(Phosphoric acid mono-[5-(4-carbamoyl-thiazol-2-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethyl] ester)adinocinemonophasfate)adinocinemonophasfate

ID: ALA2364562

Chembl Id: CHEMBL2364562

PubChem CID: 71716568

Max Phase: Preclinical

Molecular Formula: C19H25N7O14P2S

Molecular Weight: 669.46

Molecule Type: Small molecule

Names and Identifiers

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

Alternative Forms

1. Parent:

   

   ALA2364562

   [[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2S,3R,4S,5S)-5-(4-carbamoyl-1,3-thiazol-2-yl)-3,4-dihydroxyoxolan-2-yl]methyl hydrogen phosphate

Molecule Features

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: 669.46

Molecular Weight (Monoisotopic): 669.0655

AlogP: -2.30

#Rotatable Bonds: 11

Polar Surface Area: 327.27

Molecular Species: ACID

HBA: 19

HBD: 8

#RO5 Violations: 3

HBA (Lipinski): 21

HBD (Lipinski): 10

#RO5 Violations (Lipinski): 3

CX Acidic pKa: 1.86

CX Basic pKa: 4.92

CX LogP: -5.89

CX LogD: -8.52

Aromatic Rings: 3

Heavy Atoms: 43

QED Weighted: 0.10

Np 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

Source(1):

• Scientific Literature