2-((3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)-3-methyl-5-(2-(trifluoromethyl)pyridin-3-ylthio)pyrimidin-4(3H)-one

ID: ALA4531137

PubChem CID: 124150544

Max Phase: Preclinical

Molecular Formula: C20H24F3N5O2S

Molecular Weight: 455.51

Molecule Type: Unknown

This compound is available for customization.

Associated Items:

Bioactivity Summary Target Summary Assay Summary

Names and Identifiers

Canonical SMILES: C[C@@H]1OCC2(CCN(c3ncc(Sc4cccnc4C(F)(F)F)c(=O)n3C)CC2)[C@@H]1N

Standard InChI: InChI=1S/C20H24F3N5O2S/c1-12-15(24)19(11-30-12)5-8-28(9-6-19)18-26-10-14(17(29)27(18)2)31-13-4-3-7-25-16(13)20(21,22)23/h3-4,7,10,12,15H,5-6,8-9,11,24H2,1-2H3/t12-,15+/m0/s1

Standard InChI Key: NNUUVQNSRWHSDO-SWLSCSKDSA-N

Molfile:

 
     RDKit          2D

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    8.3039  -19.8689    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.0799  -20.1253    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    9.5636  -19.4666    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.0865  -18.8031    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.9466  -17.0248    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.9455  -17.8443    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.6535  -18.2533    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.3632  -17.8438    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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    5.4814  -18.2361    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.1900  -17.8283    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.1889  -17.0102    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.4792  -16.5998    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.8965  -18.2338    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.8945  -19.0520    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.5982  -19.4605    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.3103  -18.2372    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.6021  -17.8242    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.0690  -18.2395    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.4814  -19.0533    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.3808  -19.4707    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.3430  -18.0272    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.6493  -15.7987    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.3558  -15.3880    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    1.9404  -15.3923    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    2.6414  -14.9777    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
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M  END

Associated Targets(Human)

PTPN11 Tchem Protein-tyrosine phosphatase 2C (2297 Activities)

Discover Target: PTPN11

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

KYSE-520 cell line (216 Activities)

Explore this target

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

KCNH2 Tclin HERG (29587 Activities)

Discover Target: KCNH2

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Natural Product: No	Oral: No	Chemical Probe: No	Parenteral: No
Molecule Type: Unknown	Topical: No	First In Class: No	Black Box: No
Chirality: No	Availability: No	Prodrug: No

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Unknown

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 455.51	Molecular Weight (Monoisotopic): 455.1603	AlogP: 2.68	#Rotatable Bonds: 3
Polar Surface Area: 86.27	Molecular Species: BASE	HBA: 8	HBD: 1
#RO5 Violations: ┄	HBA (Lipinski): 7	HBD (Lipinski): 2	#RO5 Violations (Lipinski): ┄
CX Acidic pKa: ┄	CX Basic pKa: 9.18	CX LogP: 1.77	CX LogD: 0.01
Aromatic Rings: 2	Heavy Atoms: 31	QED Weighted: 0.76	Np Likeness Score: -0.60

References

1. Sarver P, Acker M, Bagdanoff JT, Chen Z, Chen YN, Chan H, Firestone B, Fodor M, Fortanet J, Hao H, Hentemann M, Kato M, Koenig R, LaBonte LR, Liu G, Liu S, Liu C, McNeill E, Mohseni M, Sendzik M, Stams T, Spence S, Tamez V, Tichkule R, Towler C, Wang H, Wang P, Williams SL, Yu B, LaMarche MJ.. (2019) 6-Amino-3-methylpyrimidinones as Potent, Selective, and Orally Efficacious SHP2 Inhibitors., 62 (4): [PMID:30688459] [10.1021/acs.jmedchem.8b01726]
2. Lawrence, Harshani R and 10 more authors. 2008-08-28 Inhibitors of Src homology-2 domain containing protein tyrosine phosphatase-2 (Shp2) based on oxindole scaffolds. [PMID:18680359]
3. Geronikaki, A A and 5 more authors. 2008-09-11 2-Thiazolylimino/heteroarylimino-5-arylidene-4-thiazolidinones as new agents with SHP-2 inhibitory action. [PMID:18702480]
4. Dawson, Marcia I MI and 21 more authors. 2008-09-25 Adamantyl-substituted retinoid-derived molecules that interact with the orphan nuclear receptor small heterodimer partner: effects of replacing the 1-adamantyl or hydroxyl group on inhibition of cancer cell growth, induction of cancer cell apoptosis, and inhibition of SRC homology 2 domain-containing protein tyrosine phosphatase-2 activity. [PMID:18759424]
5. He, Yantao and 6 more authors. 2013-02-14 Discovery and evaluation of novel inhibitors of mycobacterium protein tyrosine phosphatase B from the 6-Hydroxy-benzofuran-5-carboxylic acid scaffold. [PMID:23305444]
6. He, Yantao Y and 11 more authors. 2013-06-27 A potent and selective small-molecule inhibitor for the lymphoid-specific tyrosine phosphatase (LYP), a target associated with autoimmune diseases. [PMID:23713581]
7. Zeng, Li-Fan LF and 12 more authors. 2014-08-14 Therapeutic potential of targeting the oncogenic SHP2 phosphatase. [PMID:25003231]
8. Tautz, Lutz L, Senis, Yotis A YA, Oury, Cécile C and Rahmouni, Souad S. 2015-06-15 Perspective: Tyrosine phosphatases as novel targets for antiplatelet therapy. [PMID:25921264]
9. Sun, Wenlong W and 6 more authors. 2017-08-01 Varic acid analogues from fungus as PTP1B inhibitors: Biological evaluation and structure-activity relationships. [PMID:28642102]
10. Xie, Jingjing J and 10 more authors. 2017-12-28 Allosteric Inhibitors of SHP2 with Therapeutic Potential for Cancer Treatment. [PMID:29155585]
11. Du, Yongli Y, Zhang, Yanhui Y, Ling, Hao H, Li, Qunyi Q and Shen, Jingkang J. 2018-01-20 Discovery of novel high potent and cellular active ADC type PTP1B inhibitors with selectivity over TC-PTP via modification interacting with C site. [PMID:29289892]
12. Kim, Bohee and 6 more authors. 2020-01-01 Development and structure-activity relationship study of SHP2 inhibitor containing 3,4,6-trihydroxy-5-oxo-5H-benzo[7]annulene. [PMID:31784318]
13. Wang, Mingliang; Lu, Jianfeng; Wang, Mi; Yang, Chao-Yie and Wang, Shaomeng. 2020-07-23 Discovery of SHP2-D26 as a First, Potent, and Effective PROTAC Degrader of SHP2 Protein. [PMID:32437146]
14. Yuan, Xinrui; Bu, Hong; Zhou, Jinpei; Yang, Chao-Yie and Zhang, Huibin. 2020-10-22 Recent Advances of SHP2 Inhibitors in Cancer Therapy: Current Development and Clinical Application. [PMID:32460492]

2-((3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)-3-methyl-5-(2-(trifluoromethyl)pyridin-3-ylthio)pyrimidin-4(3H)-one

Names and Identifiers

Alternative Forms

Associated Targets(Human)

Molecule Features

Drug Indications

Mechanisms of Action

Calculated Properties

References

Source