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Matthew H Todd

Publications and source records attributed to Matthew H Todd.

6 recordsLinked to original sources
PubMed2006

Design and synthesis of new tetrazolyl- and carboxy-biphenylylmethyl-quinazolin-4-one derivatives as angiotensin II AT1 receptor antagonists.

A series of novel quinazolin-4-ones was designed and their molecular modeling simulation fitting to a new HipHop 3D pharmacophore model using CATALYST was examined. Several compounds showed significant high simulation fit values. The designed compounds were synthesized and eight of them were biologically evaluated in vitro using an AT1 receptor binding assay, where compound XX competed weakly against radiolabeled Sar1Ile8-angiotensin II (Ang II) binding, compounds XIV and XXII showed moderate competition, and compound XXV showed almost equal ability to displace radiolabeled Sar1Ile8-Ang II binding to AT1 receptors as losartan. In vivo biological evaluation study of compounds XIV, XXII, and XXV on both normotensive and hypertensive rats revealed that compound XXV demonstrated higher hypotensive and antihypertensive activity than the reference compound losartan. To obtain a highly active compound from a candidate set of only eight tested compounds illustrates the power and utility of our pharmacophore model.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2005

Computer-aided organic synthesis.

It is tempting for those in the field of organic synthesis to liken the process of retrosynthesis to a game of chess. That the world chess champion was recently defeated by a computer leads us to think that perhaps new and powerful computing methods could be applied to synthetic problems. Here the analogy between synthesis and chess is outlined. Achievements in the 35-year history of computer-aided synthetic design are described, followed by some more recent developments.

Acrylonitrile↗
PubMed2002

Amino acid derived heterocycles: lewis acid catalyzed and radical cyclizations from peptide acetals.

Bicyclization of peptide acetals via nucleophilic attack of a phenyl group on an endocyclic acyliminium ion 4 was explored as a route to novel amino acid derived heterocycles and peptidomimetic scaffolds. In the presence of protic acid, bridged structures such as 6 are formed readily from phenylalanine derivatives, but the fused-ring analogues 5 could not be obtained in good yield. In contrast, radical cyclization of the bromophenyl dihydropyrazinone 7 provides an effective alternative for the synthesis of 5 (n = 0, 1, 2). Additional versatility in this process was demonstrated by efficient synthesis of a different fused ring system, represented by the antihelmintic praziquantel, 8.

Acetals↗
PubMed2002

Asymmetric autocatalysis: product recruitment for the increase in the chiral environment (PRICE).

Asymmetric catalytic reactions are possible via efficient transfer of the chiral environment of a reaction to the transition state. In theory any asymmetric structure may contribute to this, including the product of the reaction itself. For product influence to be significant, a nonlinear effect needs to operate, whereby one diastereomer of the product/catalyst assists the reaction, and the other does not. When these conditions are satisfied, we obtain an asymmetric autocatalytic reaction in which the enantiomeric excess of a compound (that is both product and catalyst) actually increases as the reaction iterates. It is only recently that we have seen reports of such processes. Of particular interest are Soai's reports of the alkylation of aromatic heterocycles. Such reactions, aside from their inherent interest, may offer clues into the origins of asymmetric molecular replication that predated the origin of life.

Journal Article↗
PubMed2002

The use of FTICR-MS to detect chemical tags from a combinatorial library.

The use of tagging in combinatorial chemistry permits tracking of the solid phase as it is taken through iterative split and mix cycles. Several analytical approaches to the identification of tags (and hence the chemical history of the support) have been described. We describe herein a novel chemical tagging strategy for combinatorial solid phase chemistry. The identities of the tags attached to a single bead are discovered by the high resolution, accurate mass technique of Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS).

Journal Article↗