ID: ALA491636

Max Phase: Preclinical

Molecular Formula: C17H27N3O6

Molecular Weight: 369.42

Molecule Type: Small molecule

Representations

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

Standard InChI:  InChI=1S/C17H27N3O6/c1-4-7(2)12-13(26-17(12)25)15(22)19-10-5-9(10)6-11(16(23)24)20-14(21)8(3)18/h7-13H,4-6,18H2,1-3H3,(H,19,22)(H,20,21)(H,23,24)/t7-,8-,9-,10-,11-,12-,13+/m0/s1

Standard InChI Key:  ZSYIAUXMQLVKIL-BLTCOFLISA-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: 369.42

Molecular Weight (Monoisotopic): 369.1900

AlogP: -0.61

#Rotatable Bonds: 9

Polar Surface Area: 147.82

Molecular Species: ACID

HBA: 6

HBD: 4

#RO5 Violations: 0

HBA (Lipinski): 9

HBD (Lipinski): 5

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 3.66

CX Basic pKa: 8.39

CX LogP: -2.69

CX LogD: -2.73

Aromatic Rings: 0

Heavy Atoms: 26

QED Weighted: 0.40

Np Likeness Score: 0.73

References

1. Hasegawa M, Kinoshita K, Nishimura C, Matsumura U, Shionyu M, Ikeda S, Mizukami T..  (2008)  Affinity labeling of the proteasome by a belactosin A derived inhibitor.,  18  (20): [PMID:18801655] [10.1016/j.bmcl.2008.08.073]

2. Nakamura H, Watanabe M, Ban HS, Nabeyama W, Asai A..  (2009)  Synthesis and biological evaluation of boron peptide analogues of Belactosin C as proteasome inhibitors.,  19  (12): [PMID:19428245] [10.1016/j.bmcl.2009.04.103]

3. Kawamura S, Unno Y, List A, Mizuno A, Tanaka M, Sasaki T, Arisawa M, Asai A, Groll M, Shuto S..  (2013)  Potent proteasome inhibitors derived from the unnatural cis-cyclopropane isomer of Belactosin A: synthesis, biological activity, and mode of action.,  56  (9): [PMID:23547757] [10.1021/jm4002296]

4. Kawamura S, Unno Y, Tanaka M, Sasaki T, Yamano A, Hirokawa T, Kameda T, Asai A, Arisawa M, Shuto S..  (2013)  Investigation of the noncovalent binding mode of covalent proteasome inhibitors around the transition state by combined use of cyclopropylic strain-based conformational restriction and computational modeling.,  56  (14): [PMID:23837692] [10.1021/jm400542h]

5. Kawamura S, Unno Y, Asai A, Arisawa M, Shuto S..  (2014)  Structurally novel highly potent proteasome inhibitors created by the structure-based hybridization of nonpeptidic belactosin derivatives and peptide boronates.,  57  (6): [PMID:24524217] [10.1021/jm500045x]

6. Kawamura S, Unno Y, Asai A, Arisawa M, Shuto S..  (2014)  Development of a new class of proteasome inhibitors with an epoxyketone warhead: Rational hybridization of non-peptidic belactosin derivatives and peptide epoxyketones.,  22  (12): [PMID:24814885] [10.1016/j.bmc.2014.04.032]

7. Gill KA, Berrué F, Arens JC, Carr G, Kerr RG..  (2015)  Cystargolides, 20S Proteasome Inhibitors Isolated from Kitasatospora cystarginea.,  78  (4): [PMID:25769015] [10.1021/np501060k]

Source

Source(1):

• Scientific Literature