NZ507560A - Hydroxamic acid derivatives as antibacterials - Google Patents
Hydroxamic acid derivatives as antibacterialsInfo
- Publication number
- NZ507560A NZ507560A NZ507560A NZ50756099A NZ507560A NZ 507560 A NZ507560 A NZ 507560A NZ 507560 A NZ507560 A NZ 507560A NZ 50756099 A NZ50756099 A NZ 50756099A NZ 507560 A NZ507560 A NZ 507560A
- Authority
- NZ
- New Zealand
- Prior art keywords
- hydrogen
- alkyl
- group
- isopropyl
- methyl
- Prior art date
Links
- 230000000844 anti-bacterial effect Effects 0.000 title abstract 2
- 229940088710 antibiotic agent Drugs 0.000 title abstract 2
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 title 1
- 239000002253 acid Substances 0.000 title 1
- 229910052739 hydrogen Inorganic materials 0.000 abstract 8
- 239000001257 hydrogen Substances 0.000 abstract 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 8
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 7
- -1 amino, hydroxy Chemical group 0.000 abstract 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 abstract 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 2
- 125000005843 halogen group Chemical group 0.000 abstract 2
- 125000000623 heterocyclic group Chemical group 0.000 abstract 2
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 abstract 2
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 abstract 1
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 abstract 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 abstract 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 abstract 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 abstract 1
- 125000002252 acyl group Chemical group 0.000 abstract 1
- 125000004450 alkenylene group Chemical group 0.000 abstract 1
- 125000003118 aryl group Chemical group 0.000 abstract 1
- 125000004429 atom Chemical group 0.000 abstract 1
- 230000001580 bacterial effect Effects 0.000 abstract 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 abstract 1
- 125000001246 bromo group Chemical group Br* 0.000 abstract 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract 1
- 125000001309 chloro group Chemical group Cl* 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 125000004093 cyano group Chemical group *C#N 0.000 abstract 1
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 abstract 1
- 125000001153 fluoro group Chemical group F* 0.000 abstract 1
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 125000002346 iodo group Chemical group I* 0.000 abstract 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract 1
- 229910052757 nitrogen Inorganic materials 0.000 abstract 1
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 1
Classifications
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4453—Non condensed piperidines, e.g. piperocaine only substituted in position 1, e.g. propipocaine, diperodon
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- 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
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/426—1,3-Thiazoles
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- Pain & Pain Management (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9810464.9A GB9810464D0 (en) | 1998-05-16 | 1998-05-16 | Hydroxamic acid derivatives |
| PCT/GB1999/001541 WO1999059568A1 (en) | 1998-05-16 | 1999-05-14 | Hydroxamic acid derivatives as antibacterials |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ507560A true NZ507560A (en) | 2003-06-30 |
Family
ID=10832125
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ507560A NZ507560A (en) | 1998-05-16 | 1999-05-14 | Hydroxamic acid derivatives as antibacterials |
Country Status (23)
| Country | Link |
|---|---|
| US (3) | US6441042B1 (https=) |
| EP (2) | EP1079819B1 (https=) |
| JP (1) | JP2002515427A (https=) |
| KR (1) | KR100634089B1 (https=) |
| CN (1) | CN1300210A (https=) |
| AT (1) | ATE347356T1 (https=) |
| AU (1) | AU754063B2 (https=) |
| BR (1) | BR9910488A (https=) |
| CA (1) | CA2332713C (https=) |
| CY (1) | CY1106452T1 (https=) |
| DE (1) | DE69934309T2 (https=) |
| DK (1) | DK1079819T3 (https=) |
| ES (1) | ES2278444T3 (https=) |
| GB (2) | GB9810464D0 (https=) |
| HU (1) | HUP0102290A3 (https=) |
| IL (2) | IL139059A0 (https=) |
| NO (1) | NO20005782L (https=) |
| NZ (1) | NZ507560A (https=) |
| PL (1) | PL344438A1 (https=) |
| PT (1) | PT1079819E (https=) |
| TR (1) | TR200003376T2 (https=) |
| WO (1) | WO1999059568A1 (https=) |
| ZA (1) | ZA200006131B (https=) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2349884A (en) * | 1998-02-07 | 2000-11-15 | British Biotech Pharm | Antibacterial agents |
| GB9810464D0 (en) * | 1998-05-16 | 1998-07-15 | British Biotech Pharm | Hydroxamic acid derivatives |
| US6908911B1 (en) * | 1999-08-10 | 2005-06-21 | British Biotech Pharmaceuticals Limited | Antibacterial agents |
| WO2001040198A2 (fr) * | 1999-11-30 | 2001-06-07 | Aventis Pharma S.A. | Derives macrocycliques de l'acide hydroxamique et leur utilisation en tant qu'antimicrobiens |
| FR2801591B1 (fr) * | 1999-11-30 | 2002-03-01 | Aventis Pharma Sa | Derives macrocycliques de l'acide hydroxamique, leur preparation et les compositions qui les contiennent |
| GB9929979D0 (en) * | 1999-12-17 | 2000-02-09 | Darwin Discovery Ltd | Hydroxamic acid derivatives |
| EP1237862A1 (en) * | 1999-12-17 | 2002-09-11 | Versicor, Inc. | Succinate compounds, compositions and methods of use and preparation |
| AU2002230385A1 (en) * | 2000-09-25 | 2002-04-15 | Questcor Pharmaceuticals, Inc. | Peptide deformylase inhibitors |
| WO2002041886A1 (en) * | 2000-11-23 | 2002-05-30 | British Biotech Pharmaceuticals Ltd | Ydroxamic acid or n-formyl hydroxylamine derivatives as inhibitors of bakterial polypeptide deformylase for treating microbial infections |
| EP1372692A4 (en) * | 2001-03-19 | 2005-10-26 | Sloan Kettering Inst Cancer | ASYMMETRIC SYNTHESIS OF (S, S, R) - (-) - ACTINONE AND ITS ANALOG AND USES THEREOF |
| US20040267015A1 (en) * | 2001-04-05 | 2004-12-30 | Ajita Bhat | Peptide deformylase inhibitors |
| GB0128943D0 (en) * | 2001-12-04 | 2002-01-23 | Novo Pharmaceuticals De Ltd | Bacterial enzyme inhibitors |
| JP4190862B2 (ja) * | 2001-12-18 | 2008-12-03 | シャープ株式会社 | 表示装置およびその駆動方法 |
| GB0208579D0 (en) * | 2002-04-13 | 2002-05-22 | British Biotech Pharm | Antibacterial agents |
| DE10320453A1 (de) * | 2003-05-08 | 2004-11-25 | Morphochem AG Aktiengesellschaft für kombinatorische Chemie | Neue Bioisostere von Actinonin |
| US8993641B2 (en) * | 2007-11-29 | 2015-03-31 | Innolex Investment Corporation | Preservation of cosmetics, toiletry and pharmaceutical compositions |
| DE102011088962A1 (de) * | 2011-12-19 | 2013-06-20 | Beiersdorf Ag | Wirkstoffkombinationen aus einer oder mehreren Carbonsäuren, insbesondereHydroxycarbonsäuren, und einer oder mehreren physiologisch unbedenklichen Hydroxamsäure sowie kosmetische oder dermatologische Zubereitungen, solcheWirkstoffkombinationen enthaltend |
| US10829440B2 (en) | 2015-06-12 | 2020-11-10 | Brown University | Antibacterial compounds and methods of making and using same |
| US11653649B2 (en) | 2017-06-29 | 2023-05-23 | Kimberly-Clark Worldwide, Inc. | Antimicrobial composition including a dihydroxamic acid and methods of inhibiting microbial growth utilizing the same |
| CN108672095A (zh) * | 2018-05-04 | 2018-10-19 | 广东省资源综合利用研究所 | γ-羟基烷基羟肟酸及其制备方法与应用 |
| US11555010B2 (en) | 2019-07-25 | 2023-01-17 | Brown University | Diamide antimicrobial agents |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1028921A (en) * | 1962-01-23 | 1966-05-11 | Ranjeet Bhagwan Singh | New antibiotic |
| US4303662A (en) * | 1980-11-24 | 1981-12-01 | E. R. Squibb & Sons, Inc. | Carboxyacyl, mercapto and acylmercapto derivatives of heterobicyclo compounds |
| JPH0670019B2 (ja) * | 1989-07-21 | 1994-09-07 | 明治製菓株式会社 | 新抗生物質ｓｆ２１９７ｃ物質およびその製造法 |
| GB8919251D0 (en) * | 1989-08-24 | 1989-10-04 | British Bio Technology | Compounds |
| JPH03157372A (ja) * | 1989-11-13 | 1991-07-05 | Yamanouchi Pharmaceut Co Ltd | Ｙｌ―０１８６９ｐ物質及びその製造法 |
| WO1992022523A2 (en) * | 1991-06-14 | 1992-12-23 | Research Corporation Technologies, Inc. | Peptide derivatives of collagenase inhibitor |
| GB9223904D0 (en) * | 1992-11-13 | 1993-01-06 | British Bio Technology | Inhibition of cytokine production |
| FI960803A7 (fi) | 1993-08-23 | 1996-04-22 | Immunex Corp | TNF-alfa-sekreetion inhibiittoreita |
| JP3157372B2 (ja) | 1993-11-29 | 2001-04-16 | 三洋電機株式会社 | フィルタ |
| JPH10501806A (ja) * | 1994-06-22 | 1998-02-17 | ブリティッシュ バイオテック ファーマシューティカルズ リミテッド | 金属タンパク質分解酵素阻害剤 |
| US5532265A (en) | 1994-11-30 | 1996-07-02 | The Board Of Trustees Of The Leland Stanford Junior University | Treatment of central nervous system inflammatory disease with matrix metalloprotease inhibitors |
| GB9507799D0 (en) | 1995-04-18 | 1995-05-31 | British Biotech Pharm | Metalloproteinase inhibitors |
| US6281245B1 (en) * | 1996-10-28 | 2001-08-28 | Versicor, Inc. | Methods for solid-phase synthesis of hydroxylamine compounds and derivatives, and combinatorial libraries thereof |
| AU5187698A (en) * | 1996-12-06 | 1998-06-29 | Cancerforskningsfondet Af 1989 | Inhibition of invasive remodelling |
| ZA9711121B (en) * | 1996-12-13 | 1998-06-23 | Handelman Joseph H | Reduction of hair growth. |
| GB2349884A (en) * | 1998-02-07 | 2000-11-15 | British Biotech Pharm | Antibacterial agents |
| GB9810464D0 (en) * | 1998-05-16 | 1998-07-15 | British Biotech Pharm | Hydroxamic acid derivatives |
-
1998
- 1998-05-16 GB GBGB9810464.9A patent/GB9810464D0/en not_active Ceased
-
1999
- 1999-05-14 BR BR9910488-1A patent/BR9910488A/pt not_active Application Discontinuation
- 1999-05-14 WO PCT/GB1999/001541 patent/WO1999059568A1/en not_active Ceased
- 1999-05-14 ES ES99922317T patent/ES2278444T3/es not_active Expired - Lifetime
- 1999-05-14 DK DK99922317T patent/DK1079819T3/da active
- 1999-05-14 US US09/700,424 patent/US6441042B1/en not_active Expired - Fee Related
- 1999-05-14 EP EP99922317A patent/EP1079819B1/en not_active Expired - Lifetime
- 1999-05-14 CN CN99806057A patent/CN1300210A/zh active Pending
- 1999-05-14 IL IL13905999A patent/IL139059A0/xx not_active IP Right Cessation
- 1999-05-14 PT PT99922317T patent/PT1079819E/pt unknown
- 1999-05-14 JP JP2000549233A patent/JP2002515427A/ja not_active Withdrawn
- 1999-05-14 GB GB0024789A patent/GB2353708A/en not_active Withdrawn
- 1999-05-14 AU AU39421/99A patent/AU754063B2/en not_active Ceased
- 1999-05-14 HU HU0102290A patent/HUP0102290A3/hu unknown
- 1999-05-14 EP EP06009622A patent/EP1754477A3/en not_active Withdrawn
- 1999-05-14 PL PL99344438A patent/PL344438A1/xx unknown
- 1999-05-14 CA CA002332713A patent/CA2332713C/en not_active Expired - Fee Related
- 1999-05-14 NZ NZ507560A patent/NZ507560A/xx unknown
- 1999-05-14 DE DE69934309T patent/DE69934309T2/de not_active Expired - Fee Related
- 1999-05-14 KR KR1020007012819A patent/KR100634089B1/ko not_active Expired - Fee Related
- 1999-05-14 AT AT99922317T patent/ATE347356T1/de not_active IP Right Cessation
- 1999-05-14 TR TR2000/03376T patent/TR200003376T2/xx unknown
-
2000
- 2000-10-16 IL IL139059A patent/IL139059A/en unknown
- 2000-10-30 ZA ZA200006131A patent/ZA200006131B/en unknown
- 2000-11-15 NO NO20005782A patent/NO20005782L/no not_active Application Discontinuation
-
2002
- 2002-06-26 US US10/179,227 patent/US6992190B2/en not_active Expired - Fee Related
-
2005
- 2005-08-22 US US11/207,813 patent/US7323563B2/en not_active Expired - Fee Related
-
2007
- 2007-03-01 CY CY20071100285T patent/CY1106452T1/el unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PSEA | Patent sealed | ||
| RENW | Renewal (renewal fees accepted) | ||
| RENW | Renewal (renewal fees accepted) |