SID24799629

ID: ALA1535899

PubChem CID: 16191300

Max Phase: Preclinical

Molecular Formula: C22H24N2O2

Molecular Weight: 348.45

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Cc1oc(-c2ccc(-c3ccccc3)cc2)nc1CN(C)C1CCOC1

Standard InChI:  InChI=1S/C22H24N2O2/c1-16-21(14-24(2)20-12-13-25-15-20)23-22(26-16)19-10-8-18(9-11-19)17-6-4-3-5-7-17/h3-11,20H,12-15H2,1-2H3

Standard InChI Key:  CIKIRRFWSMBYHX-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 26 29  0  0  0  0  0  0  0  0999 V2000
    0.3399    0.0137    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3746   -4.5878    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.4199   -0.7709    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.0379   -2.4933    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.1649    0.0137    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7524   -1.2558    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.6498    0.6812    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0850   -0.7709    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7524   -2.0808    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.6197    2.0161    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3143    1.4349    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.4703    0.5950    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0379   -3.3183    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7992    2.1023    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.9552    1.2624    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1046    2.6835    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6996   -1.0258    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6295   -3.8032    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7054   -3.8032    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.7691    3.4372    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.9251    2.5973    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.6765   -2.0808    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.4504   -4.5878    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.2540    4.1046    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4100    3.2647    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.0745    4.0184    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  5  1  0
  1  8  1  0
  2 18  1  0
  2 23  1  0
  3  5  2  0
  3  6  1  0
  4  9  1  0
  4 13  1  0
  4 22  1  0
  5  7  1  0
  6  8  2  0
  6  9  1  0
  7 11  2  0
  7 12  1  0
  8 17  1  0
 10 14  2  0
 10 15  1  0
 10 16  1  0
 11 14  1  0
 12 15  2  0
 13 18  1  0
 13 19  1  0
 16 20  2  0
 16 21  1  0
 19 23  1  0
 20 24  1  0
 21 25  2  0
 24 26  2  0
 25 26  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA1535899

   N-[(2-biphenyl-4-yl-5-methyl-1,3-oxazol-4-yl)methyl]-N-methyltetrahydrofuran-3-amine

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: 348.45

Molecular Weight (Monoisotopic): 348.1838

AlogP: 4.54

#Rotatable Bonds: 5

Polar Surface Area: 38.50

Molecular Species: NEUTRAL

HBA: 4

HBD: ┄

#RO5 Violations: ┄

HBA (Lipinski): 4

HBD (Lipinski): ┄

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: 6.94

CX LogP: 3.71

CX LogD: 3.58

Aromatic Rings: 3

Heavy Atoms: 26

QED Weighted: 0.68

Np Likeness Score: -1.11

References

1. PubChem BioAssay data set, 

2. PubChem BioAssay data set, 

3. Kung, Pei-Pei PP and 15 more authors.  2008-12-01  Dihydroxylphenyl amides as inhibitors of the Hsp90 molecular chaperone.  [PMID:18929486]

4. Zehnder, Luke L and 25 more authors.  2011-05-12  Optimization of potent, selective, and orally bioavailable pyrrolodinopyrimidine-containing inhibitors of heat shock protein 90. Identification of development candidate 2-amino-4-{4-chloro-2-[2-(4-fluoro-1H-pyrazol-1-yl)ethoxy]-6-methylphenyl}-N-(2,2-difluoropropyl)-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidine-6-carboxamide.  [PMID:21438541]

5. Zapf, Christoph W CW and 14 more authors.  2011-08-01  Discovery of a stable macrocyclic o-aminobenzamide Hsp90 inhibitor which significantly decreases tumor volume in a mouse xenograft model.  [PMID:21715165]

6. Suda, Atsushi A and 15 more authors.  2012-01-15  Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors.  [PMID:22192591]

7. Taldone, Tony and 10 more authors.  2013-09-12  Experimental and structural testing module to analyze paralogue-specificity and affinity in the Hsp90 inhibitors series.  [PMID:23965125]

8. Ernst, Justin T JT and 8 more authors.  2014-01-01  Correlation between chemotype-dependent binding conformations of HSP90α/β and isoform selectivity-Implications for the structure-based design of HSP90α/β selective inhibitors for treating neurodegenerative diseases.  [PMID:24332488]

9. Suda, Atsushi A and 16 more authors.  2014-01-15  Design and synthesis of 2-amino-6-(1H,3H-benzo[de]isochromen-6-yl)-1,3,5-triazines as novel Hsp90 inhibitors.  [PMID:24369839]

10. Ernst, Justin T JT and 18 more authors.  2014-04-24  Identification of novel HSP90α/β isoform selective inhibitors using structure-based drug design. demonstration of potential utility in treating CNS disorders such as Huntington's disease.  [PMID:24673104]

11. Li, Zhenyu Z and 10 more authors.  2014-11-24  Discovery of diamine-linked 17-aroylamido-17-demethoxygeldanamycins as potent Hsp90 inhibitors.  [PMID:25277067]

12. Chen, Danqi D and 18 more authors.  2014-11-24  Discovery of potent N-(isoxazol-5-yl)amides as HSP90 inhibitors.  [PMID:25313505]

13. Patel, Hardik J HJ and 17 more authors.  2015-05-14  Structure-activity relationship in a purine-scaffold compound series with selectivity for the endoplasmic reticulum Hsp90 paralog Grp94.  [PMID:25901531]

14. Crowley, Vincent M VM and 11 more authors.  2016-04-14  Development of Glucose Regulated Protein 94-Selective Inhibitors Based on the BnIm and Radamide Scaffold.  [PMID:27003516]

15. Zhang, Chi C and 7 more authors.  2017-01-05  Design, synthesis and pharmacological evaluation of 4,5-diarylisoxazols bearing amino acid residues within the 3-amido motif as potent heat shock protein 90 (Hsp90) inhibitors.  [PMID:27688186]

16. Jeong, Ju Hui JH and 6 more authors.  2016-11-29  Targeting the entry region of Hsp90's ATP binding pocket with a novel 6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl amide.  [PMID:27783977]

17. Khandelwal, Anuj A, Crowley, Vincent M VM and Blagg, Brian S J BSJ.  2017-10-12  Resorcinol-Based Grp94-Selective Inhibitors.  [PMID:29057043]

18. Que, Nanette L S and 6 more authors.  2018-04-12  Structure Based Design of a Grp94-Selective Inhibitor: Exploiting a Key Residue in Grp94 To Optimize Paralog-Selective Binding.  [PMID:29528635]

19. Ojha, Ritu R and 10 more authors.  2018-04-25  1-Aroylindoline-hydroxamic acids as anticancer agents, inhibitors of HSP90 and HDAC.  [PMID:29567459]

20. Jiang, Fen F, Guo, An-Ping AP, Xu, Jia-Chen JC, You, Qi-Dong QD and Xu, Xiao-Li XL.  2018-11-08  Discovery of a Potent Grp94 Selective Inhibitor with Anti-Inflammatory Efficacy in a Mouse Model of Ulcerative Colitis.  [PMID:30351001]

21. Yao, Hong H and 9 more authors.  2019-04-01  Design, synthesis, and biological evaluation of truncated deguelin derivatives as Hsp90 inhibitors.  [PMID:30784881]

22. Li, Li; Wang, Lei; You, Qi-Dong and Xu, Xiao-Li.  2020-03-12  Heat Shock Protein 90 Inhibitors: An Update on Achievements, Challenges, and Future Directions.  [PMID:31663736]

23. Ojha, Ritu and 14 more authors.  2020-03-15  Isoindoline scaffold-based dual inhibitors of HDAC6 and HSP90 suppressing the growth of lung cancer in vitro and in vivo.  [PMID:32058238]

24. Xu, Mengyang and 7 more authors.  2021-02-25  Discovering High Potent Hsp90 Inhibitors as Antinasopharyngeal Carcinoma Agents through Fragment Assembling Approach.  [PMID:33543615]

Source

Source(1):

• PubChem BioAssays