phosphodiesterase 9A inhibitor as a potential hypoglycemic agent.  [PMID:25432025]
30. Sawant, Sanghapal D SD and 13 more authors.  2015-05-01  Discovery of novel pyrazolopyrimidinone analogs as potent inhibitors of phosphodiesterase type-5.  [PMID:25801159]
31. Rabal, Obdulia O and 15 more authors.  2016-10-13  Design, Synthesis, and Biological Evaluation of First-in-Class Dual Acting Histone Deacetylases (HDACs) and Phosphodiesterase 5 (PDE5) Inhibitors for the Treatment of Alzheimer's Disease.  [PMID:27606546]
32. Wu, Deyan D and 11 more authors.  2017-08-10  Discovery and Optimization of Chromeno[2,3-c]pyrrol-9(2H)-ones as Novel Selective and Orally Bioavailable Phosphodiesterase 5 Inhibitors for the Treatment of Pulmonary Arterial Hypertension.  [PMID:28686445]
33. Fiorito, Jole J and 8 more authors.  2017-11-09  Identification of a Novel 1,2,3,4-Tetrahydrobenzo[b][1,6]naphthyridine Analogue as a Potent Phosphodiesterase 5 Inhibitor with Improved Aqueous Solubility for the Treatment of Alzheimer's Disease.  [PMID:28985058]
34. 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]
35. Helal, Christopher J CJ and 28 more authors.  2018-02-08  Identification of a Potent, Highly Selective, and Brain Penetrant Phosphodiesterase 2A Inhibitor Clinical Candidate.  [PMID:29293004]
36. Rabal, Obdulia O and 15 more authors.  2018-04-25  Design, synthesis, biological evaluation and in vivo testing of dual phosphodiesterase 5 (PDE5) and histone deacetylase 6 (HDAC6)-selective inhibitors for the treatment of Alzheimer's disease.  [PMID:29549837]
37. Dow, Robert L RL and 13 more authors.  2018-04-12  2-Aminopyridine-Based Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 (MAP4K4) Inhibitors: Assessment of Mechanism-Based Safety.  [PMID:29570292]
38. Wu, Deyan D and 10 more authors.  2018-09-27  Optimization of Chromeno[2,3- c]pyrrol-9(2 H)-ones as Highly Potent, Selective, and Orally Bioavailable PDE5 Inhibitors: Structure-Activity Relationship, X-ray Crystal Structure, and Pharmacodynamic Effect on Pulmonary Arterial Hypertension.  [PMID:30148362]
39. Zheng, Hongbo H and 9 more authors.  2018-10-05  Discovery of furyl/thienyl β-carboline derivatives as potent and selective PDE5 inhibitors with excellent vasorelaxant effect.  [PMID:30245400]
40. Wang, Zhen Z and 22 more authors.  2019-05-23  Pharmacokinetics-Driven Optimization of 4(3 H)-Pyrimidinones as Phosphodiesterase Type 5 Inhibitors Leading to TPN171, a Clinical Candidate for the Treatment of Pulmonary Arterial Hypertension.  [PMID:31021628]
41. Zhang, Pengfei P, Xu, Shengtao S, Zhu, Zheying Z and Xu, Jinyi J.  2019-08-15  Multi-target design strategies for the improved treatment of Alzheimer's disease.  [PMID:31103902]
42. Bollenbach, Maud M and 8 more authors.  2019-09-01  Design and synthesis of 3-aminophthalazine derivatives and structural analogues as PDE5 inhibitors: anti-allodynic effect against neuropathic pain in a mouse model.  [PMID:31158744]
43. Huang, Xian-Feng and 5 more authors.  2020-05-01  Novel PDE5 inhibitors derived from rutaecarpine for the treatment of Alzheimer's disease.  [PMID:32171616]
44. 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]
45. Zhang, Tianhua and 7 more authors.  2020-09-10  Discovery of Evodiamine Derivatives as Highly Selective PDE5 Inhibitors Targeting a Unique Allosteric Pocket.  [PMID:32794708]

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