(R)-2,3,6,7-tetramethoxy-9,10,11,12,12a,13-hexahydro-9a-aza-cyclopenta[b]triphenylene

ID: ALA258137

Chembl Id: CHEMBL258137

Cas Number: 111408-21-0

PubChem CID: 10883727

Max Phase: Preclinical

Molecular Formula: C24H27NO4

Molecular Weight: 393.48

Molecule Type: Small molecule

Names and Identifiers

Synonyms: GNF-Pf-838 | Tylophorine, (-)-|(-)-Tylophorine|7-Methoxyantofine|111408-21-0|(-)-(R)-Tylophorine|Tylophorine L-form [MI]|34U46VP03Y|DCB-3500|UNII-34U46VP03Y|(13aR)-9,11,12,13,13a,14-Hexahydro-2,3,6,7-tetramethoxydibenzo(f,H)pyrrolo(1,2-b)isoquinoline|GNF-PF-838|Dibenzo(f,H)pyrrolo(1,2-b)isoquinoline, 9,11,12,13,13a,14-hexahydro-2,3,6,7-tetramethoxy-, (13aR)-|CHEMBL258137|SCHEMBL8977400|AKOS040754280|Q27256392|(13aR)-2,3,6,7-tetramethoxy-9,11,12,13,13a,14-hexahydrophenanthro[9,10-f]indolizine

Canonical SMILES:  COc1cc2c3c(c4cc(OC)c(OC)cc4c2cc1OC)CN1CCC[C@@H]1C3

Standard InChI:  InChI=1S/C24H27NO4/c1-26-21-9-16-15-8-14-6-5-7-25(14)13-20(15)19-12-24(29-4)23(28-3)11-18(19)17(16)10-22(21)27-2/h9-12,14H,5-8,13H2,1-4H3/t14-/m1/s1

Standard InChI Key:  SSEUDFYBEOIWGF-CQSZACIVSA-N

Alternative Forms

1. Parent:

   

   ALA258137

   TYLOPHORINE

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

Calculated Properties

Molecular Weight: 393.48

Molecular Weight (Monoisotopic): 393.1940

AlogP: 4.55

#Rotatable Bonds: 4

Polar Surface Area: 40.16

Molecular Species: BASE

HBA: 5

HBD: ┄

#RO5 Violations: ┄

HBA (Lipinski): 5

HBD (Lipinski): ┄

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: ┄

CX Basic pKa: 8.67

CX LogP: 3.77

CX LogD: 2.48

Aromatic Rings: 3

Heavy Atoms: 29

QED Weighted: 0.61

Np Likeness Score: 0.40

References

1. Gao W, Chen AP, Leung CH, Gullen EA, Fürstner A, Shi Q, Wei L, Lee KH, Cheng YC..  (2008)  Structural analogs of tylophora alkaloids may not be functional analogs.,  18  (2): [PMID:18077159] [10.1016/j.bmcl.2007.11.054]

2. Damu AG, Kuo PC, Shi LS, Li CY, Kuoh CS, Wu PL, Wu TS..  (2005)  Phenanthroindolizidine alkaloids from the stems of Ficus septica.,  68  (7): [PMID:16038551] [10.1021/np050095o]

3. Staerk D, Lykkeberg AK, Christensen J, Budnik BA, Abe F, Jaroszewski JW..  (2002)  In vitro cytotoxic activity of phenanthroindolizidine alkaloids from Cynanchum vincetoxicum and Tylophora tanakae against drug-sensitive and multidrug-resistant cancer cells.,  65  (9): [PMID:12350151] [10.1021/np0106384]

4. Plouffe D, Brinker A, McNamara C, Henson K, Kato N, Kuhen K, Nagle A, Adrián F, Matzen JT, Anderson P, Nam TG, Gray NS, Chatterjee A, Janes J, Yan SF, Trager R, Caldwell JS, Schultz PG, Zhou Y, Winzeler EA..  (2008)  In silico activity profiling reveals the mechanism of action of antimalarials discovered in a high-throughput screen.,  105  (26): [PMID:18579783] [10.1073/pnas.0802982105]

5. Ueda JY, Takagi M, Shin-ya K..  (2009)  Aminocaprophenone- and pyrrolidine-type alkaloids from the leaves of Ficus septica.,  72  (12): [PMID:19938815] [10.1021/np900580f]

6. Wang Z, Wu M, Wang Y, Li Z, Wang L, Han G, Chen F, Liu Y, Wang K, Zhang A, Meng L, Wang Q..  (2012)  Synthesis and SAR studies of phenanthroindolizidine and phenanthroquinolizidine alkaloids as potent anti-tumor agents.,  51  [PMID:22417638] [10.1016/j.ejmech.2012.02.048]

7. Niphakis MJ, Gay BC, Hong KH, Bleeker NP, Georg GI..  (2012)  Synthesis and evaluation of the anti-proliferative and NF-κB activities of a library of simplified tylophorine analogs.,  20  (19): [PMID:22910225] [10.1016/j.bmc.2012.07.044]

8. Lee YZ, Yang CW, Hsu HY, Qiu YQ, Yeh TK, Chang HY, Chao YS, Lee SJ..  (2012)  Synthesis and biological evaluation of tylophorine-derived dibenzoquinolines as orally active agents: exploration of the role of tylophorine e ring on biological activity.,  55  (23): [PMID:23167614] [10.1021/jm300705j]

9. Wang K, Su B, Wang Z, Wu M, Li Z, Hu Y, Fan Z, Mi N, Wang Q..  (2010)  Synthesis and antiviral activities of phenanthroindolizidine alkaloids and their derivatives.,  58  (5): [PMID:20000413] [10.1021/jf902543r]

10. Wang K, Hu Y, Liu Y, Mi N, Fan Z, Liu Y, Wang Q..  (2010)  Design, synthesis, and antiviral evaluation of phenanthrene-based tylophorine derivatives as potential antiviral agents.,  58  (23): [PMID:21058739] [10.1021/jf103440s]

11. Wang Z, Wei P, Wang L, Wang Q..  (2012)  Design, synthesis, and anti-tobacco mosaic virus (TMV) activity of phenanthroindolizidines and their analogues.,  60  (41): [PMID:23035814] [10.1021/jf303550a]

12. Wen T, Wang Z, Meng X, Wu M, Li Y, Wu X, Zhao L, Wang P, Yin Z, Li-Ling J, Wang Q..  (2014)  Synthesis of novel tylophorine derivatives and evaluation of their anti-inflammatory activity.,  5  (9): [PMID:25221661] [10.1021/ml500255j]

Source

Source(2):

• Scientific Literature
• Novartis Malaria Screening