5-(3-cyclopropylpropyl)-2-(pent-2-ynyloxy)-3H-pyrano[2,3-d]pyrimidine-4,7-dione

ID: ALA1939049

PubChem CID: 24953853

Max Phase: Preclinical

Molecular Formula: C18H20N2O4

Molecular Weight: 328.37

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  CCC#CCOc1nc2oc(=O)cc(CCCC3CC3)c2c(=O)[nH]1

Standard InChI:  InChI=1S/C18H20N2O4/c1-2-3-4-10-23-18-19-16(22)15-13(7-5-6-12-8-9-12)11-14(21)24-17(15)20-18/h11-12H,2,5-10H2,1H3,(H,19,20,22)

Standard InChI Key:  JGSQJXUOKYUXPA-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 24 26  0  0  0  0  0  0  0  0999 V2000
    4.0333  -11.7042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.0333  -12.5333    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.7454  -12.9417    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.7454  -11.2917    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.7443  -13.7667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.3186  -11.2922    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.4615  -11.7042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.4626  -12.5333    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.1772  -12.9447    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.8954  -12.5315    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.8943  -11.7023    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.1751  -11.2864    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.1771  -13.7697    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.0293  -14.1783    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.6087  -11.2896    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    8.3233  -11.7020    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.0376  -11.2893    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.7509  -10.8750    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.4643  -10.4606    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.1798  -10.8712    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.0283  -15.0033    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.3133  -15.4149    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.4892  -15.4164    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.9008  -16.1314    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
 10 11  1  0
 11 12  2  0
  1  2  1  0
  9 13  2  0
  1  6  2  0
  5 14  1  0
  7  8  2  0
 11 15  1  0
  1  4  1  0
 15 16  1  0
  2  3  2  0
 16 17  1  0
  3  8  1  0
 17 18  3  0
  7  4  1  0
 18 19  1  0
 19 20  1  0
  3  5  1  0
 14 21  1  0
  7 12  1  0
 21 22  1  0
 23 22  1  0
 24 23  1  0
 22 24  1  0
  8  9  1  0
  9 10  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA1939049

   5-(3-cyclopropylpropyl)-2-pent-2-ynoxy-3H-pyrano[2,3-d]pyrimidine-4,7-dione

Molecule Features

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: 328.37

Molecular Weight (Monoisotopic): 328.1423

AlogP: 2.40

#Rotatable Bonds: 6

Polar Surface Area: 85.19

Molecular Species: NEUTRAL

HBA: 5

HBD: 1

#RO5 Violations: ┄

HBA (Lipinski): 6

HBD (Lipinski): 1

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 6.69

CX Basic pKa: ┄

CX LogP: 3.66

CX LogD: 3.07

Aromatic Rings: 2

Heavy Atoms: 24

QED Weighted: 0.82

Np Likeness Score: 0.06

References

1. Huang X, Su J, Rao AU, Tang H, Zhou W, Zhu X, Chen X, Liu Z, Huang Y, Degrado S, Xiao D, Qin J, Aslanian R, McKittrick BA, Greenfeder S, Heek Mv, Chintala M, Palani A..  (2012)  SAR studies of C2 ethers of 2H-pyrano[2,3-d]pyrimidine-2,4,7(1H,3H)-triones as nicotinic acid receptor (NAR) agonist.,  22  (2): [PMID:22209457] [10.1016/j.bmcl.2011.12.041]

2. Wise, Alan A and 16 more authors.  2003-03-14  Molecular identification of high and low affinity receptors for nicotinic acid.  [PMID:12522134]

3. Taggart, Andrew K P AK and 17 more authors.  2005-07-22  (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G.  [PMID:15929991]

4. Jung, Jae-Kyu JK and 11 more authors.  2007-04-05  Analogues of acifran: agonists of the high and low affinity niacin receptors, GPR109a and GPR109b.  [PMID:17358052]

5. Semple, Graeme G and 21 more authors.  2008-08-28  3-(1H-tetrazol-5-yl)-1,4,5,6-tetrahydro-cyclopentapyrazole (MK-0354): a partial agonist of the nicotinic acid receptor, G-protein coupled receptor 109a, with antilipolytic but no vasodilatory activity in mice.  [PMID:18665582]

6. Tang, Hua H, Lu, Jenny Ying-Lin JY, Zheng, Xiaomu X, Yang, Yuhua Y and Reagan, Jeff D JD.  2008-10-31  The psoriasis drug monomethylfumarate is a potent nicotinic acid receptor agonist.  [PMID:18722346]

7. Deng, Qiaolin Q and 13 more authors.  2008-09-15  Molecular modeling aided design of nicotinic acid receptor GPR109A agonists.  [PMID:18760600]

8. Boatman, P Douglas PD, Richman, Jeremy G JG and Semple, Graeme G.  2008-12-25  Nicotinic acid receptor agonists.  [PMID:18983141]

9. Ren, Ning N and 9 more authors.  2009-05  Phenolic acids suppress adipocyte lipolysis via activation of the nicotinic acid receptor GPR109A (HM74a/PUMA-G).  [PMID:19136666]

10. Shen, Hong C HC and 23 more authors.  2010-03-25  Discovery of a biaryl cyclohexene carboxylic acid (MK-6892): a potent and selective high affinity niacin receptor full agonist with reduced flushing profiles in animals as a preclinical candidate.  [PMID:20184326]

11. van Veldhoven, J P D JP and 8 more authors.  2011-05-01  Structure-activity relationships of trans-substituted-propenoic acid derivatives on the nicotinic acid receptor HCA2 (GPR109A).  [PMID:21167710]

12. Boatman, P Douglas PD and 26 more authors.  2012-04-26  (1aR,5aR)1a,3,5,5a-Tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid (MK-1903): a potent GPR109a agonist that lowers free fatty acids in humans.  [PMID:22435740]

13. Qin, Jun J and 22 more authors.  2011-02-10  Discovery of a potent nicotinic Acid receptor agonist for the treatment of dyslipidemia.  [PMID:24900295]

14. Palani, Anandan A and 29 more authors.  2012-01-12  Discovery of SCH 900271, a Potent Nicotinic Acid Receptor Agonist for the Treatment of Dyslipidemia.  [PMID:24900372]

15. Sprecher, Dennis D and 6 more authors.  2015-06-05  Discovery and characterization of GSK256073, a non-flushing hydroxy-carboxylic acid receptor 2 (HCA2) agonist.  [PMID:25773497]

16. Singh, L Ravithej LR and 8 more authors.  2018-05-25  Discovery of coumarin-dihydroquinazolinone analogs as niacin receptor 1 agonist with in-vivo anti-obesity efficacy.  [PMID:29709786]

Source

Source(1):

• Scientific Literature