Markush structures

There is a gateway to QUESTEL, making the Derwent file for Markush structures, Markush Dare, accessible to the searcher (Sect. 7.8). 

Maikush structures are mainly used in patents, for protecting compounds related to an invention. The first generic claim, submitted by Markush, was granted in 1924 by the US Patent Office [87-90]. 

Nowadays, Markush structures are utilixed mainly in patent databases, where they describe a number of different chemical compounds. Searching in patent databases is very important for companies to ascertain whether a new compound is... 

Figure 2-62. The substituted phenyl derivative is an example of a typical Markush structure. Herein, a number of compounds are described in one structure diagram by fill-ins. Phenylalanine is one of these structures when r is COOH, is H, and X is H.

Today, fragment coding is still quite important in patent databases (sec Chapter 5, Section 5.11, e.g., Dei went) where Markush structures are also stored. There, the fragments can be applied to substructure or othei types of searches where the fragments arc defined, c.g., on the basis of chemical properties. 

Markush structures rcprcHL-uts compound families - widespread in patents nianual in/ontput convertible into otlicr representations high number of compounds less compact code ambiguous difficult to extract individual compounds... 

Patent databases are therefore integrated databases because facts, text, tables, graphics, and structures are combined. In patents that include chemical aspects (mostly synthesis or processing), the chemical compounds are often represented by Markush structures (see Chapter 2, Section 2.7.1). These generic structures cover many compound families in a very compact maimer. A Markush structure has a core structure diagram with specific atoms and with variable parts (R-groups), which are defined in a text caption. The retrieval of chemical compounds from Markush structures is a complicated task that is not yet solved completely satisfactorily. 

MARPAT Chemical Abstracts Service (CAS), USA Markush structures in patents struc- ture, Mar- kush, biblio. 180000 records, 505 000 Markush struct. patent ofBces STN commercial CD-ROM, online weekly www.cas.org/ ONLINE/ DBSS/mar- patss.html... 

Fig. 3. Typical Markush structure where R is H, C 2o kylj i-20 sulfonate, or carboxylate is H or alkyl and X is H, alkyl, phenyl...

We should not minimize the effects that electronic searching of patents has had on the business of research. In 1990, CAS introduced MARPAT, which is a database of Markush (generic) structures found in patent documents [1]. This database provided a valuable tool for patent searching in a more comprehensive way than had been available previously. In 1995, CAS launched SciFinder, which provided access to the patent literature for chemists on their desktops. Using the SciFinder interface, one may search for research topics, authors, companies, or structures/reactions. From a practical viewpoint, SciFinder did more to enhance the searching capabilities of the medicinal chemist than any other tool. Even today, SciFinder continues to provide a first pass through the patent literature when chemists want to include patents in their searching. Indeed, when a search is performed, patent references are included in the answer set. Only very recently have there been additional tools to search the patent literature that have found widespread use. 

The concept of minimum AE and maximum Emw is illustrated with the generalized sequence shown in Scheme 4.7 under stoichiometric conditions with complete recovery of reaction solvents, catalysts, and post-reaction materials. Markush structures are used to show both variable R groups and necessarily invariant atoms. This analysis is useful in studying combinatorial hbraries where a constant scaffold structure is selected and then is decorated with, in principle, an unlimited number of possible R groups. 

Markovnikov rule, 20 774 Markov property, 26 1022 Markush chemical structures, indexing and searching, 18 242. See also WPI entries... 

Markush DARC system, 18 212, 230, 245 Markush structures, 18 206 Markush TOPFRAG programs, 18 226 Marl, 15 28... 

Barnard, J.M., Downs, G.M., ScHOLLEY-PFAB, A.V., and Brown, R. D. Use of Markush structure analysis techniques for descriptor generation and clustering of large combinatorial libraries./. Mol. Graph. 2000, 38, 452-463. 

Fig. 3. Markush structure of tripeptoids. R, 2R, and 3R are positions where various side chains (building blocks) are attached.

Computational methods described in this work are tested using a tripeptoid combinatorial library described by Zuckermann et al. (35). These authors described chemical structures of 24 amines used as building blocks for the pep-toid synthesis. The common Markush structure of tripeptoids is shown in Fig. 3 where R1, R2, and R3 are the alkyl portions of primary amines used as building blocks. The structures of the building blocks are shown in Fig. 4 and we followed the abbreviations used in the original publication. 

Fig. 2.4. Product enumerations of a combinatorial library. For reaction-based enumeration, individual groups of —N(R1)(R2) and —(C0)-R3 are replaced by corresponding molecular fragments from reactants A and B. For template-based enumeration, the R-groups R1, R2, and R3 are replaced by independent lists of molecular fragments. Note that some combinations of R1 and R2 may not exist in component A for reaction-based enumerations. The template-based product structure with R-groups is also called Markush structure and its enumeration is called Markush enumeration or Markush exemplification.

Pipeline Pilot distributed by Accelrys Inc. can be used to enumerate libraries defined either by reactions or by Markush structures http //accelrys.com/resource-center/case-studies/enumeration.html, last accessed February, 2010. 

Having the desired reactant lists, the chemist can now create a virtual library by enumerating the product structures in a fully combinatorial manner. Enumeration instructions are prevalidated for all PGVL registered reactions for a user-specified reaction, PGVL Hub enables enumeration via the Markush representation of the reaction scheme. Once the products are... 

Using the same set of software capabilities, PGVL Hub also supports other design scenarios such as Singleton Design that is commonly practiced by medicinal chemists, Markush Exemplification where the reaction scheme becomes a Markush core structure, and reactant sets become R-group sets, and Lead Centric Mining (29). 

WPIM (World Patents Index Markush), produced by Derwent Publications, Ltd., contains the specific and generic structure records for compounds in the patents included in Derwent Sections B (Farmdoc), C (Agdoc), and E (Chemdoc) since 1987. Sources include patents from 29 industrialized countries as well as European and PCT patents and also items from Research Disclosure and International Technology Disclosures. The compound numbers of relevant references found in WPIM can be searched in Derwent s WPI database to retrieve the corresponding bibliographic information. 

Between the time of their filing the patent application and its issue, the company was planning several clinical studies when it came to their attention that another issued U.S. patent existed, which was filed before their chemist synthesized the compound of formula I. The patent of concern was directed to steroidal compounds, although it did not disclose their particular compound of formula I, nor did it indicate any specific utility in combination with a progestin for contraception. The patent specification (the entirety of the document) disclosed a number of Markush structures of varying scope as well as a description of the compounds as having utility for the treatment of prostate cancer. Claim 13 from the issued patent is illustrated in Figure 1.5 and it particularly concerned them. 

Before diving into claim interpretation, let s first review some basic aspects of claims, such as the types of claims, the structure of claims, universal claim transitions, and finally, Markush claiming in chemical patents. 

A simpler but equivalent way of presenting these three claims is illustrated in Figure 5.2. The Markush structure is not repeated because it is understood that the dependent claim is importing the entire Markush that it is dependent from, and then further limiting that structure according to the specified language. 

---