(S)-2-(((1r,4S)-4-(4-Amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclohexyl)amino)-N,4-dimethylpentanamide

ID: ALA4085262

PubChem CID: 131632971

Max Phase: Preclinical

Molecular Formula: C31H38N6O2

Molecular Weight: 526.69

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  CNC(=O)[C@H](CC(C)C)N[C@H]1CC[C@H](n2cc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)CC1

Standard InChI:  InChI=1S/C31H38N6O2/c1-20(2)17-27(31(38)33-3)36-22-11-13-23(14-12-22)37-18-26(28-29(32)34-19-35-30(28)37)21-9-15-25(16-10-21)39-24-7-5-4-6-8-24/h4-10,15-16,18-20,22-23,27,36H,11-14,17H2,1-3H3,(H,33,38)(H2,32,34,35)/t22-,23-,27-/m0/s1

Standard InChI Key:  QWSTVNCCNITNGB-WCYRKSIYSA-N

Molfile:  

     RDKit          2D

 39 43  0  0  0  0  0  0  0  0999 V2000
   36.5981   -6.2040    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   36.5968   -7.0313    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.3117   -7.4442    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   37.3099   -5.7912    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.0252   -6.2004    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.0301   -7.0314    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.8220   -7.2836    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   39.3065   -6.6084    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.8141   -5.9390    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   39.0644   -5.1529    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   39.8696   -4.9822    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   40.1199   -4.1970    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   39.5641   -3.5862    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.7545   -3.7660    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.5079   -4.5510    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   39.0792   -8.0645    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.5287   -8.6801    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   38.7852   -9.4605    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   39.5925   -9.6315    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   40.1432   -9.0158    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   39.8863   -8.2291    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   39.8484  -10.4101    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   39.8133   -2.7998    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   40.6191   -2.6224    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   41.1739   -3.2322    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   41.9789   -3.0554    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   42.2289   -2.2682    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   41.6677   -1.6578    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   40.8647   -1.8378    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   37.3074   -4.9663    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   40.6559  -10.5790    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   40.9133  -11.3628    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   41.2059   -9.9642    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   42.0134  -10.1331    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   40.9485   -9.1804    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   40.3633  -11.9777    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   40.6208  -12.7614    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   39.5558  -11.8087    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   42.5634   -9.5181    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  2  0
  2  3  1  0
  3  6  2  0
  5  4  2  0
  4  1  1  0
  5  6  1  0
  6  7  1  0
  7  8  1  0
  8  9  2  0
  9  5  1  0
  9 10  1  0
 10 11  2  0
 11 12  1  0
 12 13  2  0
 13 14  1  0
 14 15  2  0
 15 10  1  0
 16 17  1  0
 16 21  1  0
 17 18  1  0
 18 19  1  0
 19 20  1  0
 20 21  1  0
 16  7  1  1
 19 22  1  6
 13 23  1  0
 23 24  1  0
 24 25  2  0
 25 26  1  0
 26 27  2  0
 27 28  1  0
 28 29  2  0
 29 24  1  0
  4 30  1  0
 22 31  1  0
 31 32  1  6
 31 33  1  0
 33 34  1  0
 33 35  2  0
 32 36  1  0
 36 37  1  0
 36 38  1  0
 34 39  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4085262

   ---

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: 526.69

Molecular Weight (Monoisotopic): 526.3056

AlogP: 5.71

#Rotatable Bonds: 9

Polar Surface Area: 107.09

Molecular Species: BASE

HBA: 7

HBD: 3

#RO5 Violations: 2

HBA (Lipinski): 8

HBD (Lipinski): 4

#RO5 Violations (Lipinski): 2

CX Acidic pKa: ┄

CX Basic pKa: 9.55

CX LogP: 5.11

CX LogD: 2.96

Aromatic Rings: 4

Heavy Atoms: 39

QED Weighted: 0.26

Np Likeness Score: -0.47

References

1. Yuki H, Kikuzato K, Koda Y, Mikuni J, Tomabechi Y, Kukimoto-Niino M, Tanaka A, Shirai F, Shirouzu M, Koyama H, Honma T..  (2017)  Activity cliff for 7-substituted pyrrolo-pyrimidine inhibitors of HCK explained in terms of predicted basicity of the amine nitrogen.,  25  (16): [PMID:28662963] [10.1016/j.bmc.2017.05.053]

2. Das, Jagabandhu J and 20 more authors.  2006-11-16  2-aminothiazole as a novel kinase inhibitor template. Structure-activity relationship studies toward the discovery of N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1- piperazinyl)]-2-methyl-4-pyrimidinyl]amino)]-1,3-thiazole-5-carboxamide (dasatinib, BMS-354825) as a potent pan-Src kinase inhibitor.  [PMID:17154512]

3. Apsel, Beth and 9 more authors.  2008-11  Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases.  [PMID:18849971]

4. Remsing Rix, L L LL and 11 more authors.  2009-03  Global target profile of the kinase inhibitor bosutinib in primary chronic myeloid leukemia cells.  [PMID:19039322]

5. Byrd, John C JC and 29 more authors.  2016-01-28  Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia.  [PMID:26641137]

6. Daydé-Cazals, Bénédicte B and 11 more authors.  2016-04-28  Rational Design, Synthesis, and Biological Evaluation of 7-Azaindole Derivatives as Potent Focused Multi-Targeted Kinase Inhibitors.  [PMID:27010810]

7. Fraser, Craig C and 13 more authors.  2016-05-26  Rapid Discovery and Structure-Activity Relationships of Pyrazolopyrimidines That Potently Suppress Breast Cancer Cell Growth via SRC Kinase Inhibition with Exceptional Selectivity over ABL Kinase.  [PMID:27115835]

8. Bachegowda, Lohith L and 35 more authors.  2016-08-15  Pexmetinib: A Novel Dual Inhibitor of Tie2 and p38 MAPK with Efficacy in Preclinical Models of Myelodysplastic Syndromes and Acute Myeloid Leukemia.  [PMID:27287719]

9. Zhang, Chun-Hui CH and 17 more authors.  2016-11-10  From Lead to Drug Candidate: Optimization of 3-(Phenylethynyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine Derivatives as Agents for the Treatment of Triple Negative Breast Cancer.  [PMID:27739679]

10. Yuki, Hitomi H and 10 more authors.  2017-08-15  Activity cliff for 7-substituted pyrrolo-pyrimidine inhibitors of HCK explained in terms of predicted basicity of the amine nitrogen.  [PMID:28662963]

11. Klaeger, Susan S and 47 more authors.  2017-12-01  The target landscape of clinical kinase drugs.  [PMID:29191878]

12. He, Linhong L and 9 more authors.  2018-02-10  Design, synthesis and biological evaluation of 7H-pyrrolo[2,3-d]pyrimidin-4-amine derivatives as selective Btk inhibitors with improved pharmacokinetic properties for the treatment of rheumatoid arthritis.  [PMID:29324347]

13. Dart, Melanie L and 11 more authors.  2018-06-14  Homogeneous Assay for Target Engagement Utilizing Bioluminescent Thermal Shift.  [PMID:29937980]

14. Narayan, Satya S and 7 more authors.  2019-01-01  ASR352, A potent anticancer agent: Synthesis, preliminary SAR, and biological activities against colorectal cancer bulk, 5-fluorouracil/oxaliplatin resistant and stem cells.  [PMID:30384048]

Source

Source(1):

• Scientific Literature