This document discusses benzimidazole derivatives as H+/K+ ATPase inhibitors for treating acid-related gastrointestinal disorders. It provides background on drugs like cimetidine and omeprazole that inhibit acid secretion. It then describes the synthesis of new benzimidazole derivatives containing oxycyclic pyridine rings. Introducing 5- or 6-membered oxycyclic rings to the pyridine portion potentiated the inhibitory activity of the compounds against the H+/K+ ATPase, regardless of the size or position of the oxycyclic ring attachment. The document concludes that oxycyclic pyridine-containing benzimidazole derivatives show promise as novel acid secretion inhibitors.
Calcium channel blockers - Medicinal chemistry for B.Pharm.Purna Nagasree K
This ppt describes about the drugs used as calcium channel blockers, their mechanism of action, metabolism and Structure activity relationship of dihydropyridines
Calcium channel blockers - Medicinal chemistry for B.Pharm.Purna Nagasree K
This ppt describes about the drugs used as calcium channel blockers, their mechanism of action, metabolism and Structure activity relationship of dihydropyridines
This presentation highlights on the introduction, classification, structures, SAR and mechanism of action of different Diuretics. Pharmacy students will be benefited by this content.
Chemistry of Anti Anginal Drugs by Professor BeubenzProfessor Beubenz
This presentation will give you an idea about the chemistry of Anti-anginal drugs along with its classification, mechanism of action & Structural Activity Relationship.
#Professor_Beubenz
For more such videos do
#Subscribe
#Share
#Like
to the Channel Professor Beubenz
Thank You.
https://www.youtube.com/watch?v=-7yjQm4zzX8&t=1183s
A condition in which the heart is unable to pump sufficient blood
to meet the metabolic demand of the body and also unable to receive it back because every time after a systole.
A comprehensive interpretation of pellets based on their definitions, advantages, disadvantages, mechanism of pellet formation and growth, pelletization techniques, formulation requirements, and the equipment system for manufacture of pellets.
This ppt covers the classification, structures and IUPAC names, Mechanism of action and uses of individual drugs...under anticonvulsants topic..Side effects/metabolism are also given for few
SULPHATE REDUCTION AND INCORPORATION OF SULPHUR INTO AMINO ACIDSmeetpadhiyar88
SULPHATE REDUCTION AND INCORPORATION OF SULPHUR INTO AMINO ACIDS
Sulphur introduction
Sulphate assimilation
Sulphate reduction
H2S IS FIXED IN THE FORM OF CYSTEINE
Glutathione
SYNTHESIS OF METHIONINE FROM CYSTEINE
This presentation highlights on the introduction, classification, structures, SAR and mechanism of action of different Diuretics. Pharmacy students will be benefited by this content.
Chemistry of Anti Anginal Drugs by Professor BeubenzProfessor Beubenz
This presentation will give you an idea about the chemistry of Anti-anginal drugs along with its classification, mechanism of action & Structural Activity Relationship.
#Professor_Beubenz
For more such videos do
#Subscribe
#Share
#Like
to the Channel Professor Beubenz
Thank You.
https://www.youtube.com/watch?v=-7yjQm4zzX8&t=1183s
A condition in which the heart is unable to pump sufficient blood
to meet the metabolic demand of the body and also unable to receive it back because every time after a systole.
A comprehensive interpretation of pellets based on their definitions, advantages, disadvantages, mechanism of pellet formation and growth, pelletization techniques, formulation requirements, and the equipment system for manufacture of pellets.
This ppt covers the classification, structures and IUPAC names, Mechanism of action and uses of individual drugs...under anticonvulsants topic..Side effects/metabolism are also given for few
SULPHATE REDUCTION AND INCORPORATION OF SULPHUR INTO AMINO ACIDSmeetpadhiyar88
SULPHATE REDUCTION AND INCORPORATION OF SULPHUR INTO AMINO ACIDS
Sulphur introduction
Sulphate assimilation
Sulphate reduction
H2S IS FIXED IN THE FORM OF CYSTEINE
Glutathione
SYNTHESIS OF METHIONINE FROM CYSTEINE
APPLICATIONS OF MULTICOMPONENT ASSEMBLY PROCESSES TO THE FACILE SYNTHESES OF ...JamesSahn
Several multicomponent assembly processes have been developed for the synthesis of intermediates that may be elaborated by a variety of cyclizations to generate a diverse array of highly functionalized heterocycles from readily-available starting materials. The overall approach enables the efficient preparation of libraries of small molecules derived from fused, privileged scaffolds. Source: Heterocycles 84:2 2012 pg 1089-1112
The Chichibabin reaction is a method for producing 2-aminopyridine derivatives by the reaction of pyridine with sodium amide. It was reported by Aleksei Chichibabin in 1914. The following is the overall form of the general reaction: The direct amination of pyridine with sodium amide takes place in liquid ammonia
1. BENZIMIDAZOLE DERIVATIVES AS
H+/K+ ATPASE INHIBITORS
- Syed Baseeruddin Alvi
Presented by
Under the guidance of mrs.iffath rizwana
2. INTRODUCTION
GASTRIC ACID HAS BEEN KNOWN FOR MANY
DECADES TO BE A KEY FACTOR IN NORMAL UPPER
GASTROINTESTINAL FUNCTIONS, INCLUDING
PROTEIN DIGESTION AND CALCIUM ABSORPTION AS
WELL AS PROVIDING SOME PROTECTION AGAINST
BACTERIAL INFECTIONS…..
INAPPROPRIATE LEVELS OF ACID CAN GIVE RISE TO
SEVERE PATHOLOGICAL CONDITIONS LIKE
GERD (Gastroesophageal reflux disease)
PEPTIC ULCERS…etc etc….
THESE IF LEFT UNTREATED COULD BE LIFE
THREATENING..
3. CIMETIDINE
IT IS A CLASSICAL DRUG USED IN THE TREATMENT OF ACID
RELATED DISORDERS.
IT ACTS BY BLOCKING H2 RECEPTORS, THEREBY INHIBITING
GASTRIC ACID RELEASE.
IT ALSO INHIBITS THE RELEASE OF PENTAGASTRIN,
RESPONSIBLE FOR THE STIMULATION OF ACID RELEASE.
THE PARENT COMPOUND OF CIMETIDINE IS HISTAMINE.
4. SAR OF CIMETIDINE
GUANIDINE ANALOGUE OF HISTAMINE POSSESS WEAK ANTAGONIST
ACTIVITY TO THE ACID SECRETORY ACTIVITY OF HISTAMINE.
INCREASING THE LENGTH OF SIDE CHAIN FROM 2 TO 4 CARBONS
COUPLED WITH REPLACEMENT OF STRONGLY BASIC GUANIDINE
GROUP BY NEUTRAL METHYL THIOUREA FUNCTION LEADS TO
BURIMAMIDE.
Burimamide
Guanidine
5. INSERTION OF ELECTRONEGATIVE THIOETHER IN THE SIDE
CHAIN OF METHYLENE GROUP FAVOURS
N- TAUTOMER
&
INTRODUCTION OF 5-METHYL GROUP FAVOURS H2
RECEPTOR SELECTIVITY
BECAUSE OF INCREASED TOXICITY
REPLACING THIOUREA SULPHUR
WITH CYANO-IMINO FUNCTION
TO GIVE CIMETIDINE. Metiamide
Cyano-imino function
7. NITRO KETENE AMINAL GROUP IS OPTIMUM FOR
ACTIVITY
PLACING THE SULFUR NEXT TO THE RING LOWERS
ACTIVITY
2,5-DISUBSTITUTION IS BEST…
VARIATION ON DIMETHYL AMINO GROUP CAN BE
DONE…
8.
9. MECHANISM OF ACTION
OMEPRAZOLE – A PRODRUG GETS CONVERTED INTO ITS
ACTIVE FORM IN ACIDIC ENVIRONMENT.
IT IS ACTIVATED BY PROTON-CATALYSED PROCESS TO
GENERATE A SULFENAMIDE.
SULFENAMIDE INTERACTS COVALENTLY WITH SULFHYDRYL
GROUPS OF CYSTEINE RESIDUE IN H+/K+ ATPase
10. SAR OF OMEPRAZOLE
OMEPRAZOLE CONSISTS OF 3 PARTS –
SUBSTITUTED BENZIMIDAZOLE RING
SUBSTITUTED PYRIDINE RING
CH2SO CHAIN
SUBSTITUTION OF PYRIDINE RING WITH ALKYL OR ALKOXY
GROUPS ( EXCEPT 6- POSITION) GIVES GOOD ANTISECRETORY
ACTIVITY
METHOXY GROUP AT FOURTH POSITION OF PYRIDINE RING
DONATES ELECTRONS TO PYRIDINE NITROGEN, THEREBY
INCREASING THE % OF CATIONIC PYRIDINE.
11. THIS ALSO INCREASES THE NUCLEOPHILIC CHARACTER OF
PPI’s.
CATIONIC PYRIDINE FACILITATES THE INTRAMOLECULAR
NUCLEOPHILIC ATTACK AT C2 OF BENZIMIDAZOLE RING
LEADING TO THE FORMATION OF ACTIVE SULFENAMIDE AND
SULFENIC ACID.
PRESENCE OF METHYL GROUP AT 3 AND 5 POSITIONS
ENHANCES NUCLEOPHILIC CHARACTER OF UNIONIZED
PYRIDINE NITROGEN.
12. BENZIMIDAZOLE DERIVATIVES
CONTAINING OXYCYCLIC PYRIDINE
THESE DERIVATIVES ARE SYNTHESISED BY REACTING
2-MERCAPTOBENZIMIDAZOLE WITH CHLOROMETHYL OXYCYCLIC
PYRIDINE COMPOUNDS FOLLOWED BY LOW-TEMPERATURE OXIDATION
WITH m-CHLOROPERBENZOIC ACID.
13. OXYCYCLIC PYRIDINES WERE CONVERTED TO N-OXIDES BY
CYANATED OXYCYCLIC PYRIDINE WHICH WAS OBTAINED
UNDER TRIMETHYL SILYL CYANIDE CONDITION .UPON FURTHER
TREATMENT CHLOROMETHYL OXYCYCLIC PYRIDINES WAS
OBTAINED.
14. THE OXYCYCLIC PYRANO AND FUROPYRIDINES ARE
PREPARED BY PALLADIUM CATALYSED CYCLIZATION OF
IODOPYRIDINEALLYL ETHER OR BY THERMAL SIGMATROPIC
REARRANGEMENT OF 4-PYRIDINE PROPARGYL ETHER
15. CONCLUSION
INTRODUCTION OF 5-MEMBERED OR 6-MEMBERED OXYCYCLES
TO PYRIDINE POTENTIATED THE INHIBITORY ACTIVITY OF THE
COMPOUNDS WHERE THE SIZE AND POSITION OF ATTACHMENT
OF OXYCYCLES DID NOT PRODUCE ANY SIGNIFICANT CHANGE.