(S)-4-(2,5-difluorophenyl)-N-((3R,4S)-3-fluoro-1-methylpiperidin-4-yl)-2-(hydroxymethyl)-N-methyl-2-phenyl-2H-pyrrole-1(5H)-carboxamide

ID: ALA481931

Chembl Id: CHEMBL481931

Cas Number: 845256-65-7

PubChem CID: 11655511

Max Phase: Preclinical

Molecular Formula: C25H28F3N3O2

Molecular Weight: 459.51

Molecule Type: Small molecule

Associated Items:

Names and Identifiers

Synonyms: MK-0731 | MK-0731|845256-65-7|ALR-3456|MK 0731|8HIJ5G3O02|CHEMBL481931|(2S)-4-(2,5-difluorophenyl)-N-[(3R,4S)-3-fluoro-1-methylpiperidin-4-yl]-2-(hydroxymethyl)-N-methyl-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxamide|(-)-MK-0731|(S)-4-(2,5-difluorophenyl)-N-((3R,4S)-3-fluoro-1-methylpiperidin-4-yl)-2-(hydroxymethyl)-N-methyl-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxamide.|1H-Pyrrole-1-carboxamide, 4-(2,5-difluorophenyl)-N-((3R,4S)-3-fluoro-1-methyl-4-piperidinyl)-2,5-dihydro-2-(hydroxymethyl)-N-meShow More

Canonical SMILES:  CN1CC[C@H](N(C)C(=O)N2CC(c3cc(F)ccc3F)=C[C@@]2(CO)c2ccccc2)[C@H](F)C1

Standard InChI:  InChI=1S/C25H28F3N3O2/c1-29-11-10-23(22(28)15-29)30(2)24(33)31-14-17(20-12-19(26)8-9-21(20)27)13-25(31,16-32)18-6-4-3-5-7-18/h3-9,12-13,22-23,32H,10-11,14-16H2,1-2H3/t22-,23+,25-/m1/s1

Standard InChI Key:  MYBGWENAVMIGMM-GIFXNVAJSA-N

Associated Targets(Human)

KCNH2 Tclin HERG (29587 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
A2780 (11979 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CENPE Tchem Centromere-associated protein E (102 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
KIF23 Tbio Kinesin-like protein KIF23 (56 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
KIF3A Tbio Kinesin-like protein KIF3A (1 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
KIF1B Tbio Kinesin-like protein KIF1B (1 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
KIF5B Tbio Kinesin-1 heavy chain (22 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
KIF5A Tbio Kinesin heavy chain isoform 5A (48 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
KIF14 Tbio Kinesin-like protein KIF14 (1 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
KIF2C Tbio Kinesin-like protein KIF2C (17 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
KB 3-1 (1143 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Associated Targets(non-human)

Mus musculus (284745 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Rattus norvegicus (775804 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Canis familiaris (36305 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Rhesus monkey (3147 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

Calculated Properties

Molecular Weight: 459.51Molecular Weight (Monoisotopic): 459.2134AlogP: 3.65#Rotatable Bonds: 4
Polar Surface Area: 47.02Molecular Species: NEUTRALHBA: 3HBD: 1
#RO5 Violations: HBA (Lipinski): 5HBD (Lipinski): 1#RO5 Violations (Lipinski):
CX Acidic pKa: CX Basic pKa: 6.98CX LogP: 2.93CX LogD: 2.79
Aromatic Rings: 2Heavy Atoms: 33QED Weighted: 0.76Np Likeness Score: -0.57

References

1. Cox CD, Coleman PJ, Breslin MJ, Whitman DB, Garbaccio RM, Fraley ME, Buser CA, Walsh ES, Hamilton K, Schaber MD, Lobell RB, Tao W, Davide JP, Diehl RE, Abrams MT, South VJ, Huber HE, Torrent M, Prueksaritanont T, Li C, Slaughter DE, Mahan E, Fernandez-Metzler C, Yan Y, Kuo LC, Kohl NE, Hartman GD..  (2008)  Kinesin spindle protein (KSP) inhibitors. 9. Discovery of (2S)-4-(2,5-difluorophenyl)-n-[(3R,4S)-3-fluoro-1-methylpiperidin-4-yl]-2-(hydroxymethyl)-N-methyl-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxamide (MK-0731) for the treatment of taxane-refractory cancer.,  51  (14): [PMID:18578472] [10.1021/jm800386y]
2. Kaan HY, Weiss J, Menger D, Ulaganathan V, Tkocz K, Laggner C, Popowycz F, Joseph B, Kozielski F..  (2011)  Structure-activity relationship and multidrug resistance study of new S-trityl-L-cysteine derivatives as inhibitors of Eg5.,  54  (6): [PMID:21344920] [10.1021/jm100991m]
3. Meanwell NA..  (2011)  Synopsis of some recent tactical application of bioisosteres in drug design.,  54  (8): [PMID:21413808] [10.1021/jm1013693]

Source