3-(1-(3-(Biphenyl-4-ylamino)-3-oxopropyl)-1H-1,2,3-triazol-4-yl)-6-hydroxy-1-methyl-2-phenyl-1H-indole-5-carboxylic Acid

ID: ALA590043

Cas Number: 1143579-78-5

PubChem CID: 25262527

Max Phase: Preclinical

Molecular Formula: C33H27N5O4

Molecular Weight: 557.61

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Cn1c(-c2ccccc2)c(-c2cn(CCC(=O)Nc3ccc(-c4ccccc4)cc3)nn2)c2cc(C(=O)O)c(O)cc21

Standard InChI:  InChI=1S/C33H27N5O4/c1-37-28-19-29(39)26(33(41)42)18-25(28)31(32(37)23-10-6-3-7-11-23)27-20-38(36-35-27)17-16-30(40)34-24-14-12-22(13-15-24)21-8-4-2-5-9-21/h2-15,18-20,39H,16-17H2,1H3,(H,34,40)(H,41,42)

Standard InChI Key:  RATFAFAWIWHLMR-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 42 47  0  0  0  0  0  0  0  0999 V2000
    2.1677    3.0811    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3830    3.3361    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    4.3111    3.4936    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.8821    3.4936    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.6130    0.5491    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    4.3111    1.0186    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.5966    3.0811    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.1281   -0.1183    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.0255    2.2561    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.5966    2.2561    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.3435    0.1366    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.6588   -1.3181    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.8821    1.8436    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.8189   -2.4742    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.1677    2.2561    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.3111    1.8436    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3830    2.0012    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.8981    2.6686    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.1281    4.1207    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0731    2.6686    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3394    1.9542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1644    1.9542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.5769    2.6686    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1644    3.3831    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3394    3.3831    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.1281    1.2166    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.3435    0.9616    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3240   -0.3483    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2377   -1.1688    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.9052   -1.6537    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4864   -2.9591    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4001   -3.7796    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0676   -4.2645    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8212   -3.9289    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.9075   -3.1085    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.2400   -2.6235    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.4887   -4.4139    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.4024   -5.2344    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.0699   -5.7193    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.8236   -5.3837    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.9098   -4.5632    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.2424   -4.0783    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  1  4  1  0
  1 15  2  0
 18  2  1  0
 19  2  1  0
  7  3  1  0
  4  7  2  0
  5  8  2  0
 26  5  1  0
 16  6  2  0
  7 10  1  0
  8 11  1  0
 16  9  1  0
 10 13  2  0
 10 16  1  0
 27 11  1  0
 28 11  1  0
 30 12  2  0
 13 15  1  0
 30 14  1  0
 31 14  1  0
 15 17  1  0
 17 18  2  0
 26 17  1  0
 20 18  1  0
 20 21  2  0
 20 25  1  0
 21 22  1  0
 22 23  2  0
 23 24  1  0
 24 25  2  0
 26 27  2  0
 28 29  1  0
 29 30  1  0
 31 32  2  0
 31 36  1  0
 32 33  1  0
 33 34  2  0
 34 35  1  0
 34 37  1  0
 35 36  2  0
 37 38  2  0
 37 42  1  0
 38 39  1  0
 39 40  2  0
 40 41  1  0
 41 42  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA590043

   3-{1-[3-(biphenyl-4-ylamino)-3-oxopropyl]-1H-1,2,3-triazol-4-yl}-6-hydroxy-1-methyl-2-phenyl-1H-indole-5-carboxylic acid

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: 557.61

Molecular Weight (Monoisotopic): 557.2063

AlogP: 6.20

#Rotatable Bonds: 8

Polar Surface Area: 122.27

Molecular Species: ACID

HBA: 7

HBD: 3

#RO5 Violations: 2

HBA (Lipinski): 9

HBD (Lipinski): 3

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 3.37

CX Basic pKa: ┄

CX LogP: 6.74

CX LogD: 3.33

Aromatic Rings: 6

Heavy Atoms: 42

QED Weighted: 0.20

Np Likeness Score: -0.89

References

1. Zhang X, He Y, Liu S, Yu Z, Jiang ZX, Yang Z, Dong Y, Nabinger SC, Wu L, Gunawan AM, Wang L, Chan RJ, Zhang ZY..  (2010)  Salicylic acid based small molecule inhibitor for the oncogenic Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2).,  53  (6): [PMID:20170098] [10.1021/jm901645u]

2. Zhang X, He Y, Liu S, Yu Z, Jiang ZX, Yang Z, Dong Y, Nabinger SC, Wu L, Gunawan AM, Wang L, Chan RJ, Zhang ZY..  (2010)  Salicylic acid based small molecule inhibitor for the oncogenic Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2).,  53  (6): [PMID:20170098] [10.1021/jm901645u]

3. He Y, Zeng LF, Yu ZH, He R, Liu S, Zhang ZY..  (2012)  Bicyclic benzofuran and indole-based salicylic acids as protein tyrosine phosphatase inhibitors.,  20  (6): [PMID:22133902] [10.1016/j.bmc.2011.11.004]

4. Zeng LF, Zhang RY, Yu ZH, Li S, Wu L, Gunawan AM, Lane BS, Mali RS, Li X, Chan RJ, Kapur R, Wells CD, Zhang ZY..  (2014)  Therapeutic potential of targeting the oncogenic SHP2 phosphatase.,  57  (15): [PMID:25003231] [10.1021/jm5006176]

5. Garcia Fortanet J, Chen CH, Chen YN, Chen Z, Deng Z, Firestone B, Fekkes P, Fodor M, Fortin PD, Fridrich C, Grunenfelder D, Ho S, Kang ZB, Karki R, Kato M, Keen N, LaBonte LR, Larrow J, Lenoir F, Liu G, Liu S, Lombardo F, Majumdar D, Meyer MJ, Palermo M, Perez L, Pu M, Ramsey T, Sellers WR, Shultz MD, Stams T, Towler C, Wang P, Williams SL, Zhang JH, LaMarche MJ..  (2016)  Allosteric Inhibition of SHP2: Identification of a Potent, Selective, and Orally Efficacious Phosphatase Inhibitor.,  59  (17): [PMID:27347692] [10.1021/acs.jmedchem.6b00680]

6. Mostinski Y,Heynen GJJE,López-Alberca MP,Paul J,Miksche S,Radetzki S,Schaller D,Shanina E,Seyffarth C,Kolomeets Y,Ziebart N,de Schryver J,Oestreich S,Neuenschwander M,Roske Y,Heinemann U,Rademacher C,Volkamer A,von Kries JP,Birchmeier W,Nazaré M.  (2020)  From Pyrazolones to Azaindoles: Evolution of Active-Site SHP2 Inhibitors Based on Scaffold Hopping and Bioisosteric Replacement.,  63  (23.0): [PMID:33210922] [10.1021/acs.jmedchem.0c01265]

7. Song Y, Wang S, Zhao M, Yang X, Yu B..  (2022)  Strategies Targeting Protein Tyrosine Phosphatase SHP2 for Cancer Therapy.,  65  (4.0): [PMID:35157464] [10.1021/acs.jmedchem.1c02008]

Source

Source(1):

• Scientific Literature