ID: ALA71917

Max Phase: Preclinical

Molecular Formula: C37H37F2N3O4S

Molecular Weight: 657.78

Molecule Type: Small molecule

Representations

Synonyms (1): T-98475
Synonyms from Alternative Forms(1):

Canonical SMILES:  CC(C)OC(=O)c1cn(Cc2c(F)cccc2F)c2sc(-c3ccc(NC(=O)C(C)C)cc3)c(CN(C)Cc3ccccc3)c2c1=O

Standard InChI:  InChI=1S/C37H37F2N3O4S/c1-22(2)35(44)40-26-16-14-25(15-17-26)34-28(19-41(5)18-24-10-7-6-8-11-24)32-33(43)29(37(45)46-23(3)4)21-42(36(32)47-34)20-27-30(38)12-9-13-31(27)39/h6-17,21-23H,18-20H2,1-5H3,(H,40,44)

Standard InChI Key:  RANJJVIMTOIWIN-UHFFFAOYSA-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: 657.78

Molecular Weight (Monoisotopic): 657.2473

AlogP: 7.85

#Rotatable Bonds: 11

Polar Surface Area: 80.64

Molecular Species: NEUTRAL

HBA: 7

HBD: 1

#RO5 Violations: 2

HBA (Lipinski): 7

HBD (Lipinski): 1

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 13.81

CX Basic pKa: 7.37

CX LogP: 8.27

CX LogD: 7.99

Aromatic Rings: 5

Heavy Atoms: 47

QED Weighted: 0.15

Np Likeness Score: -1.22

References

1. Wilcoxen KM, Zhu YF, Connors PJ, Saunders J, Gross TD, Gao Y, Reinhart GJ, Struthers RS, Chen C..  (2002)  Synthesis and initial structure-activity relationships of a novel series of imidazolo[1,2-a]pyrimid-5-ones as potent GnRH receptor antagonists.,  12  (16): [PMID:12127532] [10.1016/s0960-894x(02)00370-0]

2. Guo Z, Chen Y, Wu D, Zhu YF, Struthers RS, Saunders J, Xie Q, Chen C..  (2003)  Synthesis and structure-activity relationships of thieno[2,3-d]pyrimidine-2,4-dione derivatives as potent GnRH receptor antagonists.,  13  (20): [PMID:14505682] [10.1016/s0960-894x(03)00746-7]

3. Zhu YF, Struthers RS, Connors PJ, Gao Y, Gross TD, Saunders J, Wilcoxen K, Reinhart GJ, Ling N, Chen C..  (2002)  Initial structure-activity relationship studies of a novel series of pyrrolo[1,2-a]pyrimid-7-ones as GnRH receptor antagonists.,  12  (3): [PMID:11814806] [10.1016/s0960-894x(01)00779-x]

4. Tucci FC, Zhu YF, Struthers RS, Guo Z, Gross TD, Rowbottom MW, Acevedo O, Gao Y, Saunders J, Xie Q, Reinhart GJ, Liu XJ, Ling N, Bonneville AK, Chen T, Bozigian H, Chen C..  (2005)  3-[(2R)-Amino-2-phenylethyl]-1-(2,6-difluorobenzyl)-5-(2-fluoro-3-methoxyphenyl)- 6-methylpyrimidin-2,4-dione (NBI 42902) as a potent and orally active antagonist of the human gonadotropin-releasing hormone receptor. Design, synthesis, and in vitro and in vivo characterization.,  48  (4): [PMID:15715483] [10.1021/jm049218c]

5. Imada T, Cho N, Imaeda T, Hayase Y, Sasaki S, Kasai S, Harada M, Matsumoto H, Endo S, Suzuki N, Furuya S..  (2006)  Design, synthesis, and structure-activity relationships of thieno[2,3-b]pyridin-4-one derivatives as a novel class of potent, orally active, non-peptide luteinizing hormone-releasing hormone receptor antagonists.,  49  (13): [PMID:16789738] [10.1021/jm0512894]

6. Betz SF, Zhu YF, Chen C, Struthers RS..  (2008)  Non-peptide gonadotropin-releasing hormone receptor antagonists.,  51  (12): [PMID:18419112] [10.1021/jm701249f]

7. PubChem BioAssay data set, 

8. Mark Wenlock and Nicholas Tomkinson. Experimental in vitro DMPK and physicochemical data on a set of publicly disclosed compounds,  [10.6019/CHEMBL3301361]

9. Fjellaksel R, Boomgaren M, Sundset R, Haraldsen IH, Hansen JH, Riss PJ..  (2017)  Small molecule piperazinyl-benzimidazole antagonists of the gonadotropin-releasing hormone (GnRH) receptor.,  8  (10): [PMID:30108717] [10.1039/C7MD00320J]

Source

Source(3):

• Scientific Literature
• PubChem BioAssays
• AstraZeneca Deposited Data