ID: ALA1098427

Max Phase: Preclinical

Molecular Formula: C28H46O5

Molecular Weight: 462.67

Molecule Type: Small molecule

Representations

Synonyms (1): Hippuristanol
Synonyms from Alternative Forms(1):

Canonical SMILES:  C[C@H]1C[C@@]2(O[C@H]3C[C@H]4[C@@H]5CC[C@H]6C[C@H](O)CC[C@]6(C)[C@H]5[C@@H](O)C[C@]4(C)[C@H]3[C@@]2(C)O)OC1(C)C

Standard InChI:  InChI=1S/C28H46O5/c1-15-13-28(33-24(15,2)3)27(6,31)23-21(32-28)12-19-18-8-7-16-11-17(29)9-10-25(16,4)22(18)20(30)14-26(19,23)5/h15-23,29-31H,7-14H2,1-6H3/t15-,16-,17+,18-,19-,20-,21-,22+,23-,25-,26-,27+,28+/m0/s1

Standard InChI Key:  HPHXKNOXVBFETI-SHCCRYCOSA-N

Molecule Features

Natural Product: Yes

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

Properties

Molecular Weight: 462.67

Molecular Weight (Monoisotopic): 462.3345

AlogP: 4.27

#Rotatable Bonds: 0

Polar Surface Area: 79.15

Molecular Species: NEUTRAL

HBA: 5

HBD: 3

#RO5 Violations: 0

HBA (Lipinski): 5

HBD (Lipinski): 3

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 12.86

CX Basic pKa:

CX LogP: 3.27

CX LogD: 3.27

Aromatic Rings: 0

Heavy Atoms: 33

QED Weighted: 0.50

Np Likeness Score: 3.19

References

1. Li W, Dang Y, Liu JO, Yu B..  (2010)  Structural and stereochemical requirements of the spiroketal group of hippuristanol for antiproliferative activity.,  20  (10): [PMID:20409710] [10.1016/j.bmcl.2010.03.093]

2. Bordeleau ME, Mori A, Oberer M, Lindqvist L, Chard LS, Higa T, Belsham GJ, Wagner G, Tanaka J, Pelletier J..  (2006)  Functional characterization of IRESes by an inhibitor of the RNA helicase eIF4A.,  2  (4): [PMID:16532013] [10.1038/nchembio776]

3. Somaiah R, Ravindar K, Cencic R, Pelletier J, Deslongchamps P..  (2014)  Synthesis of the antiproliferative agent hippuristanol and its analogues from hydrocortisone via Hg(II)-catalyzed spiroketalization: structure-activity relationship.,  57  (6): [PMID:24588834] [10.1021/jm401799j]

4. Ito M, Iwatani M, Kamada Y, Sogabe S, Nakao S, Tanaka T, Kawamoto T, Aparicio S, Nakanishi A, Imaeda Y..  (2017)  Discovery of selective ATP-competitive eIF4A3 inhibitors.,  25  (7): [PMID:28283335] [10.1016/j.bmc.2017.02.035]

5. Tillotson J, Kedzior M, Guimarães L, Ross AB, Peters TL, Ambrose AJ, Schmidlin CJ, Zhang DD, Costa-Lotufo LV, Rodríguez AD, Schatz JH, Chapman E..  (2017)  ATP-competitive, marine derived natural products that target the DEAD box helicase, eIF4A.,  27  (17): [PMID:28757063] [10.1016/j.bmcl.2017.07.045]

6. Ito M, Tanaka T, Cary DR, Iwatani-Yoshihara M, Kamada Y, Kawamoto T, Aparicio S, Nakanishi A, Imaeda Y..  (2017)  Discovery of Novel 1,4-Diacylpiperazines as Selective and Cell-Active eIF4A3 Inhibitors.,  60  (8): [PMID:28358513] [10.1021/acs.jmedchem.6b01904]

7. Ernst JT, Thompson PA, Nilewski C, Sprengeler PA, Sperry S, Packard G, Michels T, Xiang A, Tran C, Wegerski CJ, Eam B, Young NP, Fish S, Chen J, Howard H, Staunton J, Molter J, Clarine J, Nevarez A, Chiang GG, Appleman JR, Webster KR, Reich SH..  (2020)  Design of Development Candidate eFT226, a First in Class Inhibitor of Eukaryotic Initiation Factor 4A RNA Helicase.,  63  (11): [PMID:32470302] [10.1021/acs.jmedchem.0c00182]

8. Fan A, Sharp PP..  (2021)  Inhibitors of Eukaryotic Translational Machinery as Therapeutic Agents.,  64  (5.0): [PMID:33592144] [10.1021/acs.jmedchem.0c01746]

Source

Source(1):

• Scientific Literature