Polymorphs and Polymorphic Cocrystals of Temozolomide

Babu, N. Jagadeesh; Reddy, L. Sreenivas; Aitipamula, Srinivasulu; Nangia, Ashwini

doi:10.1002/asia.200800070

Cited by 83 publications

(72 citation statements)

References 69 publications

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“…They may be classified as synthon polymorphs at the secondary level, because the strong hydrogen bonding is the same but there are differences at the weak interactions level. 8 The graph set notation 9 of the hydrogen bond motifs for the N-H 3 3 3 O dimer, N-H 3 3 3 O catemer, C-H 3 3 3 O chelate, and C-H 3 3 3 O dimer are R 2 2 (8), C(4), R 2 1 (6), and R 2 2 (16). Changes in molecular conformation are listed as torsion angles in Table 4.…”

Section: Resultsmentioning

confidence: 99%

Polymorphism in Secondary Benzene Sulfonamides

Sanphui

Sarma

Nangia

2010

Crystal Growth & Design

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The role of about 20 different solvents in the crystallization of polymorphs for 13 N-phenyl benzene sulfonamides was studied. Five compounds (1, 2, 3, 7, and 11) are dimorphic, and one is trimorphic (6). All the crystalline solids were characterized by powder and single crystal X-ray diffraction, thermal analysis, hot stage microscopy, and IR and Raman spectroscopy. The phase transition from a metastable form to the stable form was examined visually for two compounds (1, 11) on a HSM and confirmed by differential scanning calorimetry and X-ray diffraction. The N-H 3 3 3 O hydrogen bond catemer (chain) and dimer (cyclic) motifs of the sulfonamide group were analyzed as the main difference between polymorphs of 1, 3, and 6. Weaker C-H 3 3 3 O interactions differentiate the molecular packing of other polymorphic systems. Accordingly, these crystal structures are referred to as synthon polymorphs. The occurrence of N-H 3 3 3 O catemer and dimer synthon in secondary sulfonamides is compared with crystal structures in the Cambridge database. The nearly equal probability of the dimer and catemer motifs for secondary sulfonamides (∼19%) is attributed to the possibility of making the catemer synthon via both anti and syn oxygen atoms of the SO 2 NH group, with the former acceptor being preferred in two-thirds of the cases.

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Section: Resultsmentioning

confidence: 99%

Polymorphism in Secondary Benzene Sulfonamides

Sanphui

Sarma

Nangia

2010

Crystal Growth & Design

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“…Ten polymorphs of TMZ are covered in the patent literature [31,32], of which four have had X-ray structures solved [33,34]. TMZ can easily form a dimer via intermolecular hydrogen bonds between the carboxamide groups (Figure 7).…”

Section: Temozolomide Co-crystalsmentioning

confidence: 99%

The Medicinal Chemistry of Imidazotetrazine Prodrugs

Moody

Wheelhouse

2014

Pharmaceuticals

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Temozolomide (TMZ) is the standard first line treatment for malignant glioma, reaching “blockbuster” status in 2010, yet it remains the only drug in its class. The main constraints on the clinical effectiveness of TMZ therapy are its requirement for active DNA mismatch repair (MMR) proteins for activity, and inherent resistance through O6-methyl guanine-DNA methyl transferase (MGMT) activity. Moreover, acquired resistance, due to MMR mutation, results in aggressive TMZ-resistant tumour regrowth following good initial responses. Much of the attraction in TMZ as a drug lies in its PK/PD properties: it is acid stable and has 100% oral bioavailability; it also has excellent distribution properties, crosses the blood-brain barrier, and there is direct evidence of tumour localisation. This review seeks to unravel some of the mysteries of the imidazotetrazine class of compounds to which TMZ belongs. In addition to an overview of different synthetic strategies, we explore the somewhat unusual chemical reactivity of the imidazotetrazines, probing their mechanisms of reaction, examining which attributes are required for an active drug molecule and reviewing the use of this combined knowledge towards the development of new and improved anti-cancer agents.

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“…In contrast, the studies on the polymorphism in cocrystallization appear relatively at the early stage. While the intermolecular interactions within the cocrystals are usually designed for reliable cocrystal formation, subtle changes of the interactions and the subsequent differences in the molecular packing could result in the polymorphism of cocrystallization [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Phase Transformation of Adefovir Dipivoxil/Succinic Acid Cocrystals Regulated by Polymeric Additives

Jung

Kim

2013

Polymers

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Abstract:The polymorphic phase transformation in the cocrystallization of adefovir dipivoxil (AD) and succinic acid (SUC) was investigated. Inspired by biological and biomimetic crystallization, polymeric additives were utilized to control the phase transformation. With addition of poly(acrylic acid), the metastable phase newly identified through the analysis of X-ray diffraction was clearly isolated from the previously reported stable form. Without additives, mixed phases were obtained even at the early stage of cocrystallization. Also, infrared spectroscopy analysis verified the alteration of the hydrogen bonding that was mainly responsible for the cocrystal formation between AD and SUC. The hydrogen bonding in the metastable phase was relatively stronger than that in the stable form, which indicated the locally strong AD/SUC coupling in the initial stage of cocrystallization followed by the overall stabilization during the phase transformation. The stronger hydrogen bonding could be responsible for the faster nucleation of the initially observed metastable phase. The present study demonstrated that the polymeric additives could function as effective regulators for the polymorph-selective cocrystallization.

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Polymorphs and Polymorphic Cocrystals of Temozolomide

Cited by 83 publications

References 69 publications

Polymorphism in Secondary Benzene Sulfonamides

Polymorphism in Secondary Benzene Sulfonamides

The Medicinal Chemistry of Imidazotetrazine Prodrugs

Phase Transformation of Adefovir Dipivoxil/Succinic Acid Cocrystals Regulated by Polymeric Additives

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