المحاضرة الثالثة QSAR
تعريف SAR
وشنو Quantitative للSAR
شنو الخصائص الي تدرسها QSAR ?
تدرس خصائص فيزيائية وكيمائية وهيكلية بس اهم الخصائص الي تتدرسها most common
Hydrophobic , electronic polar ,nonpolar and steric
Hydropbobic اسهل من
Electronic and steric تكون more difficult
شنو هن physicochemical ؟ 3 نقاط
Partition coefficient , molcular refractivty steric , hammett substitution constant
كل وحدة وتعريفهم
شنو هي خطوات التقسيم للعلاج بالخلية partition steps ؟
(a) leaving the aqueous extracellular fluids,
(b) passing through lipid membranes,
(c) entering other aqueous environments before reaching the receptor
شنو patition coefficient ؟
is the ratio of the molar concentration of chemical in the nonaqueous phase (usually 1-octanol) versus that in the aqueous phase because much of the time the drug's movement across membranes is a partitioning process, the partition coefficient has become the most common physicochemical property.
Water-saturated octanol
شكد يحتوي نسبة ماء وليش ?
contains 2.3 M water because the small water molecule easily clusters around octanol's hydroxy moiety.
n-Octanol-saturated water شنو يحتوي وليش ؟
contains little of the organic phase because of the large hydrophobic 8-carbon chain of octanol.
The water in the n-octanol phase apparently approximates the polar properties of the lipid bilayer, whereas the lack of octanol in the water phase mimics the physiological aqueous compartments,
partitioning systems مثل شنو وع شنو يحتوي ؟
such as hexane/water and chloroform/water contain so little water in the organic phase that they are poor models for the lipid bilayer/water system found in the body.
to cross hydrophobic cell membranes, a drug has to be reasonably lipophilic (fat loving).
العلاج حتى يمر من غشاء الخلية الي يكون كاره للدهون لازم يكون العلاج
lipophilic (fat loving).
ولكن ميكون can not be too lipophilic ؟ ليش
جواب
If it is, then it would be extracted very easily from an aqueous bloodstream and be stored away in the fatty tissues of the body.
الادوية شنو تحتاج حتى ترتبط بالرسبتر
تحتاج polar or ionic group
الادوية الي ترتبط بقوة بالرسبتر شتكون ؟ تكون قطبية جدا ومتاينة ومتكدر تمر من غشاء الخلية لان هي قطبية
The drugs which bind most strongly to the receptor are often very polar, ionized compounds, but have no chance of crossing the fatty cell membranes of the intestinal wall.
الادوية الي يكونها ارتباطها ضعيف بالرسبتر تكدر تمر من غشاء الخلية بسهولة
the drugs which can easily pass through the fatty cell membranes deposited by fat tissue or are too weak to bind to their receptor sites.
شنو افضل ادوية best drugs ?
are neither too lipophilic nor too hydrophilic.
الادوية الي تاثر عدها pka من 6_8
شوكت تتاين وتتوازن
most effective drugs have a pK, value in the range 6-8. In other words, they are drugs which are partially ionized at blood pH and can easily equilibrate between their ionized and non ionized forms.
تعبر غشاء الخلية بشكل غير متاين وترتبط بالرسبتر بشكل متاين
allows them to cross cell membranes in the non
ionized form and to bind to their receptor in the
ionized form.
بعض الادوية تكون متاينة بشكل كامل وغير قادرة ع المرور من خلال غشاء الخلية ومثالها مهم
sometimes useful to have a fully ionized drug which is incapable of crossing cell membranes. For example, highly ionized sulfonamides are used against gastrointestinal infections. They are incapable of crossing the gut wall and are therefore directed efficiently against the infection.
تعريف SAR
وشنو Quantitative للSAR
شنو الخصائص الي تدرسها QSAR ?
تدرس خصائص فيزيائية وكيمائية وهيكلية بس اهم الخصائص الي تتدرسها most common
Hydrophobic , electronic polar ,nonpolar and steric
Hydropbobic اسهل من
Electronic and steric تكون more difficult
شنو هن physicochemical ؟ 3 نقاط
Partition coefficient , molcular refractivty steric , hammett substitution constant
كل وحدة وتعريفهم
شنو هي خطوات التقسيم للعلاج بالخلية partition steps ؟
(a) leaving the aqueous extracellular fluids,
(b) passing through lipid membranes,
(c) entering other aqueous environments before reaching the receptor
شنو patition coefficient ؟
is the ratio of the molar concentration of chemical in the nonaqueous phase (usually 1-octanol) versus that in the aqueous phase because much of the time the drug's movement across membranes is a partitioning process, the partition coefficient has become the most common physicochemical property.
Water-saturated octanol
شكد يحتوي نسبة ماء وليش ?
contains 2.3 M water because the small water molecule easily clusters around octanol's hydroxy moiety.
n-Octanol-saturated water شنو يحتوي وليش ؟
contains little of the organic phase because of the large hydrophobic 8-carbon chain of octanol.
The water in the n-octanol phase apparently approximates the polar properties of the lipid bilayer, whereas the lack of octanol in the water phase mimics the physiological aqueous compartments,
partitioning systems مثل شنو وع شنو يحتوي ؟
such as hexane/water and chloroform/water contain so little water in the organic phase that they are poor models for the lipid bilayer/water system found in the body.
to cross hydrophobic cell membranes, a drug has to be reasonably lipophilic (fat loving).
العلاج حتى يمر من غشاء الخلية الي يكون كاره للدهون لازم يكون العلاج
lipophilic (fat loving).
ولكن ميكون can not be too lipophilic ؟ ليش
جواب
If it is, then it would be extracted very easily from an aqueous bloodstream and be stored away in the fatty tissues of the body.
الادوية شنو تحتاج حتى ترتبط بالرسبتر
تحتاج polar or ionic group
الادوية الي ترتبط بقوة بالرسبتر شتكون ؟ تكون قطبية جدا ومتاينة ومتكدر تمر من غشاء الخلية لان هي قطبية
The drugs which bind most strongly to the receptor are often very polar, ionized compounds, but have no chance of crossing the fatty cell membranes of the intestinal wall.
الادوية الي يكونها ارتباطها ضعيف بالرسبتر تكدر تمر من غشاء الخلية بسهولة
the drugs which can easily pass through the fatty cell membranes deposited by fat tissue or are too weak to bind to their receptor sites.
شنو افضل ادوية best drugs ?
are neither too lipophilic nor too hydrophilic.
الادوية الي تاثر عدها pka من 6_8
شوكت تتاين وتتوازن
most effective drugs have a pK, value in the range 6-8. In other words, they are drugs which are partially ionized at blood pH and can easily equilibrate between their ionized and non ionized forms.
تعبر غشاء الخلية بشكل غير متاين وترتبط بالرسبتر بشكل متاين
allows them to cross cell membranes in the non
ionized form and to bind to their receptor in the
ionized form.
بعض الادوية تكون متاينة بشكل كامل وغير قادرة ع المرور من خلال غشاء الخلية ومثالها مهم
sometimes useful to have a fully ionized drug which is incapable of crossing cell membranes. For example, highly ionized sulfonamides are used against gastrointestinal infections. They are incapable of crossing the gut wall and are therefore directed efficiently against the infection.
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توجد 3 model of QSAR شنو هن ؟
Linear
Non linear
Bilinear
كل وحدة وشنو معادلتها والرسم كلش مهمات
Griesofulvin مثال ع linear
الرسم مهم والمعادلة مالته
الاسبرين مثال ع nonlinear والرسم مهم
QSARبشنو تستخدم ؟
بحركية الدواء pharmacokinetic وشنو مثالها barbitutrate absorption
الاستجابة الدوائية شوكت تصير ؟
من يصير تفاعل بين العلاج والرسبتر وهذا التفاعل ياخذ مكانه بالرسبتر المخصص اله من خلال قوة رابطة
biological response is produced by the interaction of a drug with the biological receptor site.
شوكت يغادر العلاج الرسبتر ؟
من يقل التركيز السائل خارج الخلية
is desirable for the drug to leave the receptor site when the concentration decreases in the extracellular fluids.
شوكت يكون العلاج revercible و irrevercible ؟
يكون revercible من يرتبط بالرسبتر باصرة ايونية الي تكون رابطة ضعيفة
ويكون irrevercible من يرتبط بالرسبتر باصرة تساهمية
most drugs are held to their receptors by ionic or weaker bonds which mean reversible drug receptor interaction.
When relatively long-lasting or irreversible effects are desired (e.g., antibacterial, anticancer), drugs that form covalent bonds with the effective and useful.
اخر فقرة الروابط حفظ عدد وشرحهن
Linear
Non linear
Bilinear
كل وحدة وشنو معادلتها والرسم كلش مهمات
Griesofulvin مثال ع linear
الرسم مهم والمعادلة مالته
الاسبرين مثال ع nonlinear والرسم مهم
QSARبشنو تستخدم ؟
بحركية الدواء pharmacokinetic وشنو مثالها barbitutrate absorption
الاستجابة الدوائية شوكت تصير ؟
من يصير تفاعل بين العلاج والرسبتر وهذا التفاعل ياخذ مكانه بالرسبتر المخصص اله من خلال قوة رابطة
biological response is produced by the interaction of a drug with the biological receptor site.
شوكت يغادر العلاج الرسبتر ؟
من يقل التركيز السائل خارج الخلية
is desirable for the drug to leave the receptor site when the concentration decreases in the extracellular fluids.
شوكت يكون العلاج revercible و irrevercible ؟
يكون revercible من يرتبط بالرسبتر باصرة ايونية الي تكون رابطة ضعيفة
ويكون irrevercible من يرتبط بالرسبتر باصرة تساهمية
most drugs are held to their receptors by ionic or weaker bonds which mean reversible drug receptor interaction.
When relatively long-lasting or irreversible effects are desired (e.g., antibacterial, anticancer), drugs that form covalent bonds with the effective and useful.
اخر فقرة الروابط حفظ عدد وشرحهن
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