(2S,4R)-1-((S)-2-(3-(2-(5-(4-(3-chloro-4-fluorophenylamino)-7-methoxyquinazolin-6-yloxy)pentyloxy)ethoxy)propanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide

ID: ALA4587573

Cas Number: 2230821-27-7

PubChem CID: 135156947

Product Number: G287801, Order Now?

Max Phase: Preclinical

Molecular Formula: C47H57ClFN7O8S

Molecular Weight: 934.53

Molecule Type: Unknown

In stock!

Associated Items:

Bioactivity Summary Target Summary Assay Summary

Names and Identifiers

Canonical SMILES: COc1cc2ncnc(Nc3ccc(F)c(Cl)c3)c2cc1OCCCCCOCCOCCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)NCc1ccc(-c2scnc2C)cc1)C(C)(C)C

Standard InChI: InChI=1S/C47H57ClFN7O8S/c1-29-42(65-28-53-29)31-11-9-30(10-12-31)25-50-45(59)38-22-33(57)26-56(38)46(60)43(47(2,3)4)55-41(58)15-18-63-20-19-62-16-7-6-8-17-64-40-23-34-37(24-39(40)61-5)51-27-52-44(34)54-32-13-14-36(49)35(48)21-32/h9-14,21,23-24,27-28,33,38,43,57H,6-8,15-20,22,25-26H2,1-5H3,(H,50,59)(H,55,58)(H,51,52,54)/t33-,38+,43-/m1/s1

Standard InChI Key: NICKHWYZMNLEPJ-TZSMONEZSA-N

Molfile:

 
     RDKit          2D

 65 70  0  0  0  0  0  0  0  0999 V2000
   -7.7949   -4.3418    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -7.7938   -5.1613    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -7.0903   -5.5703    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -7.0885   -3.9329    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -6.3774   -4.3382    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -6.3781   -5.1572    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.6669   -5.5643    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.9636   -5.1535    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.9672   -4.3313    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.6778   -3.9280    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -7.0839   -6.3875    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -7.7887   -6.7977    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.2609   -3.9184    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -4.2641   -3.1013    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.2532   -5.5593    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5478   -5.1480    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8373   -5.5538    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1319   -5.1425    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4214   -5.5483    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7160   -5.1370    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0056   -5.5428    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -8.5007   -6.3874    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -9.2060   -6.7970    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -9.2074   -7.6150    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -8.4930   -8.0218    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -7.7849   -7.6099    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -9.9173   -6.3897    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   -9.9127   -8.0262    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    0.7034   -5.1315    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.4127   -5.5373    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.1188   -5.1260    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.8281   -5.5318    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.5342   -5.1205    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.2435   -5.5263    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.9496   -5.1150    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    4.2467   -6.3435    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.6589   -5.5208    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.3650   -5.1094    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.6621   -6.3380    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.9560   -6.7493    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.3714   -6.7438    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.6543   -7.1525    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.0743   -5.5153    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.3619   -4.2923    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    7.1598   -6.3277    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.9598   -6.4945    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.3657   -5.7851    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.8164   -5.1801    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.2951   -7.2397    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    7.9825   -4.3799    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.7585   -4.1237    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.3684   -4.6677    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.1444   -4.4115    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.3727   -3.8360    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   10.7508   -4.9555    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.5261   -4.6999    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.6929   -3.8990    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.0781   -3.3542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.3051   -3.6127    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.4685   -3.6418    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.1307   -4.1203    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.7889   -3.6359    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   13.5317   -2.8602    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.7145   -2.8653    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   13.1342   -4.9374    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  2  0
  8  9  1  0
  9 10  2  0
 10  5  1  0
  3 11  1  0
 11 12  1  0
  9 13  1  0
 13 14  1  0
  8 15  1  0
 15 16  1  0
 16 17  1  0
 17 18  1  0
 18 19  1  0
 19 20  1  0
 20 21  1  0
 12 22  2  0
 22 23  1  0
 23 24  2  0
 24 25  1  0
 25 26  2  0
 26 12  1  0
 23 27  1  0
 24 28  1  0
 21 29  1  0
 29 30  1  0
 30 31  1  0
 31 32  1  0
 32 33  1  0
 33 34  1  0
 34 35  1  0
 34 36  2  0
 37 35  1  0
 37 38  1  0
 37 39  1  6
 39 40  1  0
 39 41  1  0
 39 42  1  0
 38 43  1  0
 38 44  2  0
 43 45  1  0
 45 46  1  0
 46 47  1  0
 47 48  1  0
 48 43  1  0
 46 49  1  1
 48 50  1  6
 50 51  1  0
 51 52  1  0
 52 53  1  0
 50 54  2  0
 53 55  2  0
 55 56  1  0
 56 57  2  0
 57 58  1  0
 58 59  2  0
 59 53  1  0
 57 60  1  0
 60 61  2  0
 61 62  1  0
 62 63  2  0
 63 64  1  0
 64 60  1  0
 61 65  1  0
M  END

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

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: 934.53	Molecular Weight (Monoisotopic): 933.3662	AlogP: 7.39	#Rotatable Bonds: 22
Polar Surface Area: 186.36	Molecular Species: NEUTRAL	HBA: 13	HBD: 4
#RO5 Violations: 3	HBA (Lipinski): 15	HBD (Lipinski): 4	#RO5 Violations (Lipinski): 3
CX Acidic pKa: 12.50	CX Basic pKa: 5.04	CX LogP: 5.43	CX LogD: 5.43
Aromatic Rings: 5	Heavy Atoms: 65	QED Weighted: 0.05	Np Likeness Score: -0.90

References

1. Cheng M, Yu X, Lu K, Xie L, Wang L, Meng F, Han X, Chen X, Liu J, Xiong Y, Jin J.. (2020) Discovery of Potent and Selective Epidermal Growth Factor Receptor (EGFR) Bifunctional Small-Molecule Degraders., 63 (3): [PMID:31895569] [10.1021/acs.jmedchem.9b01566]
2. Zhao HY,Yang XY,Lei H,Xi XX,Lu SM,Zhang JJ,Xin M,Zhang SQ. (2020) Discovery of potent small molecule PROTACs targeting mutant EGFR., 208 [PMID:32883633] [10.1016/j.ejmech.2020.112781]
3. García Jiménez D, Rossi Sebastiano M, Vallaro M, Mileo V, Pizzirani D, Moretti E, Ermondi G, Caron G.. (2022) Designing Soluble PROTACs: Strategies and Preliminary Guidelines., 65 (19.0): [PMID:35469399] [10.1021/acs.jmedchem.2c00201]
4. Yu X, Cheng M, Lu K, Shen Y, Zhong Y, Liu J, Xiong Y, Jin J.. (2022) Exploring Degradation of Mutant and Wild-Type Epidermal Growth Factor Receptors Induced by Proteolysis-Targeting Chimeras., 65 (12.0): [PMID:35675209] [10.1021/acs.jmedchem.2c00345]
5. Wang C, Zhang Y, Wang J, Xing D.. (2022) VHL-based PROTACs as potential therapeutic agents: Recent progress and perspectives., 227 [PMID:34656901] [10.1016/j.ejmech.2021.113906]
6. Zhao HY, Wang HP, Mao YZ, Zhang H, Xin M, Xi XX, Lei H, Mao S, Li DH, Zhang SQ.. (2022) Discovery of Potent PROTACs Targeting EGFR Mutants through the Optimization of Covalent EGFR Ligands., 65 (6.0): [PMID:35254067] [10.1021/acs.jmedchem.1c01827]

(2S,4R)-1-((S)-2-(3-(2-(5-(4-(3-chloro-4-fluorophenylamino)-7-methoxyquinazolin-6-yloxy)pentyloxy)ethoxy)propanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide

Names and Identifiers

Alternative Forms

Associated Targets(Human)

Molecule Features

Drug Indications

Mechanisms of Action

Calculated Properties

References

Source