(S)-2-((trans-4-(4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclohexyl)amino)-3-phenylpropanoic acid

ID: ALA4216163

Max Phase: Preclinical

Molecular Formula: C33H33N5O3

Molecular Weight: 547.66

Molecule Type: Small molecule

This compound is available for customization.

Associated Items:

Bioactivity Summary Target Summary Assay Summary

Names and Identifiers

Canonical SMILES: Nc1ncnc2c1c(-c1ccc(Oc3ccccc3)cc1)cn2[C@H]1CC[C@H](N[C@@H](Cc2ccccc2)C(=O)O)CC1

Standard InChI: InChI=1S/C33H33N5O3/c34-31-30-28(23-11-17-27(18-12-23)41-26-9-5-2-6-10-26)20-38(32(30)36-21-35-31)25-15-13-24(14-16-25)37-29(33(39)40)19-22-7-3-1-4-8-22/h1-12,17-18,20-21,24-25,29,37H,13-16,19H2,(H,39,40)(H2,34,35,36)/t24-,25-,29-/m0/s1

Standard InChI Key: XLRGWOQAKMIFSL-QEMZJVQQSA-N

Molfile:

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M  END

Associated Targets(Human)

HCK Tclin Tyrosine-protein kinase HCK (2743 Activities)

Discover Target: HCK

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

FLT3 Tclin Tyrosine-protein kinase receptor FLT3 (13481 Activities)

Discover Target: FLT3

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: Small molecule	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: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 547.66	Molecular Weight (Monoisotopic): 547.2583	AlogP: 6.24	#Rotatable Bonds: 9
Polar Surface Area: 115.29	Molecular Species: ZWITTERION	HBA: 7	HBD: 3
#RO5 Violations: 2	HBA (Lipinski): 8	HBD (Lipinski): 4	#RO5 Violations (Lipinski): 2
CX Acidic pKa: 1.16	CX Basic pKa: 10.93	CX LogP: 3.61	CX LogD: 3.42
Aromatic Rings: 5	Heavy Atoms: 41	QED Weighted: 0.20	Np Likeness Score: -0.33

References

1. Koda Y, Kikuzato K, Mikuni J, Tanaka A, Yuki H, Honma T, Tomabechi Y, Kukimoto-Niino M, Shirouzu M, Shirai F, Koyama H.. (2017) Identification of pyrrolo[2,3-d]pyrimidines as potent HCK and FLT3-ITD dual inhibitors., 27 (22): [PMID:29037944] [10.1016/j.bmcl.2017.10.012]
2. Das, Jagabandhu J and 20 more authors. 2006-11-16 2-aminothiazole as a novel kinase inhibitor template. Structure-activity relationship studies toward the discovery of N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1- piperazinyl)]-2-methyl-4-pyrimidinyl]amino)]-1,3-thiazole-5-carboxamide (dasatinib, BMS-354825) as a potent pan-Src kinase inhibitor. [PMID:17154512]
3. Apsel, Beth and 9 more authors. 2008-11 Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. [PMID:18849971]
4. Remsing Rix, L L LL and 11 more authors. 2009-03 Global target profile of the kinase inhibitor bosutinib in primary chronic myeloid leukemia cells. [PMID:19039322]
5. Byrd, John C JC and 29 more authors. 2016-01-28 Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia. [PMID:26641137]
6. Daydé-Cazals, Bénédicte B and 11 more authors. 2016-04-28 Rational Design, Synthesis, and Biological Evaluation of 7-Azaindole Derivatives as Potent Focused Multi-Targeted Kinase Inhibitors. [PMID:27010810]
7. Fraser, Craig C and 13 more authors. 2016-05-26 Rapid Discovery and Structure-Activity Relationships of Pyrazolopyrimidines That Potently Suppress Breast Cancer Cell Growth via SRC Kinase Inhibition with Exceptional Selectivity over ABL Kinase. [PMID:27115835]
8. Bachegowda, Lohith L and 35 more authors. 2016-08-15 Pexmetinib: A Novel Dual Inhibitor of Tie2 and p38 MAPK with Efficacy in Preclinical Models of Myelodysplastic Syndromes and Acute Myeloid Leukemia. [PMID:27287719]
9. Zhang, Chun-Hui CH and 17 more authors. 2016-11-10 From Lead to Drug Candidate: Optimization of 3-(Phenylethynyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine Derivatives as Agents for the Treatment of Triple Negative Breast Cancer. [PMID:27739679]
10. Yuki, Hitomi H and 10 more authors. 2017-08-15 Activity cliff for 7-substituted pyrrolo-pyrimidine inhibitors of HCK explained in terms of predicted basicity of the amine nitrogen. [PMID:28662963]
11. Klaeger, Susan S and 47 more authors. 2017-12-01 The target landscape of clinical kinase drugs. [PMID:29191878]
12. He, Linhong L and 9 more authors. 2018-02-10 Design, synthesis and biological evaluation of 7H-pyrrolo[2,3-d]pyrimidin-4-amine derivatives as selective Btk inhibitors with improved pharmacokinetic properties for the treatment of rheumatoid arthritis. [PMID:29324347]
13. Dart, Melanie L and 11 more authors. 2018-06-14 Homogeneous Assay for Target Engagement Utilizing Bioluminescent Thermal Shift. [PMID:29937980]
14. Narayan, Satya S and 7 more authors. 2019-01-01 ASR352, A potent anticancer agent: Synthesis, preliminary SAR, and biological activities against colorectal cancer bulk, 5-fluorouracil/oxaliplatin resistant and stem cells. [PMID:30384048]

(S)-2-((trans-4-(4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclohexyl)amino)-3-phenylpropanoic acid

Names and Identifiers

Alternative Forms

Associated Targets(Human)

Molecule Features

Drug Indications

Mechanisms of Action

Calculated Properties

References

Source