DE2364129A1 - Pharmazeutisch wertvolle neue 1,2,4oxadiazolyl-essigsaeure-derivate und verfahren zu ihrer herstellung und ihre verwendung - Google Patents
Pharmazeutisch wertvolle neue 1,2,4oxadiazolyl-essigsaeure-derivate und verfahren zu ihrer herstellung und ihre verwendungInfo
- Publication number
- DE2364129A1 DE2364129A1 DE2364129A DE2364129A DE2364129A1 DE 2364129 A1 DE2364129 A1 DE 2364129A1 DE 2364129 A DE2364129 A DE 2364129A DE 2364129 A DE2364129 A DE 2364129A DE 2364129 A1 DE2364129 A1 DE 2364129A1
- Authority
- DE
- Germany
- Prior art keywords
- group
- oxadiazol
- alkyl
- acid
- phenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 238000000034 method Methods 0.000 title claims description 71
- 238000004519 manufacturing process Methods 0.000 title claims description 23
- WBDQZHONDVMBJO-UHFFFAOYSA-N 2-(1,2,4-oxadiazol-3-yl)acetic acid Chemical class OC(=O)CC=1N=CON=1 WBDQZHONDVMBJO-UHFFFAOYSA-N 0.000 title claims description 9
- -1 isopropyl-j Chemical group 0.000 claims description 134
- 150000001875 compounds Chemical class 0.000 claims description 98
- 239000000203 mixture Substances 0.000 claims description 98
- 125000000217 alkyl group Chemical group 0.000 claims description 96
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 93
- 239000002253 acid Substances 0.000 claims description 91
- 239000000047 product Substances 0.000 claims description 76
- 238000006243 chemical reaction Methods 0.000 claims description 75
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 74
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical group CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 63
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 56
- 125000001424 substituent group Chemical group 0.000 claims description 48
- 238000002360 preparation method Methods 0.000 claims description 45
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 43
- 150000002148 esters Chemical class 0.000 claims description 31
- 229910052757 nitrogen Inorganic materials 0.000 claims description 29
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 28
- 150000007513 acids Chemical class 0.000 claims description 26
- 125000003545 alkoxy group Chemical group 0.000 claims description 26
- YGBFLZPYDUKSPT-MRVPVSSYSA-N cephalosporanic acid Chemical class S1CC(COC(=O)C)=C(C(O)=O)N2C(=O)C[C@H]21 YGBFLZPYDUKSPT-MRVPVSSYSA-N 0.000 claims description 25
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 24
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 24
- RBKMMJSQKNKNEV-RITPCOANSA-N penicillanic acid Chemical compound OC(=O)[C@H]1C(C)(C)S[C@@H]2CC(=O)N21 RBKMMJSQKNKNEV-RITPCOANSA-N 0.000 claims description 24
- 239000012948 isocyanate Substances 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 23
- 150000002513 isocyanates Chemical class 0.000 claims description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 21
- SPLXTCXODDVKKW-UHFFFAOYSA-N 2-(3-methyl-1,2,4-oxadiazol-5-yl)acetic acid Chemical compound CC1=NOC(CC(O)=O)=N1 SPLXTCXODDVKKW-UHFFFAOYSA-N 0.000 claims description 20
- 150000001408 amides Chemical class 0.000 claims description 20
- 239000007858 starting material Substances 0.000 claims description 20
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 19
- 125000000623 heterocyclic group Chemical group 0.000 claims description 19
- 229910052708 sodium Inorganic materials 0.000 claims description 19
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 18
- 229910052801 chlorine Inorganic materials 0.000 claims description 18
- 239000011734 sodium Substances 0.000 claims description 18
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 17
- 125000003118 aryl group Chemical group 0.000 claims description 17
- 229910052744 lithium Inorganic materials 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 16
- 239000003054 catalyst Substances 0.000 claims description 15
- 239000003153 chemical reaction reagent Substances 0.000 claims description 13
- 229910052731 fluorine Inorganic materials 0.000 claims description 13
- 125000001153 fluoro group Chemical group F* 0.000 claims description 13
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 claims description 13
- 239000003795 chemical substances by application Substances 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 229910052751 metal Inorganic materials 0.000 claims description 12
- 239000002184 metal Substances 0.000 claims description 12
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 11
- 150000001412 amines Chemical class 0.000 claims description 10
- 125000003277 amino group Chemical group 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- 125000004429 atom Chemical group 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 239000000460 chlorine Substances 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 9
- PXSGMGFLCWXLJN-UHFFFAOYSA-N 2-(5-methyl-1,2,4-oxadiazol-3-yl)acetic acid Chemical compound CC1=NC(CC(O)=O)=NO1 PXSGMGFLCWXLJN-UHFFFAOYSA-N 0.000 claims description 8
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 8
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 8
- NGHVIOIJCVXTGV-ALEPSDHESA-N 6-aminopenicillanic acid Chemical compound [O-]C(=O)[C@H]1C(C)(C)S[C@@H]2[C@H]([NH3+])C(=O)N21 NGHVIOIJCVXTGV-ALEPSDHESA-N 0.000 claims description 7
- XAKBSHICSHRJCL-UHFFFAOYSA-N [CH2]C(=O)C1=CC=CC=C1 Chemical compound [CH2]C(=O)C1=CC=CC=C1 XAKBSHICSHRJCL-UHFFFAOYSA-N 0.000 claims description 7
- 125000004423 acyloxy group Chemical group 0.000 claims description 7
- 150000008064 anhydrides Chemical class 0.000 claims description 7
- 150000003931 anilides Chemical class 0.000 claims description 7
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 7
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 7
- 125000004185 ester group Chemical group 0.000 claims description 7
- 239000013067 intermediate product Substances 0.000 claims description 7
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 7
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 7
- 238000005406 washing Methods 0.000 claims description 7
- NGHVIOIJCVXTGV-UHFFFAOYSA-N 6beta-amino-penicillanic acid Natural products OC(=O)C1C(C)(C)SC2C(N)C(=O)N21 NGHVIOIJCVXTGV-UHFFFAOYSA-N 0.000 claims description 6
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 6
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 238000011065 in-situ storage Methods 0.000 claims description 6
- 239000002609 medium Substances 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 5
- GIIIZOIAVVQNOF-UHFFFAOYSA-N 2-[3-(2,4,6-trimethylphenyl)-1,2,4-oxadiazol-5-yl]acetic acid Chemical compound CC1=CC(C)=CC(C)=C1C1=NOC(CC(O)=O)=N1 GIIIZOIAVVQNOF-UHFFFAOYSA-N 0.000 claims description 5
- 150000008065 acid anhydrides Chemical class 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 230000000844 anti-bacterial effect Effects 0.000 claims description 5
- 238000003763 carbonization Methods 0.000 claims description 5
- 239000000543 intermediate Substances 0.000 claims description 5
- 238000001465 metallisation Methods 0.000 claims description 5
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 5
- 150000002825 nitriles Chemical class 0.000 claims description 5
- 150000002902 organometallic compounds Chemical class 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- FZERHIULMFGESH-UHFFFAOYSA-N N-phenylacetamide Chemical compound CC(=O)NC1=CC=CC=C1 FZERHIULMFGESH-UHFFFAOYSA-N 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- 150000001340 alkali metals Chemical class 0.000 claims description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 4
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 4
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 4
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims description 4
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical group 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 4
- 230000000269 nucleophilic effect Effects 0.000 claims description 4
- 150000007530 organic bases Chemical class 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000006239 protecting group Chemical group 0.000 claims description 4
- 150000003254 radicals Chemical class 0.000 claims description 4
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 4
- 125000005307 thiatriazolyl group Chemical group S1N=NN=C1* 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 125000001425 triazolyl group Chemical group 0.000 claims description 4
- CFGDUGSIBUXRMR-UHFFFAOYSA-N 1,2-dihydropyrrol-2-ide Chemical compound C=1C=[C-]NC=1 CFGDUGSIBUXRMR-UHFFFAOYSA-N 0.000 claims description 3
- UOFCMZQYBMRUDL-UHFFFAOYSA-N 2-(3-benzyl-1,2,4-oxadiazol-5-yl)acetic acid Chemical compound O1C(CC(=O)O)=NC(CC=2C=CC=CC=2)=N1 UOFCMZQYBMRUDL-UHFFFAOYSA-N 0.000 claims description 3
- KENPOHOXFDQEPU-UHFFFAOYSA-N 2-(3-ethyl-1,2,4-oxadiazol-5-yl)propanoic acid Chemical compound CCC1=NOC(C(C)C(O)=O)=N1 KENPOHOXFDQEPU-UHFFFAOYSA-N 0.000 claims description 3
- ZGEQHSPJXNZGSY-UHFFFAOYSA-N 2-[3-(methoxymethyl)-1,2,4-oxadiazol-5-yl]acetic acid Chemical compound COCC1=NOC(CC(O)=O)=N1 ZGEQHSPJXNZGSY-UHFFFAOYSA-N 0.000 claims description 3
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 claims description 3
- HCXJFMDOHDNDCC-UHFFFAOYSA-N 5-$l^{1}-oxidanyl-3,4-dihydropyrrol-2-one Chemical group O=C1CCC(=O)[N]1 HCXJFMDOHDNDCC-UHFFFAOYSA-N 0.000 claims description 3
- 208000035143 Bacterial infection Diseases 0.000 claims description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical group [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 3
- 241001465754 Metazoa Species 0.000 claims description 3
- 229960001413 acetanilide Drugs 0.000 claims description 3
- 150000001242 acetic acid derivatives Chemical class 0.000 claims description 3
- 150000001540 azides Chemical class 0.000 claims description 3
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 3
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 150000001718 carbodiimides Chemical class 0.000 claims description 3
- 150000001768 cations Chemical class 0.000 claims description 3
- 125000002720 diazolyl group Chemical group 0.000 claims description 3
- 229910052749 magnesium Inorganic materials 0.000 claims description 3
- WWTDLWAXEOSRIL-UHFFFAOYSA-N methyl 2-(3-methyl-1,2,4-oxadiazol-5-yl)acetate Chemical compound COC(=O)CC1=NC(C)=NO1 WWTDLWAXEOSRIL-UHFFFAOYSA-N 0.000 claims description 3
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 3
- 125000002971 oxazolyl group Chemical group 0.000 claims description 3
- 238000005507 spraying Methods 0.000 claims description 3
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- 150000007970 thio esters Chemical class 0.000 claims description 3
- 125000006000 trichloroethyl group Chemical group 0.000 claims description 3
- MSUCFOOHNSOKSQ-UHFFFAOYSA-N 2-(3-ethyl-1,2,4-oxadiazol-5-yl)-n-methyl-n-phenylacetamide Chemical compound CCC1=NOC(CC(=O)N(C)C=2C=CC=CC=2)=N1 MSUCFOOHNSOKSQ-UHFFFAOYSA-N 0.000 claims description 2
- YOSHHEJHTHHXPC-UHFFFAOYSA-N 2-(3-methyl-1,2,4-oxadiazol-5-yl)-n-(5-methyl-1,2-oxazol-3-yl)acetamide Chemical compound CC1=NOC(CC(=O)NC2=NOC(C)=C2)=N1 YOSHHEJHTHHXPC-UHFFFAOYSA-N 0.000 claims description 2
- AHKRYBQOKJFZTJ-UHFFFAOYSA-N 2-(5-ethyl-1,2,4-oxadiazol-3-yl)acetic acid Chemical compound CCC1=NC(CC(O)=O)=NO1 AHKRYBQOKJFZTJ-UHFFFAOYSA-N 0.000 claims description 2
- SYRIGWYHNNKJHH-UHFFFAOYSA-N 2-[3-(hydroxymethyl)-1,2,4-oxadiazol-5-yl]acetic acid Chemical compound OCC1=NOC(CC(O)=O)=N1 SYRIGWYHNNKJHH-UHFFFAOYSA-N 0.000 claims description 2
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 2
- GGIXJYHJALOVJF-UHFFFAOYSA-N CC1=NOC(C(C(O)=O)C(C=C2)=CC=C2Br)=N1 Chemical compound CC1=NOC(C(C(O)=O)C(C=C2)=CC=C2Br)=N1 GGIXJYHJALOVJF-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- 125000004849 alkoxymethyl group Chemical group 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 125000003368 amide group Chemical group 0.000 claims description 2
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 2
- SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 claims description 2
- 239000000645 desinfectant Substances 0.000 claims description 2
- 125000004970 halomethyl group Chemical group 0.000 claims description 2
- YXSRUVMVSFGRQE-UHFFFAOYSA-N heptyl 2-(3-methyl-1,2,4-oxadiazol-5-yl)acetate Chemical compound CCCCCCCOC(=O)CC1=NC(C)=NO1 YXSRUVMVSFGRQE-UHFFFAOYSA-N 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 claims description 2
- PKSNWTNICZHQNE-UHFFFAOYSA-N n-phenyl-2-[3-(2,4,6-trimethylphenyl)-1,2,4-oxadiazol-5-yl]acetamide Chemical compound CC1=CC(C)=CC(C)=C1C1=NOC(CC(=O)NC=2C=CC=CC=2)=N1 PKSNWTNICZHQNE-UHFFFAOYSA-N 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 125000005544 phthalimido group Chemical group 0.000 claims description 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 4
- 125000000842 isoxazolyl group Chemical group 0.000 claims 3
- 125000004076 pyridyl group Chemical group 0.000 claims 3
- 150000004820 halides Chemical class 0.000 claims 2
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims 2
- HHFYBKKTYYHIPY-AULQQCHISA-N (6R)-3-azido-4-methyl-7-[[2-(5-methyl-1,2,4-oxadiazol-3-yl)acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CC1=NC(=NO1)CC(=O)NC1[C@@H]2N(C(=C(C(S2)C)N=[N+]=[N-])C(=O)O)C1=O HHFYBKKTYYHIPY-AULQQCHISA-N 0.000 claims 1
- BZUFFQRDGZGZGV-UHFFFAOYSA-N 2-(3-ethyl-1,2,4-oxadiazol-5-yl)-n-(1,3-thiazol-2-yl)acetamide Chemical compound CCC1=NOC(CC(=O)NC=2SC=CN=2)=N1 BZUFFQRDGZGZGV-UHFFFAOYSA-N 0.000 claims 1
- YZMYSOVWUBONMM-UHFFFAOYSA-N 2-(5-benzyl-1,2,4-oxadiazol-3-yl)acetic acid Chemical compound OC(=O)CC1=NOC(CC=2C=CC=CC=2)=N1 YZMYSOVWUBONMM-UHFFFAOYSA-N 0.000 claims 1
- FSHPIAFDYKCABV-UHFFFAOYSA-N 2-(5-methyl-1,2,4-oxadiazol-3-yl)acetamide Chemical compound CC1=NC(CC(N)=O)=NO1 FSHPIAFDYKCABV-UHFFFAOYSA-N 0.000 claims 1
- BVUPYGIRWZZRLH-UHFFFAOYSA-N 2-[3-(2,6-dichlorophenyl)-1,2,4-oxadiazol-5-yl]acetic acid Chemical compound O1C(CC(=O)O)=NC(C=2C(=CC=CC=2Cl)Cl)=N1 BVUPYGIRWZZRLH-UHFFFAOYSA-N 0.000 claims 1
- GOLXRNDWAUTYKT-UHFFFAOYSA-N 3-(1H-indol-3-yl)propanoic acid Chemical compound C1=CC=C2C(CCC(=O)O)=CNC2=C1 GOLXRNDWAUTYKT-UHFFFAOYSA-N 0.000 claims 1
- JKFFDCOBRHBUGJ-FFFFSGIJSA-N CC1=NC(=NO1)CC(=O)NC1[C@@H]2N(C(=C(CS2)CN=[N+]=[N-])C(=O)O)C1=O Chemical compound CC1=NC(=NO1)CC(=O)NC1[C@@H]2N(C(=C(CS2)CN=[N+]=[N-])C(=O)O)C1=O JKFFDCOBRHBUGJ-FFFFSGIJSA-N 0.000 claims 1
- 238000005917 acylation reaction Methods 0.000 claims 1
- 125000004935 benzoxazolinyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims 1
- 125000000068 chlorophenyl group Chemical group 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- SEOVTRFCIGRIMH-UHFFFAOYSA-N indole-3-acetic acid Chemical compound C1=CC=C2C(CC(=O)O)=CNC2=C1 SEOVTRFCIGRIMH-UHFFFAOYSA-N 0.000 claims 1
- 150000002736 metal compounds Chemical class 0.000 claims 1
- HJCGNQPNJXPGAT-UHFFFAOYSA-N methyl 2-(5-methyl-1,2,4-oxadiazol-3-yl)acetate Chemical compound COC(=O)CC1=NOC(C)=N1 HJCGNQPNJXPGAT-UHFFFAOYSA-N 0.000 claims 1
- 239000012434 nucleophilic reagent Substances 0.000 claims 1
- NQLVQOSNDJXLKG-UHFFFAOYSA-N prosulfocarb Chemical compound CCCN(CCC)C(=O)SCC1=CC=CC=C1 NQLVQOSNDJXLKG-UHFFFAOYSA-N 0.000 claims 1
- 238000007363 ring formation reaction Methods 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 222
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 218
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 138
- 239000000243 solution Substances 0.000 description 129
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 117
- 239000010410 layer Substances 0.000 description 100
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 86
- 239000011541 reaction mixture Substances 0.000 description 53
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- UIUXUFNYAYAMOE-UHFFFAOYSA-N methylsilane Chemical compound [SiH3]C UIUXUFNYAYAMOE-UHFFFAOYSA-N 0.000 description 1
- 150000002780 morpholines Chemical class 0.000 description 1
- 229940035363 muscle relaxants Drugs 0.000 description 1
- 239000003158 myorelaxant agent Substances 0.000 description 1
- MXSRFTKHLJSHEQ-UHFFFAOYSA-N n-(2-chlorophenyl)-2-(3-methyl-1,2,4-oxadiazol-5-yl)acetamide Chemical compound CC1=NOC(CC(=O)NC=2C(=CC=CC=2)Cl)=N1 MXSRFTKHLJSHEQ-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 150000004866 oxadiazoles Chemical class 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 229940051027 pasteurella multocida Drugs 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 229940056360 penicillin g Drugs 0.000 description 1
- 229940056367 penicillin v Drugs 0.000 description 1
- 229950009506 penicillinase Drugs 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- BPLBGHOLXOTWMN-MBNYWOFBSA-N phenoxymethylpenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)COC1=CC=CC=C1 BPLBGHOLXOTWMN-MBNYWOFBSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 150000003140 primary amides Chemical class 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000006049 ring expansion reaction Methods 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 239000011833 salt mixture Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 125000004436 sodium atom Chemical group 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 230000008022 sublimation Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003511 tertiary amides Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 1
- 150000003557 thiazoles Chemical class 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 150000003952 β-lactams Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Cephalosporin Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB5952472A GB1459392A (en) | 1972-12-22 | 1972-12-22 | Heterocyclic compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2364129A1 true DE2364129A1 (de) | 1974-07-25 |
Family
ID=10483917
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2364129A Withdrawn DE2364129A1 (de) | 1972-12-22 | 1973-12-21 | Pharmazeutisch wertvolle neue 1,2,4oxadiazolyl-essigsaeure-derivate und verfahren zu ihrer herstellung und ihre verwendung |
| DE2365705A Pending DE2365705A1 (de) | 1972-12-22 | 1973-12-21 | Pharmazeutisch wertvolle neue 1,2,4-oxadiazolyl-essigsaeure-derivate und verfahren zu ihrer herstellung und ihre verwendung |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2365705A Pending DE2365705A1 (de) | 1972-12-22 | 1973-12-21 | Pharmazeutisch wertvolle neue 1,2,4-oxadiazolyl-essigsaeure-derivate und verfahren zu ihrer herstellung und ihre verwendung |
Country Status (10)
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3905893A (en) * | 1973-08-22 | 1975-09-16 | Gulf Research Development Co | Plural stage residue hydrodesulfurization process |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1364453A (en) * | 1970-11-06 | 1974-08-21 | Gist Brocades Nv | Penicillanic and cepholosporanic acid derivatives |
-
1972
- 1972-12-22 GB GB5952472A patent/GB1459392A/en not_active Expired
-
1973
- 1973-12-19 FR FR7345508A patent/FR2211232B1/fr not_active Expired
- 1973-12-20 NL NL7317432.A patent/NL162654C/xx active
- 1973-12-21 AT AT1072573A patent/AT344318B/de not_active IP Right Cessation
- 1973-12-21 ES ES421726A patent/ES421726A1/es not_active Expired
- 1973-12-21 BE BE139223A patent/BE809037A/xx unknown
- 1973-12-21 DE DE2364129A patent/DE2364129A1/de not_active Withdrawn
- 1973-12-21 JP JP48143379A patent/JPS4994695A/ja active Pending
- 1973-12-21 DE DE2365705A patent/DE2365705A1/de active Pending
- 1973-12-21 HU HUGI197A patent/HU167924B/hu unknown
-
1974
- 1974-03-06 ES ES423962A patent/ES423962A1/es not_active Expired
- 1974-03-06 ES ES423963A patent/ES423963A1/es not_active Expired
-
1976
- 1976-01-02 FR FR7600026A patent/FR2289171A1/fr not_active Withdrawn
- 1976-10-07 SE SE7611135A patent/SE7611135L/xx unknown
- 1976-10-07 SE SE7611134A patent/SE7611134L/xx unknown
-
1977
- 1977-11-30 JP JP14377377A patent/JPS5377088A/ja active Pending
- 1977-11-30 JP JP14377477A patent/JPS5373565A/ja active Pending
-
1978
- 1978-06-30 NL NL7807076A patent/NL7807076A/xx not_active Application Discontinuation
-
1979
- 1979-07-03 SE SE7905814A patent/SE7905814L/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| BE809037A (fr) | 1974-06-21 |
| ES421726A1 (es) | 1976-04-16 |
| SE7905814L (sv) | 1979-07-03 |
| NL162654C (nl) | 1980-06-16 |
| AT344318B (de) | 1978-07-10 |
| ES423962A1 (es) | 1976-07-01 |
| ATA1072573A (de) | 1977-11-15 |
| JPS5377088A (en) | 1978-07-08 |
| DE2365705A1 (de) | 1976-01-15 |
| ES423963A1 (es) | 1976-07-01 |
| FR2289171A1 (fr) | 1976-05-28 |
| GB1459392A (en) | 1976-12-22 |
| SE7611134L (sv) | 1976-10-07 |
| JPS5373565A (en) | 1978-06-30 |
| NL7807076A (nl) | 1978-10-31 |
| FR2211232B1 (enrdf_load_stackoverflow) | 1978-01-13 |
| FR2211232A1 (enrdf_load_stackoverflow) | 1974-07-19 |
| SE7611135L (sv) | 1976-10-07 |
| HU167924B (enrdf_load_stackoverflow) | 1976-01-28 |
| NL7317432A (enrdf_load_stackoverflow) | 1974-06-25 |
| JPS4994695A (enrdf_load_stackoverflow) | 1974-09-09 |
| NL162654B (nl) | 1980-01-15 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8139 | Disposal/non-payment of the annual fee |