NAVOXIMOD

ID: ALA3989951

Chembl Id: CHEMBL3989951

Max Phase: Phase

Molecular Formula: C18H21FN2O2

Molecular Weight: 316.38

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Navoximod | GDC-0919 | IDO-IN-7 | NLG-919 | NLG919 | RG-6078 | RG6078 | RO-7077339 | RO7077339 | RO7077339-001

Canonical SMILES:  O[C@H](C[C@H]1c2c(F)cccc2-c2cncn21)[C@H]1CC[C@H](O)CC1

Standard InChI:  InChI=1S/C18H21FN2O2/c19-14-3-1-2-13-16-9-20-10-21(16)15(18(13)14)8-17(23)11-4-6-12(22)7-5-11/h1-3,9-12,15,17,22-23H,4-8H2/t11-,12-,15-,17+/m0/s1

Standard InChI Key:  YGACXVRLDHEXKY-WXRXAMBDSA-N

Alternative Forms

1. Parent:

   

   ALA3989951

   NAVOXIMOD

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: 316.38

Molecular Weight (Monoisotopic): 316.1587

AlogP: 2.89

#Rotatable Bonds: 3

Polar Surface Area: 58.28

Molecular Species: NEUTRAL

HBA: 4

HBD: 2

#RO5 Violations: 0

HBA (Lipinski): 4

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 11.76

CX Basic pKa: 6.01

CX LogP: 1.76

CX LogD: 1.74

Aromatic Rings: 2

Heavy Atoms: 23

QED Weighted: 0.92

Np Likeness Score: 0.05

References

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

2. Weng T, Qiu X, Wang J, Li Z, Bian J..  (2018)  Recent discovery of indoleamine-2,3-dioxygenase 1 inhibitors targeting cancer immunotherapy.,  143  [PMID:29220788] [10.1016/j.ejmech.2017.11.088]

3. Unpublished dataset, 

4. Parr BT, Pastor R, Sellers BD, Pei Z, Jaipuri FA, Castanedo GM, Gazzard L, Kumar S, Li X, Liu W, Mendonca R, Pavana RK, Potturi H, Shao C, Velvadapu V, Waldo JP, Wu G, Yuen PW, Zhang Z, Zhang Y, Harris SF, Oh AJ, DiPasquale A, Dement K, La H, Goon L, Gustafson A, VanderPorten EC, Mautino MR, Liu Y..  (2020)  Implementation of the CYP Index for the Design of Selective Tryptophan-2,3-dioxygenase Inhibitors.,  11  (4): [PMID:32292562] [10.1021/acsmedchemlett.0c00004]

5. Wang XX, Sun SY, Dong QQ, Wu XX, Tang W, Xing YQ..  (2019)  Recent advances in the discovery of indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors.,  10  (10): [PMID:32055299] [10.1039/C9MD00208A]

6. Tu W, Yang F, Xu G, Chi J, Liu Z, Peng W, Hu B, Zhang L, Wan H, Yu N, Jin F, Hu Q, Zhang L, He F, Tao W..  (2019)  Discovery of Imidazoisoindole Derivatives as Highly Potent and Orally Active Indoleamine-2,3-dioxygenase Inhibitors.,  10  (6): [PMID:31223453] [10.1021/acsmedchemlett.9b00114]

7. Kumar S, Waldo JP, Jaipuri FA, Marcinowicz A, Van Allen C, Adams J, Kesharwani T, Zhang X, Metz R, Oh AJ, Harris SF, Mautino MR..  (2019)  Discovery of Clinical Candidate (1R,4r)-4-((R)-2-((S)-6-Fluoro-5H-imidazo[5,1-a]isoindol-5-yl)-1-hydroxyethyl)cyclohexan-1-ol (Navoximod), a Potent and Selective Inhibitor of Indoleamine 2,3-Dioxygenase 1.,  62  (14): [PMID:31264862] [10.1021/acs.jmedchem.9b00662]

8. Cui G,Lai F,Wang X,Chen X,Xu B.  (2020)  Design, synthesis and biological evaluation of indole-2-carboxylic acid derivatives as IDO1/TDO dual inhibitors.,  188  [PMID:31881488] [10.1016/j.ejmech.2019.111985]

9. Hamilton MM, Mseeh F, McAfoos TJ, Leonard PG, Reyna NJ, Harris AL, Xu A, Han M, Soth MJ, Czako B, Theroff JP, Mandal PK, Burke JP, Virgin-Downey B, Petrocchi A, Pfaffinger D, Rogers NE, Parker CA, Yu SS, Jiang Y, Krapp S, Lammens A, Trevitt G, Tremblay MR, Mikule K, Wilcoxen K, Cross JB, Jones P, Marszalek JR, Lewis RT..  (2021)  Discovery of IACS-9779 and IACS-70465 as Potent Inhibitors Targeting Indoleamine 2,3-Dioxygenase 1 (IDO1) Apoenzyme.,  64  (15.0): [PMID:34292726] [10.1021/acs.jmedchem.1c00679]

10. Huo C, Luo Z, Ning X, Kang X, Yan Q, Guo Y, Li G, Wang Z, Li Y, Qian S..  (2022)  4,6-Disubstituted-1H-Indazole-4-Amine derivatives with immune-chemotherapy effect and in vivo antitumor activity.,  241  [PMID:35952399] [10.1016/j.ejmech.2022.114625]

11. Tang K, Wang B, Yu B, Liu HM..  (2022)  Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors and PROTAC-based degraders for cancer therapy.,  227  [PMID:34752953] [10.1016/j.ejmech.2021.113967]

12. Ning XL, Li YZ, Huo C, Deng J, Gao C, Zhu KR, Wang M, Wu YX, Yu JL, Ren YL, Luo ZY, Li G, Chen Y, Wang SY, Peng C, Yang LL, Wang ZY, Wu Y, Qian S, Li GB..  (2021)  X-ray Structure-Guided Discovery of a Potent, Orally Bioavailable, Dual Human Indoleamine/Tryptophan 2,3-Dioxygenase (hIDO/hTDO) Inhibitor That Shows Activity in a Mouse Model of Parkinson's Disease.,  64  (12.0): [PMID:34110158] [10.1021/acs.jmedchem.1c00303]

13. Zhang Y, Hu Z, Zhang J, Ren C, Wang Y..  (2022)  Dual-target inhibitors of indoleamine 2, 3 dioxygenase 1 (Ido1): A promising direction in cancer immunotherapy.,  238  [PMID:35696861] [10.1016/j.ejmech.2022.114524]

Source

Source(3):

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