ID: ALA1170455

Max Phase: Preclinical

Molecular Formula: C13H26O6

Molecular Weight: 278.35

Molecule Type: Small molecule

Representations

Synonyms (1): Alpha-D-Heptylmannoside
Synonyms from Alternative Forms(1):

Canonical SMILES:  CCCCCCCO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]1O

Standard InChI:  InChI=1S/C13H26O6/c1-2-3-4-5-6-7-18-13-12(17)11(16)10(15)9(8-14)19-13/h9-17H,2-8H2,1H3/t9-,10-,11+,12+,13+/m1/s1

Standard InChI Key:  NIDYWHLDTIVRJT-BNDIWNMDSA-N

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

Properties

Molecular Weight: 278.35

Molecular Weight (Monoisotopic): 278.1729

AlogP: -0.23

#Rotatable Bonds: 8

Polar Surface Area: 99.38

Molecular Species: NEUTRAL

HBA: 6

HBD: 4

#RO5 Violations: 0

HBA (Lipinski): 6

HBD (Lipinski): 4

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 12.21

CX Basic pKa:

CX LogP: 0.37

CX LogD: 0.37

Aromatic Rings: 0

Heavy Atoms: 19

QED Weighted: 0.46

Np Likeness Score: 1.91

References

1. Han Z, Pinkner JS, Ford B, Obermann R, Nolan W, Wildman SA, Hobbs D, Ellenberger T, Cusumano CK, Hultgren SJ, Janetka JW..  (2010)  Structure-based drug design and optimization of mannoside bacterial FimH antagonists.,  53  (12): [PMID:20507142] [10.1021/jm100438s]

2. Klein T, Abgottspon D, Wittwer M, Rabbani S, Herold J, Jiang X, Kleeb S, Lüthi C, Scharenberg M, Bezençon J, Gubler E, Pang L, Smiesko M, Cutting B, Schwardt O, Ernst B..  (2010)  FimH antagonists for the oral treatment of urinary tract infections: from design and synthesis to in vitro and in vivo evaluation.,  53  (24): [PMID:21105658] [10.1021/jm101011y]

3. Schwardt O, Rabbani S, Hartmann M, Abgottspon D, Wittwer M, Kleeb S, Zalewski A, Smieško M, Cutting B, Ernst B..  (2011)  Design, synthesis and biological evaluation of mannosyl triazoles as FimH antagonists.,  19  (21): [PMID:21962988] [10.1016/j.bmc.2011.08.057]

4. Jiang X, Abgottspon D, Kleeb S, Rabbani S, Scharenberg M, Wittwer M, Haug M, Schwardt O, Ernst B..  (2012)  Antiadhesion therapy for urinary tract infections--a balanced PK/PD profile proved to be key for success.,  55  (10): [PMID:22519985] [10.1021/jm300192x]

5. Scharenberg M, Schwardt O, Rabbani S, Ernst B..  (2012)  Target Selectivity of FimH Antagonists.,  55  (22): [PMID:23088608] [10.1021/jm3010338]

6. Brument S, Sivignon A, Dumych TI, Moreau N, Roos G, Guérardel Y, Chalopin T, Deniaud D, Bilyy RO, Darfeuille-Michaud A, Bouckaert J, Gouin SG..  (2013)  Thiazolylaminomannosides as potent antiadhesives of type 1 piliated Escherichia coli isolated from Crohn's disease patients.,  56  (13): [PMID:23795713] [10.1021/jm400723n]

7. Roos G, Wellens A, Touaibia M, Yamakawa N, Geerlings P, Roy R, Wyns L, Bouckaert J..  (2013)  Validation of Reactivity Descriptors to Assess the Aromatic Stacking within the Tyrosine Gate of FimH.,  4  (11): [PMID:24900609] [10.1021/ml400269v]

8. Vanwetswinkel S, Volkov AN, Sterckx YG, Garcia-Pino A, Buts L, Vranken WF, Bouckaert J, Roy R, Wyns L, van Nuland NA..  (2014)  Study of the structural and dynamic effects in the FimH adhesin upon α-d-heptyl mannose binding.,  57  (4): [PMID:24476493] [10.1021/jm401666c]

9. Kleeb S, Pang L, Mayer K, Eris D, Sigl A, Preston RC, Zihlmann P, Sharpe T, Jakob RP, Abgottspon D, Hutter AS, Scharenberg M, Jiang X, Navarra G, Rabbani S, Smiesko M, Lüdin N, Bezençon J, Schwardt O, Maier T, Ernst B..  (2015)  FimH antagonists: bioisosteres to improve the in vitro and in vivo PK/PD profile.,  58  (5): [PMID:25666045] [10.1021/jm501524q]

10. Tomasic T, Rabbani S, Gobec M, Rascan IM, Podlipnik C, Ernst B, Anderluh M.  (2014)  Branched -d-mannopyranosides: a new class of potent FimH antagonists,  5  (8): [10.1039/C4MD00093E]

11. Mayer K, Eris D, Schwardt O, Sager CP, Rabbani S, Kleeb S, Ernst B..  (2017)  Urinary Tract Infection: Which Conformation of the Bacterial Lectin FimH Is Therapeutically Relevant?,  60  (13): [PMID:28471659] [10.1021/acs.jmedchem.7b00342]

12. Tomašič T, Rabbani S, Jakob RP, Reisner A, Jakopin Ž, Maier T, Ernst B, Anderluh M..  (2021)  Does targeting Arg98 of FimH lead to high affinity antagonists?,  211  [PMID:33340913] [10.1016/j.ejmech.2020.113093]

13. Singh K, Kulkarni SS..  (2022)  Small Carbohydrate Derivatives as Potent Antibiofilm Agents.,  65  (13.0): [PMID:35777073] [10.1021/acs.jmedchem.1c01039]

Source

Source(1):

• Scientific Literature