(2S,4R)-1-((S)-2-(5-(4-(4-(5-chloro-4-(2-(isopropylsulfonyl)phenylamino)pyrimidin-2-ylamino)-5-isopropoxy-2-methylphenyl)piperidin-1-yl)-5-oxopentanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide

ID: ALA4580597

PubChem CID: 139293028

Max Phase: Preclinical

Molecular Formula: C56H72ClN9O8S2

Molecular Weight: 1098.83

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  Cc1cc(Nc2ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n2)c(OC(C)C)cc1C1CCN(C(=O)CCCC(=O)N[C@H](C(=O)N2C[C@H](O)C[C@H]2C(=O)N[C@@H](C)c2ccc(-c3scnc3C)cc2)C(C)(C)C)CC1

Standard InChI:  InChI=1S/C56H72ClN9O8S2/c1-32(2)74-46-28-41(34(5)26-44(46)62-55-58-29-42(57)52(64-55)61-43-14-11-12-15-47(43)76(72,73)33(3)4)38-22-24-65(25-23-38)49(69)17-13-16-48(68)63-51(56(8,9)10)54(71)66-30-40(67)27-45(66)53(70)60-35(6)37-18-20-39(21-19-37)50-36(7)59-31-75-50/h11-12,14-15,18-21,26,28-29,31-33,35,38,40,45,51,67H,13,16-17,22-25,27,30H2,1-10H3,(H,60,70)(H,63,68)(H2,58,61,62,64)/t35-,40+,45-,51+/m0/s1

Standard InChI Key:  OLQKKOBOIAQEBA-RJKOKIJFSA-N

Molfile:  

 
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M  END

Alternative Forms

1. Parent:

   

   ALA4580597

   ---

Molecule Features

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: 1098.83

Molecular Weight (Monoisotopic): 1097.4634

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

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

2. 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]

3. 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]

4. 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]

5. 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]

6. 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]

7. 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]

8. 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]

9. 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]

10. 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]

11. 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]

12. 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]

13. 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]

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

15. 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]

16. 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]

17. 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]

18. 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]

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

20. 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]

21. 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]

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

23. 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]

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

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

26. 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]

27. 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]

28. 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]

29. 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]

30. 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