Fluorine in PDB 3r4o: 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: 3r4o was solved by K.S.Gajiwala, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	19.88 / 2.65
Space group	P 21 21 21
Cell size a, b, c (Å), α, β, γ (°)	43.149, 79.523, 130.101, 90.00, 90.00, 90.00
R / Rfree (%)	23.5 / 30.8

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 also contains other interesting chemical elements:

Chlorine

(Cl)

4 atoms

The binding sites of Fluorine 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 3r4o). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 6 binding sites of Fluorine where 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: 3r4o:
Jump to Fluorine binding site number: 1; 2; 3; 4; 5; 6;

Fluorine binding site 1 out of 6 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 Fluorine with other atoms in the F 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:F901 b:26.6 occ:1.00 F29 A:FU3901 0.0 26.6 1.0 C21 A:FU3901 1.3 24.7 1.0 F30 A:FU3901 2.2 25.7 1.0 F31 A:FU3901 2.2 23.4 1.0 C9 A:FU3901 2.3 25.1 1.0 C8 A:FU3901 2.9 22.3 1.0 CB A:ASP54 3.6 17.1 1.0 NZ A:LYS58 3.6 23.8 1.0 O A:ASP54 4.1 14.1 1.0 C A:ASP54 4.1 13.8 1.0 CE A:LYS58 4.1 25.9 1.0 C10 A:FU3901 4.3 22.3 1.0 CD A:LYS58 4.4 24.8 1.0 OD2 A:ASP54 4.5 23.4 1.0 CA A:ASP54 4.5 16.1 1.0 N A:ALA55 4.5 11.7 1.0 CG A:ASP54 4.5 20.0 1.0 CA A:ALA55 4.9 11.2 1.0 O28 A:FU3901 4.9 23.3 1.0

Fluorine binding site 2 out of 6 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 Fluorine with other atoms in the F binding site number 2 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:F901 b:25.7 occ:1.00 F30 A:FU3901 0.0 25.7 1.0 C21 A:FU3901 1.3 24.7 1.0 F31 A:FU3901 2.2 23.4 1.0 F29 A:FU3901 2.2 26.6 1.0 C9 A:FU3901 2.3 25.1 1.0 C20 A:FU3901 3.7 20.6 1.0 N26 A:FU3901 3.7 20.9 1.0 C8 A:FU3901 3.7 22.3 1.0 N25 A:FU3901 3.9 21.8 1.0 CD A:LYS58 3.9 24.8 1.0 C7 A:FU3901 3.9 20.1 1.0 O27 A:FU3901 4.1 20.8 1.0 C4 A:FU3901 4.1 22.3 1.0 NZ A:LYS58 4.2 23.8 1.0 C6 A:FU3901 4.2 20.4 1.0 CG2 A:ILE96 4.3 14.7 1.0 CE A:LYS58 4.4 25.9 1.0 CA A:ALA55 4.5 11.2 1.0 C15 A:FU3901 4.6 18.9 1.0 C19 A:FU3901 4.6 21.4 1.0 CB A:LYS58 4.7 18.6 1.0 C14 A:FU3901 4.7 20.4 1.0 O A:ASP54 4.7 14.1 1.0 N A:ALA55 4.7 11.7 1.0 CG A:LYS58 4.7 21.8 1.0 C10 A:FU3901 4.8 22.3 1.0 C A:ASP54 4.8 13.8 1.0 O28 A:FU3901 4.9 23.3 1.0 CB A:ALA55 4.9 9.1 1.0

Fluorine binding site 3 out of 6 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 Fluorine with other atoms in the F binding site number 3 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:F901 b:23.4 occ:1.00 F31 A:FU3901 0.0 23.4 1.0 C21 A:FU3901 1.3 24.7 1.0 F30 A:FU3901 2.2 25.7 1.0 F29 A:FU3901 2.2 26.6 1.0 C9 A:FU3901 2.4 25.1 1.0 C8 A:FU3901 2.9 22.3 1.0 N A:ALA55 3.0 11.7 1.0 CA A:ALA55 3.3 11.2 1.0 C A:ASP54 3.3 13.8 1.0 CB A:ASP54 3.4 17.1 1.0 O A:ASN51 3.6 14.2 1.0 CB A:ALA55 3.7 9.1 1.0 O A:ASP54 3.7 14.1 1.0 CA A:ASP54 4.0 16.1 1.0 C15 A:FU3901 4.1 18.9 1.0 C7 A:FU3901 4.2 20.1 1.0 O28 A:FU3901 4.2 23.3 1.0 C10 A:FU3901 4.2 22.3 1.0 C14 A:FU3901 4.4 20.4 1.0 N26 A:FU3901 4.4 20.9 1.0 N23 A:FU3901 4.5 19.1 1.0 C6 A:FU3901 4.6 20.4 1.0 C A:ASN51 4.7 14.6 1.0 C A:ALA55 4.7 10.6 1.0 N A:ASP54 4.7 17.4 1.0 CG A:ASP54 4.8 20.0 1.0 CG2 A:ILE96 4.9 14.7 1.0 C17 A:FU3901 5.0 21.0 1.0

Fluorine binding site 4 out of 6 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 Fluorine with other atoms in the F binding site number 4 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 B:F901 b:30.7 occ:1.00 F29 B:FU3901 0.0 30.7 1.0 C21 B:FU3901 1.3 27.0 1.0 F30 B:FU3901 2.2 29.7 1.0 F31 B:FU3901 2.2 29.3 1.0 C9 B:FU3901 2.3 25.8 1.0 C8 B:FU3901 2.9 23.2 1.0 CD B:LYS58 3.5 12.3 1.0 NZ B:LYS58 4.0 16.2 1.0 CE B:LYS58 4.1 16.2 1.0 CG B:LYS58 4.2 11.5 1.0 CB B:ASP54 4.2 11.3 1.0 C10 B:FU3901 4.3 23.6 1.0 O B:ASP54 4.6 10.2 1.0 C B:ASP54 4.6 9.2 1.0 N B:ALA55 4.9 8.3 1.0 O28 B:FU3901 4.9 22.7 1.0

Fluorine binding site 5 out of 6 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 Fluorine with other atoms in the F binding site number 5 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 B:F901 b:29.7 occ:1.00 F30 B:FU3901 0.0 29.7 1.0 C21 B:FU3901 1.3 27.0 1.0 F29 B:FU3901 2.2 30.7 1.0 F31 B:FU3901 2.2 29.3 1.0 C9 B:FU3901 2.3 25.8 1.0 CD B:LYS58 3.0 12.3 1.0 N26 B:FU3901 3.6 21.6 1.0 C7 B:FU3901 3.7 20.4 1.0 C8 B:FU3901 3.7 23.2 1.0 C20 B:FU3901 3.7 23.2 1.0 N25 B:FU3901 3.9 23.6 1.0 CA B:ALA55 4.0 8.2 1.0 CG B:LYS58 4.0 11.5 1.0 CE B:LYS58 4.1 16.2 1.0 C6 B:FU3901 4.2 20.6 1.0 CB B:ALA55 4.2 6.2 1.0 CG2 B:ILE96 4.2 10.5 1.0 O27 B:FU3901 4.3 25.1 1.0 C15 B:FU3901 4.3 21.0 1.0 N B:ALA55 4.3 8.3 1.0 C4 B:FU3901 4.3 22.1 1.0 C14 B:FU3901 4.5 20.8 1.0 C B:ASP54 4.6 9.2 1.0 O B:ASP54 4.6 10.2 1.0 NZ B:LYS58 4.7 16.2 1.0 C19 B:FU3901 4.7 22.0 1.0 O28 B:FU3901 4.8 22.7 1.0 C10 B:FU3901 4.8 23.6 1.0 CB B:LYS58 4.9 9.5 1.0

Fluorine binding site 6 out of 6 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 Fluorine with other atoms in the F binding site number 6 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 B:F901 b:29.3 occ:1.00 F31 B:FU3901 0.0 29.3 1.0 C21 B:FU3901 1.3 27.0 1.0 F30 B:FU3901 2.2 29.7 1.0 F29 B:FU3901 2.2 30.7 1.0 C9 B:FU3901 2.3 25.8 1.0 C8 B:FU3901 2.9 23.2 1.0 N B:ALA55 3.0 8.3 1.0 CB B:ASP54 3.0 11.3 1.0 C B:ASP54 3.2 9.2 1.0 CA B:ALA55 3.4 8.2 1.0 O B:ASN51 3.6 11.6 1.0 O B:ASP54 3.6 10.2 1.0 CA B:ASP54 3.7 9.7 1.0 CB B:ALA55 3.8 6.2 1.0 CD B:LYS58 4.2 12.3 1.0 C10 B:FU3901 4.3 23.6 1.0 CG B:ASP54 4.4 12.2 1.0 O28 B:FU3901 4.4 22.7 1.0 CG B:LYS58 4.6 11.5 1.0 N B:ASP54 4.6 7.9 1.0 OD2 B:ASP54 4.6 14.7 1.0 C B:ASN51 4.6 10.5 1.0 C15 B:FU3901 4.7 21.0 1.0 C7 B:FU3901 4.8 20.4 1.0 C B:ALA55 4.9 7.9 1.0 C14 B:FU3901 4.9 20.8 1.0 CA B:ASN51 5.0 10.7 1.0 N26 B:FU3901 5.0 21.6 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