1,4-Benzodiazepine

Hydrolyzability: Ring opening produces yellow 2-methylamino-chloro-benzophenone and glycine

metabolized by liver

Amide bond at positions 1 and 2:

Imine bond at positions 4 and 5: reversible ring opening, ring closing by neutral and alkaline dehydration; when there are strong electron-withdrawing groups at positions 7 and 12, cyclization is easy to proceed

Under acidic conditions, hydrolysis of the ring is easy to occur; Zolams increase stability due to the merging of heterocycles at positions 1 and 2; Tezolams have a benzene ring replaced by thiophene

Amobarbital: copper pyridine sulfate → purple complex

Thiopental sodium: copper pyridine sulfate → green complex

Weakly acidic: lactam-lactimide, forming enol form; soluble in sodium hydroxide, sodium carbonate, insoluble in sodium bicarbonate; weaker than carbonic acid, sodium salt is unstable, easy to absorb carbon dioxide and precipitate

Hydrolyzability: tautomeric bilactimide structure, easier to hydrolyze than amides; shows orange-yellow-orange red color when compared with sodium nitrite-sulfuric acid test solution

Non-specific structure: affected by pKa and lgP; the length of action is related to the metabolic process of the 5, 5-position substituent in the body (whether it is stable)

Physical and chemical properties:

Metabolism: oxidatively combines hydroxyl groups with glucuronic acid

structure

Physical and chemical properties

Synthetic route: Ullmann reaction

structure

Store at room temperature away from light, the color will deepen when exposed to light; explain the part about exposure to light

Avoid lactose in tablet prescriptions

structure

Good oral absorption, significant first-pass elimination

Representatives of atypical antipsychotics: block DA receptors and antagonize 5-HT2 receptors

Typical side effects: Agranulocytosis

Reducibility: oxidized in air to produce pseudo (bis)morphine

Aqueous solutions of morphine salts are stable in acidic conditions and are oxidized in neutral or alkaline conditions; ways to prevent morphine oxidation are ① Adjust Ph3-5 ② Inject nitrogen ③ Add antioxidants

Dehydration rearrangement: Heating in an acidic solution produces apomorphine with a catechol structure (a dopamine receptor agonist; it is easily oxidized and can be oxidized to o-phthaloquinone with dilute nitric acid to produce a red color, which can be used for identification); Can be used as an antiemetic

Morphine is oxidized by potassium ferricyanide and reacts with ferric chloride solution to form potassium ferrocyanide (Prussian blue), which appears blue-green. Codeine has no such reaction and is used for identification.

Alkaloid reaction: Morphine reacts with alkaloid chromogen and formaldehyde sulfuric acid test solution to show purple color; reacts with molybdenum sulfuric acid test solution from purple → blue → brown-green

C3-phenolic hydroxyl alkylation (etherification and acylation): reduced analgesia and reduced addiction; methyl etherified codeine, a weak μ receptor agonist, mildly addictive; antitussive

After C3-hydroxyl C6-hydroxyl is acetylated, heroin is obtained; (side) effects are enhanced;

The C6-hydroxyl group is oxidized to form a ketone, and the double bond hydrogen at the C7 and 8 positions is reduced to obtain hydromorphone (the hydroxyl group on the 14th position is oxymorphone); the hydroxyl group at the 3rd position of the two is methylated to obtain hydrocodone (methyl etherification). , Oxycodone

C6 and 14 positions are bridged and C7 is changed; etorphine (the bridge vinyl group is hydrogenated to obtain dihydroetorphine, and N-methyl is replaced with cyclopropylmethyl group to obtain buprenorphine); buprenorphine: partial agonist (Both labor pain and resistance)

C17-N changes:

A flat structure that binds to the benzene ring of the drug through van der Waals forces

An anionic binding site is electrostatically bound to the positive center of the drug; the basic center is on the same plane as the flat structure

A properly oriented hole fits into the piperidine ring (the hydrocarbyl group protrudes in front of the plane)

Partial agonist, weakly antagonizes mu receptors, acts on k receptors

Mildly antagonistic morphine at high doses

Is the first non-addictive opioid for clinical use

Typical mu receptor agonist

Only keep A and D rings

Physical and chemical properties

structure

The levorotatory body has strong effects, and the racemic body is used clinically.

μ receptor agonist; mild side effects; used in addiction treatment

The steric hindrance of the carbonyl group is large, the reaction activity is significantly reduced, and semicarbazone and hydrazone cannot be generated; it is also not reduced by sodium amalgam or aluminum isopropoxide.

Imipramine is demethylated in the body to form desipramine, which is a secondary amine and has a stronger effect.

structure

Treatment of endogenous, reactive, menopausal depression, and can be used for enuresis in children

Hepatic metabolism, metabolite desipramine (desimipramine)

The S-isomer has strong activity; the racemate is used clinically

Good oral absorption, high bioavailability, long-lasting effects

Absorbed from gastrointestinal tract, metabolized by liver to active product: desfluoxetine