Caroxazone

Caroxazone
Clinical data
Pregnancy; category	?;
Routes of; administration	Oral
ATC code	none;
Legal status
Legal status	BR: Class C1 (Other controlled substances); In general: ℞ (Prescription only);
Identifiers
	IUPAC name 2-(2-oxo-4H-1,3-benzoxazin-3-yl)acetamide;
CAS Number	18464-39-6;
PubChem CID	29083;
ChemSpider	27057;
UNII	807N226MNL;
ChEMBL	ChEMBL2104164;
CompTox Dashboard (EPA)	DTXSID10171598 ;
ECHA InfoCard	100.038.481
Chemical and physical data
Formula	C10H10N2O3
Molar mass	206.201 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C(N)CN2C(=O)Oc1ccccc1C2;

Caroxazone (Surodil, Timostenil) is an antidepressant which was formerly used for the treatment of depression but is now no longer marketed.^[2]^[3] It acts as a reversible monoamine oxidase inhibitor (RIMA) of both MAO-A and MAO-B subtypes, with five-fold preference for the latter.^[4]^[5]^[6]^[7]^[8]

Synthesis

Caroxazone synthesis:^[9]^[10]^[11]^[12]^[13]

Synthesis starts by reductive amination of salicylaldehyde and glycinamide to give 3. The synthesis is completed by reaction with phosgene and NaHCO₃.

References

^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
^ Dictionary of organic compounds. London: Chapman & Hall. 1996. ISBN 0-412-54090-8.
^ Cecchini S, Petri P, Ardito R, Bareggi SR, Torriti A (1978). "A comparative double-blind trial of the new antidepressant caroxazone and amitriptyline". The Journal of International Medical Research. 6 (5): 388–94. doi:10.1177/030006057800600507. PMID 359383. S2CID 40464443.
^ Monoamine oxidase inhibitors in neurological diseases. New York: M. Dekker. 1994. ISBN 0-8247-9082-0.
^ Moretti A, Caccia C, Martini A, Bonollo L, Amico A, Sega R, et al. (May 1981). "Effect of caroxazone, a new antidepressant drug, on monoamine oxidases in healthy volunteers". British Journal of Clinical Pharmacology. 11 (5): 511–5. doi:10.1111/j.1365-2125.1981.tb01158.x. PMC 1401585. PMID 7272163.
^ Moretti A, Caccia C, Calderini G, Menozzi M, Amico A (October 1981). "Studies on the mechanism of action of caroxazone, a new antidepressant drug". Biochemical Pharmacology. 30 (19): 2728–31. doi:10.1016/0006-2952(81)90549-9. PMID 6170295.
^ Martini A, Bonollo L, Nicolis FB, Sega R, Palermo A (June 1981). "Effects of caroxazone, a reversible monoamine oxidase inhibitor, on the pressor response to oral tyramine in man". British Journal of Clinical Pharmacology. 11 (6): 611–5. doi:10.1111/j.1365-2125.1981.tb01178.x. PMC 1402186. PMID 7272178.
^ Martini A, Bonollo L, Nicolis FB, Sega R, Palermo A, Braibanti E (June 1981). "Effects of caroxazone, a reversible monoamine oxidase inhibitor, on the pressor response to intravenous tyramine in man". British Journal of Clinical Pharmacology. 11 (6): 605–10. doi:10.1111/j.1365-2125.1981.tb01177.x. PMC 1402193. PMID 7272177.
^ Bernardi L, Coda S, Nicolella V, Vicario GP, Gioia B, Minghetti A, et al. (1979). "Radioisotopic and synthetic studies related to caroxazone metabolism in man". Arzneimittel-Forschung. 29 (9): 1412–6. PMID 583252.
^ Bernardi L, Coda S, Pegrassi L, Suchowsky GK (August 1968). "Pharmacological properties of some derivatives of 1,3-benzoxazine". Experientia. 24 (8): 774–5. doi:10.1007/bf02144859. PMID 5683159. S2CID 30917127.
^ Bernardi L, Coda S, Bonsignori A, Pegrassi L, Suchowsky GK (August 1969). "Central depressant properties of 3,1-benzoxazine derivates". Experientia. 25 (8): 787–8. doi:10.1007/bf01897874. PMID 5348526. S2CID 5347811.
^ GB 1115759, "Carboxamidoalkyl-1,3-benzoxazines", published 1968-05-29, assigned to Societa Farmaceutici Italia
^ L. Bernardi et al., U.S. patent 3,427,313 (1969 to Soc. Farma. Italia).

[1] Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.

[isbn0-412-54090-8-2] Dictionary of organic compounds. London: Chapman & Hall. 1996. ISBN 0-412-54090-8.

[pmid359383-3] Cecchini S, Petri P, Ardito R, Bareggi SR, Torriti A (1978). "A comparative double-blind trial of the new antidepressant caroxazone and amitriptyline". The Journal of International Medical Research. 6 (5): 388–94. doi:10.1177/030006057800600507. PMID 359383. S2CID 40464443.

[isbn0-8247-9082-0-4] Monoamine oxidase inhibitors in neurological diseases. New York: M. Dekker. 1994. ISBN 0-8247-9082-0.

[pmid7272163-5] Moretti A, Caccia C, Martini A, Bonollo L, Amico A, Sega R, et al. (May 1981). "Effect of caroxazone, a new antidepressant drug, on monoamine oxidases in healthy volunteers". British Journal of Clinical Pharmacology. 11 (5): 511–5. doi:10.1111/j.1365-2125.1981.tb01158.x. PMC 1401585. PMID 7272163.

[pmid6170295-6] Moretti A, Caccia C, Calderini G, Menozzi M, Amico A (October 1981). "Studies on the mechanism of action of caroxazone, a new antidepressant drug". Biochemical Pharmacology. 30 (19): 2728–31. doi:10.1016/0006-2952(81)90549-9. PMID 6170295.

[pmid7272178-7] Martini A, Bonollo L, Nicolis FB, Sega R, Palermo A (June 1981). "Effects of caroxazone, a reversible monoamine oxidase inhibitor, on the pressor response to oral tyramine in man". British Journal of Clinical Pharmacology. 11 (6): 611–5. doi:10.1111/j.1365-2125.1981.tb01178.x. PMC 1402186. PMID 7272178.

[pmid7272177-8] Martini A, Bonollo L, Nicolis FB, Sega R, Palermo A, Braibanti E (June 1981). "Effects of caroxazone, a reversible monoamine oxidase inhibitor, on the pressor response to intravenous tyramine in man". British Journal of Clinical Pharmacology. 11 (6): 605–10. doi:10.1111/j.1365-2125.1981.tb01177.x. PMC 1402193. PMID 7272177.

[9] Bernardi L, Coda S, Nicolella V, Vicario GP, Gioia B, Minghetti A, et al. (1979). "Radioisotopic and synthetic studies related to caroxazone metabolism in man". Arzneimittel-Forschung. 29 (9): 1412–6. PMID 583252.

[10] Bernardi L, Coda S, Pegrassi L, Suchowsky GK (August 1968). "Pharmacological properties of some derivatives of 1,3-benzoxazine". Experientia. 24 (8): 774–5. doi:10.1007/bf02144859. PMID 5683159. S2CID 30917127.

[11] Bernardi L, Coda S, Bonsignori A, Pegrassi L, Suchowsky GK (August 1969). "Central depressant properties of 3,1-benzoxazine derivates". Experientia. 25 (8): 787–8. doi:10.1007/bf01897874. PMID 5348526. S2CID 5347811.

[12] GB 1115759, "Carboxamidoalkyl-1,3-benzoxazines", published 1968-05-29, assigned to Societa Farmaceutici Italia

[13] L. Bernardi et al., U.S. patent 3,427,313 (1969 to Soc. Farma. Italia).

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[1]

[9]

[10]

[11]

[12]

[13]

Clinical data

Pregnancy category	?
Routes of administration	Oral
ATC code	none
Legal status
Legal status	BR: Class C1 (Other controlled substances)^[1] In general: ℞ (Prescription only)
Identifiers
IUPAC name 2-(2-oxo-4H-1,3-benzoxazin-3-yl)acetamide
CAS Number	18464-39-6
PubChem CID	29083
ChemSpider	27057
UNII	807N226MNL
ChEMBL	ChEMBL2104164
CompTox Dashboard (EPA)	DTXSID10171598
ECHA InfoCard	100.038.481
Chemical and physical data
Formula	C₁₀H₁₀N₂O₃
Molar mass	206.201 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES O=C(N)CN2C(=O)Oc1ccccc1C2

Caroxazone

Synthesis

See also

References