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Revision as of 11:41, 18 January 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers from ChemSpider, CommonChemistry and FDA for the Chem/Drugbox validation project - Updated: UNII ChEMBL.← Previous edit Latest revision as of 16:20, 21 October 2024 edit undoJWBE (talk | contribs)Extended confirmed users10,111 edits removed Category:Phenols; added Category:4-Hydroxyphenyl compounds using HotCat 
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{{Short description|Chemical compound}}
{{Drugbox {{Drugbox
| Verifiedfields = changed
⚫ | verifiedrevid = 402196816
| Watchedfields = changed
⚫ | IUPAC_name = (6''R'',7''R'')-7-{amino}-7-methoxy-3-{methyl}-8-oxo-5-oxa-1-azabicyclooct-2-ene-2-carboxylic acid
⚫ | verifiedrevid = 408571626
⚫ | image = Latamoxef.svg
⚫ | IUPAC_name = (6''R'',7''R'')-7-{amino}-7-methoxy-3-{methyl}-8-oxo-5-oxa-1-azabicyclooct-2-ene-2-carboxylic acid
⚫ | CASNo_Ref = {{cascite|correct|CAS}}
⚫ | image = Latamoxef.svg
<!--Clinical data-->
| tradename =
| Drugs.com = {{drugs.com|international|latamoxef}}
⚫ | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
⚫ | pregnancy_US = <!-- A / B / C / D / X -->
⚫ | pregnancy_category =
⚫ | legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
⚫ | legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
⚫ | legal_UK = <!-- GSL / P / POM / CD / Class A, B, C -->
⚫ | legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
⚫ | legal_status =
⚫ | routes_of_administration = ], ]
<!--Pharmacokinetic data-->
⚫ | bioavailability =
⚫ | protein_bound = 35 to 50%
⚫ | metabolism = Nil
⚫ | elimination_half-life = 2 hours
⚫ | excretion = Mostly ], unchanged; also biliary
<!--Identifiers-->
⚫ | CAS_number_Ref = {{cascite|correct|??}}
⚫ | CAS_number = 64952-97-2
⚫ | ATC_prefix = J01
⚫ | ATC_suffix = DD06
⚫ | PubChem = 47499
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
⚫ | DrugBank = DB04570
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 43215 | ChemSpiderID = 43215
| UNII_Ref = {{fdacite|correct|FDA}} | UNII_Ref = {{fdacite|correct|FDA}}
| UNII = VUF6C936Z3 | UNII = VUF6C936Z3
| KEGG_Ref = {{keggcite|correct|kegg}}
| InChI = 1/C20H20N6O9S/c1-25-19(22-23-24-25)36-8-10-7-35-18-20(34-2,17(33)26(18)13(10)16(31)32)21-14(28)12(15(29)30)9-3-5-11(27)6-4-9/h3-6,12,18,27H,7-8H2,1-2H3,(H,21,28)(H,29,30)(H,31,32)/t12?,18-,20+/m1/s1
⚫ | KEGG = D08109
| InChIKey = JWCSIUVGFCSJCK-CAVRMKNVBQ
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 599928
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 74632 | ChEMBL = 74632
<!--Chemical data-->
⚫ | C=20 | H=20 | N=6 | O=9 | S=1
⚫ | smiles = O=C2N1/C(=C(\CO12(OC)NC(=O)C(c3ccc(O)cc3)C(=O)O)CSc4nnnn4C)C(=O)O
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C20H20N6O9S/c1-25-19(22-23-24-25)36-8-10-7-35-18-20(34-2,17(33)26(18)13(10)16(31)32)21-14(28)12(15(29)30)9-3-5-11(27)6-4-9/h3-6,12,18,27H,7-8H2,1-2H3,(H,21,28)(H,29,30)(H,31,32)/t12?,18-,20+/m1/s1 | StdInChI = 1S/C20H20N6O9S/c1-25-19(22-23-24-25)36-8-10-7-35-18-20(34-2,17(33)26(18)13(10)16(31)32)21-14(28)12(15(29)30)9-3-5-11(27)6-4-9/h3-6,12,18,27H,7-8H2,1-2H3,(H,21,28)(H,29,30)(H,31,32)/t12?,18-,20+/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = JWCSIUVGFCSJCK-CAVRMKNVSA-N | StdInChIKey = JWCSIUVGFCSJCK-CAVRMKNVSA-N
| melting_point = 117
⚫ | CAS_number = 64952-97-2
| melting_high = 122
⚫ | ATC_prefix = J01
| melting_notes = (dec.)
⚫ | ATC_suffix = DD06
⚫ | PubChem = 47499
⚫ | DrugBank =
⚫ | KEGG = D08109
⚫ | smiles = O=C2N1/C(=C(\CO12(OC)NC(=O)C(c3ccc(O)cc3)C(=O)O)CSc4nnnn4C)C(=O)O
⚫ | C=20|H=20|N=6|O=9|S=1
| molecular_weight = 520.474 g/mol
⚫ | bioavailability =
⚫ | protein_bound = 35 to 50%
⚫ | metabolism = Nil
⚫ | elimination_half-life = 2 hours
⚫ | excretion = Mostly ], unchanged; also biliary
⚫ | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
⚫ | pregnancy_US = <!-- A / B / C / D / X -->
⚫ | pregnancy_category=
⚫ | legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
⚫ | legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
⚫ | legal_UK = <!-- GSL / P / POM / CD / Class A, B, C -->
⚫ | legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
⚫ | legal_status =
⚫ | routes_of_administration = ], ]
}} }}
'''Latamoxef''' (or '''moxalactam''') is an ] ] usually grouped with the ]s. In oxacephems such as latamoxef, the ] atom of the cephalosporin core is replaced with an ] atom. '''Latamoxef''' (or '''moxalactam''') is an ] ] usually grouped with the ]s. In oxacephems such as latamoxef, the ] atom of the cephalosporin core is replaced with an ] atom.


Latamoxef has been associated with prolonged ], and several cases of ], some fatal, were reported during the 1980s.<ref>{{cite journal |author=Weitekamp MR, Aber RC |title=Prolonged bleeding times and bleeding diathesis associated with moxalactam administration |journal=] |volume=249 |issue=1 |pages=69–71 |year=1983 |pmid=6217353 |doi=10.1001/jama.249.1.69}}</ref><ref>{{cite journal |author=Brown RB, Klar J, Lemeshow S, Teres D, Pastides H, Sands M |title=Enhanced bleeding with cefoxitin or moxalactam. Statistical analysis within a defined population of 1493 patients |journal=Arch Intern Med |volume=146 |issue=11 |pages=2159–64 |year=1986 |pmid=3778044 |doi=10.1001/archinte.146.11.2159}}</ref> Latamoxef is no longer available in the United States. As with other ] with a methylthiotetrazole side chain, latamoxef causes an ] reaction when mixed with alcohol. Additionally the methylthiotetrazole side chain inhibits γ-carboxylation of glutamic acid; this can interfere with the actions of vitamin K. Latamoxef has been associated with prolonged ], and several cases of ], some fatal, were reported during the 1980s.<ref>{{cite journal | vauthors = Weitekamp MR, Aber RC | title = Prolonged bleeding times and bleeding diathesis associated with moxalactam administration | journal = JAMA | volume = 249 | issue = 1 | pages = 69–71 | date = January 1983 | pmid = 6217353 | doi = 10.1001/jama.249.1.69 }}</ref><ref>{{cite journal | vauthors = Brown RB, Klar J, Lemeshow S, Teres D, Pastides H, Sands M | title = Enhanced bleeding with cefoxitin or moxalactam. Statistical analysis within a defined population of 1493 patients | journal = Archives of Internal Medicine | volume = 146 | issue = 11 | pages = 2159–2164 | date = November 1986 | pmid = 3778044 | doi = 10.1001/archinte.146.11.2159 }}</ref> Latamoxef is no longer available in the United States. As with other cephalosporins with a methylthiotetrazole side chain, latamoxef causes a ] reaction when mixed with alcohol. Additionally, the methylthiotetrazole side chain inhibits γ-carboxylation of glutamic acid; this can interfere with the actions of vitamin K.{{cn|date=January 2023}}


It has been described as a third generation cephalosporin.<ref name="pmid3296254">{{cite journal |author=Salem RR, McIndoe A, Matkin JA, Lidou AC, Clarke A, Wood CB |title=The hematologic effects of latamoxef sodium when used as a prophylaxis during surgical treatment |journal=Surg Gynecol Obstet |volume=164 |issue=6 |pages=525–9 |year=1987 |month=June |pmid=3296254 |doi= |url=}}</ref> It has been described as a third-generation cephalosporin.<ref name="pmid3296254">{{cite journal | vauthors = Salem RR, McIndoe A, Matkin JA, Lidou AC, Clarke A, Wood CB | title = The hematologic effects of latamoxef sodium when used as a prophylaxis during surgical treatment | journal = Surgery, Gynecology & Obstetrics | volume = 164 | issue = 6 | pages = 525–529 | date = June 1987 | pmid = 3296254 }}</ref>


==References== == Synthesis ==
Oxa-substituted third generation cephalosporin antibiotic (oxacephalosporin).
|assign=] | inventor = Nagata W, Narisada M }}</ref><ref>{{cite patent | inventor = Nagata W, Narisada M | country = US | number = 4138486 | gdate = 1979 | assign1 = ] }}</ref><ref>{{cite journal | vauthors = Narisada M, Yoshida T, Onoue H, Ohtani M, Okada T, Tsuji T, Kikkawa I, Haga N, Satoh H, Itani H, Nagata W | display-authors = 6 | title = Synthetic studies on β-lactam antibiotics. Part 10. Synthesis of 7β-&#91;2-carboxy-2-(4-hydroxyphenyl)acetamido&#93;-7.alpha.-methoxy-3-&#91;&#91;(1-methyl-1H-tetrazol-5-yl)thio&#93;methyl&#93;-1-oxa-1-dethia-3-cephem-4-carboxylic acid disodium salt (6059-S) and its related 1-oxacephems| journal = Journal of Medicinal Chemistry | volume = 22 | issue = 7 | pages = 757–759 | date = July 1979 | pmid = 448673 | doi = 10.1021/jm00193a001 }}</ref><ref>{{cite journal | vauthors = Otsuka H, Nagata W, Yoshioka M, Narisada M, Yoshida T, Harada Y, Yamada H | title = Discovery and development of Moxalactam (6059-S): the chemistry and biology of 1-oxacephems | journal = Medicinal Research Reviews | volume = 1 | issue = 3 | pages = 217–248 | year = 1981 | pmid = 6213825 | doi = 10.1002/med.2610010302 | s2cid = 45623930 }}</ref><ref>{{cite journal | vauthors = Narisada M, Onoue H, Nagata W |doi=10.3987/S-1977-02-0839|title=Synthetic Studies on b-Lactam Antibiotics. Part 5. A Synthesis of 7b-Acylamino-3-methyl-1-oxadethia-3-cephem-4-carboxylic Acids |journal=Heterocycles |volume=7 |issue=2 |pages=839 |year=1977 |doi-access=free }}</ref> (excerpt from Lednicer book 3)]]
The ] ester of 6-Aminopenicillanic acid (]) is S-chlorinated and treated with base whereupon the intermediate ] fragments (to '''2'''). Next, displacement with ] in the presence of ] gives predominanntly the stereochemistry represented by diastereoisomer '''3'''. The side chain is protected as the phenylacetylamide; the triple bond is partially reduced with a 5% Pd-CaCO3 (]) and then epoxidized with ] to give '''4'''. The epoxide is opened at the least hindered end with 1-methyl-1''H''-tetrazole-5-thiol to put in place the future C-3 side chain and give intermediate '''5'''. Jones oxidation followed in turn by ozonolysis (reductive work-up with zinc-AcOH) and reaction with ] and ] give halide '''6'''. The stage is now wet for intramolecular ]. Displacement with ] and Wittig olefination gives 1-oxacephem '''7'''. Next a sequence is undertaken of side chain exchange and introduction of a 7-methoxyl group analogous to that which is present in ] and gives them the enhanced ] stability. First '''7''' is converted to the imino chloride with ] and then to the imino methyl ether (with ]) and next hydrolyzed to the free amine ('''8'''). Imine formation with 3,5-di-t-butyl-4-hydroxybenzaldehyde is next carried out leading to '''9'''. Oxidation with ] gives iminoquinone methide '''10''', to which methanol is added in a conjugate sense and in the sterechemistry represented by formula '''11'''. The imine is exchanged with ] to give '''12''', and this is acylated by a suitable protected arylmalonate, as the hemiester hemiacid chloride so as to give 11. Deblocking with ] and anisole gives moxalactam '''14'''.

== References ==
{{Reflist}} {{Reflist}}


⚫ {{antibiotic-stub}}
{{CephalosporinAntiBiotics}} {{CephalosporinAntiBiotics}}


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⚫ {{antibiotic-stub}}