discodermolide

ID: ALA364447

Cas Number: 127943-53-7

PubChem CID: 643668

Max Phase: Phase

Molecular Formula: C33H55NO8

Molecular Weight: 593.80

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Discodermolide | XAA 296 | XAA-296 | XAA296 | Discodermolide|Disermolide|(+)-Discodermolide|Disermolide [INN]|127943-53-7|XAA-296|XAA 296|[(3Z,5S,6S,7S,8R,9S,11Z,13S,14S,15S,16Z,18S)-8,14,18-trihydroxy-19-[(2S,3R,4S,5R)-4-hydroxy-3,5-dimethyl-6-oxooxan-2-yl]-5,7,9,11,13,15-hexamethylnonadeca-1,3,11,16-tetraen-6-yl] carbamate|DHG59994DN|CHEBI:80700|(3Z,5S,6S,7S,8R,9S,11Z,13S,14S,15S,16Z,18S)-8,14,18-Trihydroxy-19-((2S,3R,4S,5R)-4-hydroxy-3,5-dimethyl-6-oxotetrahydro-2H-pyran-2-yl)-5,7,9,11,13,15-Show More⌵

Canonical SMILES:  C=C/C=C\[C@H](C)[C@H](OC(N)=O)[C@@H](C)[C@H](O)[C@@H](C)C/C(C)=C\[C@H](C)[C@@H](O)[C@@H](C)/C=C\[C@@H](O)C[C@@H]1OC(=O)[C@H](C)[C@@H](O)[C@H]1C

Standard InChI:  InChI=1S/C33H55NO8/c1-10-11-12-20(4)31(42-33(34)40)24(8)29(37)22(6)16-18(2)15-21(5)28(36)19(3)13-14-26(35)17-27-23(7)30(38)25(9)32(39)41-27/h10-15,19-31,35-38H,1,16-17H2,2-9H3,(H2,34,40)/b12-11-,14-13-,18-15-/t19-,20-,21-,22-,23-,24-,25+,26+,27-,28-,29+,30-,31-/m0/s1

Standard InChI Key:  AADVCYNFEREWOS-OBRABYBLSA-N

Molfile:  

     RDKit          2D

 42 42  0  0  0  0  0  0  0  0999 V2000
   -4.7364    5.5098    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.7364    6.3348    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.4509    6.7473    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -6.1654    6.3348    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -6.1654    5.5098    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.4509    5.0973    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -5.4509    7.5723    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -4.0219    6.7473    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.0219    5.0973    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -6.8798    5.0973    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -6.8799    6.7473    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -6.8798    4.2723    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -7.5943    3.8598    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -6.1654    3.8598    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -7.5943    3.0348    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -6.8798    2.6223    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -6.8798    1.7973    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -6.1654    3.0348    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -6.1654    1.3848    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -7.5943    1.3848    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -6.1654    0.5598    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.4509    1.7973    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.4509    0.1473    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.4509   -0.6777    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.7364    0.5598    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.0220    0.1473    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.3075    0.5598    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5930    0.1473    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.3075    1.3848    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -4.0220   -0.6777    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8785    0.5598    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5930   -0.6777    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1641    0.1473    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8785    1.3848    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4496    0.5598    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1641   -0.6777    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4496   -1.0902    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.2649   -0.6777    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.9793   -1.0902    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1641    1.7973    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.1641    2.6223    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4496    1.3848    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  6  1  1  0
  2  3  1  0
  3  4  1  0
  4  5  1  0
  5  6  1  0
  3  7  1  6
  2  8  1  1
  1  9  2  0
  5 10  1  1
  4 11  1  6
 10 12  1  0
 12 13  1  0
 12 14  1  6
 13 15  2  0
 15 16  1  0
 16 17  1  0
 16 18  1  6
 17 19  1  0
 17 20  1  1
 19 21  1  0
 19 22  1  1
 21 23  2  0
 23 24  1  0
 23 25  1  0
 25 26  1  0
 26 27  1  0
 27 28  1  0
 27 29  1  1
 26 30  1  1
 28 31  1  0
 28 32  1  1
 31 33  1  0
 31 34  1  1
 33 35  1  1
 33 36  1  0
 36 37  2  0
 37 38  1  0
 38 39  2  0
 34 40  1  0
 40 41  1  0
 40 42  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA364447

   DISERMOLIDE

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: Yes

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 593.80

Molecular Weight (Monoisotopic): 593.3928

AlogP: 4.30

#Rotatable Bonds: 16

Polar Surface Area: 159.54

Molecular Species: NEUTRAL

HBA: 8

HBD: 5

#RO5 Violations: 1

HBA (Lipinski): 9

HBD (Lipinski): 6

#RO5 Violations (Lipinski): 2

CX Acidic pKa: ┄

CX Basic pKa: ┄

CX LogP: 4.17

CX LogD: 4.17

Aromatic Rings: ┄

Heavy Atoms: 42

QED Weighted: 0.10

Np Likeness Score: 2.66

References

1. Choy N, Shin Y, Nguyen PQ, Curran DP, Balachandran R, Madiraju C, Day BW..  (2003)  Simplified discodermolide analogues: synthesis and biological evaluation of 4-epi-7-dehydroxy-14,16-didemethyl-(+)-discodermolides as microtubule-stabilizing agents.,  46  (14): [PMID:12825928] [10.1021/jm0204136]

2. Smith AB, Freeze BS, LaMarche MJ, Sager J, Kinzler KW, Vogelstein B..  (2005)  Discodermolide analogues as the chemical component of combination bacteriolytic therapy.,  15  (15): [PMID:15979874] [10.1016/j.bmcl.2005.05.068]

3. Paterson I, Menche D, Håkansson AE, Longstaff A, Wong D, Barasoain I, Buey RM, Díaz JF..  (2005)  Design, synthesis and biological evaluation of novel, simplified analogues of laulimalide: modification of the side chain.,  15  (9): [PMID:15837302] [10.1016/j.bmcl.2005.03.018]

4. Zhu G, Yang F, Balachandran R, Höök P, Vallee RB, Curran DP, Day BW..  (2006)  Synthesis and biological evaluation of purealin and analogues as cytoplasmic dynein heavy chain inhibitors.,  49  (6): [PMID:16539395] [10.1021/jm051030l]

5. Shaw SJ, Sundermann KF, Burlingame MA, Zhang D, Petryka J, Myles DC..  (2006)  A series of 23,24-dihydrodiscodermolide analogues with simplified lactone regions.,  16  (7): [PMID:16413186] [10.1016/j.bmcl.2005.12.066]

6. Jung WH, Harrison C, Shin Y, Fournier JH, Balachandran R, Raccor BS, Sikorski RP, Vogt A, Curran DP, Day BW..  (2007)  Total synthesis and biological evaluation of C16 analogs of (-)-dictyostatin.,  50  (13): [PMID:17542572] [10.1021/jm061385k]

7. Paterson I, Gardner NM, Poullennec KG, Wright AE..  (2007)  Synthesis and biological evaluation of novel analogues of dictyostatin.,  17  (9): [PMID:17336522] [10.1016/j.bmcl.2007.02.031]

8. Paterson I, Gardner NM, Poullennec KG, Wright AE..  (2008)  Synthesis and biological evaluation of 10,11-dihydrodictyostatin, a potent analogue of the marine anticancer agent dictyostatin.,  71  (3): [PMID:18081257] [10.1021/np070547s]

9. Gunasekera SP, Longley RE, Isbrucker RA..  (2001)  Acetylated analogues of the microtubule-stabilizing agent discodermolide: preparation and biological activity.,  64  (2): [PMID:11429994] [10.1021/np000423e]

10. Paterson I, Gardner NM, Guzmán E, Wright AE..  (2008)  Total synthesis and biological evaluation of potent analogues of dictyostatin: modification of the C2-C6 dienoate region.,  18  (23): [PMID:18951787] [10.1016/j.bmcl.2008.09.109]

11. Gunasekera SP, Mickel SJ, Daeffler R, Niederer D, Wright AE, Linley P, Pitts T..  (2004)  Synthetic analogues of the microtubule-stabilizing agent (+)-discodermolide: preparation and biological activity.,  67  (5): [PMID:15165132] [10.1021/np030493w]

12. Gunasekera SP, Longley RE, Isbrucker RA..  (2002)  Semisynthetic analogues of the microtubule-stabilizing agent discodermolide: preparation and biological activity.,  65  (12): [PMID:12502323] [10.1021/np0203234]

13. Gunasekera SP, Paul GK, Longley RE, Isbrucker RA, Pomponi SA..  (2002)  Five new discodermolide analogues from the marine sponge Discodermia species.,  65  (11): [PMID:12444691] [10.1021/np020219m]

14. Fan Y, Schreiber EM, Day BW..  (2009)  Human liver microsomal metabolism of (+)-discodermolide.,  72  (10): [PMID:19775091] [10.1021/np900245k]

15. Buey RM, Calvo E, Barasoain I, Pineda O, Edler MC, Matesanz R, Cerezo G, Vanderwal CD, Day BW, Sorensen EJ, López JA, Andreu JM, Hamel E, Díaz JF..  (2007)  Cyclostreptin binds covalently to microtubule pores and lumenal taxoid binding sites.,  3  (2): [PMID:17206139] [10.1038/nchembio853]

16. Fourches D, Barnes JC, Day NC, Bradley P, Reed JZ, Tropsha A..  (2010)  Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.,  23  (1): [PMID:20014752] [10.1021/tx900326k]

17. Smith AB, Sugasawa K, Atasoylu O, Yang CP, Horwitz SB..  (2011)  Design and synthesis of (+)-discodermolide-paclitaxel hybrids leading to enhanced biological activity.,  54  (18): [PMID:21870795] [10.1021/jm200692n]

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

19. Brunden KR, Gardner NM, James MJ, Yao Y, Trojanowski JQ, Lee VM, Paterson I, Ballatore C, Smith AB..  (2013)  MT-Stabilizer, Dictyostatin, Exhibits Prolonged Brain Retention and Activity: Potential Therapeutic Implications.,  4  (9): [PMID:24900764] [10.1021/ml400233e]

20. Joshi P, Vishwakarma RA, Bharate SB..  (2017)  Natural alkaloids as P-gp inhibitors for multidrug resistance reversal in cancer.,  138  [PMID:28675836] [10.1016/j.ejmech.2017.06.047]

21. Nadaradjane C, Yang CH, Rodriguez-Gabin A, Ye K, Sugasawa K, Atasoylu O, Smith AB, Horwitz SB, McDaid HM..  (2018)  Improved Dose-Response Relationship of (+)-Discodermolide-Taxol Hybrid Congeners.,  81  (3): [PMID:29522336] [10.1021/acs.jnatprod.8b00111]

22. Demeritte A, Wuest WM..  (2020)  A look around the West Indies: The spices of life are secondary metabolites.,  28  (23.0): [PMID:33038665] [10.1016/j.bmc.2020.115792]

Source

Source(2):

• Scientific Literature
• USP Dictionary of USAN and International Drug Names