ID: ALA375586

Max Phase: Preclinical

Molecular Formula: C31H52N2O23

Molecular Weight: 820.75

Molecule Type: Small molecule

Representations

Synonyms (4): Sialyl lewis-x | sialyl LewisX | Sialyl LeX | sLex
Synonyms from Alternative Forms(4):

Canonical SMILES:  CC(=O)N[C@H]1[C@H]([C@H](O)[C@H](O)CO)O[C@@](O[C@H]2[C@@H](O)[C@@H](CO)O[C@@H](O[C@@H]([C@H](O[C@@H]3O[C@@H](C)[C@@H](O)[C@@H](O)[C@@H]3O)[C@H](C=O)NC(C)=O)[C@H](O)CO)[C@@H]2O)(C(=O)O)C[C@@H]1O

Standard InChI:  InChI=1S/C31H52N2O23/c1-9-18(43)21(46)22(47)28(51-9)53-24(12(5-34)32-10(2)38)25(15(42)7-36)54-29-23(48)27(20(45)16(8-37)52-29)56-31(30(49)50)4-13(40)17(33-11(3)39)26(55-31)19(44)14(41)6-35/h5,9,12-29,35-37,40-48H,4,6-8H2,1-3H3,(H,32,38)(H,33,39)(H,49,50)/t9-,12-,13-,14+,15+,16+,17+,18+,19+,20-,21+,22-,23+,24+,25+,26+,27-,28-,29-,31-/m0/s1

Standard InChI Key:  LAQPKDLYOBZWBT-NYLDSJSYSA-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: 820.75

Molecular Weight (Monoisotopic): 820.2961

AlogP: -9.39

#Rotatable Bonds: 18

Polar Surface Area: 410.71

Molecular Species: ACID

HBA: 22

HBD: 15

#RO5 Violations: 3

HBA (Lipinski): 25

HBD (Lipinski): 15

#RO5 Violations (Lipinski): 3

CX Acidic pKa: 2.84

CX Basic pKa:

CX LogP: -8.75

CX LogD: -12.24

Aromatic Rings: 0

Heavy Atoms: 56

QED Weighted: 0.06

Np Likeness Score: 1.49

References

1. Kogan TP, Dupré B, Bui H, McAbee KL, Kassir JM, Scott IL, Hu X, Vanderslice P, Beck PJ, Dixon RA..  (1998)  Novel synthetic inhibitors of selectin-mediated cell adhesion: synthesis of 1,6-bis[3-(3-carboxymethylphenyl)-4-(2-alpha-D- mannopyranosyloxy)phenyl]hexane (TBC1269).,  41  (7): [PMID:9544210] [10.1021/jm9704917]

2. De Vleeschauwer M, Vaillancourt M, Goudreau N, Guindon Y, Gravel D..  (2001)  Design and synthesis of a new sialyl Lewis X mimetic: how selective are the selectin receptors?,  11  (9): [PMID:11354355] [10.1016/s0960-894x(01)00130-5]

3. De Vleeschauwer M, Vaillancourt M, Goudreau N, Guindon Y, Gravel D..  (2001)  Design and synthesis of a new sialyl Lewis X mimetic: how selective are the selectin receptors?,  11  (9): [PMID:11354355] [10.1016/s0960-894x(01)00130-5]

4. De Vleeschauwer M, Vaillancourt M, Goudreau N, Guindon Y, Gravel D..  (2001)  Design and synthesis of a new sialyl Lewis X mimetic: how selective are the selectin receptors?,  11  (9): [PMID:11354355] [10.1016/s0960-894x(01)00130-5]

5. Ohmoto H, Nakamura K, Inoue T, Kondo N, Inoue Y, Yoshino K, Kondo H, Ishida H, Kiso M, Hasegawa A..  (1996)  Studies on selectin blocker. 1. Structure-activity relationships of sialyl Lewis X analogs.,  39  (6): [PMID:8632441] [10.1021/jm9506478]

6. Roy R, Park WK, Srivastava OP, Foxall C.  (1996)  Combined glycomimetic and multivalent strategies for the design of potent selectin antagonists,  6  (12): [10.1016/0960-894X(96)00240-5]

7. Hiramatsu Y, Tsukida T, Nakai Y, Inoue Y, Kondo H..  (2000)  Study on selectin blocker. 8. Lead discovery of a non-sugar antagonist using a 3D-pharmacophore model.,  43  (8): [PMID:10780903] [10.1021/jm990342j]

8. Kaila N, Thomas BE, Thakker P, Alvarez JC, Camphausen RT, Crommie D..  (2001)  Design and synthesis of sialyl Lewis x mimics as E-selectin inhibitors.,  11  (2): [PMID:11206447] [10.1016/s0960-894x(00)00623-5]

9. Kaila N, Chen L, Thomas BE, Tsao D, Tam S, Bedard PW, Camphausen RT, Alvarez JC, Ullas G..  (2002)  Beta-C-mannosides as selectin inhibitors.,  45  (8): [PMID:11931610] [10.1021/jm010390f]

10. Kaila N, Chen L, Thomas BE, Tsao D, Tam S, Bedard PW, Camphausen RT, Alvarez JC, Ullas G..  (2002)  Beta-C-mannosides as selectin inhibitors.,  45  (8): [PMID:11931610] [10.1021/jm010390f]

11. Bradley SJ, Fazli A, Kiefel MJ, von Itzstein M..  (2001)  Synthesis of novel sialylmimetics as biological probes.,  11  (12): [PMID:11412987] [10.1016/s0960-894x(01)00276-1]

12. Kurokawa K, Kumihara H, Kondo H..  (2000)  A solid-phase synthesis for beta-turn mimetics of sialyl Lewis X.,  10  (16): [PMID:10969978] [10.1016/s0960-894x(00)00358-9]

13. Wada Y, Saito T, Matsuda N, Ohmoto H, Yoshino K, Ohashi M, Kondo H, Ishida H, Kiso M, Hasegawa A..  (1996)  Studies on selectin blockers. 2. Novel selectin blocker as potential therapeutics for inflammatory disorders.,  39  (10): [PMID:8642564] [10.1021/jm950877m]

14. Slee DH, Romano SJ, Yu J, Nguyen TN, John JK, Raheja NK, Axe FU, Jones TK, Ripka WC..  (2001)  Development of potent non-carbohydrate imidazole-based small molecule selectin inhibitors with antiinflammatory activity.,  44  (13): [PMID:11405647] [10.1021/jm000508c]

15. Tsai CY, Park WK, Weitz-Schmidt G, Ernst B, Wong CH..  (1998)  Synthesis of sialyl Lewis X mimetics using the Ugi four-component reaction.,  8  (17): [PMID:9873537] [10.1016/s0960-894x(98)00422-3]

16. Bamford MJ, Bird M, Gore PM, Holmes DS, Priest R, Prodger JC, Saez V.  (1996)  Synthesis and biological activity of conformationally constrained sialyl Lewis X analogues with reduced carbohydrate character,  6  (3): [10.1016/0960-894X(96)00008-X]

17. Ragan JA, Cooper K.  (1994)  Synthesis of a galactose-fucose disaccharide mimic of sialyl Lewis X,  4  (21): [10.1016/S0960-894X(01)80284-5]

18. Birkbeck AA, Ley SV, Prodger JC.  (1995)  Spiroketal glycomimetics: the synthesis of a conformationally restrained Sialyl Lewis X mimic,  5  (22): [10.1016/0960-894X(95)00469-A]

19. Lin C, Kimura T, Wu S, Weitz-Schmidt G, Wong C.  (1996)  Liposome-like fucopeptides as sialyl lewis X mimetics,  6  (22): [10.1016/S0960-894X(96)00509-4]

20. Hanessian S, Huynh HK, Reddy GV, McNaughton-Smith G, Ernst B, Kolb HC, Magnani J, Sweeley C..  (1998)  Exploration of beta-turn scaffolding motifs as components of sialyl Le(X) mimetics and their relevance to P-selectin.,  8  (19): [PMID:9873626] [10.1016/s0960-894x(98)00500-9]

21. Tsukida T, Hiramatsu Y, Tsujishita H, Kiyoi T, Yoshida M, Kurokawa K, Moriyama H, Ohmoto H, Wada Y, Saito T, Kondo H..  (1997)  Studies on selection blockers. 5. Design, synthesis, and biological profile of sialyl Lewis x mimetics based on modified serine-glutamic acid dipeptides.,  40  (22): [PMID:9357520] [10.1021/jm970262k]

22. Tsukida T, Moriyama H, Kurokawa K, Achiha T, Inoue Y, Kondo H..  (1998)  Studies on selectin blockers. 7. Structure-activity relationships of sialyl Lewis X mimetics based on modified Ser-Glu dipeptides.,  41  (22): [PMID:9784103] [10.1021/jm980267x]

23. Hiramatsu Y, Tsujishita H, Kondo H..  (1996)  Studies on selectin blocker. 3. Investigation of the carbohydrate ligand sialyl Lewis X recognition site of P-selectin.,  39  (23): [PMID:8917642] [10.1021/jm960134g]

24. Kogan TP, Dupré B, Keller KM, Scott IL, Bui H, Market RV, Beck PJ, Voytus JA, Revelle BM, Scott D..  (1995)  Rational design and synthesis of small molecule, non-oligosaccharide selectin inhibitors: (alpha-D-mannopyranosyloxy)biphenyl-substituted carboxylic acids.,  38  (26): [PMID:8544173] [10.1021/jm00026a004]

25. Dupre B, Bui H, Scott IL, Market RV, Keller KM, Beck PJ, Kogan TP.  (1996)  Glycomimetic selectin inhibitors: (-D-mannopyranosyloxy)methylbiphenyls,  6  (5): [10.1016/0960-894X(96)00071-6]

26. Matsuda M, Nishimura S, Nakajima F, Nishimura T..  (2001)  Heterobifunctional ligands: practical chemoenzymatic synthesis of a cell adhesive glycopeptide that interacts with both selectins and integrins.,  44  (5): [PMID:11262082] [10.1021/jm000295r]

27. Ulbrich HK, Luxenburger A, Prech P, Eriksson EE, Soehnlein O, Rotzius P, Lindbom L, Dannhardt G..  (2006)  A novel class of potent nonglycosidic and nonpeptidic pan-selectin inhibitors.,  49  (20): [PMID:17004713] [10.1021/jm060468y]

28. Kranich R, Busemann AS, Bock D, Schroeter-Maas S, Beyer D, Heinemann B, Meyer M, Schierhorn K, Zahlten R, Wolff G, Aydt EM..  (2007)  Rational design of novel, potent small molecule pan-selectin antagonists.,  50  (6): [PMID:17302397] [10.1021/jm060536g]

29. Huang A, Moretto A, Janz K, Lowe M, Bedard PW, Tam S, Di L, Clerin V, Sushkova N, Tchernychev B, Tsao DH, Keith JC, Shaw GD, Schaub RG, Wang Q, Kaila N..  (2010)  Discovery of 2-[1-(4-chlorophenyl)cyclopropyl]-3-hydroxy-8-(trifluoromethyl)quinoline-4-carboxylic acid (PSI-421), a P-selectin inhibitor with improved pharmacokinetic properties and oral efficacy in models of vascular injury.,  53  (16): [PMID:20718494] [10.1021/jm9013696]

30. Calosso M, Tambutet G, Charpentier D, St-Pierre G, Vaillancourt M, Bencheqroun M, Gratton JP, Prévost M, Guindon Y..  (2014)  Acyclic tethers mimicking subunits of polysaccharide ligands: selectin antagonists.,  5  (9): [PMID:25221666] [10.1021/ml500266x]

Source

Source(1):

• Scientific Literature