ID: ALA1688852

Max Phase: Phase

First Approval: 1999

Molecular Formula: C31H52N2O5S

Molecular Weight: 564.83

Molecule Type: Small molecule

Representations

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

Canonical SMILES:  C=C[C@]1(C)C[C@@H](OC(=O)CSC(C)(C)CNC(=O)[C@H](N)C(C)C)[C@]2(C)[C@H](C)CC[C@]3(CCC(=O)[C@H]32)[C@@H](C)[C@@H]1O

Standard InChI:  InChI=1S/C31H52N2O5S/c1-10-29(8)15-22(38-23(35)16-39-28(6,7)17-33-27(37)24(32)18(2)3)30(9)19(4)11-13-31(20(5)26(29)36)14-12-21(34)25(30)31/h10,18-20,22,24-26,36H,1,11-17,32H2,2-9H3,(H,33,37)/t19-,20+,22-,24-,25+,26+,29-,30+,31+/m1/s1

Standard InChI Key:  LLYYNOVSVPBRGV-MVNKZKPCSA-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: Yes

Availability: No

Prodrug: No

Properties

Molecular Weight: 564.83

Molecular Weight (Monoisotopic): 564.3597

AlogP: 4.50

#Rotatable Bonds: 9

Polar Surface Area: 118.72

Molecular Species: BASE

HBA: 7

HBD: 3

#RO5 Violations: 1

HBA (Lipinski): 7

HBD (Lipinski): 4

#RO5 Violations (Lipinski): 1

CX Acidic pKa:

CX Basic pKa: 8.51

CX LogP: 3.97

CX LogD: 2.83

Aromatic Rings: 0

Heavy Atoms: 39

QED Weighted: 0.28

Np Likeness Score: 1.46

References

1. Kadlec K, Schwarz S..  (2010)  Identification of a plasmid-borne resistance gene cluster comprising the resistance genes erm(T), dfrK, and tet(L) in a porcine methicillin-resistant Staphylococcus aureus ST398 strain.,  54  (2): [PMID:20008780] [10.1128/aac.01091-09]

2. Kadlec K, Schwarz S..  (2009)  Novel ABC transporter gene, vga(C), located on a multiresistance plasmid from a porcine methicillin-resistant Staphylococcus aureus ST398 strain.,  53  (8): [PMID:19470508] [10.1128/aac.00570-09]

3. Long KS, Munck C, Andersen TM, Schaub MA, Hobbie SN, Böttger EC, Vester B..  (2010)  Mutations in 23S rRNA at the peptidyl transferase center and their relationship to linezolid binding and cross-resistance.,  54  (11): [PMID:20696869] [10.1128/aac.00644-10]

4. Dreier I, Kumar S, Søndergaard H, Rasmussen ML, Hansen LH, List NH, Kongsted J, Vester B, Nielsen P..  (2012)  A click chemistry approach to pleuromutilin derivatives, part 2: conjugates with acyclic nucleosides and their ribosomal binding and antibacterial activity.,  55  (5): [PMID:22280300] [10.1021/jm201266b]

5. Wang X, Ling Y, Wang H, Yu J, Tang J, Zheng H, Zhao X, Wang D, Chen G, Qiu W, Tao J..  (2012)  Novel pleuromutilin derivatives as antibacterial agents: synthesis, biological evaluation and molecular docking studies.,  22  (19): [PMID:22932314] [10.1016/j.bmcl.2012.08.021]

6. USP Dictionary of USAN and International Names (2010 edition) and USAN registrations 2007-date, 

7. PubChem BioAssay data set, 

8. Shang R, Liu Y, Xin Z, Guo W, Guo Z, Hao B, Jianping L..  (2013)  Synthesis and antibacterial evaluation of novel pleuromutilin derivatives.,  63  [PMID:23501109] [10.1016/j.ejmech.2013.01.048]

9. Dreier I, Hansen LH, Nielsen P, Vester B..  (2014)  A click chemistry approach to pleuromutilin derivatives. Part 3: extended footprinting analysis and excellent MRSA inhibition for a derivative with an adenine phenyl side chain.,  24  (4): [PMID:24486133] [10.1016/j.bmcl.2014.01.019]

10. Shang R, Pu X, Xu X, Xin Z, Zhang C, Guo W, Liu Y, Liang J..  (2014)  Synthesis and biological activities of novel pleuromutilin derivatives with a substituted thiadiazole moiety as potent drug-resistant bacteria inhibitors.,  57  (13): [PMID:24892980] [10.1021/jm500374c]

11. Gao ML, Zeng J, Fang X, Luo J, Jin Z, Liu YH, Tang YZ..  (2017)  Design, synthesis and antibacterial evaluation of novel pleuromutilin derivatives possessing piperazine linker.,  127  [PMID:28068600] [10.1016/j.ejmech.2017.01.004]

12. Siricilla S, Mitachi K, Yang J, Eslamimehr S, Lemieux MR, Meibohm B, Ji Y, Kurosu M..  (2017)  A New Combination of a Pleuromutilin Derivative and Doxycycline for Treatment of Multidrug-Resistant Acinetobacter baumannii.,  60  (7): [PMID:28291943] [10.1021/acs.jmedchem.6b01805]

13. Lemieux MR, Siricilla S, Mitachi K, Eslamimehr S, Wang Y, Yang D, Pressly JD, Kong Y, Park F, Franzblau SG, Kurosu M..  (2018)  An antimycobacterial pleuromutilin analogue effective against dormant bacilli.,  26  (17): [PMID:30145051] [10.1016/j.bmc.2018.07.034]

14. Jacobs RT, Lunde CS, Freund YR, Hernandez V, Li X, Xia Y, Carter DS, Berry PW, Halladay J, Rock F, Stefanakis R, Easom E, Plattner JJ, Ford L, Johnston KL, Cook DAN, Clare R, Cassidy A, Myhill L, Tyrer H, Gamble J, Guimaraes AF, Steven A, Lenz F, Ehrens A, Frohberger SJ, Koschel M, Hoerauf A, Hübner MP, McNamara CW, Bakowski MA, Turner JD, Taylor MJ, Ward SA..  (2019)  Boron-Pleuromutilins as Anti- Wolbachia Agents with Potential for Treatment of Onchocerciasis and Lymphatic Filariasis.,  62  (5): [PMID:30730745] [10.1021/acs.jmedchem.8b01854]

15. Heidtmann CV,Voukia F,Hansen LN,Sørensen SH,Urlund B,Nielsen S,Pedersen M,Kelawi N,Andersen BN,Pedersen M,Reinholdt P,Kongsted J,Nielsen CU,Klitgaard JK,Nielsen P.  (2020)  Discovery of a Potent Adenine-Benzyltriazolo-Pleuromutilin Conjugate with Pronounced Antibacterial Activity against MRSA.,  63  (24): [PMID:33325700] [10.1021/acs.jmedchem.0c01328]

16. Bernhard Ellinger, Justus Dick, Vanessa Lage-Rupprecht, Bruce Schultz, Andrea Zaliani, Marcin Namysl, Stephan Gebel, Ole Pless, Jeanette Reinshagen, Christian Ebeling, Alexander Esser, Marc Jacobs, Carsten Claussen, and Martin Hofmann-Apitius.  (2021)  HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators,  [10.6019/CHEMBL4808148]

17. Ding R, Wang X, Fu J, Chang Y, Li Y, Liu Y, Liu Y, Ma J, Hu J..  (2022)  Design, synthesis and antibacterial activity of novel pleuromutilin derivatives with thieno[2,3-d]pyrimidine substitution.,  237  [PMID:35468515] [10.1016/j.ejmech.2022.114398]

18. Yong C, Yu J, Wu C, Zhang X, Li Y, Xie C, He X, Liu D, Wang Z, Lai P, Zhang Y..  (2023)  Design, Synthesis, and Biological Activity of Thioguanine-Modified Pleuromutilin Derivatives.,  14  (6): [PMID:37312858] [10.1021/acsmedchemlett.3c00004]

Source

Source(4):

• Scientific Literature
• PubChem BioAssays
• USP Dictionary of USAN and International Drug Names
• Fraunhofer HDAC6