(R)-3-hydroxy-N,N-dimethyl-4-(2-(1-(5-methylfuran-2-yl)propylamino)-3,4-dioxocyclobut-1-enylamino)picolinamide

ID: ALA4574181

PubChem CID: 49763036

Max Phase: Preclinical

Molecular Formula: C20H22N4O5

Molecular Weight: 398.42

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  CC[C@@H](Nc1c(Nc2ccnc(C(=O)N(C)C)c2O)c(=O)c1=O)c1ccc(C)o1

Standard InChI:  InChI=1S/C20H22N4O5/c1-5-11(13-7-6-10(2)29-13)22-14-15(19(27)18(14)26)23-12-8-9-21-16(17(12)25)20(28)24(3)4/h6-9,11,22,25H,5H2,1-4H3,(H,21,23)/t11-/m1/s1

Standard InChI Key:  MYZKJLUOSGMNEZ-LLVKDONJSA-N

Molfile:  

 
     RDKit          2D

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    3.8519   -8.9428    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.8507   -9.7623    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.5588  -10.1713    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.2684   -9.7619    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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    4.5570   -8.5339    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.5586  -10.9885    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
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    8.0770   -8.3658    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    8.0770  -10.3387    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    8.8901  -10.3346    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.2951   -9.6248    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.3022  -11.0402    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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    8.9793  -11.7865    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.5893  -12.3303    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.2950  -11.9181    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.1209  -11.1196    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   11.0432  -12.2466    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1427  -10.1704    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.4353   -9.7612    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.1420  -10.9876    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.4359   -8.9440    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7273  -10.1693    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  3  2  0
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  3 25  1  0
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 26 29  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4574181

   3-hydroxy-N,N-dimethyl-4-[[2-[[(1R)-1-(5-methylfuran-2-yl)propyl]amino]-3,4-dioxocyclobuten-1-yl]amino]pyridine-2-carboxamide

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Unknown

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 398.42

Molecular Weight (Monoisotopic): 398.1590

AlogP: 2.29

#Rotatable Bonds: 7

Polar Surface Area: 124.77

Molecular Species: NEUTRAL

HBA: 8

HBD: 3

#RO5 Violations: ┄

HBA (Lipinski): 9

HBD (Lipinski): 3

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 7.15

CX Basic pKa: 3.56

CX LogP: 1.73

CX LogD: 1.30

Aromatic Rings: 3

Heavy Atoms: 29

QED Weighted: 0.52

Np Likeness Score: -0.85

References

1. Che J, Song R, Chen B, Dong X..  (2020)  Targeting CXCR1/2: The medicinal potential as cancer immunotherapy agents, antagonists research highlights and challenges ahead.,  185  [PMID:31732253] [10.1016/j.ejmech.2019.111853]

2. Cutshall, N S NS, Ursino, R R, Kucera, K A KA, Latham, J J and Ihle, N C NC.  2001-07-23  Nicotinamide N-oxides as CXCR2 antagonists.  [PMID:11459668]

3. Cutshall, Neil S NS, Kucera, Kristin A KA, Ursino, Rocky R, Latham, John J and Ihle, Nathan C NC.  2002-06-03  Nicotinanilides as inhibitors of neutrophil chemotaxis.  [PMID:12031332]

4. Widdowson, Katherine L KL and 14 more authors.  2004-03-11  Evaluation of potent and selective small-molecule antagonists for the CXCR2 chemokine receptor.  [PMID:14998320]

5. Karlström, Sofia S and 20 more authors.  2013-04-25  Substituted 7-amino-5-thio-thiazolo[4,5-d]pyrimidines as potent and selective antagonists of the fractalkine receptor (CX3CR1).  [PMID:23516963]

6. Bachelerie, Francoise F and 22 more authors.  2014  International Union of Basic and Clinical Pharmacology. [corrected]. LXXXIX. Update on the extended family of chemokine receptors and introducing a new nomenclature for atypical chemokine receptors.  [PMID:24218476]

7. Austin, Rupert P RP and 14 more authors.  2015-04-01  Discovery and evaluation of a novel monocyclic series of CXCR2 antagonists.  [PMID:25708618]

8. Maeda, Dean Y and 8 more authors.  2015-06-01  Boronic acid-containing CXCR1/2 antagonists: Optimization of metabolic stability, in vivo evaluation, and a proposed receptor binding model.  [PMID:25933594]

9. Miller, Bruce E and 8 more authors.  2015-06-20  The pharmacokinetics and pharmacodynamics of danirixin (GSK1325756)--a selective CXCR2 antagonist --in healthy adult subjects.  [PMID:26092545]

10. Schuler, Aaron D and 8 more authors.  2015-09-15  Boronic acid-containing aminopyridine- and aminopyrimidinecarboxamide CXCR1/2 antagonists: Optimization of aqueous solubility and oral bioavailability.  [PMID:26248802]

11. Xu, Heng H and 19 more authors.  2016-04-14  Discovery of CNS Penetrant CXCR2 Antagonists for the Potential Treatment of CNS Demyelinating Disorders.  [PMID:27096048]

12. Gege, Christian and 15 more authors.  2018-05-15  Identification and biological evaluation of thiazole-based inverse agonists of RORγt.  [PMID:29631962]

Source

Source(1):

• Scientific Literature