NO301472B1 - Nye 7-substituerte-9-substituert amino-6-demetyl-6-deoksytetracykliner, og preparater derav - Google Patents

Nye 7-substituerte-9-substituert amino-6-demetyl-6-deoksytetracykliner, og preparater derav Download PDF

Info

Publication number: NO301472B1
Authority: NO; Norway
Prior art keywords: amino; dimethylamino; dioxo; bis; tetrahydroxy
Prior art date: 1991-10-04

Application number

NO923857A

Other languages

English (en)

Norwegian (no)

Other versions

NO923857L (no

NO923857D0 (no

Inventor

Joseph J Hlavka

Phaik-Eng Sum

Yakov Gluzman

Ving J Lee

Adma A Ross

Original Assignee

American Cyanamid Co

Priority date (The priority date 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 date listed.)

1991-10-04

Filing date

1992-10-02

Publication date

1997-11-03

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=25092264&utm_source=***_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=NO301472(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1992-10-02 Application filed by American Cyanamid Co filed Critical American Cyanamid Co

1992-10-02 Publication of NO923857D0 publication Critical patent/NO923857D0/no

1993-04-05 Publication of NO923857L publication Critical patent/NO923857L/no

1997-11-03 Publication of NO301472B1 publication Critical patent/NO301472B1/no

Links

238000002360 preparation method Methods 0.000 title claims description 12
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 117
150000001875 compounds Chemical class 0.000 claims abstract description 63
-1 monosubstituted amino Chemical group 0.000 claims description 187
125000000217 alkyl group Chemical group 0.000 claims description 153
229910052739 hydrogen Inorganic materials 0.000 claims description 76
239000001257 hydrogen Substances 0.000 claims description 75
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 60
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 58
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 55
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 52
125000001424 substituent group Chemical group 0.000 claims description 43
229910052736 halogen Inorganic materials 0.000 claims description 42
150000002367 halogens Chemical class 0.000 claims description 42
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 42
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 42
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 41
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 38
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 34
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 32
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 28
125000003118 aryl group Chemical group 0.000 claims description 28
125000000623 heterocyclic group Chemical group 0.000 claims description 28
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 27
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 26
150000003839 salts Chemical class 0.000 claims description 24
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 23
125000003282 alkyl amino group Chemical group 0.000 claims description 23
150000002431 hydrogen Chemical class 0.000 claims description 20
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 19
125000004093 cyano group Chemical group *C#N 0.000 claims description 18
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 16
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
125000002252 acyl group Chemical group 0.000 claims description 14
125000003435 aroyl group Chemical group 0.000 claims description 14
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 13
229910052760 oxygen Inorganic materials 0.000 claims description 13
229910052717 sulfur Inorganic materials 0.000 claims description 13
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 12
125000003545 alkoxy group Chemical group 0.000 claims description 12
125000002344 aminooxy group Chemical group [H]N([H])O[*] 0.000 claims description 12
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
125000003396 thiol group Chemical class [H]S* 0.000 claims description 12
125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 claims description 11
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 11
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 10
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 10
239000000460 chlorine Substances 0.000 claims description 10
229910052801 chlorine Inorganic materials 0.000 claims description 10
125000005843 halogen group Chemical group 0.000 claims description 10
125000005842 heteroatom Chemical group 0.000 claims description 10
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 10
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 9
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 9
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 9
229910052794 bromium Inorganic materials 0.000 claims description 9
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
125000002102 aryl alkyloxo group Chemical group 0.000 claims description 8
125000004744 butyloxycarbonyl group Chemical group 0.000 claims description 8
125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 8
125000000753 cycloalkyl group Chemical group 0.000 claims description 8
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 8
229910052751 metal Chemical class 0.000 claims description 8
239000002184 metal Chemical class 0.000 claims description 8
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 8
125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 claims description 8
125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 8
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 8
125000004742 propyloxycarbonyl group Chemical group 0.000 claims description 8
229910052711 selenium Inorganic materials 0.000 claims description 8
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 7
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 7
125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
125000003710 aryl alkyl group Chemical group 0.000 claims description 6
239000000039 congener Substances 0.000 claims description 6
125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 6
125000005252 haloacyl group Chemical group 0.000 claims description 6
125000002757 morpholinyl group Chemical group 0.000 claims description 6
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 5
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 5
229910052731 fluorine Inorganic materials 0.000 claims description 5
239000011737 fluorine Substances 0.000 claims description 5
239000012458 free base Substances 0.000 claims description 5
229910052740 iodine Inorganic materials 0.000 claims description 5
239000011630 iodine Substances 0.000 claims description 5
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
239000000825 pharmaceutical preparation Substances 0.000 claims description 5
125000005918 1,2-dimethylbutyl group Chemical group 0.000 claims description 4
QWCKQJZIFLGMSD-UHFFFAOYSA-N 2-Aminobutanoic acid Natural products CCC(N)C(O)=O QWCKQJZIFLGMSD-UHFFFAOYSA-N 0.000 claims description 4
125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 claims description 4
125000005916 2-methylpentyl group Chemical group 0.000 claims description 4
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 4
QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 claims description 4
QWCKQJZIFLGMSD-GSVOUGTGSA-N D-alpha-aminobutyric acid Chemical compound CC[C@@H](N)C(O)=O QWCKQJZIFLGMSD-GSVOUGTGSA-N 0.000 claims description 4
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 4
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 4
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
125000004423 acyloxy group Chemical group 0.000 claims description 4
125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 4
125000004659 aryl alkyl thio group Chemical group 0.000 claims description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
125000005605 benzo group Chemical group 0.000 claims description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
239000011575 calcium Substances 0.000 claims description 4
229910052791 calcium Inorganic materials 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
229960002449 glycine Drugs 0.000 claims description 4
235000013905 glycine and its sodium salt Nutrition 0.000 claims description 4
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 4
GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 claims description 4
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims description 4
230000003287 optical effect Effects 0.000 claims description 4
239000001301 oxygen Substances 0.000 claims description 4
ONIBWKKTOPOVIA-UHFFFAOYSA-M prolinate Chemical compound [O-]C(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-M 0.000 claims description 4
125000006628 propoxycarbonylamino group Chemical group 0.000 claims description 4
229920006395 saturated elastomer Chemical group 0.000 claims description 4
239000011593 sulfur Substances 0.000 claims description 4
125000006633 tert-butoxycarbonylamino group Chemical group 0.000 claims description 4
LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 claims description 4
125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 4
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 4
235000001014 amino acid Nutrition 0.000 claims description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims description 3
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 3
229910052742 iron Inorganic materials 0.000 claims description 3
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 3
150000003467 sulfuric acid derivatives Chemical class 0.000 claims description 3
125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims description 2
125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
UTQNKKSJPHTPBS-UHFFFAOYSA-N 2,2,2-trichloroethanone Chemical group ClC(Cl)(Cl)[C]=O UTQNKKSJPHTPBS-UHFFFAOYSA-N 0.000 claims description 2
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 2
AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 claims description 2
XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 2
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 2
PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 claims description 2
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 2
150000008052 alkyl sulfonates Chemical class 0.000 claims description 2
125000004414 alkyl thio group Chemical group 0.000 claims description 2
239000004411 aluminium Substances 0.000 claims description 2
229910052782 aluminium Inorganic materials 0.000 claims description 2
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 2
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 2
125000001691 aryl alkyl amino group Chemical group 0.000 claims description 2
125000005228 aryl sulfonate group Chemical group 0.000 claims description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
125000004181 carboxyalkyl group Chemical group 0.000 claims description 2
235000018417 cysteine Nutrition 0.000 claims description 2
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 2
125000000350 glycoloyl group Chemical group O=C([*])C([H])([H])O[H] 0.000 claims description 2
239000011777 magnesium Substances 0.000 claims description 2
229910052749 magnesium Inorganic materials 0.000 claims description 2
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 2
239000011572 manganese Substances 0.000 claims description 2
229910052748 manganese Inorganic materials 0.000 claims description 2
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 2
125000004706 n-propylthio group Chemical group C(CC)S* 0.000 claims description 2
125000004344 phenylpropyl group Chemical group 0.000 claims description 2
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 2
229940095064 tartrate Drugs 0.000 claims description 2
229920002554 vinyl polymer Polymers 0.000 claims description 2
KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims 4
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims 3
125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 2
125000002981 3-(trifluoromethyl)benzoyl group Chemical group FC(C=1C=C(C(=O)*)C=CC1)(F)F 0.000 claims 2
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims 2
150000002148 esters Chemical class 0.000 claims 2
125000004494 ethyl ester group Chemical group 0.000 claims 2
KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 claims 2
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 1
125000001999 4-Methoxybenzoyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C(*)=O 0.000 claims 1
ZXFCRFYULUUSDW-UHFFFAOYSA-N C1C2CC3=CC=CC(O)=C3C(=O)C2=C(O)C2(O)C1CC(O)=C(C(=O)N)C2=O Chemical compound C1C2CC3=CC=CC(O)=C3C(=O)C2=C(O)C2(O)C1CC(O)=C(C(=O)N)C2=O ZXFCRFYULUUSDW-UHFFFAOYSA-N 0.000 claims 1
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims 1
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims 1
SOWBFZRMHSNYGE-UHFFFAOYSA-N Monoamide-Oxalic acid Natural products NC(=O)C(O)=O SOWBFZRMHSNYGE-UHFFFAOYSA-N 0.000 claims 1
229910002651 NO3 Inorganic materials 0.000 claims 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims 1
229910019142 PO4 Inorganic materials 0.000 claims 1
RFSXUZYKRDCQTD-UHFFFAOYSA-N S(=O)(=O)(O)O.COC(N)=O Chemical compound S(=O)(=O)(O)O.COC(N)=O RFSXUZYKRDCQTD-UHFFFAOYSA-N 0.000 claims 1
125000005110 aryl thio group Chemical group 0.000 claims 1
125000006309 butyl amino group Chemical group 0.000 claims 1
229910052799 carbon Inorganic materials 0.000 claims 1
125000006311 cyclobutyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
125000006317 cyclopropyl amino group Chemical group 0.000 claims 1
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims 1
125000006125 ethylsulfonyl group Chemical group 0.000 claims 1
125000001245 hexylamino group Chemical group [H]N([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims 1
125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
125000001736 nosyl group Chemical group S(=O)(=O)(C1=CC=C([N+](=O)[O-])C=C1)* 0.000 claims 1
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 claims 1
125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
125000004894 pentylamino group Chemical group C(CCCC)N* 0.000 claims 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 1
239000010452 phosphate Substances 0.000 claims 1
125000006308 propyl amino group Chemical group 0.000 claims 1
238000000034 method Methods 0.000 abstract description 58
239000004098 Tetracycline Substances 0.000 abstract description 40
235000019364 tetracycline Nutrition 0.000 abstract description 35
150000003522 tetracyclines Chemical class 0.000 abstract description 28
229940040944 tetracyclines Drugs 0.000 abstract description 15
230000000694 effects Effects 0.000 abstract description 11
239000000543 intermediate Substances 0.000 abstract description 7
238000001228 spectrum Methods 0.000 abstract description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 147
239000000047 product Substances 0.000 description 119
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 60
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 48
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 46
239000007787 solid Substances 0.000 description 45
239000000243 solution Substances 0.000 description 44
239000000203 mixture Substances 0.000 description 37
229960002180 tetracycline Drugs 0.000 description 25
229930101283 tetracycline Natural products 0.000 description 25
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 24
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
239000011541 reaction mixture Substances 0.000 description 19
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
238000006243 chemical reaction Methods 0.000 description 18
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 17
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 17
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 15
239000000706 filtrate Substances 0.000 description 15
239000001632 sodium acetate Substances 0.000 description 15
235000017281 sodium acetate Nutrition 0.000 description 15
230000014616 translation Effects 0.000 description 15
XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 14
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
101150015970 tetM gene Proteins 0.000 description 14
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical group [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 12
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
230000000844 anti-bacterial effect Effects 0.000 description 11
239000000284 extract Substances 0.000 description 11
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 11
FFTVPQUHLQBXQZ-KVUCHLLUSA-N (4s,4as,5ar,12ar)-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1C2=C(N(C)C)C=CC(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O FFTVPQUHLQBXQZ-KVUCHLLUSA-N 0.000 description 10
230000003115 biocidal effect Effects 0.000 description 10
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
229960004023 minocycline Drugs 0.000 description 10
238000001243 protein synthesis Methods 0.000 description 10
241000894006 Bacteria Species 0.000 description 9
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 9
239000002253 acid Substances 0.000 description 9
239000003054 catalyst Substances 0.000 description 9
GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 9
238000000338 in vitro Methods 0.000 description 9
239000012044 organic layer Substances 0.000 description 9
210000003705 ribosome Anatomy 0.000 description 9
229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
235000017557 sodium bicarbonate Nutrition 0.000 description 9
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 8
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 8
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
230000001580 bacterial effect Effects 0.000 description 8
238000003756 stirring Methods 0.000 description 8
241000588724 Escherichia coli Species 0.000 description 7
238000005481 NMR spectroscopy Methods 0.000 description 7
125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
239000007788 liquid Substances 0.000 description 7
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
241001465754 Metazoa Species 0.000 description 6
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 6
238000001727 in vivo Methods 0.000 description 6
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 6
239000002244 precipitate Substances 0.000 description 6
229910000029 sodium carbonate Inorganic materials 0.000 description 6
VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 6
239000002904 solvent Substances 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 5
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 5
235000019253 formic acid Nutrition 0.000 description 5
229910017604 nitric acid Inorganic materials 0.000 description 5
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
239000003242 anti bacterial agent Substances 0.000 description 4
229910052786 argon Inorganic materials 0.000 description 4
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 4
238000001914 filtration Methods 0.000 description 4
208000015181 infectious disease Diseases 0.000 description 4
230000005764 inhibitory process Effects 0.000 description 4
230000007246 mechanism Effects 0.000 description 4
229940098779 methanesulfonic acid Drugs 0.000 description 4
108090000623 proteins and genes Proteins 0.000 description 4
239000000725 suspension Substances 0.000 description 4
238000012360 testing method Methods 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
239000005909 Kieselgur Substances 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
241000191940 Staphylococcus Species 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
239000000908 ammonium hydroxide Substances 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
230000037396 body weight Effects 0.000 description 3
210000004027 cell Anatomy 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
CYDMQBQPVICBEU-UHFFFAOYSA-N chlorotetracycline Natural products C1=CC(Cl)=C2C(O)(C)C3CC4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O CYDMQBQPVICBEU-UHFFFAOYSA-N 0.000 description 3
229960004475 chlortetracycline Drugs 0.000 description 3
CYDMQBQPVICBEU-XRNKAMNCSA-N chlortetracycline Chemical compound C1=CC(Cl)=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O CYDMQBQPVICBEU-XRNKAMNCSA-N 0.000 description 3
235000019365 chlortetracycline Nutrition 0.000 description 3
201000010099 disease Diseases 0.000 description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
239000006185 dispersion Substances 0.000 description 3
239000010410 layer Substances 0.000 description 3
238000004519 manufacturing process Methods 0.000 description 3
244000005700 microbiome Species 0.000 description 3
229920001223 polyethylene glycol Polymers 0.000 description 3
239000004317 sodium nitrate Substances 0.000 description 3
235000010344 sodium nitrate Nutrition 0.000 description 3
239000000126 substance Substances 0.000 description 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 2
HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 2
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
LRTRXDSAJLSRTG-UHFFFAOYSA-N 4-bromobutanoyl chloride Chemical compound ClC(=O)CCCBr LRTRXDSAJLSRTG-UHFFFAOYSA-N 0.000 description 2
229920001817 Agar Polymers 0.000 description 2
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
239000004099 Chlortetracycline Substances 0.000 description 2
208000035473 Communicable disease Diseases 0.000 description 2
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
241000606790 Haemophilus Species 0.000 description 2
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 description 2
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
108010040201 Polymyxins Proteins 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
241000194017 Streptococcus Species 0.000 description 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
230000009471 action Effects 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
239000000654 additive Substances 0.000 description 2
239000008272 agar Substances 0.000 description 2
230000001476 alcoholic effect Effects 0.000 description 2
150000001299 aldehydes Chemical class 0.000 description 2
229910000147 aluminium phosphate Inorganic materials 0.000 description 2
150000001413 amino acids Chemical class 0.000 description 2
229940040526 anhydrous sodium acetate Drugs 0.000 description 2
229940088710 antibiotic agent Drugs 0.000 description 2
239000002585 base Substances 0.000 description 2
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
239000002775 capsule Substances 0.000 description 2
239000000969 carrier Substances 0.000 description 2
210000000170 cell membrane Anatomy 0.000 description 2
230000001419 dependent effect Effects 0.000 description 2
239000012153 distilled water Substances 0.000 description 2
229940079593 drug Drugs 0.000 description 2
239000003814 drug Substances 0.000 description 2
238000011156 evaluation Methods 0.000 description 2
238000000855 fermentation Methods 0.000 description 2
230000004151 fermentation Effects 0.000 description 2
229940071870 hydroiodic acid Drugs 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
230000000670 limiting effect Effects 0.000 description 2
230000001404 mediated effect Effects 0.000 description 2
229910001960 metal nitrate Inorganic materials 0.000 description 2
WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 2
229930182817 methionine Natural products 0.000 description 2
239000003921 oil Substances 0.000 description 2
235000019198 oils Nutrition 0.000 description 2
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 2
229910003446 platinum oxide Inorganic materials 0.000 description 2
239000011591 potassium Substances 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
239000000843 powder Substances 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
235000018102 proteins Nutrition 0.000 description 2
102000004169 proteins and genes Human genes 0.000 description 2
239000002516 radical scavenger Substances 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000007858 starting material Substances 0.000 description 2
238000003860 storage Methods 0.000 description 2
239000000375 suspending agent Substances 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Chemical compound O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 2
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 2
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 2
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
238000005406 washing Methods 0.000 description 2
HZDNNJABYXNPPV-UHFFFAOYSA-N (2-chloro-2-oxoethyl) acetate Chemical compound CC(=O)OCC(Cl)=O HZDNNJABYXNPPV-UHFFFAOYSA-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
RPAJSBKBKSSMLJ-DFWYDOINSA-N (2s)-2-aminopentanedioic acid;hydrochloride Chemical class Cl.OC(=O)[C@@H](N)CCC(O)=O RPAJSBKBKSSMLJ-DFWYDOINSA-N 0.000 description 1
MTCQOMXDZUULRV-ADOAZJKMSA-N (4s,4as,5ar,12ar)-4-(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical group C1C2=CC=CC(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O MTCQOMXDZUULRV-ADOAZJKMSA-N 0.000 description 1
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
HHCLNZBCCQDVOQ-UHFFFAOYSA-N 1-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]pyrazol-3-yl]methyl]piperazin-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(N1CC2=C(CC1)NN=N2)=O)CN1C(CNCC1)=O HHCLNZBCCQDVOQ-UHFFFAOYSA-N 0.000 description 1
QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 description 1
AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 1
238000005160 1H NMR spectroscopy Methods 0.000 description 1
VQVBNWUUKLBHGI-UHFFFAOYSA-N 2-(4-bromophenyl)acetyl chloride Chemical compound ClC(=O)CC1=CC=C(Br)C=C1 VQVBNWUUKLBHGI-UHFFFAOYSA-N 0.000 description 1
BUZJPENZWLUHJD-UHFFFAOYSA-N 2-(benzylamino)acetic acid;hydrochloride Chemical compound Cl.OC(=O)CNCC1=CC=CC=C1 BUZJPENZWLUHJD-UHFFFAOYSA-N 0.000 description 1
FKASAVXZZLJTNX-UHFFFAOYSA-N 2-(dimethylamino)acetic acid;hydrochloride Chemical compound [Cl-].C[NH+](C)CC(O)=O FKASAVXZZLJTNX-UHFFFAOYSA-N 0.000 description 1
MVAXDKDOPWPFML-UHFFFAOYSA-N 2-(dimethylamino)acetyl chloride;hydrochloride Chemical compound [Cl-].C[NH+](C)CC(Cl)=O MVAXDKDOPWPFML-UHFFFAOYSA-N 0.000 description 1
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
LSTRKXWIZZZYAS-UHFFFAOYSA-N 2-bromoacetyl bromide Chemical compound BrCC(Br)=O LSTRKXWIZZZYAS-UHFFFAOYSA-N 0.000 description 1
SYZRZLUNWVNNNV-UHFFFAOYSA-N 2-bromoacetyl chloride Chemical compound ClC(=O)CBr SYZRZLUNWVNNNV-UHFFFAOYSA-N 0.000 description 1
ILLHORFDXDLILE-UHFFFAOYSA-N 2-bromopropanoyl bromide Chemical compound CC(Br)C(Br)=O ILLHORFDXDLILE-UHFFFAOYSA-N 0.000 description 1
IPOVOSHRRIJKBR-UHFFFAOYSA-N 2-ethylpropanedioyl dichloride Chemical compound CCC(C(Cl)=O)C(Cl)=O IPOVOSHRRIJKBR-UHFFFAOYSA-N 0.000 description 1
JJKWHOSQTYYFAE-UHFFFAOYSA-N 2-methoxyacetyl chloride Chemical compound COCC(Cl)=O JJKWHOSQTYYFAE-UHFFFAOYSA-N 0.000 description 1
GUGQQGROXHPINL-UHFFFAOYSA-N 2-oxobutanoyl chloride Chemical compound CCC(=O)C(Cl)=O GUGQQGROXHPINL-UHFFFAOYSA-N 0.000 description 1
AUUTXOKCFQTKPL-UHFFFAOYSA-N 2-oxopropanoyl chloride Chemical compound CC(=O)C(Cl)=O AUUTXOKCFQTKPL-UHFFFAOYSA-N 0.000 description 1
UJXIOVIFPTXDHU-UHFFFAOYSA-N 2-phenylethanethioyl chloride Chemical compound ClC(=S)CC1=CC=CC=C1 UJXIOVIFPTXDHU-UHFFFAOYSA-N 0.000 description 1
QISAUDWTBBNJIR-UHFFFAOYSA-N 2-phenylmethoxyacetyl chloride Chemical compound ClC(=O)COCC1=CC=CC=C1 QISAUDWTBBNJIR-UHFFFAOYSA-N 0.000 description 1
UXVCEKRAZBZVSL-UHFFFAOYSA-N 2-pyridin-2-ylacetamide Chemical compound NC(=O)CC1=CC=CC=N1 UXVCEKRAZBZVSL-UHFFFAOYSA-N 0.000 description 1
DCVGCQPXTOSWEA-UHFFFAOYSA-N 4-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]pyrazol-3-yl]methyl]-1-methylpiperazin-2-one Chemical compound CN1CCN(CC2=NN(CC(=O)N3CCC4=C(C3)N=NN4)C=C2C2=CN=C(NC3CC4=C(C3)C=CC=C4)N=C2)CC1=O DCVGCQPXTOSWEA-UHFFFAOYSA-N 0.000 description 1
XHCNINMOALIGKM-UHFFFAOYSA-N 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetrazacyclotetradecane Chemical compound CC1CC(C)(C)NCCNC(C)CC(C)(C)NCCN1 XHCNINMOALIGKM-UHFFFAOYSA-N 0.000 description 1
RREANTFLPGEWEN-MBLPBCRHSA-N 7-[4-[[(3z)-3-[4-amino-5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidin-2-yl]imino-5-fluoro-2-oxoindol-1-yl]methyl]piperazin-1-yl]-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(\N=C/3C4=CC(F)=CC=C4N(CN4CCN(CC4)C=4C(=CC=5C(=O)C(C(O)=O)=CN(C=5C=4)C4CC4)F)C\3=O)=NC=2)N)=C1 RREANTFLPGEWEN-MBLPBCRHSA-N 0.000 description 1
241000607534 Aeromonas Species 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
229910000761 Aluminium amalgam Inorganic materials 0.000 description 1
239000005995 Aluminium silicate Substances 0.000 description 1
244000105624 Arachis hypogaea Species 0.000 description 1
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
241000193830 Bacillus <bacterium> Species 0.000 description 1
208000035143 Bacterial infection Diseases 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
239000004322 Butylated hydroxytoluene Substances 0.000 description 1
NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
101150041968 CDC13 gene Proteins 0.000 description 1
101100294106 Caenorhabditis elegans nhr-3 gene Proteins 0.000 description 1
241000589876 Campylobacter Species 0.000 description 1
206010012735 Diarrhoea Diseases 0.000 description 1
235000019739 Dicalciumphosphate Nutrition 0.000 description 1
241000588921 Enterobacteriaceae Species 0.000 description 1
241000495778 Escherichia faecalis Species 0.000 description 1
241000192125 Firmicutes Species 0.000 description 1
241000233866 Fungi Species 0.000 description 1
241000207202 Gardnerella Species 0.000 description 1
229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
QZRGKCOWNLSUDK-UHFFFAOYSA-N Iodochlorine Chemical compound ICl QZRGKCOWNLSUDK-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
108010052285 Membrane Proteins Proteins 0.000 description 1
102000018697 Membrane Proteins Human genes 0.000 description 1
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
241000204031 Mycoplasma Species 0.000 description 1
XCOBLONWWXQEBS-KPKJPENVSA-N N,O-bis(trimethylsilyl)trifluoroacetamide Chemical compound C[Si](C)(C)O\C(C(F)(F)F)=N\[Si](C)(C)C XCOBLONWWXQEBS-KPKJPENVSA-N 0.000 description 1
TZYWCYJVHRLUCT-VABKMULXSA-N N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-leucinal Chemical compound CC(C)C[C@@H](C=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)OCC1=CC=CC=C1 TZYWCYJVHRLUCT-VABKMULXSA-N 0.000 description 1
AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 1
208000005141 Otitis Diseases 0.000 description 1
206010034133 Pathogen resistance Diseases 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
241000588769 Proteus <enterobacteria> Species 0.000 description 1
241000589516 Pseudomonas Species 0.000 description 1
239000007868 Raney catalyst Substances 0.000 description 1
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
229910000564 Raney nickel Inorganic materials 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
229930003427 Vitamin E Natural products 0.000 description 1
206010048038 Wound infection Diseases 0.000 description 1
240000008042 Zea mays Species 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
DAEJUPKPHRBQHZ-UHFFFAOYSA-N [Sn].[Hg] Chemical compound [Sn].[Hg] DAEJUPKPHRBQHZ-UHFFFAOYSA-N 0.000 description 1
IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
150000001263 acyl chlorides Chemical class 0.000 description 1
230000002411 adverse Effects 0.000 description 1
238000002814 agar dilution Methods 0.000 description 1
235000004279 alanine Nutrition 0.000 description 1
125000005236 alkanoylamino group Chemical group 0.000 description 1
125000004448 alkyl carbonyl group Chemical group 0.000 description 1
125000000266 alpha-aminoacyl group Chemical group 0.000 description 1
235000012211 aluminium silicate Nutrition 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
208000022362 bacterial infectious disease Diseases 0.000 description 1
230000003385 bacteriostatic effect Effects 0.000 description 1
229910052788 barium Inorganic materials 0.000 description 1
CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
238000000262 chemical ionisation mass spectrometry Methods 0.000 description 1
239000012295 chemical reaction liquid Substances 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
229940125782 compound 2 Drugs 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
235000008504 concentrate Nutrition 0.000 description 1
238000001816 cooling Methods 0.000 description 1
TVZPLCNGKSPOJA-UHFFFAOYSA-N copper zinc Chemical compound [Cu].[Zn] TVZPLCNGKSPOJA-UHFFFAOYSA-N 0.000 description 1
239000002285 corn oil Substances 0.000 description 1
235000005687 corn oil Nutrition 0.000 description 1
239000012043 crude product Substances 0.000 description 1
KZZKOVLJUKWSKX-UHFFFAOYSA-N cyclobutanamine Chemical compound NC1CCC1 KZZKOVLJUKWSKX-UHFFFAOYSA-N 0.000 description 1
ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 1
230000001086 cytosolic effect Effects 0.000 description 1
125000004663 dialkyl amino group Chemical group 0.000 description 1
239000012954 diazonium Substances 0.000 description 1
IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical compound [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 1
NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
229940038472 dicalcium phosphate Drugs 0.000 description 1
229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000037213 diet Effects 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
VFNGKCDDZUSWLR-UHFFFAOYSA-L disulfate(2-) Chemical compound [O-]S(=O)(=O)OS([O-])(=O)=O VFNGKCDDZUSWLR-UHFFFAOYSA-L 0.000 description 1
208000019258 ear infection Diseases 0.000 description 1
239000008157 edible vegetable oil Substances 0.000 description 1
PQLFROTZSIMBKR-UHFFFAOYSA-N ethenyl carbonochloridate Chemical compound ClC(=O)OC=C PQLFROTZSIMBKR-UHFFFAOYSA-N 0.000 description 1
230000029142 excretion Effects 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
238000009472 formulation Methods 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
238000007429 general method Methods 0.000 description 1
239000008187 granular material Substances 0.000 description 1
230000009036 growth inhibition Effects 0.000 description 1
230000002140 halogenating effect Effects 0.000 description 1
230000036541 health Effects 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
238000009905 homogeneous catalytic hydrogenation reaction Methods 0.000 description 1
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
229910000041 hydrogen chloride Inorganic materials 0.000 description 1
239000001863 hydroxypropyl cellulose Substances 0.000 description 1
235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
230000006872 improvement Effects 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
238000001802 infusion Methods 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
239000002054 inoculum Substances 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
230000007154 intracellular accumulation Effects 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
239000007928 intraperitoneal injection Substances 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 1
239000008101 lactose Substances 0.000 description 1
208000004396 mastitis Diseases 0.000 description 1
239000000463 material Substances 0.000 description 1
239000002609 medium Substances 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
229910052976 metal sulfide Inorganic materials 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical compound COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 description 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
230000002906 microbiologic effect Effects 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
150000002780 morpholines Chemical class 0.000 description 1
FVZBTUWCBYLDJQ-UHFFFAOYSA-M n,n,n-trimethylbenzenemethanaminium dichloroiodate Chemical compound [Cl-].ICl.C[N+](C)(C)CC1=CC=CC=C1 FVZBTUWCBYLDJQ-UHFFFAOYSA-M 0.000 description 1
VBTQNRFWXBXZQR-UHFFFAOYSA-N n-bromoacetamide Chemical compound CC(=O)NBr VBTQNRFWXBXZQR-UHFFFAOYSA-N 0.000 description 1
150000002823 nitrates Chemical class 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
239000002736 nonionic surfactant Substances 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
BSCHIACBONPEOB-UHFFFAOYSA-N oxolane;hydrate Chemical compound O.C1CCOC1 BSCHIACBONPEOB-UHFFFAOYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 1
125000003386 piperidinyl group Chemical class 0.000 description 1
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
229920005862 polyol Polymers 0.000 description 1
150000003077 polyols Chemical class 0.000 description 1
229920001184 polypeptide Polymers 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
230000008569 process Effects 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
CAEWJEXPFKNBQL-UHFFFAOYSA-N prop-2-enyl carbonochloridate Chemical compound ClC(=O)OCC=C CAEWJEXPFKNBQL-UHFFFAOYSA-N 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
238000010992 reflux Methods 0.000 description 1
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
QBERHIJABFXGRZ-UHFFFAOYSA-M rhodium;triphenylphosphane;chloride Chemical compound [Cl-].[Rh].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QBERHIJABFXGRZ-UHFFFAOYSA-M 0.000 description 1
239000004576 sand Substances 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
206010040872 skin infection Diseases 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
229910052979 sodium sulfide Inorganic materials 0.000 description 1
GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
JHLVEBNWCCKSGY-UHFFFAOYSA-N tert-butyl n-methylcarbamate Chemical compound CNC(=O)OC(C)(C)C JHLVEBNWCCKSGY-UHFFFAOYSA-N 0.000 description 1
101150045159 tetB gene Proteins 0.000 description 1
229940072172 tetracycline antibiotic Drugs 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
239000011135 tin Substances 0.000 description 1
229910052718 tin Inorganic materials 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
238000013518 transcription Methods 0.000 description 1
230000035897 transcription Effects 0.000 description 1
238000009901 transfer hydrogenation reaction Methods 0.000 description 1
230000009466 transformation Effects 0.000 description 1
238000000844 transformation Methods 0.000 description 1
238000013519 translation Methods 0.000 description 1
PTMFUWGXPRYYMC-UHFFFAOYSA-N triethylazanium;formate Chemical compound OC=O.CCN(CC)CC PTMFUWGXPRYYMC-UHFFFAOYSA-N 0.000 description 1
SIOVKLKJSOKLIF-HJWRWDBZSA-N trimethylsilyl (1z)-n-trimethylsilylethanimidate Chemical compound C[Si](C)(C)OC(/C)=N\[Si](C)(C)C SIOVKLKJSOKLIF-HJWRWDBZSA-N 0.000 description 1
208000019206 urinary tract infection Diseases 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
235000019165 vitamin E Nutrition 0.000 description 1
229940046009 vitamin E Drugs 0.000 description 1
239000011709 vitamin E Substances 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/24—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton
- C07C237/26—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton of a ring being part of a condensed ring system formed by at least four rings, e.g. tetracycline
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- 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
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/44—Acylated amino or imino radicals
- C07D277/46—Acylated amino or imino radicals by carboxylic acids, or sulfur or nitrogen analogues thereof
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/30—Hetero atoms other than halogen
- C07D333/34—Sulfur atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/40—Ortho- or ortho- and peri-condensed systems containing four condensed rings
- C07C2603/42—Ortho- or ortho- and peri-condensed systems containing four condensed rings containing only six-membered rings
- C07C2603/44—Naphthacenes; Hydrogenated naphthacenes
- C07C2603/46—1,4,4a,5,5a,6,11,12a- Octahydronaphthacenes, e.g. tetracyclines

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Oncology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Communicable Diseases (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Peptides Or Proteins (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Furan Compounds (AREA)
Thiazole And Isothizaole Compounds (AREA)
Moulding By Coating Moulds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Pyrrole Compounds (AREA)
Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Hydrogenated Pyridines (AREA)
Saccharide Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

NO923857A 1991-10-04 1992-10-02 Nye 7-substituerte-9-substituert amino-6-demetyl-6-deoksytetracykliner, og preparater derav NO301472B1 (no)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US77157691A	1991-10-04	1991-10-04

Publications (3)

Publication Number	Publication Date
NO923857D0 NO923857D0 (no)	1992-10-02
NO923857L NO923857L (no)	1993-04-05
NO301472B1 true NO301472B1 (no)	1997-11-03

Family

ID=25092264

Family Applications (3)

Application Number	Title	Priority Date	Filing Date
NO923857A NO301472B1 (no)	1991-10-04	1992-10-02	Nye 7-substituerte-9-substituert amino-6-demetyl-6-deoksytetracykliner, og preparater derav
NO2006015C NO2006015I2 (no)	1991-10-04	2006-11-15	Tigecyklin.
NO2017037C NO2017037I1 (no)	1991-10-04	2017-08-01	Tygacil er et antibiotika inneholdende en tetracyklinforbindelse betegnet tigecyklin

Family Applications After (2)

Application Number	Title	Priority Date	Filing Date
NO2006015C NO2006015I2 (no)	1991-10-04	2006-11-15	Tigecyklin.
NO2017037C NO2017037I1 (no)	1991-10-04	2017-08-01	Tygacil er et antibiotika inneholdende en tetracyklinforbindelse betegnet tigecyklin

Country Status (28)

Country	Link
EP (1)	EP0536515B1 (es)
JP (1)	JP3186863B2 (es)
KR (1)	KR100269072B1 (es)
CN (1)	CN1048240C (es)
AT (1)	ATE211128T1 (es)
AU (1)	AU654049B2 (es)
BR (1)	BR1100853A (es)
CA (1)	CA2079692C (es)
CL (1)	CL2004001623A1 (es)
CZ (2)	CZ284209B6 (es)
DE (4)	DE122006000058I1 (es)
DK (1)	DK0536515T3 (es)
ES (1)	ES2168254T3 (es)
FI (1)	FI114911B (es)
HK (1)	HK1011348A1 (es)
HU (2)	HU219973B (es)
IL (3)	IL119590A (es)
LU (1)	LU91279I2 (es)
MX (1)	MX9205532A (es)
NL (1)	NL300244I2 (es)
NO (3)	NO301472B1 (es)
NZ (1)	NZ244585A (es)
PL (4)	PL173311B1 (es)
PT (1)	PT536515E (es)
SG (1)	SG52361A1 (es)
SK (2)	SK280837B6 (es)
TW (1)	TW275616B (es)
ZA (1)	ZA927607B (es)

Families Citing this family (39)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5284963A (en) *	1992-08-13	1994-02-08	American Cyanamid Company	Method of producing 7-(substituted)-9-[(substituted glycyl)-amidol]-6-demethyl-6-deoxytetra-cyclines
US5328902A (en) *	1992-08-13	1994-07-12	American Cyanamid Co.	7-(substituted)-9-[(substituted glycyl)amido]-6-demethyl-6-deoxytetracyclines
US5420272A (en) *	1992-08-13	1995-05-30	American Cyanamid Company	7-(substituted)-8-(substituted)-9-](substituted glycyl)amido]-6-demethyl-6-deoxytetracyclines
AU1279095A (en) *	1994-02-17	1995-09-04	Pfizer Inc.	9-(substituted amino)-alpha-6-deoxy-5-oxy tetracycline derivatives, their preparation and their use as antibiotics
EP1666453A1 (en)	1999-09-14	2006-06-07	Trustees Of Tufts College	Methods of preparing substituted tetracyclines with transition metal-based chemistries
US8106225B2 (en)	1999-09-14	2012-01-31	Trustees Of Tufts College	Methods of preparing substituted tetracyclines with transition metal-based chemistries
CA2404628A1 (en)	2000-03-31	2001-10-11	Stuart B. Levy	7-and 9-carbamate, urea, thiourea, thiocarbamate, and heteroaryl-amino substituted tetracycline compounds
AU2001259701A1 (en) *	2000-05-15	2001-11-26	Paratek Pharmaceuticals, Inc	7-substituted fused ring tetracycline compounds
US7094806B2 (en)	2000-07-07	2006-08-22	Trustees Of Tufts College	7, 8 and 9-substituted tetracycline compounds
IL153639A0 (en)	2000-07-07	2003-07-06	Tufts College	9-substituted minocycline compounds
US7553828B2 (en)	2001-03-13	2009-06-30	Paratek Pharmaceuticals, Inc.	9-aminomethyl substituted minocycline compounds
WO2002072506A2 (en)	2001-03-13	2002-09-19	Paratek Pharmaceuticals, Inc.	7-pyrollyl tetracycline compounds and methods of use thereof
EP1241160A1 (en)	2001-03-13	2002-09-18	Glaxo Group Limited	Tetracycline derivatives and their use as antibiotic agents
EP1368305B1 (en)	2001-03-13	2008-08-13	Paratek Pharmaceuticals, Inc.	7, 9-substituted tetracycline compounds
US20040092490A1 (en) *	2001-04-24	2004-05-13	Michael Draper	Substituted tetracycline compounds for the treatment of malaria
WO2003005971A2 (en)	2001-07-13	2003-01-23	Paratek Pharmaceuticals, Inc.	Tetracycline compounds having target therapeutic activities
AU2002365120A1 (en)	2001-08-02	2003-07-15	Paratek Pharmaceuticals, Inc.	Medicaments
EP2311798A1 (en)	2002-01-08	2011-04-20	Paratek Pharmaceuticals, Inc.	4-dedimethylamino tetracycline compounds
KR101093842B1 (ko) *	2002-03-08	2011-12-13	파라테크 파마슈티컬스, 인크.	아미노-메틸 치환된 테트라시클린 화합물
CA2531728A1 (en)	2003-07-09	2005-02-03	Paratek Pharmaceuticals, Inc.	Substituted tetracycline compounds
UA83266C2 (en) *	2003-12-08	2008-06-25	Уайет	Oxazole derivatives of tetracyclines
PT1753713T (pt)	2004-05-21	2016-11-08	Harvard College	Síntese de tetraciclinas e seus análogos
PA8652001A1 (es)	2004-11-05	2006-10-13	Wyeth Corp	Metabolitos glucuronidos de tigeciclina y epimeros de los mismos
AR057649A1 (es)	2005-05-27	2007-12-12	Wyeth Corp	Formas solidas cristalinas de tigeciclina y metodos para preparar las mismas
JP2009507793A (ja) *	2005-08-31	2009-02-26	ワイス	グリシルサイクリンの９−アミノカルボニル置換誘導体
JP2009543544A (ja)	2006-05-15	2009-12-10	パラテックファーマシューティカルズインコーポレイテッド	置換されたテトラサイクリン化合物を用いて、遺伝子または遺伝子産物の発現を調節する方法
JP4729133B2 (ja)	2007-11-29	2011-07-20	アクテリオンファーマシューティカルズリミテッド	ホスホン酸誘導体及びｐ２ｙ１２受容体拮抗剤としてのそれらの使用
PT2271348T (pt)	2008-03-28	2018-04-16	Paratek Pharm Innc	Formulação de comprimido oral de composto de tetraciclina
ITMI20080807A1 (it)	2008-05-05	2009-11-06	Antibioticos Spa	Procedimento per la preparazione di tigeciclina in forma amorfa
TW202021946A (zh)	2008-05-23	2020-06-16	美商派洛泰克藥物股份有限公司	四環素化合物之甲苯磺酸鹽及同素異形體
WO2010017470A1 (en) *	2008-08-08	2010-02-11	Tetraphase Pharmaceuticals, Inc.	C7-fluoro substituted tetracycline compounds
EP2424834B1 (en)	2009-04-30	2018-07-11	President and Fellows of Harvard College	Synthesis of tetracyclines and intermediates thereof
CN102459153A (zh)	2009-05-08	2012-05-16	四相制药公司	四环素类化合物
CN105622496B (zh)	2009-08-28	2019-03-05	四相制药公司	四环素类化合物
ES2613738T3 (es)	2010-05-12	2017-05-25	Rempex Pharmaceuticals, Inc.	Composiciones de tetraciclina
CN103635456B (zh) *	2011-07-26	2016-03-09	山东亨利医药科技有限责任公司	替加环素衍生物
CN108329312B (zh)	2012-08-31	2021-12-31	四相制药公司	四环素化合物
US20160143925A1 (en)	2013-11-12	2016-05-26	Galenicum Health S.L.	Stable pharmaceutical compositions
CN110582486B (zh)	2016-10-19	2024-01-12	四相制药公司	艾若威四环素的结晶形式

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3338963A (en) *	1960-10-28	1967-08-29	American Cyanamid Co	Tetracycline compounds
US3579579A (en) *	1968-04-18	1971-05-18	American Cyanamid Co	Substituted 7- and/or 9-amino-6-demethyl-6-deoxytetracyclines

1992
- 1992-08-21 SG SG1996003437A patent/SG52361A1/en unknown
- 1992-08-21 PT PT92114281T patent/PT536515E/pt unknown
- 1992-08-21 DE DE1992632302 patent/DE122006000058I1/de active Pending
- 1992-08-21 DE DE200612000058 patent/DE122006000058I2/de active Active
- 1992-08-21 ES ES92114281T patent/ES2168254T3/es not_active Expired - Lifetime
- 1992-08-21 DK DK92114281T patent/DK0536515T3/da active
- 1992-08-21 DE DE69232302T patent/DE69232302T4/de not_active Expired - Lifetime
- 1992-08-21 EP EP92114281A patent/EP0536515B1/en not_active Expired - Lifetime
- 1992-08-21 AT AT92114281T patent/ATE211128T1/de active
- 1992-08-21 DE DE69232302A patent/DE69232302D1/de not_active Expired - Lifetime
- 1992-08-27 TW TW081106768A patent/TW275616B/zh not_active IP Right Cessation
- 1992-09-29 MX MX9205532A patent/MX9205532A/es unknown
- 1992-09-30 HU HU9203110A patent/HU219973B/hu unknown
- 1992-09-30 SK SK2984-92A patent/SK280837B6/sk not_active IP Right Cessation
- 1992-09-30 CZ CZ973093A patent/CZ284209B6/cs not_active IP Right Cessation
- 1992-09-30 SK SK1149-99A patent/SK284826B6/sk not_active IP Right Cessation
- 1992-09-30 CZ CS922984A patent/CZ284159B6/cs not_active IP Right Cessation
- 1992-10-01 IL IL11959092A patent/IL119590A/xx not_active IP Right Cessation
- 1992-10-01 IL IL10332092A patent/IL103320A/en not_active IP Right Cessation
- 1992-10-01 NZ NZ244585A patent/NZ244585A/en not_active IP Right Cessation
- 1992-10-02 PL PL92296143A patent/PL173311B1/pl unknown
- 1992-10-02 NO NO923857A patent/NO301472B1/no not_active IP Right Cessation
- 1992-10-02 AU AU26183/92A patent/AU654049B2/en not_active Expired
- 1992-10-02 PL PL92310717A patent/PL172282B1/pl unknown
- 1992-10-02 KR KR1019920018122A patent/KR100269072B1/ko not_active IP Right Cessation
- 1992-10-02 PL PL92310719A patent/PL176333B1/pl unknown
- 1992-10-02 CA CA002079692A patent/CA2079692C/en not_active Expired - Lifetime
- 1992-10-02 ZA ZA927607A patent/ZA927607B/xx unknown
- 1992-10-02 PL PL92310718A patent/PL175957B1/pl unknown
- 1992-10-02 FI FI924454A patent/FI114911B/fi active Protection Beyond IP Right Term
- 1992-10-03 CN CN92112130A patent/CN1048240C/zh not_active Expired - Lifetime
- 1992-10-05 JP JP28811492A patent/JP3186863B2/ja not_active Expired - Lifetime
1995
- 1995-04-28 HU HU95P/P00116P patent/HU211172A9/hu active Protection Beyond IP Right Term
1996
- 1996-11-10 IL IL11959096A patent/IL119590A0/xx unknown
1997
- 1997-05-12 BR BR1100853-9A patent/BR1100853A/pt active IP Right Grant
1998
- 1998-11-27 HK HK98112374A patent/HK1011348A1/xx not_active IP Right Cessation
2004
- 2004-06-25 CL CL200401623A patent/CL2004001623A1/es unknown
2006
- 2006-10-11 LU LU91279C patent/LU91279I2/fr unknown
- 2006-10-23 NL NL300244C patent/NL300244I2/nl unknown
- 2006-11-15 NO NO2006015C patent/NO2006015I2/no unknown
2017
- 2017-08-01 NO NO2017037C patent/NO2017037I1/no unknown

Also Published As

Publication number	Publication date
HU9203110D0 (en)	1992-12-28
NO2006015I2 (no)	2011-03-14
AU2618392A (en)	1993-04-08
HU219973B (hu)	2001-10-28
DE69232302T2 (de)	2002-08-14
LU91279I2 (fr)	2006-12-11
IL103320A0 (en)	1993-03-15
SK284826B6 (sk)	2005-12-01
NO2006015I1 (no)	2006-11-27
CA2079692A1 (en)	1993-04-05
ES2168254T3 (es)	2002-06-16
AU654049B2 (en)	1994-10-20
KR100269072B1 (ko)	2000-10-16
EP0536515A1 (en)	1993-04-14
PL173311B1 (pl)	1998-02-27
DE122006000058I1 (de)	2007-01-18
DE69232302T4 (de)	2003-02-13
FI114911B (fi)	2005-01-31
CA2079692C (en)	2004-06-08
CZ298492A3 (en)	1993-05-12
CN1072172A (zh)	1993-05-19
PL176333B1 (pl)	1999-05-31
PL172282B1 (pl)	1997-08-29
PT536515E (pt)	2002-05-31
FI924454A (fi)	1993-04-05
HU211172A9 (en)	1995-11-28
CN1048240C (zh)	2000-01-12
DE69232302D1 (de)	2002-01-31
TW275616B (es)	1996-05-11
KR930007894A (ko)	1993-05-20
SK298492A3 (en)	1995-03-08
JP3186863B2 (ja)	2001-07-11
CL2004001623A1 (es)	2005-06-03
DE122006000058I2 (de)	2007-09-13
CZ309397A3 (cs)	1998-09-16
SK280837B6 (sk)	2000-08-14
ATE211128T1 (de)	2002-01-15
DK0536515T3 (da)	2002-04-08
JPH05255219A (ja)	1993-10-05
PL296143A1 (en)	1993-05-31
SK114999A3 (en)	2000-07-11
MX9205532A (es)	1993-04-01
NO923857L (no)	1993-04-05
IL119590A (en)	1999-03-12
NO2017037I2 (no)	2017-08-01
CZ284159B6 (cs)	1998-08-12
EP0536515B1 (en)	2001-12-19
CZ284209B6 (cs)	1998-09-16
BR1100853A (pt)	1999-12-07
HK1011348A1 (en)	1999-07-09
NO923857D0 (no)	1992-10-02
SG52361A1 (en)	1998-09-28
NL300244I1 (nl)	2007-01-02
HUT63145A (en)	1993-07-28
NO2017037I1 (no)	2017-08-01
NL300244I2 (nl)	2007-01-02
ZA927607B (en)	1993-04-13
IL119590A0 (en)	1997-02-18
IL103320A (en)	1998-12-06
PL175957B1 (pl)	1999-03-31
FI924454A0 (fi)	1992-10-02
NZ244585A (en)	1995-07-26

Legal Events

Date	Code	Title	Description
2006-11-27	SPCF	Filing of supplementary protection certificate	Free format text: PRODUCT NAME: TIGECYKLIN; NAT. REG. NO/DATE: EU106336001/NO 20060524; FIRST REG. NO/DATE: BE , EU106336001 20060424 Spc suppl protection certif: 2006015 Filing date: 20061115
2011-03-14	SPCG	Granted supplementary protection certificate	Free format text: PRODUCT NAME: TIGECYKLIN; NAT. REG. NO/DATE: EU106336001/NO 20060524; FIRST REG. NO/DATE: BE , EU106336001 20060424 Spc suppl protection certif: 2006015 Filing date: 20061115 Extension date: 20171002
2012-11-12	MK1K	Patent expired
2017-08-07	SPCE	Application to extend a supplementary protection certificate (spc)	Free format text: PRODUCT NAME: TYGACIL ER ET ANTIBIOTIKA INNEHOLDENDE EN TETRACYKLINFORBINDELSE BETEGNET TIGECYKLIN; NAT. REG. NO/DATE: NO , EU106336001 20060524; FIRST REG. NO/DATE: BE , EU106336001 20060424 Spc suppl protection certif: 2017037 Filing date: 20170801
2017-10-09	SPCX	Expiry of an spc	Free format text: PRODUCT NAME: TIGECYKLIN; NAT. REG. NO/DATE: EU106336001/NO 20060524; FIRST REG. NO/DATE: EU106336001 20060424 Spc suppl protection certif: 2006015 Effective date: 20171002
2018-11-05	SPCH	Extension of a supplementary protection certificate (spc) granted	Free format text: PRODUCT NAME: TYGACIL ER ET ANTIBIOTIKA INNEHOLDENDE EN TETRACYKLINFORBINDELSE BETEGNET TIGECYKLIN; NAT. REG. NO/DATE: NO , EU106336001 20060524; FIRST REG. NO/DATE: BE , EU106336001 20060424 Spc suppl protection certif: 2017037 Filing date: 20170801
2018-12-10	SPCX	Expiry of an spc	Spc suppl protection certif: 2017037

Publication	Publication Date	Title
NO301472B1 (no)	1997-11-03	Nye 7-substituerte-9-substituert amino-6-demetyl-6-deoksytetracykliner, og preparater derav
USRE40086E1 (en)	2008-02-19	Method for treating bacterial infection with novel 7-substituted-9-substituted amino 6-demethyl-6-deoxytetracyclines
EP0535346B1 (en)	1995-11-02	9-amino-7-substituted-6-demethyl-6-deoxytetracyclines
KR101014918B1 (ko)	2011-02-15	아미노-메틸 치환된 테트라시클린 화합물
KR100309539B1 (ko)	2002-08-31	신규한-7-(치환)-9-(치환글리실)아미도)-6-데메틸-6-데옥시테트라사이클린및그의중간체및그들의생산방법
US20130029943A1 (en)	2013-01-31	Methods of Preparing Substituted Tetracyclines with Transition Metal-Based Chemistries
IL119750A (en)	1998-09-24	7-) Transformed (-8-) Transformed-9-) Amino-Transformed (-6-Demethyl-6-DioxytetracyclinesNew Intermediates
USRE40183E1 (en)	2008-03-25	7-Substituted-9-substituted amino-6-demethyl-6-deoxytetracyclines
JP4848287B2 (ja)	2011-12-28	テトラサイクリンのオキサゾール誘導体
HU212267B (en)	1996-04-29	Process for preparing 9-nitro-7-(substituted)-6-demethyl-6-desoxytetracyclin derivatives