AU2021105523A4 - Synthesis of some amino acid amide derivatives as potential anticonvulsant agent - Google Patents
Synthesis of some amino acid amide derivatives as potential anticonvulsant agent Download PDFInfo
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- amide derivatives
- amino acid
- acid amide
- synthesis
- anticonvulsant
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- 239000001961 anticonvulsive agent Substances 0.000 title claims abstract description 15
- 150000001413 amino acids Chemical class 0.000 title claims abstract description 9
- 230000015572 biosynthetic process Effects 0.000 title claims description 6
- 238000003786 synthesis reaction Methods 0.000 title claims description 6
- 229940125681 anticonvulsant agent Drugs 0.000 title claims description 5
- 230000001773 anti-convulsant effect Effects 0.000 claims abstract description 10
- 239000003814 drug Substances 0.000 claims abstract description 9
- 229960003965 antiepileptics Drugs 0.000 claims abstract description 8
- 230000003993 interaction Effects 0.000 claims abstract 2
- 150000001875 compounds Chemical class 0.000 claims description 11
- 230000000694 effects Effects 0.000 claims description 9
- 229940079593 drug Drugs 0.000 claims description 8
- 231100000053 low toxicity Toxicity 0.000 claims description 2
- 230000010534 mechanism of action Effects 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 150000001408 amides Chemical class 0.000 abstract description 8
- 239000000126 substance Substances 0.000 abstract description 6
- 239000002253 acid Substances 0.000 abstract description 2
- 230000000202 analgesic effect Effects 0.000 abstract description 2
- 125000003118 aryl group Chemical group 0.000 abstract description 2
- 125000000623 heterocyclic group Chemical group 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 230000000749 insecticidal effect Effects 0.000 abstract 2
- 125000001931 aliphatic group Chemical group 0.000 abstract 1
- 150000001412 amines Chemical class 0.000 abstract 1
- 230000000507 anthelmentic effect Effects 0.000 abstract 1
- 230000000844 anti-bacterial effect Effects 0.000 abstract 1
- 230000001093 anti-cancer Effects 0.000 abstract 1
- 230000000843 anti-fungal effect Effects 0.000 abstract 1
- 230000003110 anti-inflammatory effect Effects 0.000 abstract 1
- 230000000845 anti-microbial effect Effects 0.000 abstract 1
- 230000002365 anti-tubercular Effects 0.000 abstract 1
- 229940121375 antifungal agent Drugs 0.000 abstract 1
- 230000004071 biological effect Effects 0.000 abstract 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract 1
- 238000011835 investigation Methods 0.000 abstract 1
- 238000001819 mass spectrum Methods 0.000 abstract 1
- 150000002780 morpholines Chemical class 0.000 abstract 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 abstract 1
- 238000001308 synthesis method Methods 0.000 abstract 1
- -1 piperidine aminomethyl acetate 2-amino-1-(piperidin-i-yl)ethanone Chemical compound 0.000 description 8
- 238000012360 testing method Methods 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 206010010904 Convulsion Diseases 0.000 description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 230000036461 convulsion Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 239000004471 Glycine Substances 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 206010015037 epilepsy Diseases 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 2
- 230000003556 anti-epileptic effect Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- 229960002036 phenytoin Drugs 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 1
- SHAHPWSYJFYMRX-GDLCADMTSA-N (2S)-2-(4-{[(1R,2S)-2-hydroxycyclopentyl]methyl}phenyl)propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C[C@@H]1[C@@H](O)CCC1 SHAHPWSYJFYMRX-GDLCADMTSA-N 0.000 description 1
- MQAISPIJGUNNSJ-UHFFFAOYSA-N 2-[(3-amino-3-oxopropyl)amino]ethylsulfanylphosphonic acid Chemical compound NC(=O)CCNCCSP(O)(O)=O MQAISPIJGUNNSJ-UHFFFAOYSA-N 0.000 description 1
- 229940123511 Excitatory amino acid receptor antagonist Drugs 0.000 description 1
- 238000007309 Fischer-Speier esterification reaction Methods 0.000 description 1
- HZIWGOAXOBPQGY-UHFFFAOYSA-N LY201116 Chemical compound CC1=CC=CC(C)=C1NC(=O)C1=CC=C(N)C=C1 HZIWGOAXOBPQGY-UHFFFAOYSA-N 0.000 description 1
- VQASKUSHBVDKGU-UHFFFAOYSA-N Paramethadione Chemical compound CCC1(C)OC(=O)N(C)C1=O VQASKUSHBVDKGU-UHFFFAOYSA-N 0.000 description 1
- XPFRXWCVYUEORT-UHFFFAOYSA-N Phenacemide Chemical compound NC(=O)NC(=O)CC1=CC=CC=C1 XPFRXWCVYUEORT-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical class NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229950008740 ameltolide Drugs 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- GLJPYGONZAPOSG-UHFFFAOYSA-N aminomethyl acetate Chemical compound CC(=O)OCN GLJPYGONZAPOSG-UHFFFAOYSA-N 0.000 description 1
- 150000003931 anilides Chemical class 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 230000000561 anti-psychotic effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 150000008430 aromatic amides Chemical class 0.000 description 1
- JPYQFYIEOUVJDU-UHFFFAOYSA-N beclamide Chemical compound ClCCC(=O)NCC1=CC=CC=C1 JPYQFYIEOUVJDU-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical class NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 230000001037 epileptic effect Effects 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229960003472 felbamate Drugs 0.000 description 1
- WKGXYQFOCVYPAC-UHFFFAOYSA-N felbamate Chemical compound NC(=O)OCC(COC(N)=O)C1=CC=CC=C1 WKGXYQFOCVYPAC-UHFFFAOYSA-N 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 229960002870 gabapentin Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
- 229960002623 lacosamide Drugs 0.000 description 1
- VPPJLAIAVCUEMN-GFCCVEGCSA-N lacosamide Chemical compound COC[C@@H](NC(C)=O)C(=O)NCC1=CC=CC=C1 VPPJLAIAVCUEMN-GFCCVEGCSA-N 0.000 description 1
- 229960004002 levetiracetam Drugs 0.000 description 1
- HPHUVLMMVZITSG-ZCFIWIBFSA-N levetiracetam Chemical compound CC[C@H](C(N)=O)N1CCCC1=O HPHUVLMMVZITSG-ZCFIWIBFSA-N 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- OLVZFZNHBMORRJ-UHFFFAOYSA-N n-[(2-fluorophenyl)methyl]pyridine-2-carboxamide Chemical compound FC1=CC=CC=C1CNC(=O)C1=CC=CC=N1 OLVZFZNHBMORRJ-UHFFFAOYSA-N 0.000 description 1
- KJVWWMOEXGMLMQ-UHFFFAOYSA-N n-benzyl-2-(benzylamino)-4-hydroxybutanamide Chemical compound C=1C=CC=CC=1CNC(=O)C(CCO)NCC1=CC=CC=C1 KJVWWMOEXGMLMQ-UHFFFAOYSA-N 0.000 description 1
- NNIFYECULHSHBH-UHFFFAOYSA-N n-benzylpyridine-2-carboxamide Chemical compound C=1C=CC=NC=1C(=O)NCC1=CC=CC=C1 NNIFYECULHSHBH-UHFFFAOYSA-N 0.000 description 1
- JIAOUYONZMRJJD-UHFFFAOYSA-N n-benzylpyridine-3-carboxamide Chemical compound C=1C=CN=CC=1C(=O)NCC1=CC=CC=C1 JIAOUYONZMRJJD-UHFFFAOYSA-N 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- XJLSEXAGTJCILF-UHFFFAOYSA-N nipecotic acid Chemical compound OC(=O)C1CCCNC1 XJLSEXAGTJCILF-UHFFFAOYSA-N 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 229960003274 paramethadione Drugs 0.000 description 1
- 229960003396 phenacemide Drugs 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- OMOMUFTZPTXCHP-UHFFFAOYSA-N valpromide Chemical compound CCCC(C(N)=O)CCC OMOMUFTZPTXCHP-UHFFFAOYSA-N 0.000 description 1
- 229960001930 valpromide Drugs 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/06—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C07D233/61—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms not forming part of a nitro radical, attached to ring nitrogen atoms
Abstract
:
Anti-tuberculosis, anticonvulsant, anti-inflammatory, insecticidal, antifungal,
analgesic, and anticancer effects have all been linked to amide derivatives. Morpholine
derivatives have antimicrobial action across a broad spectrum, including anthelmintic,
bactericidal, and insecticidal properties. They're also used as an intermediary in the
production of medicinal drugs. A variety of biological activity is produced when amides are
conjugated with different aliphatic, aromatic, and heterocyclic rings. The interaction of a
substituted acid group (-COOH) with various substituted amines produces amide derivatives
extremely quickly. The suitable synthesis method was used to make a variety of amino acid
amide derivatives. IR, IH-NMR, 1C-NMR, and mass spectrum investigations were used to
describe these amide derivatives. Anticonvulsant action was tested on all of the produced
substances.
Description
Synthesis of some amino acid amide derivatives as Potential Anticonvulsant Agent
Background:
Epilepsy, which is caused by a sudden burst of aberrant electrical discharges, is one of
the most prevalent neurological illnesses of the brain. In affluent countries, the cumulative
incidence of epilepsy, or the total number of people who have multiple fits over a long period of
time, is around 5%. According to reports, the number of people suffering from epilepsy is
growing every day around the world. Valpromide, phenacemide, levetiracetam, betamide,
felbamate, paramethadione, and gabapentin are among the active medications available on the
market. Despite the best use of existing antiepileptic medications (AEDs), more than 20% of the
world's epileptic population is dissatisfied with the available AEDs. However, all anticonvulsant
drugs now on the market have dose-related toxicity and idiosyncratic adverse effects. As a result,
medicinal chemistry is investigating the hunt for high activity with low toxicity. Antipsychotic,
analgesic, anticonvulsant, antidepressant, and other CNS effects have been demonstrated for
amino and its derivatives. According to a thorough literature review, the amide group is a
significant pharmacophore in several anticonvulsants. As illustrated in Figure 1, several of the
active compounds have anilide and benzyl nuclei in their structures. Ameltolide, lacosamide,
isoxazolecarboxmides, N-benzyl-2-(benzylamino)-4-hydroxybutanamide, and functionalized
amino ketones are examples of anticonvulsant medicines derived from the combination of the
above functional groups.
In the search for novel excitatory amino acid receptor antagonists with anticonvulsant
efficacy, a variety of aromatic amides of aromatic and heterocyclic acids have been produced.
Benzylamides were shown to be more active than other amides in general. The most efficient
amides of acids, on the other hand, were picolinic, nicotinic, isonicotinic, nipecotic, and
isonipecotic. Picolinic acid benzylamide (Pic-BZA, PI against MES > 28.0) and nicotinic acid
benzylamide (Na-BZA, PI against MES = 4.70) were shown to be the most effective
anticonvulsants.
Some derivatives of those compounds with both rings replaced were created, produced,
and tested pharmacologically. Picolinic acid 2-fluorobenzylamide (Pic-2-F-BZA, PI against
MES = 3.40) (3) and nicotinic acid benzylamide Noxide (Nic-O-BZA, PI against MES 5.6)
ranked first and second, respectively. Figure 2 shows a variety of antiepileptic medicines that
contain amides.
Summary:
The embodiments herein and the various features and advantageous details thereof are explained
more fully with reference to the non-limiting embodiments that are illustrated in the
accompanying drawings and detailed in the following description. Descriptions of well-known
components and processing techniques are omitted so as to not unnecessarily obscure the
embodiments herein. The examples used herein are intended merely to facilitate an
understanding of ways in which the embodiments herein may be practiced and to further enable those of skill in the art to practice the embodiments herein. Accordingly, the examples should not be construed as limiting the scope of the embodiments herein.
Throughout this specification and the claims which follow, unless the context requires otherwise,
the word "comprise", and variations such as "comprises" and "comprising", will be understood
to imply the inclusion of a stated integer or step or group of integers or steps but not the
exclusion of any other integer or step or group of integers or steps.
As used herein, the singular forms "a", "an", "the" include plural referents unless the context
clearly dictates otherwise. Further, the terms "like", "as such", "for example", "including" are
meant to introduce examples which further clarify more general subject matter, and should be
contemplated for the persons skilled in the art to understand the subject matter. Although this
invention has been described in conjunction with the exemplary embodiments' below, it is
evident that many alternatives, modifications, and variations will be apparent to those skilled in
the art. Accordingly, the exemplary embodiments of the invention as set forth above are intended
to be illustrative and not limiting. Various changes may be made without departing from the
spirit and scope of the invention.
Method of Preparation:
Synthetic scheme:
0
CHOH\ 11 NH + CH 3COO-CH 2 - NH 2 C lHON-C-CH2-NH2 Reflux
piperidine aminomethyl acetate 2-amino-1-(piperidin-i-yl)ethanone 1 2 la
CHSOH 10 0 NH + CH 3COO- CH 2 - NH2 o N- C--CH 2 - NH 2 Reflux 2
morpholine aminomethyl acetate 2-amino-I-morpholinoethanone 3 2 3a
0
NH + CH 3COO-CH 2 - NH 2 C 2 H-IH N- C- CH 2 - NH 2
pyrrolidine aminomethyl acetate 2-amino-I-(pyrrolidin-I-yl)ethanone 4 2 4a
-N0
C"HOH~ 11 C 2 H + CH 3COO-CH 2 - NH 2 Reflux N -CH2- NH2
H IH-imidazole aminomethyl acetate 2-amino-i-(iH-imidazol-1-yl)ethanone 5 25a
+ - __ 9 HSO ~ .N 0j N + CH 3 COO- CH 2 - NH 2 C ow N- - CH 2- NH 2 N H IH-pyrazole aminomethyl acetate 2-amino-1-(iH-pyrazol-i-yl)ethanone 6 2 6a
General procedure for synthesis of Glycine ester (Aminomethyl acetate):
The Fischer-Speier method was used to make esterified amino acid. 0.5 gm of amino acid
(glycine) was dissolved in 10 mL of methanol and refluxed for 5 hours in this procedure.
Following the completion of the reaction, a high yield of the ester is achieved by passing steam
of dry hydrogen chloride gas. Since Fischer discovered that 5% hydrogen chloride in the reaction
mixture enabled effective esterification, the production of hydrogen chloride is protonating and
catalytic.
General procedure for synthesis of amidefrom N- containing heterocyclic compounds:
The synthesis of various amide derivatives from N-containing heterocyclic compounds
with at least one hydrogen atom is a one-step reaction in which an equimolar (0.1 mol) quantity
of various N-containing compounds with amino acid ester (glycine ester) was placed in a round
bottom flask and dissolved in ethanol, then the reaction mixture was refluxed for 5-6 hours. Solid
crystal was obtained after the reaction was completed. TLC was used to investigate the produced
chemical utilizing a solvent solution of Ethanol: water (7:3). The solid crystal was then
recrystallized using ethanol (95 percent). Physical and spectral studies were used to characterize
all of the produced substances, as shown in Tables 1 and 2.
Screening for anticonvulsant activity:
Study of anticonvulsant activity of Amino acid amide derivatives against MES (Maximal electro
shock) induced convulsion in rat.
Adult Wistar albino rats weighing 100-150 grammes were kept in microloan boxes with a regular
laboratory meal and free access to water. The animals were weighed and numbered. They were divided into ten groups, each with six rats: a) a control group, b) a group for the standard drug
Phenytoin, and c) additional groups for test compounds. To make a suspension of the test
chemical, 100 mg was mixed with 1 percent CMC solution (10 mL) to yield a dosage of 10
mg/mL.
An ear electrode was inserted on the ears of rats in the control group, and a 150 mA
current was applied for 0.2 seconds. A normal reaction was reported on test animals in the
control group after examining the result of an anticonvulsant effect. The standard group received
mg/kg of phenytoin given intraperitoneally. The test substances were given intraperitoneally
to the other group in the same way. Because the medicines are insoluble in water, CMC was used
to prepare the test compounds in suspension. The animals were treated to electrical convulsions
at the end of one hour. All of the animals recovered quickly after the experiment, and they were
maintained in a separate cage with proper care under the watch of an expert. The length of time it
took for various responses was recorded. Table 3 shows the results of the tests.
Amino acid amide derivatives were produced in a sequence. All of the substances tested
showed protection against the MES test, indicating that they can prevent seizure spread. In a
MES-induced convulsion paradigm, the described produced compounds delayed the onset and
shortened the duration of convulsions. The results in Table 3 demonstrate that amino acid amide
derivatives (la, 4a, and 6a) have highly significant activity (p 0.001), while compound 5a has
medium significant activity (p 0.01), and compound 3a has non-significant activity.
Many modifications will be apparent to those skilled in the art without departing from the scope
of the present invention as hereinbefore described with reference to the accompanying drawings.
The reference in this specification to any prior art publication (or information derived from it), or
to any matter which is known, is not, and should not be taken as an acknowledgement or admission or any form of suggestion that the prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of Endeavour to which this specification relates.
The foregoing descriptions of exemplary embodiments of the present disclosure have been
presented for purposes of illustration and description. They are not intended to be exhaustive or
to limit the disclosure to the precise forms disclosed, and obviously many modifications and
variations are possible in light of the above teaching. The exemplary embodiments were chosen
and described in order to best explain the principles of the disclosure and its practical
application, to thereby enable others skilled in the art to best utilize the disclosure and various
embodiments with various modifications as are suited to the particular use contemplated. It is
understood that various omissions, substitutions of equivalents are contemplated as circumstance
may suggest or render expedient but is intended to cover the application or implementation
without departing from the spirit or scope of the claims of the present disclosure.
Claims (4)
1) Herein we claim synthesis of some amino acid amide derivatives as Potential
Anticonvulsant Agent.
2) Compounds claimed in 1 have potential anticonvulsant activity due to novel
mechanism of action of synthesized compounds.
3) The synthesized compounds claimed in 1 have a simple pharmacokinetic profile
and we observe no interactions with existing drugs.
4) The synthesized compounds claimed in 1 have low toxicity and a wide therapeutic
window; and the synthesized compounds are inexpensive.
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| Application Number | Priority Date | Filing Date | Title |
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| AU2021105523A AU2021105523A4 (en) | 2021-08-15 | 2021-08-15 | Synthesis of some amino acid amide derivatives as potential anticonvulsant agent |
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| Publication Number | Publication Date |
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| AU2021105523A4 true AU2021105523A4 (en) | 2021-11-18 |
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ID=78513918
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| AU2021105523A Ceased AU2021105523A4 (en) | 2021-08-15 | 2021-08-15 | Synthesis of some amino acid amide derivatives as potential anticonvulsant agent |
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| Country | Link |
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| AU (1) | AU2021105523A4 (en) |
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