Enumeration of Ring–Chain Tautomers Based on SMIRKS Rules

نویسندگان

  • Laura Guasch
  • Markus Sitzmann
  • Marc C. Nicklaus
چکیده

A compound exhibits (prototropic) tautomerism if it can be represented by two or more structures that are related by a formal intramolecular movement of a hydrogen atom from one heavy atom position to another. When the movement of the proton is accompanied by the opening or closing of a ring it is called ring-chain tautomerism. This type of tautomerism is well observed in carbohydrates, but it also occurs in other molecules such as warfarin. In this work, we present an approach that allows for the generation of all ring-chain tautomers of a given chemical structure. Based on Baldwin's Rules estimating the likelihood of ring closure reactions to occur, we have defined a set of transform rules covering the majority of ring-chain tautomerism cases. The rules automatically detect substructures in a given compound that can undergo a ring-chain tautomeric transformation. Each transformation is encoded in SMIRKS line notation. All work was implemented in the chemoinformatics toolkit CACTVS. We report on the application of our ring-chain tautomerism rules to a large database of commercially available screening samples in order to identify ring-chain tautomers.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

The Impact of Tautomer Forms on Pharmacophore-Based Virtual Screening

In the field of in silico screening, many applications do not automatically consider possible tautomeric states of molecules. However, the detection of new compound candidates might rely on correct structural description, which is important for the perfect fit toward the biologically relevant interactions. In this paper, we present a new exhaustive tautomer enumeration approach implemented by m...

متن کامل

DFT Study of Kinetic and Thermodynamic Parameters of Tautomerism in 4−acyl Pyrazolone

In the present work, DFT calculations are employed to obtain the optimized structures of 4- acyl pyrazolone tautomers (19 tautomers) using B3LYP/6-311++G** calculations. In addition, molecular parameters, IR frequencies and relative energies are extracted for all tautomers. The existence of aromatic ring, keto tautomer (versus enol tautomer), N-H bond (versus C-H bond) and C=N double bond (vers...

متن کامل

Combinatorial–computational–chemoinformatics (C3) approach to finding and analyzing low-energy tautomers

Finding the most stable tautomer or a set of low-energy tautomers of molecules is critical in many aspects of molecular modelling or virtual screening experiments. Enumeration of low-energy tautomers of neutral molecules in the gas-phase or typical solvents can be performed by applying available organic chemistry knowledge. This kind of enumeration is implemented in a number of software package...

متن کامل

Tautomerism in large databases

We have used the Chemical Structure DataBase (CSDB) of the NCI CADD Group, an aggregated collection of over 150 small-molecule databases totaling 103.5 million structure records, to conduct tautomerism analyses on one of the largest currently existing sets of real (i.e. not computer-generated) compounds. This analysis was carried out using calculable chemical structure identifiers developed by ...

متن کامل

The aromatic character of thienopyrrole-modified 20π-electron porphyrinoids.

Magnetically induced current densities and current pathways have been calculated for six tautomers of substituted and nonsubstituted core-modified porphyrinoids with one of the pyrrole rings replaced by a thienopyrrole moiety. The calculations show that the aromatic properties of the porpyrinoid macrocycle are strongly influenced by the ethyl-formate substituent at the pyrrole ring of the thien...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 54  شماره 

صفحات  -

تاریخ انتشار 2014