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The Record—Prous Science Drugs of the Future (File 453)

Ric,
You mention the database, Prous Science Drugs of the Future, and the chemical synthesis information it contains. Can I get information related to routes of synthesis?

I know it's early in the development process for vatalanib info to contain synthesis data. I read about a trial using vatalanib combined with everolimus, an immunosuppressant agent, to treat patients with solid tumors. Would you see if you can find synthesis data for everolimus?

This should be my last request. Thanks for the help.

Sharon

Prous Science Drugs of the Future is an outstanding source for details regarding chemical synthesis, structure/activity relationships and in-depth pharmacological profiles.

In addition, it includes chemical structure images for most featured compounds, often complemented with cross references to images illustrating schemes of synthesis.

Many records also cite Context Tables constructed by Prous, compiling structures for drugs in given therapeutic/pharmacological categories into one record for the purposes of comparison.

File 453 also has lengthy summaries of clinical study results, with thoroughly researched bibliographies.

We'll take a look at the first part of the record everolimus in the colorectal cancer class from File 453 to see the Context tables and Synthesis Schemes.

Tip 5-9

Review the record and go to the next page.

11/19/1 
DIALOG(R)File 453: Drugs of the Future
(c) 2007 Prous Science. 
All rights reserved.

00210424
ENTRY NUMBER:   210424
DRUG NAME:      NVP-RAD-001
                RAD-001
                SDZ-RAD  Tip 5-10
GENERIC NAME    Everolimus (recommended INN; USAN)  Tip 5-11
BRAND NAME:     Certican (Novartis, CH, DE, JP, SE, US)  Tip 5-12
CHEM NAME:      (3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS
                )- 9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-Hexade
                cahydro-9,27- dihydroxy-3-(2-((1S,3R,4R)-4-(2-hydroxyetho
                xy)-3-methoxycyclohexyl)-  1(R)-methylethyl)-10,21-dimeth
                oxy-6,8,12,14,20,26-hexamethyl-23,27- epoxy-3H-pyrido(2,1
                -c)(1,4)oxaazacyclohentriacontine- 1,5,11,28,29(4H,6H,31H
                )-pentaone
                40-O-(2-Hydroxyethyl)rapamycin
                (1R,9S,12S(1'R(1''S,3''R,4''R)),15R,18R,19R,21R,23S,30S,3
                2S,35R)- 1,18-Dihydroxy-12-(2-(4-(2-hydroxyethoxy)-3-meth
                oxycyclohexyl)-1- methylethyl)-19,30-dimethoxy-15,17,21,2
                3,29,35-hexamethyl-11,36- dioxa-4-azatricyclo(30.3.1.0(4,
                9))hexatriaconta- 16(E),24(E),26(E),28(E)-tetraene-2,3,10
                ,14,20-pentaone
FORMULA:        C53H83NO14
CAS REG. NO.:   159351-69-6
chemical structure
DEVEL. PHASE:     Launched (2004)
ORIGINATOR:       Emory University
                  M.D. Anderson Cancer Center
                  National Cancer Institute (US)
                  Novartis
CLASS:            12337  (Tuberous Sclerosis, Treatment of)
                  62200  (Immunosuppressants)
                  62460  (Treatment of Transplant Rejection)
                  75016  (Astrocytoma Therapy)
                  75020  (Breast Cancer Therapy)
                  75025  (Colorectal Cancer Therapy)
                  75045  (Liver Cancer Therapy)
                  75047  (Non-Small Cell Lung Cancer Therapy)
                  75048  (Small Cell Lung Cancer Therapy)
                  75051  (Non-Hodgkin's Lymphoma Therapy)
                  75070  (Renal Cancer Therapy)
                  75080  (Solid Tumors Therapy)
                  75751  (Angiogenesis Inhibitors)
                  75855  (Inhibitors of Signal Transduction Pathways)
SYNTHESIS:        72571    Tip 5-13
Learn More
CONTEXT TABLE:    62200C (Immunosuppressants) Tip 5-14
Learn More
              

Go to the next page.


5-7

Authoritative Answers Enriched by ProQuest

Learn More #8:

To isolate the synthesis scheme for this drug (synthesis number 72571) do the following:

?E SS=72571
Ref   Items  Index-term
E1        1  SS=72428
E2        1  SS=72570
E3        1 *SS=72571
E4        1  SS=72572
E5        1  SS=73202
E6        1  SS=73252
E7        1  SS=73302

?S E3
  S1       1  SS='72571'


?T S1/19

1/19/1 
DIALOG(R)File 453: Drugs of the Future
(c) 2007 Prous Science. All rights reserved.

00500966
SYNTHESIS SCHEME: 72571
ENTRY NUMBER:     210424
REFERENCE:        Sorbera, L.A.; Leeson, P.A.; Castaner, J., "SDZ-RAD",
Drugs of the Future, Vol. 24, No. 1, p. 22, 1999

chemical structure

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Learn More #9:

Retrieving both types of cross references (Synthesis Schemes and Context Tables) is facilitated by using the MAP capabilities on Dialog.

Example: Create a Set containing the Everolimus record. Then,

MAP CX t Map the Context table from the Everolimus record to show structures of other drugs in the same drug classification.
EXS EXECUTE the search save for the context table
TYPE S1/IM/ALL TYPE out the image records from the context table.

Print page

Search Tip 5-9:

Use LIMITS on Dialog (/CONTEXT, /RELATED, /SYNTHES) to limit retrieval to Context Tables, related entries, or associated Synthesis Schemes respectively.

Example:
s s1/context


Search Tip 5-10:

These code names refer to the manufacturer.

In this case, SC = G.D. Searle and Company (see pp MISC 12-14 of the 12th edition of the Merck Index for a list of code letters used by companies for Experimental Substances (e.g., YM-177 = Yamanouchi Pharm. Co., Ltd. Japan.))

Search Tip 5-11:

Calecoxib (proposed INN (International Nonproprietary Name); USAN (US Approved Name).

Search Tip 5-12:

The countries where the product is marketed by Pharmacia are listed separately from those countries where the product is marketed by Yamanouchi.

Search Tip 5-13:

Each drug has a unique synthesis scheme (SS=) and number, in this case 65888.

Search Tip 5-14:

Context Tables illustrate the various drug classifications and lists drugs which fit into different classes.