2N-[5-(3-amino-3-iminopropylcarbamoyl)-1-methyl-1H-3-pyrrolyl]-4-(4-formamido-1-methyl-1H-2-pyrrolylcarboxamido)-1-methyl-1H-2-pyrrolecarboxamide hydrochloride(distamycin A)

ID: ALA3216873

PubChem CID: 90665028

Max Phase: Preclinical

Molecular Formula: C22H29Cl2N9O4

Molecular Weight: 481.52

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Cl.Cl.Cn1cc(NC(=O)c2cc(NC(=O)c3cc(NC=O)cn3C)cn2C)cc1C(=O)NCCC(=N)N

Standard InChI:  InChI=1S/C22H27N9O4.2ClH/c1-29-9-13(26-12-32)6-17(29)21(34)28-15-8-18(31(3)11-15)22(35)27-14-7-16(30(2)10-14)20(33)25-5-4-19(23)24;;/h6-12H,4-5H2,1-3H3,(H3,23,24)(H,25,33)(H,26,32)(H,27,35)(H,28,34);2*1H

Standard InChI Key:  SLFBHJZSKXPYCM-UHFFFAOYSA-N

Molfile:  

     RDKit          2D

 37 37  0  0  0  0  0  0  0  0999 V2000
   10.3797    4.5996    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   -1.3071    5.0236    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.5881   11.1102    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7500   -1.0323    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5206    5.8834    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.1117   12.5191    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7500   -1.0323    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3040    3.5228    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2915    9.8941    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.5571    7.3100    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0000    1.2760    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0936    5.8834    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2135    0.3943    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.0753   11.0926    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2135    0.3943    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0571    7.3100    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3252   13.4008    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0031    2.7742    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.3210    8.5240    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.5387   12.5192    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.6332   -2.2426    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.5805   -4.2220    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.3873   -4.3492    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4851   10.0174    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3421    2.9209    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.2725   14.4537    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.5026   -3.1368    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.9627   12.9852    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.1470   -3.3397    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.1255   -2.0835    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.4130   14.8270    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.9011   -5.4463    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    4.0102   -3.2959    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0318   12.8830    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.4553   -2.0031    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.6597    5.5057    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.8797    4.5996    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
  3  9  1  0
  4 13  2  0
  5  2  1  0
  6  3  1  0
  7 15  1  0
  8  2  1  0
  9 19  1  0
 10 12  1  0
 11 18  1  0
 12  2  2  0
 13 11  1  0
 14  3  2  0
 15 11  2  0
 16  5  1  0
 17  6  1  0
 18  8  1  0
 19 10  1  0
 20 14  1  0
 21  4  1  0
 22 23  2  0
 23 27  1  0
 24  9  2  0
 25  8  2  0
 26 28  1  0
 27 33  1  0
 28 20  1  0
 29 21  2  0
 30 21  1  0
 31 26  2  0
 32 23  1  0
 33 30  1  0
 34  6  1  0
 35  7  1  0
 36  5  1  0
 10 16  2  0
  7  4  1  0
 20 17  2  0
M  END

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: 481.52

Molecular Weight (Monoisotopic): 481.2186

AlogP: 0.83

#Rotatable Bonds: 10

Polar Surface Area: 181.06

Molecular Species: BASE

HBA: 8

HBD: 6

#RO5 Violations: 1

HBA (Lipinski): 13

HBD (Lipinski): 7

#RO5 Violations (Lipinski): 2

CX Acidic pKa: ┄

CX Basic pKa: 12.55

CX LogP: -1.08

CX LogD: -3.35

Aromatic Rings: 3

Heavy Atoms: 35

QED Weighted: 0.14

Np Likeness Score: -0.38

References

1. Bialer M, Yagen B, Mechoulam R, Becker Y..  (1980)  Structure-activity relationships of pyrrole amidine antiviral antibiotics. 2. Preparation of mono- and tripyrrole derivatives of congocidine.,  23  (10): [PMID:6252323] [10.1021/jm00184a018]

2. Lown JW, Krowicki K, Balzarini J, De Clercq E..  (1986)  Structure-activity relationship of novel oligopeptide antiviral and antitumor agents related to netropsin and distamycin.,  29  (7): [PMID:3027326] [10.1021/jm00157a016]

3. Baraldi PG, Beria I, Cacciari B, Cozzi P, Franzetti C, Mongelli N, Romagnoli R, Spalluto G.  (1996)  Synthesis and antitumor activity of novel distamycin derivatives,  6  (11): [10.1016/0960-894X(96)00204-1]

4. Baraldi PG, Romagnoli R, Duatti A, Bolzati C, Piffanelli A, Bianchi N, Mischiati C, Gambari R..  (2000)  Synthesis of hybrid distamycin-cysteine labeled with 99mTc: a model for a novel class of cancer imaging agents.,  10  (12): [PMID:10890173] [10.1016/s0960-894x(00)00250-x]

5. Parrick J, Porssa M, Davies LK, Dennis MF, Patel KB, Stratford MR, Wardman P.  (1993)  Targeting radiosensitizers to DNA by minor groove binding: nitroarenes based on netropsin and distamycin,  3  (8): [10.1016/S0960-894X(00)80045-1]

6. Baraldi PG, Del Carmen Nunez M, Tabrizi MA, De Clercq E, Balzarini J, Bermejo J, Estévez F, Romagnoli R..  (2004)  Design, synthesis, and biological evaluation of hybrid molecules containing alpha-methylene-gamma-butyrolactones and polypyrrole minor groove binders.,  47  (11): [PMID:15139766] [10.1021/jm031104y]

7. Krowicki K, Balzarini J, De Clercq E, Newman RA, Lown JW..  (1988)  Novel DNA groove binding alkylators: design, synthesis, and biological evaluation.,  31  (2): [PMID:2828620] [10.1021/jm00397a012]

8. Baraldi PG, Romagnoli R, Guadix AE, Pineda de las Infantas MJ, Gallo MA, Espinosa A, Martinez A, Bingham JP, Hartley JA..  (2002)  Design, synthesis, and biological activity of hybrid compounds between uramustine and DNA minor groove binder distamycin A.,  45  (17): [PMID:12166936] [10.1021/jm011113b]

9. Baraldi PG, Balboni G, Cacciari B, Guiotto A, Manfredini S, Romagnoli R, Spalluto G, Thurston DE, Howard PW, Bianchi N, Rutigliano C, Mischiati C, Gambari R..  (1999)  Synthesis, in vitro antiproliferative activity, and DNA-binding properties of hybrid molecules containing pyrrolo[2,1-c][1, 4]benzodiazepine and minor-groove-binding oligopyrrole carriers.,  42  (25): [PMID:10602698] [10.1021/jm991033w]

10. Lee M, White LA, Nobles JA, Forrow SM, Hartley JA.  (1991)  Synthesis and DNA binding properties of an amidine-linked and phenyl-containing analogue of distamycin A,  1  (11): [10.1016/S0960-894X(01)81158-6]

11. PubChem BioAssay data set, 

12. Romagnoli R, Baraldi PG, Pavani MG, Fruttarolo F, Preti D, Bovero A, Tabrizi MA, Bianchi N, Gambari R.  (2004)  Design, Synthesis and Growth Inhibition Activity of Bis-Epoxyethyl Derivatives of Stallimycin Modified on the Amidino Moiety,  13  (5): [10.1007/s00044-004-0034-6]

13. Bialer M, Yagen B, Mechoulam R, Becker Y..  (1979)  Structure--activity relationships of pyrrole amidine antiviral antibiotics. 1. Modifications of the alkylamidine side chain.,  22  (11): [PMID:230350] [10.1021/jm00197a004]

Source

Source(2):

• Scientific Literature
• PubChem BioAssays