Conivaptan: a step forward in the treatment of hyponatremia?

Hyponatremia is one of the most common electrolyte abnormalities linked to adverse outcomes and increased mortality in hospitalized patients. While the differential diagnosis for hyponatremia is diverse, most cases stem from arginine vasopressin (AVP) dysregulation, where hypoosmolality fails to suppress AVP synthesis and release. The physiological effects of AVP are currently known to depend on its interaction with any of 3 receptor subtypes V1A, V2, and V1B. Activation of V2 by AVP is the key in renal water regulation and maintenance of total body volume and plasma tonicity. Despite the long-recognized problem with excess AVP in euvolemic and hypervolemic hyponatremia, traditional therapeutic options have relied on nonspecific and potentially problematic strategies. More recently, a new class of drugs, introduced as “aquaretics,” has gained great attention among clinicians because of its ability to correct hyponatremia via direct competitive inhibition of AVP at V2 receptors to induce renal electrolyte-free water excretion. In this paper, we aim to review available clinical data on the only FDA-approved aquaretic, dual V1A/V2 receptor antagonist conivaptan, discuss its clinical indications, efficacy, safety profile, and comment on its clinical limitations

Abacavir methanol 2.5-solvate

The structure of abacavir (systematic name: {(1S,4R)-4-[2-amino-6-(cyclo­propyl­amino)-9H-purin-9-yl]cyclo­pent-2-en-1-yl}methanol), C14H18N6O·2.5CH3OH, consists of hydrogen-bonded ribbons which are further held together by additional hydrogen bonds involving the hydroxyl group and two N atoms on an adjacent purine. The asymmetric unit also contains 2.5 mol­ecules of methanol solvate which were grossly disordered and were excluded using SQUEEZE subroutine in PLATON [Spek, (2009 ▶). Acta Cryst. D65, 148–155]

(1E,3E,5E,7E)-4,4′-(Octa-1,3,5,7-tetra­ene-1,8-di­yl)dipyridine

The title compound, C18H16N2, crystallizes with one and a half independent mol­ecules in the asymmetric unit, with the half-mol­ecule being completed by crystallographic inversion symmetry. Both independent mol­ecules are almost planar, with the non-H atoms exhibiting r.m.s. deviations from the least-squares mol­ecular plane of 0.175 and 0.118 Å, respectively

1,4-Bis(4-nitrostyryl)benzene

The complete molecule of the title compound, C22H16N2O4, is generated by a crystallographic centre of inversion. The plane of the central aromatic ring is tilted by 11.85 (4)° with respect to the outer aromatic ring. The crystal packing is determined by van der Waals interactions, with stair-like stacking between adjacent aromatic rings. The stacks are staggered and each layer is approximately 3.8 Å from the next. The closest intermolecular contact (approximately 2.42 Å) is between an O atom and a vinyl H atom

Inter- and Intramolecular Interactions in Some Bromo- and Tricyanovinyl-Substituted Thiophenes and Ethylenedioxythiophenes

We report herein on the competing inter- and intramolecular interactions in seven structurally related thiophene and ethyelenedioxythiophene (EDOT) molecules, substituted with bromine and/or tricyanovinyl (TCV) groups in various combinations, using single crystal structural analyses. Br···Br Interactions of less than 3.5 Å appear to be dominant in the crystal structures of the dibromo EDOT molecules and yet are almost nonexistent in 5,5″-dibromoterthiophene (shortest Br···Br distances are >4.2 Å), indicating a cooperative role involving the Br and the ethylenedioxy moiety. Short Br···Br distances of 3.5 Å within stacks and between adjacent stacks of molecules in crystalline dibromo EDOT dimer (<b>6</b>) could be utilized for the preparation of highly ordered polymers with the perfectly planar EDOT dimer as repeating unit, similar to the work reported by Wudl. On the other hand, new dimeric motifs are formed in Br-EDOT-TCV as strong S···N (3.03 Å) intermolecular interactions in TCV-EDOT are replaced by competing N···Br (2.99 Å) interactions. Short intramolecular N···S distances ranging from 3.2 to 3.3 Å are associated with small dihedral angles between the TCV and thiophene planes ranging from 0.80 to 4.3 deg. A slight enhancement of molecular planarity apparently has a profound impact on the extent of conjugation as evident from the CC bond lengths (1.34–1.40 Å) and C–C (1.37–1.44 Å) within the thiophene rings. These findings suggest that N···S, N···Br, and Br···Br inter- and intramolecular interactions could be utilized as additional crystal engineering tools to promote molecular planarity and arrangement of higher oligomers in the solid state prior to polymerization of thiophene-based molecular materials. On the basis of the current study, these interactions appear to also enhance the stability of the structure and influence intramolecular charge transfer and π-stack formation patterns

Inter- and Intramolecular Interactions in Some Bromo- and Tricyanovinyl-Substituted Thiophenes and Ethylenedioxythiophenes

We report herein on the competing inter- and intramolecular interactions in seven structurally related thiophene and ethyelenedioxythiophene (EDOT) molecules, substituted with bromine and/or tricyanovinyl (TCV) groups in various combinations, using single crystal structural analyses. Br···Br Interactions of less than 3.5 Å appear to be dominant in the crystal structures of the dibromo EDOT molecules and yet are almost nonexistent in 5,5″-dibromoterthiophene (shortest Br···Br distances are >4.2 Å), indicating a cooperative role involving the Br and the ethylenedioxy moiety. Short Br···Br distances of 3.5 Å within stacks and between adjacent stacks of molecules in crystalline dibromo EDOT dimer (<b>6</b>) could be utilized for the preparation of highly ordered polymers with the perfectly planar EDOT dimer as repeating unit, similar to the work reported by Wudl. On the other hand, new dimeric motifs are formed in Br-EDOT-TCV as strong S···N (3.03 Å) intermolecular interactions in TCV-EDOT are replaced by competing N···Br (2.99 Å) interactions. Short intramolecular N···S distances ranging from 3.2 to 3.3 Å are associated with small dihedral angles between the TCV and thiophene planes ranging from 0.80 to 4.3 deg. A slight enhancement of molecular planarity apparently has a profound impact on the extent of conjugation as evident from the CC bond lengths (1.34–1.40 Å) and C–C (1.37–1.44 Å) within the thiophene rings. These findings suggest that N···S, N···Br, and Br···Br inter- and intramolecular interactions could be utilized as additional crystal engineering tools to promote molecular planarity and arrangement of higher oligomers in the solid state prior to polymerization of thiophene-based molecular materials. On the basis of the current study, these interactions appear to also enhance the stability of the structure and influence intramolecular charge transfer and π-stack formation patterns

Inter- and Intramolecular Interactions in Some Bromo- and Tricyanovinyl-Substituted Thiophenes and Ethylenedioxythiophenes

We report herein on the competing inter- and intramolecular interactions in seven structurally related thiophene and ethyelenedioxythiophene (EDOT) molecules, substituted with bromine and/or tricyanovinyl (TCV) groups in various combinations, using single crystal structural analyses. Br···Br Interactions of less than 3.5 Å appear to be dominant in the crystal structures of the dibromo EDOT molecules and yet are almost nonexistent in 5,5″-dibromoterthiophene (shortest Br···Br distances are >4.2 Å), indicating a cooperative role involving the Br and the ethylenedioxy moiety. Short Br···Br distances of 3.5 Å within stacks and between adjacent stacks of molecules in crystalline dibromo EDOT dimer (<b>6</b>) could be utilized for the preparation of highly ordered polymers with the perfectly planar EDOT dimer as repeating unit, similar to the work reported by Wudl. On the other hand, new dimeric motifs are formed in Br-EDOT-TCV as strong S···N (3.03 Å) intermolecular interactions in TCV-EDOT are replaced by competing N···Br (2.99 Å) interactions. Short intramolecular N···S distances ranging from 3.2 to 3.3 Å are associated with small dihedral angles between the TCV and thiophene planes ranging from 0.80 to 4.3 deg. A slight enhancement of molecular planarity apparently has a profound impact on the extent of conjugation as evident from the CC bond lengths (1.34–1.40 Å) and C–C (1.37–1.44 Å) within the thiophene rings. These findings suggest that N···S, N···Br, and Br···Br inter- and intramolecular interactions could be utilized as additional crystal engineering tools to promote molecular planarity and arrangement of higher oligomers in the solid state prior to polymerization of thiophene-based molecular materials. On the basis of the current study, these interactions appear to also enhance the stability of the structure and influence intramolecular charge transfer and π-stack formation patterns