Chlorine in PDB 3r4m: Optimization of Potent, Selective, and Orally Bioavailable Pyrrolodinopyrimidine-Containing Inhibitors of Heat Shock Protein 90. Identification of Development Candidate 2-Amino-4-{4-Chloro-2-[2-(4- Fluoro-1H-Pyrazol-1-Yl)Ethoxy]-6-Methylphenyl}-N-(2,2- Difluoropropyl)-5,7-Dihydro-6H-Pyrrolo[3,4-D]Pyrimidine-6-Carboxamide

The structure of Optimization of Potent, Selective, and Orally Bioavailable Pyrrolodinopyrimidine-Containing Inhibitors of Heat Shock Protein 90. Identification of Development Candidate 2-Amino-4-{4-Chloro-2-[2-(4- Fluoro-1H-Pyrazol-1-Yl)Ethoxy]-6-Methylphenyl}-N-(2,2- Difluoropropyl)-5,7-Dihydro-6H-Pyrrolo[3,4-D]Pyrimidine-6-Carboxamide, PDB code: 3r4m was solved by R.J.Almassy, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	24.40 / 1.70
Space group	P 1 21 1
Cell size a, b, c (Å), α, β, γ (°)	54.196, 44.126, 53.263, 90.00, 115.65, 90.00
R / Rfree (%)	19.4 / 22.3

The binding sites of Chlorine atom in the Optimization of Potent, Selective, and Orally Bioavailable Pyrrolodinopyrimidine-Containing Inhibitors of Heat Shock Protein 90. Identification of Development Candidate 2-Amino-4-{4-Chloro-2-[2-(4- Fluoro-1H-Pyrazol-1-Yl)Ethoxy]-6-Methylphenyl}-N-(2,2- Difluoropropyl)-5,7-Dihydro-6H-Pyrrolo[3,4-D]Pyrimidine-6-Carboxamide (pdb code 3r4m). This binding sites where shown within 5.0 Angstroms radius around Chlorine atom.
In total only one binding site of Chlorine was determined in the Optimization of Potent, Selective, and Orally Bioavailable Pyrrolodinopyrimidine-Containing Inhibitors of Heat Shock Protein 90. Identification of Development Candidate 2-Amino-4-{4-Chloro-2-[2-(4- Fluoro-1H-Pyrazol-1-Yl)Ethoxy]-6-Methylphenyl}-N-(2,2- Difluoropropyl)-5,7-Dihydro-6H-Pyrrolo[3,4-D]Pyrimidine-6-Carboxamide, PDB code: 3r4m:

Chlorine binding site 1 out of 1 in the Optimization of Potent, Selective, and Orally Bioavailable Pyrrolodinopyrimidine-Containing Inhibitors of Heat Shock Protein 90. Identification of Development Candidate 2-Amino-4-{4-Chloro-2-[2-(4- Fluoro-1H-Pyrazol-1-Yl)Ethoxy]-6-Methylphenyl}-N-(2,2- Difluoropropyl)-5,7-Dihydro-6H-Pyrrolo[3,4-D]Pyrimidine-6-Carboxamide


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 1 of Optimization of Potent, Selective, and Orally Bioavailable Pyrrolodinopyrimidine-Containing Inhibitors of Heat Shock Protein 90. Identification of Development Candidate 2-Amino-4-{4-Chloro-2-[2-(4- Fluoro-1H-Pyrazol-1-Yl)Ethoxy]-6-Methylphenyl}-N-(2,2- Difluoropropyl)-5,7-Dihydro-6H-Pyrrolo[3,4-D]Pyrimidine-6-Carboxamide within 5.0Å range: probe atom residue distance (Å) B Occ A:Cl501 b:14.9 occ:1.00 CL1 A:WOE501 0.0 14.9 1.0 C11 A:WOE501 1.7 11.6 1.0 N13 A:WOE501 2.6 11.0 1.0 C10 A:WOE501 2.7 10.8 1.0 O A:GLY97 3.2 11.4 1.0 O A:HOH2 3.4 9.8 1.0 C A:GLY97 3.5 11.2 1.0 N A:GLY97 3.6 10.7 1.0 CG2 A:ILE96 3.6 12.2 1.0 O A:HOH282 3.6 18.6 1.0 CG A:MET98 3.7 12.2 1.0 CB A:ALA55 3.7 8.8 1.0 O A:HOH284 3.8 17.1 1.0 CA A:GLY97 3.8 10.5 1.0 C14 A:WOE501 3.9 9.6 1.0 O A:HOH273 3.9 19.2 1.0 C9 A:WOE501 4.0 9.6 1.0 OG1 A:THR184 4.1 8.8 1.0 N A:MET98 4.2 11.2 1.0 N16 A:WOE501 4.4 9.6 1.0 C A:ILE96 4.6 11.3 1.0 O A:HOH4 4.7 12.6 1.0 CA A:ALA55 4.7 10.2 1.0 SD A:MET98 4.7 13.1 1.0 CA A:MET98 4.7 11.7 1.0 CB A:MET98 4.8 10.3 1.0 CE A:MET98 4.9 13.2 1.0 N A:ILE96 4.9 10.9 1.0 N15 A:WOE501 4.9 10.7 1.0 CB A:ILE96 4.9 12.5 1.0

L.Zehnder, M.Bennett, J.Meng, B.Huang, S.Ninkovic, F.Wang, J.Braganza, J.Tatlock, T.Jewell, J.Z.Zhou, B.Burke, J.Wang, K.Maegley, P.P.Mehta, M.J.Yin, K.S.Gajiwala, M.J.Hickey, S.Yamazaki, E.Smith, P.Kang, A.Sistla, E.Dovalsantos, M.R.Gehring, R.Kania, M.Wythes, P.P.Kung. Optimization of Potent, Selective, and Orally Bioavailable Pyrrolodinopyrimidine-Containing Inhibitors of Heat Shock Protein 90. Identification of Development Candidate 2-Amino-4-{4-Chloro-2-[2-(4-Fluoro-1H-Pyrazol-1-Yl)Ethoxy]- 6-Methylphenyl}-N-(2,2-Difluoropropyl)-5,7-Dihydro-6H- Pyrrolo[3,4-D]Pyrimidine-6-Carboxamide. J.Med.Chem. V. 54 3368 2011.
ISSN: ISSN 0022-2623
PubMed: 21438541
DOI: 10.1021/JM200128M