2-(4-(4-(5-chloro-4-(2-(isopropylsulfonyl)phenylamino)pyrimidin-2-ylamino)-5-isopropoxy-2-methylphenyl)piperidin-1-yl)-N-(17-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-ylamino)-3,6,9,12,15-pentaoxaheptadecyl)acetamide

ID: ALA4165519

PubChem CID: 137628669

Max Phase: Preclinical

Molecular Formula: C55H72ClN9O13S

Molecular Weight: 1134.75

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Cc1cc(Nc2ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n2)c(OC(C)C)cc1C1CCN(CC(=O)NCCOCCOCCOCCOCCOCCNc2cccc3c2C(=O)N(C2CCC(=O)NC2=O)C3=O)CC1

Standard InChI:  InChI=1S/C55H72ClN9O13S/c1-35(2)78-46-32-40(37(5)31-44(46)61-55-59-33-41(56)51(63-55)60-42-10-6-7-12-47(42)79(71,72)36(3)4)38-15-19-64(20-16-38)34-49(67)58-18-22-74-24-26-76-28-30-77-29-27-75-25-23-73-21-17-57-43-11-8-9-39-50(43)54(70)65(53(39)69)45-13-14-48(66)62-52(45)68/h6-12,31-33,35-36,38,45,57H,13-30,34H2,1-5H3,(H,58,67)(H,62,66,68)(H2,59,60,61,63)

Standard InChI Key:  VEKJQNCZEPLNJF-UHFFFAOYSA-N

Molfile:  

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M  END

Alternative Forms

1. Parent:

   

   ALA4165519

   ---

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: 1134.75

Molecular Weight (Monoisotopic): 1133.4659

AlogP: ┄

#Rotatable Bonds: ┄

Polar Surface Area: ┄

Molecular Species: ┄

HBA: ┄

HBD: ┄

#RO5 Violations: ┄

HBA (Lipinski): ┄

HBD (Lipinski): ┄

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: ┄

CX LogP: ┄

CX LogD: ┄

Aromatic Rings: ┄

Heavy Atoms: ┄

QED Weighted: ┄

Np Likeness Score: ┄

References

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2. Kargbo RB..  (2019)  PROTACs and Targeted Protein Degradation for Treating ALK-Mediated Cancers.,  10  (8): [PMID:31413792] [10.1021/acsmedchemlett.9b00296]

3. Galkin, Anna V AV and 16 more authors.  2007-01-02  Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK.  [PMID:17185414]

4. McDermott, Ultan U and 24 more authors.  2007-12-11  Identification of genotype-correlated sensitivity to selective kinase inhibitors by using high-throughput tumor cell line profiling.  [PMID:18077425]

5. Sabbatini, Peter P and 19 more authors.  2009-10  GSK1838705A inhibits the insulin-like growth factor-1 receptor and anaplastic lymphoma kinase and shows antitumor activity in experimental models of human cancers.  [PMID:19825801]

6. Kim, Mi-hyun MH and 6 more authors.  2011-03-15  Structure based design and syntheses of amino-1H-pyrazole amide derivatives as selective Raf kinase inhibitors in melanoma cells.  [PMID:21353571]

7. Katayama, Ryohei R and 9 more authors.  2011-05-03  Therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK.  [PMID:21502504]

8. Lovly, Christine M CM and 6 more authors.  2011-07-15  Insights into ALK-driven cancers revealed through development of novel ALK tyrosine kinase inhibitors.  [PMID:21613408]

9. Kim, Hyangmi; Kim, Minjung; Lee, Junghun; Yu, Hana and Hah, Jung-Mi.  2011-11-15  Syntheses of phenylpyrazolodiazepin-7-ones as conformationally rigid analogs of aminopyrazole amide scaffold and their antiproliferative effects on cancer cells.  [PMID:22014755]

10. Weinberg, Linda R LR and 13 more authors.  2011-12-15  2,7-Pyrrolo[2,1-f][1,2,4]triazines as JAK2 inhibitors: modification of target structure to minimize reactive metabolite formation.  [PMID:22041060]

11. Tripathy, Rabindranath R and 9 more authors.  2011-12-15  Pyrazolone-based anaplastic lymphoma kinase (ALK) inhibitors: control of selectivity by a benzyloxy group.  [PMID:22061645]

12. Song, Zilan Z and 10 more authors.  2015-01-08  Discovery of novel 2,4-diarylaminopyrimidine analogues (DAAPalogues) showing potent inhibitory activities against both wild-type and mutant ALK kinases.  [PMID:24785465]

13. Johnson, Ted W TW and 32 more authors.  2014-06-12  Discovery of (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (PF-06463922), a macrocyclic inhibitor of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) with preclinical brain exposure and broad-spectrum potency against ALK-resistant mutations.  [PMID:24819116]

14. Ott, Gregory R GR and 15 more authors.  2010-12-09  Discovery of a potent inhibitor of anaplastic lymphoma kinase with in vivo antitumor activity.  [PMID:24900237]

15. Michellys, Pierre-Yves PY and 19 more authors.  2016-02-01  Design and synthesis of novel selective anaplastic lymphoma kinase inhibitors.  [PMID:26750252]

16. Song, Dawn D and 7 more authors.  2016-04-01  Novel 2,4-diaminopyrimidines bearing tetrahydronaphthalenyl moiety against anaplastic lymphoma kinase (ALK): Synthesis, in vitro, ex vivo, and in vivo efficacy studies.  [PMID:26923695]

17. Zhang, Peilong P and 22 more authors.  2016-04-15  Design and synthesis of novel 3-sulfonylpyrazol-4-amino pyrimidines as potent anaplastic lymphoma kinase (ALK) inhibitors.  [PMID:26979157]

18. Huang, Wei-Sheng WS and 33 more authors.  2016-05-26  Discovery of Brigatinib (AP26113), a Phosphine Oxide-Containing, Potent, Orally Active Inhibitor of Anaplastic Lymphoma Kinase.  [PMID:27144831]

19. Basit, Sulman S, Ashraf, Zaman Z, Lee, Kwangho K and Latif, Muhammad M.  2017-07-07  First macrocyclic 3rd-generation ALK inhibitor for treatment of ALK/ROS1 cancer: Clinical and designing strategy update of lorlatinib.  [PMID:28431340]

20. Jang, Jaebong J and 10 more authors.  2017-08-18  Discovery of a potent dual ALK and EGFR T790M inhibitor.  [PMID:28528303]

21. Chen, Yongfei Y and 17 more authors.  2017-10-20  Discovery of N-(5-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-4-methoxy-2-(4-methyl-1,4-diazepan-1-yl)phenyl)acrylamide (CHMFL-ALK/EGFR-050) as a potent ALK/EGFR dual kinase inhibitor capable of overcoming a variety of ALK/EGFR associated drug resistant mutants in NSCLC.  [PMID:28850922]

22. Mah, Shinmee S and 10 more authors.  2017-11-22  Identification of 4-Phenoxyquinoline Based Inhibitors for L1196M Mutant of Anaplastic Lymphoma Kinase by Structure-Based Design.  [PMID:29091425]

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

24. Gao, Jun-Bo JB and 8 more authors.  2018-04-27  Isolation, Characterization, and Structure-Activity Relationship Analysis of Abietane Diterpenoids from Callicarpa bodinieri as Spleen Tyrosine Kinase Inhibitors.  [PMID:29578342]

25. Zhang, Chengwei C and 6 more authors.  2018-05-10  Proteolysis Targeting Chimeras (PROTACs) of Anaplastic Lymphoma Kinase (ALK).  [PMID:29627725]

26. Powell, Chelsea E CE and 10 more authors.  2018-05-10  Chemically Induced Degradation of Anaplastic Lymphoma Kinase (ALK).  [PMID:29660984]

27. Drilon, Alexander A and 21 more authors.  2018-10  Repotrectinib (TPX-0005) Is a Next-Generation ROS1/TRK/ALK Inhibitor That Potently Inhibits ROS1/TRK/ALK Solvent- Front Mutations.  [PMID:30093503]

28. Luo, Lian-Xiang LX and 9 more authors.  2017-10-01  Identification of a potent kinase inhibitor targeting EML4-ALK fusion protein in non-small cell lung cancer.  [PMID:30108712]

29. 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]

30. Watts, Ellen E and 8 more authors.  2019-03-14  Designing Dual Inhibitors of Anaplastic Lymphoma Kinase (ALK) and Bromodomain-4 (BRD4) by Tuning Kinase Selectivity.  [PMID:30789735]

31. Yan, Guoyi and 11 more authors.  2021-02-11  Targeting Cysteine Located Outside the Active Site: An Effective Strategy for Covalent ALKi Design.  [PMID:33471528]

Source

Source(1):

• Scientific Literature