7-[4-(4-Methyl-piperazin-1-yl)-cyclohexyl]-5-(4-phenoxy-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine

ID: ALA45177

Chembl Id: CHEMBL45177

Max Phase: Preclinical

Molecular Formula: C29H34N6O

Molecular Weight: 482.63

Molecule Type: Small molecule

Associated Items:

Names and Identifiers

Canonical SMILES:  CN1CCN([C@H]2CC[C@H](n3cc(-c4ccc(Oc5ccccc5)cc4)c4c(N)ncnc43)CC2)CC1

Standard InChI:  InChI=1S/C29H34N6O/c1-33-15-17-34(18-16-33)22-9-11-23(12-10-22)35-19-26(27-28(30)31-20-32-29(27)35)21-7-13-25(14-8-21)36-24-5-3-2-4-6-24/h2-8,13-14,19-20,22-23H,9-12,15-18H2,1H3,(H2,30,31,32)/t22-,23-

Standard InChI Key:  FDVSOQRNTAPCHB-YHBQERECSA-N

Alternative Forms

  1. Parent:

    ALA45177

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  2. Alternative Forms:

    ALA45177

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Associated Targets(Human)

LCK Tclin Tyrosine-protein kinase LCK (9212 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SRC Tclin Tyrosine-protein kinase SRC (10310 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
KDR Tclin Vascular endothelial growth factor receptor 2 (20924 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
TEK Tclin Tyrosine-protein kinase TIE-2 (3348 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
BLK Tchem Tyrosine-protein kinase BLK (2498 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CSK Tchem Tyrosine-protein kinase CSK (2395 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
FYN Tclin Tyrosine-protein kinase FYN (5308 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
LYN Tclin Tyrosine-protein kinase Lyn (4251 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
HCK Tclin Tyrosine-protein kinase HCK (2743 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
FLT3 Tclin Tyrosine-protein kinase receptor FLT3 (13481 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
MV4-11 (7307 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Associated Targets(non-human)

Mus musculus (284745 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
rep Replicase polyprotein 1ab (11336 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SARS-CoV-2 (38078 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Molecule Features

Natural Product: NoOral: NoChemical Probe: NoParenteral: No
Molecule Type: Small moleculeTopical: NoFirst In Class: NoBlack Box: No
Chirality: NoAvailability: NoProdrug: No

Drug Indications

MESH IDMESH Heading EFO IDsEFO TermsMax Phase for IndicationReferences

Mechanisms of Action

Mechanism of ActionAction Typetarget IDTarget NameTarget TypeTarget OrganismBinding Site NameReferences

Calculated Properties

Molecular Weight: 482.63Molecular Weight (Monoisotopic): 482.2794AlogP: 5.20#Rotatable Bonds: 5
Polar Surface Area: 72.44Molecular Species: BASEHBA: 7HBD: 1
#RO5 Violations: 1HBA (Lipinski): 7HBD (Lipinski): 2#RO5 Violations (Lipinski): 1
CX Acidic pKa: CX Basic pKa: 8.96CX LogP: 4.62CX LogD: 3.03
Aromatic Rings: 4Heavy Atoms: 36QED Weighted: 0.42Np Likeness Score: -0.62

References

1. Calderwood DJ, Johnston DN, Munschauer R, Rafferty P..  (2002)  Pyrrolo[2,3-d]pyrimidines containing diverse N-7 substituents as potent inhibitors of Lck.,  12  (12): [PMID:12039590] [10.1016/s0960-894x(02)00195-6]
2. Burchat AF, Calderwood DJ, Friedman MM, Hirst GC, Li B, Rafferty P, Ritter K, Skinner BS..  (2002)  Pyrazolo[3,4-d]pyrimidines containing an extended 3-substituent as potent inhibitors of Lck -- a selectivity insight.,  12  (12): [PMID:12039591] [10.1016/s0960-894x(02)00196-8]
3. Arcari JT, Beebe JS, Berliner MA, Bernardo V, Boehm M, Borzillo GV, Clark T, Cohen BD, Connell RD, Frost HN, Gordon DA, Hungerford WM, Kakar SM, Kanter A, Keene NF, Knauth EA, Lagreca SD, Lu Y, Martinez-Alsina L, Marx MA, Morris J, Patel NC, Savage D, Soderstrom CI, Thompson C, Tkalcevic G, Tom NJ, Vajdos FF, Valentine JJ, Vincent PW, Wessel MD, Chen JM..  (2013)  Discovery and synthesis of novel 4-aminopyrrolopyrimidine Tie-2 kinase inhibitors for the treatment of solid tumors.,  23  (10): [PMID:23566514] [10.1016/j.bmcl.2013.03.012]
4. Yuki H, Kikuzato K, Koda Y, Mikuni J, Tomabechi Y, Kukimoto-Niino M, Tanaka A, Shirai F, Shirouzu M, Koyama H, Honma T..  (2017)  Activity cliff for 7-substituted pyrrolo-pyrimidine inhibitors of HCK explained in terms of predicted basicity of the amine nitrogen.,  25  (16): [PMID:28662963] [10.1016/j.bmc.2017.05.053]
5. 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]
6. Pathania S, Rawal RK..  (2018)  Pyrrolopyrimidines: An update on recent advancements in their medicinal attributes.,  157  [PMID:30114661] [10.1016/j.ejmech.2018.08.023]
7. Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani.  (2020)  Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen,  [10.6019/CHEMBL4495564]
8. Andrea Zaliani, Laura Vangeel, Jeanette Reinshagen, Daniela Iaconis, Maria Kuzikov, Oliver Keminer, Markus Wolf, Bernhard Ellinger, Francesca Esposito, Angela Corona, Enzo Tramontano, Candida Manelfi, Katja Herzog, Dirk Jochmans, Steven De Jonghe, Winston Chiu, Thibault Francken, Joost Schepers, Caroline Collard, Kayvan Abbasi, Carsten Claussen , Vincenzo Summa, Andrea R. Beccari, Johan Neyts, Philip Gribbon and Pieter Leyssen.  (2020)  Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort,  [10.6019/CHEMBL4495565]
9. Chen X, Huang Y, Xu W, Cai Y, Yang Y..  (2022)  4-Aminopyrazolopyrimidine scaffold and its deformation in the design of tyrosine and serine/threonine kinase inhibitors in medicinal chemistry.,  13  (9.0): [PMID:36324498] [10.1039/d2md00139j]