(R)-3-Methyl-7-(5-methyl-2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)-2-((6-methylpyridin-2-yl)methyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one

ID: ALA4071576

PubChem CID: 122604287

Max Phase: Preclinical

Molecular Formula: C24H26N8O

Molecular Weight: 442.53

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Cc1cccc(CN2C(=O)c3cc(-c4nc(Nc5ccnn5C)ncc4C)cn3C[C@H]2C)n1

Standard InChI:  InChI=1S/C24H26N8O/c1-15-11-25-24(28-21-8-9-26-30(21)4)29-22(15)18-10-20-23(33)32(17(3)12-31(20)13-18)14-19-7-5-6-16(2)27-19/h5-11,13,17H,12,14H2,1-4H3,(H,25,28,29)/t17-/m1/s1

Standard InChI Key:  VKGZTIYOOVDXAF-QGZVFWFLSA-N

Molfile:  

     RDKit          2D

 33 37  0  0  0  0  0  0  0  0999 V2000
   15.4517  -10.5524    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.1669  -10.9645    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.4517   -9.7281    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   16.8820  -10.5524    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   16.8820   -9.7281    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.1669   -9.3160    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.6677  -10.8093    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.1834  -10.1403    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.6677   -9.4714    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.1669  -11.7887    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   17.5930  -10.9645    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.3082  -10.5524    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.3082   -9.7281    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.0234   -9.3160    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.7345   -9.7281    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.7345  -10.5524    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.0234  -10.9645    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   20.4496  -10.9645    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.1229   -9.4251    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.9471   -9.4251    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   13.3592  -10.1403    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.9471  -10.8555    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.1229  -10.8555    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.7108  -10.1403    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.7108   -8.7141    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   10.4023   -9.3789    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.6184   -9.1262    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.6184   -8.3020    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.4023   -8.0451    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.8865   -8.7141    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.6592  -10.1628    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.3592  -11.5665    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.5930   -9.3160    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  1  3  1  0
  2  4  1  0
  4  5  1  0
  5  6  1  0
  3  6  1  0
  7  8  1  0
  8  9  2  0
  3  9  1  0
  1  7  2  0
  2 10  2  0
 12 13  1  0
 13 14  2  0
 14 15  1  0
 15 16  2  0
 16 17  1  0
 12 17  2  0
 16 18  1  0
 11 12  1  0
  4 11  1  0
 19 20  1  0
 20 21  2  0
 21 22  1  0
 22 23  2  0
 23 24  1  0
 19 24  2  0
 26 27  1  0
 27 28  2  0
 28 29  1  0
 29 30  2  0
 26 30  1  0
 26 31  1  0
 25 30  1  0
 19 25  1  0
 22 32  1  0
  8 21  1  0
  5 33  1  1
M  END

Alternative Forms

1. Parent:

   

   ALA4071576

   ---

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: 442.53

Molecular Weight (Monoisotopic): 442.2230

AlogP: 3.48

#Rotatable Bonds: 5

Polar Surface Area: 93.76

Molecular Species: NEUTRAL

HBA: 8

HBD: 1

#RO5 Violations: ┄

HBA (Lipinski): 9

HBD (Lipinski): 1

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 12.78

CX Basic pKa: 4.85

CX LogP: 2.72

CX LogD: 2.72

Aromatic Rings: 4

Heavy Atoms: 33

QED Weighted: 0.51

Np Likeness Score: -1.50

References

1. Ward RA, Bethel P, Cook C, Davies E, Debreczeni JE, Fairley G, Feron L, Flemington V, Graham MA, Greenwood R, Griffin N, Hanson L, Hopcroft P, Howard TD, Hudson J, James M, Jones CD, Jones CR, Lamont S, Lewis R, Lindsay N, Roberts K, Simpson I, St-Gallay S, Swallow S, Tang J, Tonge M, Wang Z, Zhai B..  (2017)  Structure-Guided Discovery of Potent and Selective Inhibitors of ERK1/2 from a Modestly Active and Promiscuous Chemical Start Point.,  60  (8): [PMID:28376306] [10.1021/acs.jmedchem.7b00267]

2. Ward RA, Anderton MJ, Bethel P, Breed J, Cook C, Davies EJ, Dobson A, Dong Z, Fairley G, Farrington P, Feron L, Flemington V, Gibbons FD, Graham MA, Greenwood R, Hanson L, Hopcroft P, Howells R, Hudson J, James M, Jones CD, Jones CR, Li Y, Lamont S, Lewis R, Lindsay N, McCabe J, McGuire T, Rawlins P, Roberts K, Sandin L, Simpson I, Swallow S, Tang J, Tomkinson G, Tonge M, Wang Z, Zhai B..  (2019)  Discovery of a Potent and Selective Oral Inhibitor of ERK1/2 (AZD0364) That Is Efficacious in Both Monotherapy and Combination Therapy in Models of Nonsmall Cell Lung Cancer (NSCLC).,  62  (24): [PMID:31710489] [10.1021/acs.jmedchem.9b01295]

Source

Source(1):

• Scientific Literature