Pantoprazole

Common name: Pantoprazole; Protonix; Pantoprazolum; Pantozol; Pantoprazole Sodium; BY-1023; Pantoloc

Trademarks: Pantazone; Pantop-D; Pantasan; Pantrol; Prazolin; Pantochem; Pansev; Pantec; Somac; Pantecta; Pantoloc

Molecular Formula: C16H15F2N3O4S

CAS Registry Number: 102625-70-7

CAS Name: 6-(Difluoromethoxy)-2-[(3,4-dimethoxypyridin-2-yl)methylsulfinyl]-1H-benzo[d]imidazole

Molecular Weight: 383.370

SMILES: COC1=C(OC)C(CS(=O)C2=NC3=C(N2)C=C(OC(F)F)C=C3)=NC=C1
InChI Key: IQPSEEYGBUAQFF-UHFFFAOYSA-N
InChI: InChI=1S/C16H15F2N3O4S/c1-23-13-5-6-19-12(14(13)24-2)8-26(22)16-20-10-4-3-9(25-15(17)18)7-11(10)21-16/h3-7,15H,8H2,1-2H3,(H,20,21)

Activity: Anti-Helicobacter Pylori Agents, Antiulcer Drugs, Esophageal Diseases, Gastric Antisecretory Drugs, Gastroesophageal Reflux Disease, GASTROINTESTINAL DRUGS, ABCC3 Expression Enhancers, H+/K+-ATPase Inhibitors

Pantoprazole as Medicine:

Pantoprazole is in a class of medications called proton-pump inhibitors (PPIs). It works by decreasing the amount of acid made in the stomach. Pantoprazole is used to treat gastroesophageal reflux disease (GERD), a condition in which backward flow of acid from the stomach causes heartburn and possible injury of the esophagus (the tube between the throat and stomach). It is also used to treat conditions where the stomach produces too much acid, such as Zollinger-Ellison syndrome.

Pantoprazole as Chemical Compound:

It is an organic heterocyclic compound having a Benzimidazole moiety. More specifically, it is a sulfinylbenzimidazoles - a polycyclic aromatic compounds containing a sulfinyl group attached at the position 2 of a benzimidazole moiety. Other important chemical classifications are:

1. Organoflourine compound

2. Alkyl aryl ethers 

3. Pyridines and derivatives 

4. Heteroaromatic compounds 

5. Sulfoxides 

6. Sulfinyl compounds 

7. Azacyclic compounds 

8. Alkyl fluorides

9. Flouromethane compounds

Pantoprazole synthesis: J Med Chem 1992, 35(6), 1049-57

Pantoprazole synthesis: WO2002028852A1

Important chemistry involved in Pantoprazole synthesis:

1. Flourine Chemistry

2. Acetylation Chemistry

3. Reduction Process

4. Oxidation Process

Common Side-Effects

Common side effects of Pantoprazole include headache, diarrhea, nausea, and abdominal pain. Moreover, these side-effects are also reported fast or uneven heart rate, diarrhea that is watery or bloody, muscle cramps, muscle weakness, memory problems, weakness, loss of appetite, feeling unsteady, confusion, hallucinations, fainting, seizure, or shallow breathing.

Two important observations:

1. The chronic use of Pantoprazole has caused stomach cancer in animal studies, but it is not known if this medication would have the same effects in humans.

2. Long-term treatment with Pantoprazole may also make it harder for your body to absorb vitamin B-12, resulting in a deficiency of this vitamin.

References:

1. Palomo, C. A.; A process for the preparation of pantoprazole and intermediates therefor. WO2002028852A1.

2. Kohl, B.; et. al. (H+,K+)-ATPase inhibiting 2-[(2-pyridylmethyl)sulfinyl]benzimidazoles. 4. A novel series of dimethoxypyridyl-substituted inhibitors with enhanced selectivity. The selection of pantoprazole as a clinical candidate. J Med Chem, 1992, 35(6), 1049-57.

3. Mathad, V. T.; et. al. An Improved and Single-Pot Process for the Production of Pantoprazole Substantially Free from Sulfone Impurity. Org Proc Res Dev, 2004, 8(2), 266–270.

4. Rainer, G. Dr.; et. al. Substituted pyridylmethylthio-(or sulfinyl-)benzimidazoles having a secretolytic activity. EP0134400A3

For more drugs and their synthesis: Synayurajan database

Lansoprazole

Common name: Lansoprazole, AG-1749, ABT-006, CG-4801, A-65006

Trademarks: Ogast, Lanzor, Lanzo, Agopton, Opiren, Bamalite, Takepron, Lansox, Lansox, Ogastro, Monolitum, Prevacid, Zoton

Molecular Formula: C₁₆H₁₄F₃N₃O₂S

CAS Registry Number: 103577-45-3

Molecular Weight: 369.368
SMILES: CC1=C(OCC(F)(F)F)C=CN=C1CS(=O)C1=NC2=CC=CC=C2N1
InChI Key: MJIHNNLFOKEZEW-UHFFFAOYSA-N
InChI: InChI=1S/C16H14F3N3O2S/c1-10-13(20-7-6-14(10)24-9-16(17,18)19)8-25(23)15-21-11-4-2-3-5-12(11)22-15/h2-7H,8-9H2,1H3,(H,21,22)

CAS Name: 2-[3-Methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-ylmethylsulfinyl]-1H-benzimidazole; 2-(2-Benzimidazolylsulfinylmethyl)-3-methyl-4-(2,2,2-trifluoroethoxy)pyridine

Activity: Agents for Gastritis, Anti-Helicobacter Pylori Agents, Antiulcer Drugs, Esophageal Diseases, Treatment of, Gastric Antisecretory Drugs, Gastroesophageal Reflux Disease, Agents for, GASTROINTESTINAL DRUGS, Non-Ulcer Dyspepsia, Agents for, H+/K+-ATPase Inhibitors
Intermediates:4-Nitro-2,3-lutidine-N-oxide (37699-43-7)
2-Hydroxymethyl-3-methyl-4-(2,2,2-trifluoroethoxy)pyridine hydrochloride (103577-66-8)
2-Chloromethyl-3-methyl-4-(2,2,2-trifluoroethoxy)pyridine hydrochloride (127337-60-4)
2-[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methylthio-1H-benzimidazole (103577-40-8)

Lansoprazole as Medicine:

Lansoprazole belongs to a group of drugs called proton pump inhibitors (PPIs). It decreases the amount of acid produced in the stomach.  It is a racemic 1:1 mixture of the enantiomers dexlansoprazole (Dexilant, formerly named Kapidex) and levolansoprazole.

Dexlansoprazole is an enantiomerically pure active ingredient of a commercial drug as a result of the 'enantiomeric shift'.

Lansoprazole as Chemical Compound:

It is an organic heterocyclic compound having a Benzimidazole moiety. More specifically, it is a sulfinylbenzimidazoles - a polycyclic aromatic compounds containing a sulfinyl group attached at the position 2 of a benzimidazole moiety. Other important chemical classifications are:

1. Organoflourine compound

2. Alkyl aryl ethers 

3. Pyridines and derivatives 

4. Heteroaromatic compounds 

5. Sulfoxides 

6. Sulfinyl compounds 

7. Azacyclic compounds 

8. Alkyl fluorides

9. Triflouromethane compounds

Lansoprazole synthesis: US4628098; US4689333 (same in Ref. 3)

Lansoprazole synthesis: Der Chemica Sinica 2013, 4(2), 122-126 (Green Chemistry, Appel's Reaction used instead of thionyl chloride)

Lansoprazole synthesis: Bull Korean Chem Soc 2002, 23(4), 626-628

Important chemistry involved in Lansoprazole synthesis:

1. Flourine Chemistry

2. Cyanation Chemistry

3. Reduction Process

4. Oxidation Process

References:
1. Nohara, A.; et. al. Pyridine derivatives and their production. US4628098; US4689333
2. Makino, T.; et. al. Stabilized pharmaceutical composition comprising a benzimidazole compound, its production and its use as an antiulcer agent. JP87277322
3. Kubo, K.; et. al. Synthesis of 2-[[(4-fluoroalkoxy-2-pyridyl)methyl]sulfinyl]-1H- benzimidazoles as antiulcer agents. Chem Pharm Bull 1990, 38(10), 2853-2858. (synthesis and selection of Lansoprazole as clinical candidate)
4. Pai, N. R.; et. al. Green chemical route for process development of lansoprazole intermediate. Der Chemica Sinica 2013, 4(2), 122-126.
5. Ahn, K.-W.; et. al. A New Synthetic Process of Lansoprazole. Bull Korean Chem Soc 2002, 23(4), 626-628.
6. Harrington, P. J. (Eds) Lansoprazole in Pharmaceutical Process Chemistry for Synthesis: Rethinking the Routes to Scale-Up. 2011, Wiley Publications. (reports synthesis and analysis of various routes wrt yields and sustainability.)

For more drugs and their synthesis: Synayurajan database