Download to read offline
(C2=CC=CC=C2)[C@@H](C)CN(C)C
Clofedanol CN(C)CCC(C1=CC=CC=C1)(C2=CC=CC=C2Cl)O
Opium C1=C(OC(=C(C1=O)O)C(=O)O)C(=O)O
Homatropine CN1C2CCC1CC(C2)OC(=O)C(C3=CC=CC=C3)O
Phenylpropanolamine CC(C(C1=CC=CC=C1)O)N
Oxeladin CCC(CC)(C1=CC=CC=C1)C(=O)OCCOCCN(CC)CC
Pentoxyverine CCN(CC)CCOCCOC(=O)C1(CCCC1)C2=CC=CC=C2
Oxolamine CCN(CC)CCC1=NC(=NO1)C2=CC=CC=C2](https://image.slidesharecdn.com/antitussivesdrugmolecules-191108071644/85/Antitussives-drug-molecules-6-320.jpg)
![INTRENSIC WATER SOLUBILITY[LOGSW] VALUES FOR DIFFERENT
DRUGS
-10
-8
-6
-4
-2
0
SILICOS-IT LOGSW
-2.76
-6.64
-8.77
-2.45
-5.23
-5.68
-6.77
-5.92
-0.11
-2.53
-1.93
-5.97 -5.71
-5.12
Codeine Methadone Benzonatate Eucalyptol Noscapine
Pipazethate Levopropoxyphene Clofedanol Opium Homatropine
Phenylpropanolamine Oxeladin Pentoxyverine oxolamine](https://image.slidesharecdn.com/antitussivesdrugmolecules-191108071644/85/Antitussives-drug-molecules-28-320.jpg)
Antitussives drug molecules
- 1. ANTITUSSIVES REVIEW I J COMPONENT PHARMACEUTICALBIOTECHNOLOGY SUBMITTED TO: Dr VINO S ASSOCIATE PROFESSOR SBST VIT SUBMITTED BY: TEJASWINI – 18MSM0074 SANDIP HAZRA – 18MSM0090 TANIA CHATTERJEE – 18MSM0094 MRUNAL PALSOKAR – 18MSM0095
- 2. Heterogeneous classof compounds that inhibit cough through either a central or peripheral mechanism; or a mixture of two Antitussives are thought to work by inhibiting a coordinating region for coughing located in the brain stem, deterring the cough reflex arc Cough is normally produced through the stimulation of sensory receptors glossopharyngeal and vagus nerves, innervating the mucous membrane of the lower pharynx, larynx, trachea and smaller airways of respiratory system Receptors then transmit the signal to the cough center in the brain This then triggers a reflex motor response that results in contraction of the muscles to close the glottis and contraction of the muscles of expiration INTRODUCTION
- 3. The resultis sudden increase in intrathoracic pressure followed by relaxation of vocal cords, resulting in rapid expulsion of air Centrally acting agents work by inhibiting the cough center in the brain, elevating the threshold for coughing (though the exact mechanism is still poorly understood) Peripheral acting agents work either by anesthetizing the local nerve endings or acting as demulcents (agents having soothing effect on throat) Examples: Centrally acting: dextromethorphan, opiates (codeine) Peripheral acting: camphor, menthol Antitussives doesn't have any major side-effects but may cause sleepiness, irritability and dizziness
- 4. Work plan RETRIEVIAL OFANTITUSSIVE COMPOUND ACD CHEMSKETCH OF COMPOUNDS FINDING ADME FEATURES OF MOLECULES INTERPRETATION COMPARETIVE ANALYSIS USING MS EXCEL
- 5. Codeine Methadone Benzonatate Oxeladin Eucalyptol Noscapine Pipazethate Levopropoxyphene Clofedanol Opium Homatropine Phenylpropanolamine Oxeladin Pentoxyverine Oxolamine ANTITUSSIVE COMPOUNDS
- 6. COMPOUNDS WITH THEIRRESPECTIVE SMILE COMPOUND SMILES Codeine CN1CCC23C4C1CC5=C2C(=C(C=C5)OC)OC3C(C=C4)O Methadone CCC(=O)C(CC(C)N(C)C)(C1=CC=CC=C1)C2=CC=CC=C2 Benzonatate CCCCNC1=CC=C(C=C1)C(=O)OCCOCCOCCOCCOCCOCCOCCOCCOCCOC Oxeladin CCC(CC)(C1=CC=CC=C1)C(=O)OCCOCCN(CC)CC Eucalyptol CC1(C2CCC(O1)(CC2)C)C Noscapine CN1CCC2=CC3=C(C(=C2C1C4C5=C(C(=C(C=C5)OC)OC)C(=O)O4)OC)OCO3 Pipazethate C1CCN(CC1)CCOCCOC(=O)N2C3=CC=CC=C3SC4=C2N=CC=C4 Levopropoxyphene CCC(=O)O[C@@](CC1=CC=CC=C1)(C2=CC=CC=C2)[C@@H](C)CN(C)C Clofedanol CN(C)CCC(C1=CC=CC=C1)(C2=CC=CC=C2Cl)O Opium C1=C(OC(=C(C1=O)O)C(=O)O)C(=O)O Homatropine CN1C2CCC1CC(C2)OC(=O)C(C3=CC=CC=C3)O Phenylpropanolamine CC(C(C1=CC=CC=C1)O)N Oxeladin CCC(CC)(C1=CC=CC=C1)C(=O)OCCOCCN(CC)CC Pentoxyverine CCN(CC)CCOCCOC(=O)C1(CCCC1)C2=CC=CC=C2 Oxolamine CCN(CC)CCC1=NC(=NO1)C2=CC=CC=C2
- 7.
- 8.
- 9.
- 10.
- 11.
- 12.
- 13.
- 14.
- 15.
- 16.
- 17.
- 18.
- 19.
- 20.
- 21.
- 22. Molecular weights ofdifferent Drug compounds 0 200 400 600 800 MOLECULARWEIGHTS DRUG MOLECULES MW
- 23. 0 2 4 6 8 10 12 #H-BOND ACCEPTORS RANGEINNUMBERS DRUGS NO. OFHYDROGEN BOND ACCEPTORS Codeine Methadone Benzonatate Eucalyptol Noscapine Pipazethate Levopropoxyphene Clofedanol Opium Homatropine Phenylpropanolamine
- 24. #H-BOND DONORS 1 0 1 0 00 0 1 3 1 2 0 0 0 NO.OF HYDROGEN BOND DONORS Codeine Methadone Benzonatate Eucalyptol Noscapine Pipazethate Levopropoxyphene Clofedanol Opium Homatropine Phenylpropanolamine Oxeladin Pentoxyverine oxolamine
- 25. #ROTATABLE BONDS 1 7 33 0 4 8 9 5 24 2 13 11 6 NO.OF ROTATABLE BONDS Codeine Methadone Benzonatate Eucalyptol Noscapine Pipazethate Levopropoxyphene Clofedanol Opium Homatropine Phenylpropanolamine Oxeladin Pentoxyverine oxolamine
- 26. #AROMATIC HEAVY ATOMS 6 12 6 0 1212 12 12 6 6 6 6 6 11 NO. OF AROMATIC BONDS FOR DIFFERENT DRUGS Codeine Methadone Benzonatate Eucalyptol Noscapine Pipazethate Levopropoxyphene Clofedanol Opium Homatropine Phenylpropanolamine Oxeladin Pentoxyverine oxolamine
- 27. 1.8 4.06 3.6 2.67 2.55 3.38 4.18 3.52 -0.46 1.85 1.11 3.853.68 2.73 CONSENSUS LOG P LOGP VALUES FOR DIFFERENT DRUGS Codeine Methadone Benzonatate Eucalyptol Noscapine Pipazethate Levopropoxyphene Clofedanol Opium Homatropine Phenylpropanolamine Oxeladin Pentoxyverine oxolamine
- 28. INTRENSIC WATER SOLUBILITY[LOGSW]VALUES FOR DIFFERENT DRUGS -10 -8 -6 -4 -2 0 SILICOS-IT LOGSW -2.76 -6.64 -8.77 -2.45 -5.23 -5.68 -6.77 -5.92 -0.11 -2.53 -1.93 -5.97 -5.71 -5.12 Codeine Methadone Benzonatate Eucalyptol Noscapine Pipazethate Levopropoxyphene Clofedanol Opium Homatropine Phenylpropanolamine Oxeladin Pentoxyverine oxolamine
- 29. Molecule Lipinski #violations Codeine 0 Methadone 0 Benzonatate 2 Eucalyptol 0 Noscapine 0 Pipazethate0 Levopropoxyphene 1 Clofedanol 0 Opium 0 Homatropine 0 Phenylpropanolamine 0 Oxeladin 0 Pentoxyverine 0 oxolamine 0 0 0 2 0 0 0 1 0 0 0 0 0 0 0 0 0.5 1 1.5 2 2.5 Codeine Methadone Benzonatate Eucalyptol Noscapine Pipazethate Levopropoxyphene Clofedanol Opium Homatropine Phenylpropanolamine Oxeladin Pentoxyverine oxolamine LIPINSKI #VIOLATIONS Lipinski #violations
- 30. Molecule log Kp(cm/s) Codeine -7.32 Methadone -5.4 Benzonatate -8.24 Eucalyptol -5.3 Noscapine -6.9 Pipazethate -6.33 Levopropoxyphe ne -5.4 Clofedanol -5.53 Opium -7.52 Homatropine -6.61 Phenylpropanol amine -6.63 Oxeladin -5.52 Pentoxyverine -5.66 oxolamine -5.76 log Kp (cm/s), -5.76 -9 -8 -7 -6 -5 -4 -3 -2 -1 0 AxisTitle Axis Title Liphophilicity
- 31. Molecule Bioavailability Score Codeine 0.55 Methadone 0.55 Benzonatate 0.17 Eucalyptol 0.55 Noscapine 0.55 Pipazethate0.55 Levopropoxyp hene 0.55 Clofedanol 0.55 Opium 0.56 Homatropine 0.55 Phenylpropan olamine 0.55 Oxeladin 0.55 Pentoxyverine 0.55 oxolamine 0.55 0 0.1 0.2 0.3 0.4 0.5 0.6 Bioavailability Score
- 32. Molecule Leadlikeness #violations Codeine 0 Methadone 1 Benzonatate 2 Eucalyptol 1 Noscapine 1 Pipazethate2 Levopropoxyp hene 2 Clofedanol 1 Opium 1 Homatropine 0 Phenylpropano lamine 1 Oxeladin 2 Pentoxyverine 2 oxolamine 1 0 0.5 1 1.5 2 2.5 Codeine Methadone Benzonatate Eucalyptol Noscapine Pipazethate Levopropoxyphene Clofedanol Opium Homatropine Phenylpropanolamine Oxeladin Pentoxyverine oxolamine Leadlikeness #violations
- 33. Molecule Synthetic Accessibility Codeine 4.89 Methadone 3.05 Benzonatate 4.26 Eucalyptol 3.65 Noscapine 4.31 Pipazethate 3.77 Levopropoxyphene 3.52 Clofedanol 2.56 Opium 2.77 Homatropine 4.2 Phenylpropanolamine 1.62 Oxeladin3.02 Pentoxyverine 3.06 oxolamine 2.99 0 1 2 3 4 5 6 Codeine Methadone Benzonatate Eucalyptol Noscapine Pipazethate Levopropoxyphene Clofedanol Opium Homatropine Phenylpropanolamine Oxeladin Pentoxyverine oxolamine Synthetic Accessibility
- 34. INTERPRETATION From theabove compared parameters the Lipinski’s rule was applicable for most of the drugs. Among the Lipinski’s rule applicable drugs opium had high water solubility. Opium also had the highest bioavailability compared to other 12 molecules. And the next best bioavailability molecule was codeine