Drug+Design

=__**Drug Design (1)**__=


 * 1) ====Natural substance like plant or fungus which are discovered to have pharmacological properties. (they are later analysed, pruified, and concentrated to have better efficacy) Eg: morphine & salicylic acid ====
 * 2) ==== Analogues of these natural substance modified in laboratories by changing their side chain or functional group, and then being tested for their pharmacological properties. Eg: aspirin & heroin ====
 * 3) ====Substances that are acccidentally discovered to have pharmacological properties and then their analogues are produced. Eg: cis-platin & penicillin ====

====The Information and details of these drugs and their synthesization process are saved in a "library" of compound. In the past, building up a librarty takes years to do it because of its long and complicated process: isolation, purification, synthesization, and examination. Nowadays, thanks to the advent of very sensitive techniques such as __mass spectrometry to identify extremely small amounts of sunstances __, "combinatorial libraries" have developed. In cominatorial chemistry huge number of related compounds are produced in a very short time.====

(figure A) = __Drug Design (2)__ =
 * ====The starting material for this reaction are small beads of polystyrene-based resin that are convalently bonded (100 micrometer diameter)====
 * ====The first step is called "mix and split". After first coupling all the resin beads are then split into individual portions. And then they react again to produce 9 possible combination of dipeptides. After the next step there will be 27 combination of tripeptides. (see figure. A) This process can be repeated and repeated again to yield huge combination of amino acid.====
 * ====The final products are then filtered and purified.====
 * ====In the final step, the pruducts are screened by measuring their ability of affecting enzymes and binding to receptor cells. It can take place either __//in vitro//__ or //__in vivo__//.====
 * ====After the compounds are found useful, they can be massively produced.====
 * ====Knowing the the 3D shape of the acitve site on the enzyme or receptor and the shapes of active groups contained in the drug the used of virtual computer modelling software can produce a virtual library. Therefore, producing the initial compounds become unnecessary.====

__**Changing The Polarity**__
==== Many medicine and drugs are organic compound with low polarity. This gives them low solubility in wate. Which means they can not easily be transpotated in our bodies. To increase their polarity they can be made into an ionic salt. One example is compounds that contain amine. They can be converted into their hydrochloride salt by reacting with hydrochloric acid. . Fluoxetine hydrochloride (SSRI) can be another good exmple. (see figure B) This drug is so-called Prozac, usually prescribed for people suffering with depression. Opiate also contains amine group and are usually converted into their hydrochloric salt, and heroin is converted into diamorphine hydrochloride so that they are soluble to be injected into bodies. Compounds that contain carboxylic acid can also be made into polar by converting them into their anion and administering into sodium or calcium salt. This is how __** aspirin **__ is made into polar so that when it reaches a acidic environment, it reverts back to its unionized form. ====

__**Use of Chiral Auxiliaries**__
Sometimes in drug synthesis, especially optically acitve compound, a racemic mixture (50%:50%) of two enantiomers is produced. However, only one enantionmer is desired, so the mixture then has to be seperated by using chromatography togehter with an another optically active compound.

Auxiliaries are attached to the starting material to a stereochemical condition for the reaction to only the enantionmer desired. The auxiliaries are later removed and recycled. Eg: paclitaxel (Taxol, used as an anti-cancer drug) (structure of taxol)