10'-Fluorovinblastine

ID: ALA2179942

Chembl Id: CHEMBL2179942

PubChem CID: 71450169

Max Phase: Preclinical

Molecular Formula: C46H57FN4O9

Molecular Weight: 828.98

Molecule Type: Small molecule

Names and Identifiers

Synonyms: 10'-Fluorovinblastine | 10'-Fluorovinblastine|CHEMBL2179942|JQDGXTXFHANTTF-BUCYGOEWSA-N

Canonical SMILES:  CC[C@]1(O)C[C@H]2CN(CCc3c([nH]c4ccc(F)cc34)[C@@](C(=O)OC)(c3cc4c(cc3OC)N(C)[C@H]3[C@@](O)(C(=O)OC)[C@H](OC(C)=O)[C@]5(CC)C=CCN6CC[C@]43[C@@H]65)C2)C1

Standard InChI:  InChI=1S/C46H57FN4O9/c1-8-42(55)22-27-23-45(40(53)58-6,36-29(13-17-50(24-27)25-42)30-19-28(47)11-12-33(30)48-36)32-20-31-34(21-35(32)57-5)49(4)38-44(31)15-18-51-16-10-14-43(9-2,37(44)51)39(60-26(3)52)46(38,56)41(54)59-7/h10-12,14,19-21,27,37-39,48,55-56H,8-9,13,15-18,22-25H2,1-7H3/t27-,37+,38-,39-,42+,43-,44-,45+,46+/m1/s1

Standard InChI Key:  JQDGXTXFHANTTF-BUCYGOEWSA-N

Alternative Forms

1. Parent:

   

   ALA2179942

   10'-Fluorovinblastine

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: 828.98

Molecular Weight (Monoisotopic): 828.4110

AlogP: 4.13

#Rotatable Bonds: 7

Polar Surface Area: 154.10

Molecular Species: BASE

HBA: 12

HBD: 3

#RO5 Violations: 2

HBA (Lipinski): 13

HBD (Lipinski): 3

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 10.87

CX Basic pKa: 8.80

CX LogP: 4.33

CX LogD: 2.08

Aromatic Rings: 3

Heavy Atoms: 60

QED Weighted: 0.18

Np Likeness Score: 1.35

References

1. Gotoh H, Duncan KK, Robertson WM, Boger DL..  (2011)  10'-Fluorovinblastine and 10'-Fluorovincristine: Synthesis of a Key Series of Modified Vinca Alkaloids.,  2  (12): [PMID:22247789] [10.1021/ml200236a]

2. Leggans EK, Duncan KK, Barker TJ, Schleicher KD, Boger DL..  (2013)  A remarkable series of vinblastine analogues displaying enhanced activity and an unprecedented tubulin binding steric tolerance: C20' urea derivatives.,  56  (3): [PMID:23244701] [10.1021/jm3015684]

3. Lukesh JC, Carney DW, Dong H, Cross RM, Shukla V, Duncan KK, Yang S, Brody DM, Brütsch MM, Radakovic A, Boger DL..  (2017)  Vinblastine 20' Amides: Synthetic Analogues That Maintain or Improve Potency and Simultaneously Overcome Pgp-Derived Efflux and Resistance.,  60  (17): [PMID:28857558] [10.1021/acs.jmedchem.7b00958]

4. Radakovic A, Boger DL..  (2018)  High expression of class III β-tubulin has no impact on functional cancer cell growth inhibition of a series of key vinblastine analogs.,  28  (5): [PMID:29439899] [10.1016/j.bmcl.2018.02.006]

Source

Source(1):

• Scientific Literature