ID: ALA2364562

Max Phase: Preclinical

Molecular Formula: C19H25N7O14P2S

Molecular Weight: 669.46

Molecule Type: Small molecule

Associated Items:

Representations

Canonical SMILES:  NC(=O)c1csc([C@H]2O[C@@H](COP(=O)(O)OP(=O)(O)OC[C@H]3O[C@@H](n4cnc5c(N)ncnc54)[C@H](O)[C@@H]3O)[C@H](O)[C@@H]2O)n1

Standard InChI:  InChI=1S/C19H25N7O14P2S/c20-15-9-17(23-4-22-15)26(5-24-9)19-13(30)11(28)8(39-19)2-37-42(34,35)40-41(32,33)36-1-7-10(27)12(29)14(38-7)18-25-6(3-43-18)16(21)31/h3-5,7-8,10-14,19,27-30H,1-2H2,(H2,21,31)(H,32,33)(H,34,35)(H2,20,22,23)/t7-,8+,10-,11+,12-,13+,14-,19+/m0/s1

Standard InChI Key:  INQLNSVYIFCUML-YYKMIFDDSA-N

Associated Targets(Human)

K562 73714 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Inosine-5'-monophosphate dehydrogenase 2 1326 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Inosine-5'-monophosphate dehydrogenase 1 221 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Inosine-5'-monophosphate dehydrogenase (IMPDH) 61 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Associated Targets(non-human)

P388 20296 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Mus musculus 284745 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Inosine-5'-monophosphate dehydrogenase 2 19 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Glutamate dehydrogenase 27 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Alcohol dehydrogenase 205 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

L-lactate dehydrogenase B chain 52 Activities

Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Malate dehydrogenase cytoplasmic 54 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

Properties

Molecular Weight: 669.46Molecular Weight (Monoisotopic): 669.0655AlogP: -2.30#Rotatable Bonds: 11
Polar Surface Area: 327.27Molecular Species: ACIDHBA: 19HBD: 8
#RO5 Violations: 3HBA (Lipinski): 21HBD (Lipinski): 10#RO5 Violations (Lipinski): 3
CX Acidic pKa: 1.86CX Basic pKa: 4.92CX LogP: -5.89CX LogD: -8.52
Aromatic Rings: 3Heavy Atoms: 43QED Weighted: 0.10Np Likeness Score: 0.75

References

1. Gebeyehu G, Marquez VE, Van Cott A, Cooney DA, Kelley JA, Jayaram HN, Ahluwalia GS, Dion RL, Wilson YA, Johns DG..  (1985)  Ribavirin, tiazofurin, and selenazofurin: mononucleotides and nicotinamide adenine dinucleotide analogues. Synthesis, structure, and interactions with IMP dehydrogenase.,  28  (1): [PMID:2856943] [10.1021/jm00379a018]
2. Zatorski A, Goldstein BM, Colby TD, Jones JP, Pankiewicz KW..  (1995)  Potent inhibitors of human inosine monophosphate dehydrogenase type II. Fluorine-substituted analogues of thiazole-4-carboxamide adenine dinucleotide.,  38  (7): [PMID:7707313] [10.1021/jm00007a007]
3. Goldstein BM, Bell JE, Marquez VE..  (1990)  Dehydrogenase binding by tiazofurin anabolites.,  33  (4): [PMID:1969483] [10.1021/jm00166a007]
4. Pankiewicz KW, Lesiak K, Zatorski A, Goldstein BM, Carr SF, Sochacki M, Majumdar A, Seidman M, Watanabe KA..  (1997)  The practical synthesis of a methylenebisphosphonate analogue of benzamide adenine dinucleotide: inhibition of human inosine monophosphate dehydrogenase (type I and II).,  40  (8): [PMID:9111303] [10.1021/jm960641y]
5. Franchetti P, Cappellacci L, Perlini P, Jayaram HN, Butler A, Schneider BP, Collart FR, Huberman E, Grifantini M..  (1998)  Isosteric analogues of nicotinamide adenine dinucleotide derived from furanfurin, thiophenfurin, and selenophenfurin as mammalian inosine monophosphate dehydrogenase (type I and II) inhibitors.,  41  (10): [PMID:9572896] [10.1021/jm970772e]
6. Marquez VE, Tseng CK, Gebeyehu G, Cooney DA, Ahluwalia GS, Kelley JA, Dalal M, Fuller RW, Wilson YA, Johns DG..  (1986)  Thiazole-4-carboxamide adenine dinucleotide (TAD). Analogues stable to phosphodiesterase hydrolysis.,  29  (9): [PMID:2875185] [10.1021/jm00159a027]
7. Pankiewicz KW, Zeidler J, Ciszewski LA, Bell JE, Goldstein BM, Jayaram HN, Watanabe KA..  (1993)  Synthesis of isosteric analogues of nicotinamide adenine dinucleotide containing C-nucleotide of nicotinamide or picolinamide.,  36  (13): [PMID:8099976] [10.1021/jm00065a008]
8. Lesiak K, Watanabe KA, Majumdar A, Seidman M, Vanderveen K, Goldstein BM, Pankiewicz KW..  (1997)  Synthesis of nonhydrolyzable analogues of thiazole-4-carboxamide and benzamide adenine dinucleotide containing fluorine atom at the C2' of adenine nucleoside: induction of K562 differentiation and inosine monophosphate dehydrogenase inhibitory activity.,  40  (16): [PMID:9258359] [10.1021/jm970247f]
9. Pankiewicz KW, Lesiak-Watanabe KB, Watanabe KA, Patterson SE, Jayaram HN, Yalowitz JA, Miller MD, Seidman M, Majumdar A, Prehna G, Goldstein BM..  (2002)  Novel mycophenolic adenine bis(phosphonate) analogues as potential differentiation agents against human leukemia.,  45  (3): [PMID:11806722] [10.1021/jm0104116]
10. Gebeyehu G, Marquez VE, Kelley JA, Cooney DA, Jayaram HN, Johns DG..  (1983)  Synthesis of thiazole-4-carboxamide adenine dinucleotide. A powerful inhibitor of IMP dehydrogenase.,  26  (6): [PMID:6133956] [10.1021/jm00360a025]
11. Kabat MM, Pankiewicz KW, Watanabe KA..  (1987)  Synthesis of 5-beta-D-ribofuranosylnicotinamide and its N-methyl derivative. The isosteric and isoelectronic analogues of nicotinamide nucleoside.,  30  (5): [PMID:2952800] [10.1021/jm00388a030]
12. Rejman D, Olesiak M, Chen L, Patterson SE, Wilson D, Jayaram HN, Hedstrom L, Pankiewicz KW..  (2006)  Novel methylenephosphophosphonate analogues of mycophenolic adenine dinucleotide. Inhibition of inosine monophosphate dehydrogenase.,  49  (16): [PMID:16884314] [10.1021/jm060479r]
13. Felczak K, Chen L, Wilson D, Williams J, Vince R, Petrelli R, Jayaram HN, Kusumanchi P, Kumar M, Pankiewicz KW..  (2011)  Cofactor-type inhibitors of inosine monophosphate dehydrogenase via modular approach: targeting the pyrophosphate binding sub-domain.,  19  (5): [PMID:21324702] [10.1016/j.bmc.2011.01.042]

Source