5,654,301
`
`91
`morpholine)acetate, ethyl 2-acetamido-2-(N-anilino )acetate,
`ethyl 2-acetamido-2-(N-(3-pyrazolylamino))acetate, ethyl
`2-acetamido-2-(N-hydroxy amino )acetate, ethyl
`2-acetamido-2-(N-(N-methylhydroxyamino) )acetate. ethyl
`2-acetamido-2-(N-(N.0-dimethylhydroxyamino))acetate, 5
`2-acetamido-N-benzyl-2-aminoacetamide. 2-acetamido-N(cid:173)
`benzy!-2-(methylamino )acetamide. 2-acetamido-N-benzyl-
`2-(ethylamino)acetamide, 2-acetamido-N-benzyl-2-(N(cid:173)
`anilino )acetamide. 2-acetamido-N-benzy l-2(N-(3-
`pyrazolylamino))acetamide. 2-acetamido-N-benzyl-2-(N,N- 10
`dimethylamino)acetamide. 2-acetamido-N-benzyl-2-(N(cid:173)
`hydroxyamino)acetamide, 2-acetamido-N-benzyl-2-(N(cid:173)
`hydroxyamino )acetamide, 2-acetamido-N-benzyl-2-(N2
`-
`phenylhydrazino )acetamide. 2-acetamido-N-benzyl-2-(N2
`-
`benzyloxycarbonylhydrazino )acetamide, 2-acetamido-N- 15
`benzyl-2-phenoxyacetamide, 2-acetamido-N-benzy 1-2-
`(methylmercapto )acetamide, 2-acetamido-N-benzyl-2-
`(ethylmercapto)acetamide. 2-acetamido-N-benzyl-2-(N(cid:173)
`methoxyamino)acetamide. 2-acetamido-N-benzyl-2-(N-(N(cid:173)
`methylhydroxyamino ))acetamide. 2-acetamido-N-benzyl-2- 20
`(N-(N.0-dimethylhydroxyamino))acetamide, 2-acetamido(cid:173)
`N-benzyl-2-(N-isoxazolidino)acetamide, 2-acetamido-N(cid:173)
`benzyl-2-hydroxyacetamide. 2-acetamido-N-benzy 1-2-
`( ethylmercapto )acetamide. 2,2-diacetamido-N(cid:173)
`ben zylacetamide. 2-acetamido-N-benzyl-2- 25
`trifluoracetarnidoacetamide. 2-acetamido-N-benzyl-2-(N .N,
`N-trimethylammonium)acetamide tetrafiuoroborate,
`2-acetamido-N-benzyl-2-(ethylrnercapto)acetamide-S(cid:173)
`oxide, 2-acetamido-N-benzyl-2-(S-ethylmercapto)
`acetarnide-S-oxide. 2-acetamido-N-benzyl-2- 30
`( ethanesulfonyl)acetamide. 2-acetamido-N-benzyl-2-(N ,N,
`N-trimethylammonium)acetamide tetrafiuoroborate,
`2-acetamido-N-benzy 1-2-( 1-pyrrole )acetamide.
`2-acetamido-N-benzy 1-2-( 1-imidazole )acetamide,
`2-acetamido-N-benzyl-2-( 1-pyrazole) acetamide. 35
`2-acetamido-N-benzy 1-2( 1-( 1.2.4-triazole) )acetamide,
`2-acetamido-N-benzyl-2( 1-tetrazole))acetamide,
`a-acetamido-N-benzyl-2-pyridylacetamide. a-acetamido(cid:173)
`N-benzyl-2-pyridyl acetamide N-oxide, a-acetamido-N(cid:173)
`benzyl-2-(S-thiophenoxy)-acetamide, a-acetamido-N- 40
`benzyl-2-(tetrahydrofuran)acetamide, methyl a-acetamido-
`2-methyl-2-furanacetate. a-acetamido-2-methyl-2-
`furanacetic acid, a-acetamido-N-benzyl-2-methyl-2-
`furanacetamide. a-thioacetamido-N-benzyl-2-
`furanacetamide, a-thioacetamido-N-benzyl-2- 45
`furanthioacetamide, a-acetamido-N-(3-pyridinylmethyl)-2-
`furanacetamide, a-acetamido-N-(4-pyridinylmethyl)-2-
`furanacetamide. a-acetamido-N-(l-oxo-3-pyridinylmethyl)
`-2-furanacetamide. a-acetamido-N-( l-oxo-4-
`pyridinylmethyl)-2-furanacetamide. R(-)a-acetamido-N- 50
`( 4-fiuorobenzyl)-2-furanacetamide. R(-)a.-acetamido-N-( 4-
`tri:fi u oro methyl benzy l)-2-furan acetami de, methyl
`[acetamido(benzylcarbamoyl)methyl]carbomate. phenyl
`[ ac eta mi do( benzy le ar bamoy l)methy l] carboma te,
`1-[acetamido(benzylcarbamoyl)methyl]-3-methylurea), 55
`1-[ acetamido(benzylcarbamoyl )metby I ]-3-pheny I urea),
`1-[ ace tamido(be nz y lcarbamoyl) methyl ]-3-
`benzenesulfonylurea), 1-[acetamido(benzylcarbamoyl)
`methyl}-3-methylthiourea). 1-[acetamido(benzylcarbamoyl)
`methylj-3-phenylthiourea), N-[acetamido 60
`(benzylcarbamoy!)methyl]phthalamic acid). 2-acetamido(cid:173)
`N-benzyl-2-(N-succinimidyl)acetamide ), benzyl
`N-[acetamido(benzylcarbamoyl)methyl]malonamate, ethyl
`N-[acetamido(benzylcarbamoyl)methyl]glycinate, benzyl
`N-[acetamido(benzylcarbamoyl)rnethyl]glycinale, 65
`N- [ acetamido(benzylcarbomoyl)methyl]glycine,
`2-acetamide-N-benzy 1-2-( 1-pyrrole )acetamide,
`
`92
`2-acetamido-N-benzyl-2-( 1-pyr az ol e )acetamide,
`2-acetamido-N-benzyl-2-( 1-imidazole )acetamide.
`2-acetamido-N-benzyl-2-( 1-( 1.2,4-triazole) )acetarnide,
`2-acetamido-N-benzyl-2-( 1-tetrazole) )acetamide.
`a-acetamido-N-benzyl-1-( dimethylsulfamoy l)imidazole-4-
`acetamide. a-acetamido-N-benzyl-4-imidazole acetamide,
`a-acetamido-N-benzyl-2-imidazole acetamide,
`a-acetamido-N-benzyl-5-(tetrazole )acetamide,
`a-acetamido-N-benzyl-3-( 1,2,4-triazole )acetamide.
`a.-acetamido-N-benzyl-2-( carboxamide oxime )acetamide.
`a-acetamido-N-benzyl-2-(carboxamide oxime-(0-acetate))(cid:173)
`acetamide. a-acetamido-N-benzyl-3-(1.2,4-oxadiazole)
`acetamide. a-acetamido-N-benzy 1-2-( thioamide)
`acetamide), 2-acetarnido-N-benzyl-2-vinylacetarnide,
`2-acetamido-N-benzyl-2-epoxyacetamide. potassium
`2-acetamido-N-benzylacetamide-2-sulfonate, 2-acetamido-
`4-pentenic acid-N-benzylamide, a-acetamido-N-benzyl-2-
`(2-oxazole)-acetamide, and a-acetamido-N-benzyl-2-(2-
`thiazole)-acetamide.
`23. An anti-convulsant composition comprising an anti(cid:173)
`convulsant effective amount of a compound from any one of
`claims 1-15 and 22 and a pharmaceutical carrier therefor.
`24. An anti-convulsant composition comprising an anti(cid:173)
`convulsant effective amount of a compound from claim 16
`and a pharmaceutical carrier therefor.
`25. An anti-convulsant composition comprising an anti(cid:173)
`convulsant effective amount of a compound from claim 17
`and a pharmaceutical carrier therefor.
`26. An anti-convulsant composition comprising an anti(cid:173)
`convulsant effective amount of a compound from claim 18
`and a pharmaceutical carrier therefor.
`27. An anti-convulsant composition comprising an anti(cid:173)
`convulsant effective amount of a compound of claim 19 and
`a pharmaceutical carrier therefor.
`28. An anti-convulsant composition comprising an anti(cid:173)
`convulsant effective amount of a compound of claim 20 and
`a pharmaceutical carrier therefor.
`29. An anti-convulsant composition comprising an anti(cid:173)
`convulsant effective amount of a compound of claim 21 and
`a pharmaceutical carrier therefor.
`30. A method of treating CNS disorders in an animal
`comprising administering to said animal an anti-convulsant
`effective amount of a compound according to any one of
`claims 1-15 and 22.
`31. A method of treating CNS disorders in an animal
`comprising administering to said animal an anti-convulsant
`effective amount of a compound of claim 16.
`32. A method of treating CNS disorders in an animal
`comprising administering to said animal an anti-convulsant
`effective amount of a compound of claim 17.
`33. A method of treating CNS disorders in an animal
`comprising administering to said animal an anti-convulsant
`effective amount of a compound of claim 18.
`34. A method of treating CNS disorders in an animal
`comprising administering to said animal an anti-convulsant
`effective amount of a compound of claim 19.
`35. A method of treating CNS disorders in an animal
`comprising administering to said animal an anti-convulsant
`effective amount of a compound of claim 20.
`36. A method of treating CNS disorders in an animal
`comprising administering to said animal an anti-convulsant
`effective amount of a compound of claim 21.
`37. The compound according to any one of claims 1, 10.
`12 or 14 wherein n is 1 and R is lower alkyl which is
`unsubstituted or substituted with an electron donating group
`or electron withdrawing group.
`38. The compound according to any one of claims 1. 10,
`12or14 wherein n is 1; R 1 is methyl and R is lower arylalkyl
`
`-48-
`
`

`
`93
`which is unsubstituted or substituted with an electron with(cid:173)
`drawing group or electron donating group.
`39. A compound of the formula
`
`5,654,301
`
`R1
`I
`R-NH(C-CNH).C-R1
`I
`II
`II
`Q RJ
`A
`
`(I) 5
`
`94
`40. The compound according to claim 39 wherein one of
`R2 and R3 is hydrogen and the other is lower alkyl substi(cid:173)
`tuted with an electron donating group.
`41. The compound according to claim 40 wherein one of
`R2 and R3 is alkyl substituted with an electron donating
`group wherein alkyl is methyl. ethyl. propyl. isopropyl.
`butyl, isobutyl, t-butyl, amyl or hexyl.
`42. The compound according to claim 41 wherein one of
`R2 and R3 is methyl substituted with an electron donating
`group.
`43. The compound according to claim 42 wherein the
`electron donating group is lower alkoxy.
`44. The compound according to claim 43 wherein lower
`alkoxy is methoxy.
`45. The compound according to any one of claims 39-44
`15 wherein n is 1.
`46. An anti-convulsant composition comprising an anti(cid:173)
`convulsant effective amount of a compound from any one of
`claim 37-42 and a pharmaceutical carrier therefor.
`47. A method of treating CNS disorders in an animal
`comprising administering to said animal an anti-convulsant
`effective amount of a compound of any one of claims 39-44.
`
`10
`
`20
`
`* * * * *
`
`or the phannaceutically acceptable salts thereof wherein
`R is aryl. aryl lower alkyl. heterocyclic, heterocyclic
`lower alkyl. cycloalkyl or lower cycloalkyl lower alkyl,
`wherein R is unsubstituted or is substituted with at least
`one electron withdrawing group or an electron donating
`group;
`R 1 is hydrogen or lower alkyl and R, is unsubstituted or
`substituted with at least one electron withdrawing
`group or at least one electron donating group;
`A and Q are both 0;
`one of R2 and R3 is hydrogen and the other is lower alkyl
`which is substituted with an electron donating group or
`a electron withdrawing group and n is 1-4.
`
`-49-
`
`

`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`CERTIFICATE OF CORRECTION
`
`PATENT NO.
`DATED
`INVENTOR(S)
`
`: 5,654,301
`: August 5, 1997
`: Harold Kohn, et al.
`
`Page 1 of 5
`
`It is certified that error appears in the above-identified patent and that said Letters Patent is
`hereby corrected as shown below:
`
`Column 34,
`Line 59: "Ch 3 H)" should read -- C 3 H) --
`Line 59: "8.62 Hz" sl)ould read -- 8.62 (d,1=7.7 -(cid:173)
`Line 60: "H," should read -- Hz, --
`
`Column 35,
`Line 15: "form" should read -- formed -(cid:173)
`Line 35: "8.89" should read -- 8.99 -
`
`Column 37,
`Line 53: "a" should read -- 2 -(cid:173)
`Line 60: "or" should read -- of --
`
`Column 38.
`Line 65: "13c" should read -- 13 c --
`
`Column40,
`Line 25: "2.33" should read -- 2.23 -(cid:173)
`Line 25: "425" should read -- 4.25 --
`Line 67: "(M30= I)" should read -- (M+= 1) --
`
`Column 41,
`· Line 25: "2-hydroxyamino" should read -- 2-(N-hydroxyamino) --
`
`Column42,
`Line 55: "{M+ + 100)" should read -- (M+ + 1,100)--
`
`Column 19.
`Line 30: "intraperitoncally" should read -- intraperitoneally --
`
`Column 27,
`Line 45: "16 ° "should read -- 169 ° --
`
`Column28,
`Line 56: "7 .1.7" should read -- 7 .17 --
`
`Column 30,
`Line 37: "63" should read -- 6.3 -(cid:173)
`Line 64: "785" should read -- 735 --
`
`-50-
`
`

`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`CERTIFICATE OF CORRECTION
`
`PATENT NO.
`DA TED
`INVENTOR(S)
`
`: 5,654.301
`: August 5, 1997
`: Harold Kohn, et al.
`
`Page 2 of 5
`
`It is certified that error appears in the above-identified patent and that said Letters Patent is
`hereby corrected as shown below:
`
`Column 31,
`Line 21: "chloroform" should read -- chloroform -(cid:173)
`Line 49: "2.78" should read -- 2.75 --
`
`Column 33,
`Line 16: "{D,L" should read -- {D,L) -(cid:173)
`Line 38: "94:4" should read -- 96:4 -(cid:173)
`Lines 41 & 42: "80" should read -- 8.0 -(cid:173)
`Line 48: "C 3' "should read -- C 6 ' --
`
`Column 34,
`Line 15: "130" should read --139 --
`Line 4 l: "M + I" should read -- M+ + 1 --
`
`Column43,
`Lines 21 & 49: "acetamido" should read -- acetamide -(cid:173)
`Line 59: "1.84"' should read -- 1.84 --
`
`Column44,
`Line 46, "n" should read -- a --
`Line 46: "ethoxyacetamido" should read - ethoxyacetamide -(cid:173)
`Line 65: "acetamido" should read -- acetamide --
`
`Column45,
`Line 18: after "spectrum" insert -- (FD) -(cid:173)
`Line 39: "7.5" should read -- 7.52 --
`Line 56: "73.3" should read -- 7 .33 --
`
`Column46,
`Line 25: "CH 3 Cl 2 ,"should read -- CH 2 Cl2· --
`
`Column49,
`Lines 57-58: "0-methylhydroxyamino" should read -- 0-dimechylhydroxyamino --
`
`Column 50,
`Line 40: "149" should read -- 14.9 --
`
`-51-
`
`

`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`CERTIFICATE OF CORRECTION
`
`PATENT NO.
`DATED
`INVENTOR(S)
`
`: 5,654.301
`: August 5, 1997
`: Harold Kohn, et al.
`
`Page 3 of 5
`
`It is certified that error appears in the above-identified patent and that said Letters Patent is
`hereby corrected as shown below:
`
`Column 51,
`Line 24: "accetamido" should read -- acetamide -(cid:173)
`Line 38: "Dicacetamido" should read -- Diacetamide -(cid:173)
`Line 46: "and-was" should read -- and was --
`
`Column52,
`Line 16: "166.3.9" should read -- 166.39 --
`
`Column54,
`Line 16: "Time" should read -- The --
`
`Column55,
`Line 7: "H" should read -- It --
`
`Column56,
`Line 55: "C 1 "should read -- C 12 --:
`Line 66: "while" should read -- white -- ·
`Line 66: "alter" should read -- after --
`
`Column 58,
`Line 30: "dr" should read -- dt --
`
`Column59,
`Line 62: after "1.89" insert -- (s, -(cid:173)
`Line 63: Delete -- (s, --
`
`Column 60,
`Line 4: "l" should read -- 91 --
`
`Column 61,
`Line 30: "(C2), H" should read-~ CH2 ), --
`
`Coluillll 63,
`Line 38: "add" should read -- acid --
`
`Column 65,
`Line 10: "8.62" should read -- 8.61 --
`Line 21: "arthydride" should read -- anhydride --
`
`-52-
`
`

`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`CERTIFICATE OF CORRECTION
`
`PATENT NO.
`DATED
`INVENTOR(S)
`
`: 5,654.301
`: Augusts, 1997
`: Harold Kohn, et al.
`
`Page4 of 5
`
`It is certified that error appears in the above-identified patent and that said Letters Patent is
`hereby corrected as shown below:
`
`Column 66,
`Line 34: "600" should read -- 670 --
`
`Column67,
`Line 22: "63.72" should read -- 63.22 -(cid:173)
`Line 63: "170.30" should read -- 170.03 -(cid:173)
`Line 66: "N402" should read -- N4 0 2 S --
`
`Column 68,
`Line 9: "while" should read -- white -(cid:173)
`Line 67, "l.80" should read -- 181 --
`
`Column69,
`Line 8: "176.5" should read -- 176.33 --
`Lines 45-46: "Found: C,60.90: C, 61.16; H, 587; N, 1358.H, 5.77; N, 13.35." should
`read-- C, 61.16;H, 5.87; N, 13.58. Found: C, 60.90; H,5.77;N, 13.35. --
`Line 57: ''29o" should read -- 2o --
`
`Column 70,
`Line 41: "2g" should read 2q --
`
`Column 76,
`Line 3: "BF3" should read -- BF3 -(cid:173)
`Line 37, "NHH" should read-- NHH' --
`
`Column 81,
`Line 47: "irnidazo" should read -- irnidazoyl --
`
`Column 82,
`Line 6: "38.0 . 56.0" should read -- 38.0-56.0 --
`
`Column 83,
`Line 15: "CH2 CH6 Hs" should read-- CH2C6 H5 --
`
`Column 84,
`Line 63: "206" should read -- 205 --
`
`Column 86,
`Line 47: "95" should read -- 9.5 --
`
`-53-
`
`

`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`CERTIFICATE OF CORRECTION
`
`PATENT NO.
`DATED
`INVENTOR(S)
`
`: 5,654.301
`: August 5, 1997
`: Harold Kohn, et al.
`
`Page 5 of 5
`
`It is certified that error appears in the above-identified patent and that said Letters Patent is
`hereby corrected as shown below:
`
`Column 88, claim 1:
`Line 24, "SO / 1
`" should read -- S03 --
`
`Column 89, claim 10:
`Line 26, "O" should read -- A and Q --
`
`Column 90, claim 14:
`Line 28, "R 1" should read -- R2 --
`
`Column 90, claim 17:
`Line 46, "1-1 Swherein" should read -- 1-16 wherein --
`
`Column 90, claim 20:
`Line 60, "1-15" should read -- I -19 --
`
`Signed and Sealed this
`
`Twenty-seventh Day of November, 2001
`
`Alt est:
`
`Anesting Officer
`
`NICHOLAS P. GODICI
`Acting Director of the United States Patent and Trademark Office
`
`-54-