Biomedical subjects

J D Jennissen

Publications and source records attributed to J D Jennissen.

4 recordsLinked to original sources

PubMed2001

4-[3-Bromo-4-hydroxyphenyl)amino]-6,7-dimethoxyquinazolin-1-ium chloride methanol solvate and 4-[(3-hydroxyphenyl)amino]-6,7-dimethoxy-1-quinazolinium chloride.

The title compounds, C16H15BrN3(O3)(+).Cl(-).CH4O (WHI-P154) and C16H16N3(O3)(+).Cl(-) (WHI-P180), are potent inhibitors [WHI-P154 with IC50 = 5.6 microM and WHI-P180 with IC50 = 4.0 microM for epidermal growth factor receptor (EGFR) kinase inhibition] of the EGFR tyrosine kinase as well as Janus Kinase 3. The molecular structures of these compounds are very similar except for the dihedral angle between the anilino and quinazoline moieties which is 1.10 (5) degrees for WHI-P154, and 45.66 (6) and 25.29 (7) degrees for the two molecules of WHI-P180 in the asymmetric unit. The nitrogen at the N3 position is protonated in both structures and participates in hydrogen bonding with the chlorine anions.

Animals↗

PubMed2000

An inhibitor of Janus kinase 3:4-(4-hydroxyphenylamino)-6, 7-dimethoxyquinazolin-1-ium chloride methanol solvate.

The crystal structure of the title compound, C(16)H(16)N(3)O(3)(+). Cl(-).CH(4)O (WHI-P131, an inhibitor of Janus kinase 3), contains four hydrogen bonds. There are two hydrogen bonds within the asymmetric unit, i.e. interactions between WHI-P131 OH and Cl(-), and between methanol and Cl(-). There is a third interaction between WHI-P131 NH and Cl(-) (related by a 2(1) screw) and a fourth between WHI-P131 NH and methanol (related by an n-glide). The hydrogen-bond pattern for these interactions can be described by the first-level hydrogen-bond graph-set notation D(1)(1)(2)D(1)(1)(2)D(1)(1)(2)D(1)(1)(2). The second-level graph-set notation (for combinations of two hydrogen bonds) was determined to be D(1)(2)(3)D(1)(2)(3)D(2)(2)(4)D(2)(2)(9)D(2)(2)(14)C(1)(2)(9).

Crystallography, X-Ray↗

PubMed2000

Three leflunomide metabolite analogs.

The title compounds, 1-cyano-2-hydroxy-N-[4-(methylsulfonyl)phenyl]but-2-enamide, C(12)H(12)N(2)O(4)S, PHI492, 1-cyano-2-hydroxy-N-[3-(methylsulfonyl)phenyl]but-2-enamide, C(12)H(12)N(2)O(4)S, PHI493, and N-[3-bromo-4-(trifluoromethoxy)phenyl]-1-cyano-2-hydroxybut-2-e namide , C(12)H(8)BrF(3)N(2)O(3), PHI495, are potent inhibitors of Bruton's tyrosine kinase (BTK). The molecular structures of these compounds are similar and they display similar hydrogen-bonding networks and crystal packing. Examination of the crystal-packing interaction in the three compounds reveals an alternating direction of adjacent molecules in the crystalline lattice due to intermolecular cyano-amide hydrogen bonding. PHI492, a positional isomer of PHI493, does not form intermolecular O-H.O hydrogen bonds between molecules and crystallizes in a space group different from that of PHI493 and PHI495. The aromatic ring and the amide group of each molecule form a conjugated pi-system which ensures planarity, with further stabilization gained from intramolecular O-H.O hydrogen bonds.

Antineoplastic Agents↗

PubMed1999

Inhibitor of HIV-1 reverse transcriptase: N'-(5-bromo-2-pyridyl)-N-[2-(2,5-dimethoxyphenyl)ethyl]thiourea.

The crystal structure of the title compound, C16H18Br-N3O2S (HI-236), a potent non-nucleoside inhibitor of HIV-1 reverse transcriptase, revealed an intramolecular hydrogen bond between a thiourea N atom and the pyridyl-N atom [N-H...N = 2.671 (3) A, graph-set motif S1(1)(6)] that imparts a more rigid conformation to the molecule. A second hydrogen bond between a thiourea N atom and the thiocarbonyl-S atom [N-H2...S = 3.403 (2) A, graph-set motif R2(2)(8)] was observed between inversion-related molecules of HI-236. The first-level hydrogen-bond graph-set notation for HI-236 was determined to be S1(1)(6)R2(2)(8).

Crystallography, X-Ray↗