Fluorine in PDB 7r9c: Cocrystal of BRD4(D1) with N,N-Dimethyl-2-[(3R)-3-(5-{2-[2-Methyl-5- (Propan-2-Yl)Phenoxy]Pyrimidin-4-Yl}-4-[4-(Trifluoromethyl)Phenyl]- 1H-Imidazol-1-Yl)Pyrrolidin-1-Yl]Ethan-1-Amine

The structure of Cocrystal of BRD4(D1) with N,N-Dimethyl-2-[(3R)-3-(5-{2-[2-Methyl-5- (Propan-2-Yl)Phenoxy]Pyrimidin-4-Yl}-4-[4-(Trifluoromethyl)Phenyl]- 1H-Imidazol-1-Yl)Pyrrolidin-1-Yl]Ethan-1-Amine, PDB code: 7r9c was solved by H.Cui, K.Shi, H.Aihara, W.C.K.Pomerantz, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	35.57 / 1.50
Space group	P 2 21 21
Cell size a, b, c (Å), α, β, γ (°)	29.948, 37.553, 110.959, 90, 90, 90
R / Rfree (%)	16.8 / 21.6

The structure of Cocrystal of BRD4(D1) with N,N-Dimethyl-2-[(3R)-3-(5-{2-[2-Methyl-5- (Propan-2-Yl)Phenoxy]Pyrimidin-4-Yl}-4-[4-(Trifluoromethyl)Phenyl]- 1H-Imidazol-1-Yl)Pyrrolidin-1-Yl]Ethan-1-Amine also contains other interesting chemical elements:

Chlorine

(Cl)

1 atom

The binding sites of Fluorine atom in the Cocrystal of BRD4(D1) with N,N-Dimethyl-2-[(3R)-3-(5-{2-[2-Methyl-5- (Propan-2-Yl)Phenoxy]Pyrimidin-4-Yl}-4-[4-(Trifluoromethyl)Phenyl]- 1H-Imidazol-1-Yl)Pyrrolidin-1-Yl]Ethan-1-Amine (pdb code 7r9c). This binding sites where shown within 5.0 Angstroms radius around Fluorine atom.
In total 3 binding sites of Fluorine where determined in the Cocrystal of BRD4(D1) with N,N-Dimethyl-2-[(3R)-3-(5-{2-[2-Methyl-5- (Propan-2-Yl)Phenoxy]Pyrimidin-4-Yl}-4-[4-(Trifluoromethyl)Phenyl]- 1H-Imidazol-1-Yl)Pyrrolidin-1-Yl]Ethan-1-Amine, PDB code: 7r9c:
Jump to Fluorine binding site number: 1; 2; 3;

Fluorine binding site 1 out of 3 in the Cocrystal of BRD4(D1) with N,N-Dimethyl-2-[(3R)-3-(5-{2-[2-Methyl-5- (Propan-2-Yl)Phenoxy]Pyrimidin-4-Yl}-4-[4-(Trifluoromethyl)Phenyl]- 1H-Imidazol-1-Yl)Pyrrolidin-1-Yl]Ethan-1-Amine


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 1 of Cocrystal of BRD4(D1) with N,N-Dimethyl-2-[(3R)-3-(5-{2-[2-Methyl-5- (Propan-2-Yl)Phenoxy]Pyrimidin-4-Yl}-4-[4-(Trifluoromethyl)Phenyl]- 1H-Imidazol-1-Yl)Pyrrolidin-1-Yl]Ethan-1-Amine within 5.0Å range: probe atom residue distance (Å) B Occ A:F202 b:28.3 occ:1.00 F21 A:2IR202 0.0 28.3 1.0 C20 A:2IR202 1.4 25.6 1.0 F22 A:2IR202 2.2 31.0 1.0 F23 A:2IR202 2.2 28.9 1.0 C19 A:2IR202 2.3 23.2 1.0 HD1 A:PHE83 2.6 27.0 1.0 HB2 A:CYS136 2.7 32.4 1.0 HG2 A:MET132 2.7 27.4 1.0 HE1 A:PHE83 2.9 31.1 1.0 O A:MET132 3.0 24.7 1.0 HG3 A:MET132 3.0 27.4 1.0 C24 A:2IR202 3.1 20.5 1.0 H241 A:2IR202 3.1 24.7 1.0 CD1 A:PHE83 3.3 22.4 1.0 C18 A:2IR202 3.3 25.8 1.0 CG A:MET132 3.3 22.8 1.0 H181 A:2IR202 3.4 31.0 1.0 CE1 A:PHE83 3.4 25.9 1.0 H A:CYS136 3.5 31.6 1.0 CB A:CYS136 3.6 26.9 1.0 C A:MET132 3.7 24.4 1.0 HB2 A:ASN135 4.0 31.9 1.0 N A:CYS136 4.0 26.3 1.0 HB3 A:CYS136 4.1 32.4 1.0 HA A:MET132 4.1 28.4 1.0 HA A:PHE133 4.2 29.5 1.0 CA A:CYS136 4.3 23.6 1.0 CA A:MET132 4.3 23.6 1.0 HA A:CYS136 4.3 28.3 1.0 C17 A:2IR202 4.4 22.1 1.0 CB A:MET132 4.4 24.3 1.0 C25 A:2IR202 4.4 20.3 1.0 SD A:MET132 4.4 25.5 1.0 CG A:PHE83 4.5 19.8 1.0 HA A:PHE83 4.6 24.1 1.0 N A:PHE133 4.6 25.4 1.0 O A:MET105 4.6 26.8 1.0 HB3 A:PHE83 4.7 23.7 1.0 SG A:CYS136 4.7 27.8 1.0 HG A:CYS136 4.7 33.4 1.0 CZ A:PHE83 4.8 23.4 1.0 CB A:ASN135 4.8 26.6 1.0 CA A:PHE133 4.8 24.6 1.0 HB3 A:ASN135 4.9 31.9 1.0 C16 A:2IR202 4.9 22.0 1.0 HE2 A:MET132 5.0 34.6 1.0 HB3 A:MET132 5.0 29.2 1.0 HA A:ASP106 5.0 28.6 1.0 C A:ASN135 5.0 26.2 1.0

Fluorine binding site 2 out of 3 in the Cocrystal of BRD4(D1) with N,N-Dimethyl-2-[(3R)-3-(5-{2-[2-Methyl-5- (Propan-2-Yl)Phenoxy]Pyrimidin-4-Yl}-4-[4-(Trifluoromethyl)Phenyl]- 1H-Imidazol-1-Yl)Pyrrolidin-1-Yl]Ethan-1-Amine


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 2 of Cocrystal of BRD4(D1) with N,N-Dimethyl-2-[(3R)-3-(5-{2-[2-Methyl-5- (Propan-2-Yl)Phenoxy]Pyrimidin-4-Yl}-4-[4-(Trifluoromethyl)Phenyl]- 1H-Imidazol-1-Yl)Pyrrolidin-1-Yl]Ethan-1-Amine within 5.0Å range: probe atom residue distance (Å) B Occ A:F202 b:31.0 occ:1.00 F22 A:2IR202 0.0 31.0 1.0 C20 A:2IR202 1.4 25.6 1.0 F21 A:2IR202 2.2 28.3 1.0 F23 A:2IR202 2.3 28.9 1.0 C19 A:2IR202 2.4 23.2 1.0 H181 A:2IR202 2.5 31.0 1.0 C18 A:2IR202 2.8 25.8 1.0 HB2 A:ASN135 2.9 31.9 1.0 O A:HOH324 3.0 24.7 1.0 HH A:TYR97 3.1 32.7 1.0 OH A:TYR97 3.3 27.2 1.0 O A:MET105 3.3 26.8 1.0 HG3 A:MET132 3.3 27.4 1.0 HB3 A:ASN135 3.4 31.9 1.0 O A:MET132 3.5 24.7 1.0 HD22 A:ASN135 3.5 39.5 1.0 CB A:ASN135 3.6 26.6 1.0 C24 A:2IR202 3.6 20.5 1.0 HA A:MET132 3.7 28.4 1.0 H A:CYS136 3.9 31.6 1.0 HG22 A:VAL87 3.9 34.4 1.0 HG2 A:MET132 3.9 27.4 1.0 HB2 A:CYS136 4.0 32.4 1.0 HG23 A:VAL87 4.0 34.4 1.0 H241 A:2IR202 4.0 24.7 1.0 CG A:MET132 4.1 22.8 1.0 C17 A:2IR202 4.1 22.1 1.0 N A:CYS136 4.1 26.3 1.0 ND2 A:ASN135 4.3 32.8 1.0 H A:MET105 4.3 32.9 1.0 C A:MET132 4.3 24.4 1.0 CG2 A:VAL87 4.3 28.6 1.0 HD1 A:PHE83 4.4 27.0 1.0 CA A:MET132 4.4 23.6 1.0 CG A:ASN135 4.5 31.1 1.0 C A:ASN135 4.6 26.2 1.0 HA A:CYS136 4.6 28.3 1.0 C A:MET105 4.6 24.1 1.0 HG21 A:VAL87 4.6 34.4 1.0 CZ A:TYR97 4.6 24.4 1.0 CA A:ASN135 4.7 29.1 1.0 H171 A:2IR202 4.7 26.6 1.0 HA A:ASP106 4.7 28.6 1.0 CA A:CYS136 4.8 23.6 1.0 CB A:CYS136 4.8 26.9 1.0 CB A:MET132 4.8 24.3 1.0 C25 A:2IR202 4.9 20.3 1.0 HE1 A:PHE83 4.9 31.1 1.0 H A:ASN135 5.0 34.2 1.0

Fluorine binding site 3 out of 3 in the Cocrystal of BRD4(D1) with N,N-Dimethyl-2-[(3R)-3-(5-{2-[2-Methyl-5- (Propan-2-Yl)Phenoxy]Pyrimidin-4-Yl}-4-[4-(Trifluoromethyl)Phenyl]- 1H-Imidazol-1-Yl)Pyrrolidin-1-Yl]Ethan-1-Amine


Mono view


Stereo pair view

A full contact list of Fluorine with other atoms in the F binding site number 3 of Cocrystal of BRD4(D1) with N,N-Dimethyl-2-[(3R)-3-(5-{2-[2-Methyl-5- (Propan-2-Yl)Phenoxy]Pyrimidin-4-Yl}-4-[4-(Trifluoromethyl)Phenyl]- 1H-Imidazol-1-Yl)Pyrrolidin-1-Yl]Ethan-1-Amine within 5.0Å range: probe atom residue distance (Å) B Occ A:F202 b:28.9 occ:1.00 F23 A:2IR202 0.0 28.9 1.0 C20 A:2IR202 1.4 25.6 1.0 F21 A:2IR202 2.2 28.3 1.0 F22 A:2IR202 2.3 31.0 1.0 C19 A:2IR202 2.3 23.2 1.0 H241 A:2IR202 2.5 24.7 1.0 C24 A:2IR202 2.8 20.5 1.0 HD1 A:PHE83 2.9 27.0 1.0 HG3 A:MET132 2.9 27.4 1.0 HA A:PHE83 3.2 24.1 1.0 O A:MET105 3.6 26.8 1.0 HA A:ASP106 3.6 28.6 1.0 HG2 A:MET132 3.6 27.4 1.0 CG A:MET132 3.6 22.8 1.0 CD1 A:PHE83 3.6 22.4 1.0 C18 A:2IR202 3.7 25.8 1.0 HG22 A:VAL87 3.9 34.4 1.0 HB3 A:ASP106 4.0 31.1 1.0 H181 A:2IR202 4.0 31.0 1.0 HB3 A:PHE83 4.1 23.7 1.0 CA A:PHE83 4.1 20.0 1.0 HE1 A:PHE83 4.2 31.1 1.0 HG21 A:VAL87 4.2 34.4 1.0 HB2 A:ASP106 4.2 31.1 1.0 SD A:MET132 4.3 25.5 1.0 C25 A:2IR202 4.3 20.3 1.0 O A:PRO82 4.3 23.1 1.0 CE1 A:PHE83 4.4 25.9 1.0 CA A:ASP106 4.4 23.8 1.0 CG2 A:VAL87 4.4 28.6 1.0 CB A:ASP106 4.4 25.9 1.0 O A:HOH324 4.4 24.7 1.0 CB A:PHE83 4.4 19.8 1.0 HG23 A:VAL87 4.4 34.4 1.0 CG A:PHE83 4.5 19.8 1.0 O A:PHE83 4.6 24.9 1.0 C A:MET105 4.6 24.1 1.0 HB2 A:CYS136 4.7 32.4 1.0 O A:MET132 4.7 24.7 1.0 C17 A:2IR202 4.7 22.1 1.0 HA A:MET132 4.8 28.4 1.0 C A:PHE83 4.8 20.6 1.0 HH A:TYR97 4.8 32.7 1.0 CB A:MET132 4.9 24.3 1.0 H251 A:2IR202 5.0 24.4 1.0 O A:GLN85 5.0 21.8 1.0

H.Cui, A.Divakaran, Z.J.Hoell, M.O.Ellingson, C.R.Scholtz, H.Zahid, J.A.Johnson, E.C.Griffith, C.T.Gee, A.L.Lee, S.Khanal, K.Shi, H.Aihara, V.H.Shah, R.E.Lee, D.A.Harki, W.C.K.Pomerantz. A Structure-Based Design Approach For Generating High Affinity BRD4 D1-Selective Chemical Probes. J.Med.Chem. V. 65 2342 2022.
ISSN: ISSN 0022-2623
PubMed: 35007061
DOI: 10.1021/ACS.JMEDCHEM.1C01779