ZA200206218B - Dipetide nitrile cathepsin K inhibitors. - Google Patents
Dipetide nitrile cathepsin K inhibitors. Download PDFInfo
- Publication number
- ZA200206218B ZA200206218B ZA200206218A ZA200206218A ZA200206218B ZA 200206218 B ZA200206218 B ZA 200206218B ZA 200206218 A ZA200206218 A ZA 200206218A ZA 200206218 A ZA200206218 A ZA 200206218A ZA 200206218 B ZA200206218 B ZA 200206218B
- Authority
- ZA
- South Africa
- Prior art keywords
- cyanomethyl
- benzamide
- carbamoyl
- cyclohexyl
- piperazin
- Prior art date
Links
- 102000004171 Cathepsin K Human genes 0.000 title claims description 20
- 108090000625 Cathepsin K Proteins 0.000 title claims description 20
- 239000003112 inhibitor Substances 0.000 title description 9
- 150000002825 nitriles Chemical class 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 47
- 229910052799 carbon Inorganic materials 0.000 claims description 37
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
- 201000010099 disease Diseases 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 18
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- 125000000217 alkyl group Chemical group 0.000 claims description 10
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- CZNGTXVOZOWWKM-UHFFFAOYSA-N methyl 4-bromobenzoate Chemical compound COC(=O)C1=CC=C(Br)C=C1 CZNGTXVOZOWWKM-UHFFFAOYSA-N 0.000 description 1
- CAYXRIBDDOLHBR-UHFFFAOYSA-N methyl 4-piperazin-1-ylbenzoate 4-piperazin-1-ylbenzonitrile Chemical compound C(#N)C1=CC=C(C=C1)N1CCNCC1.COC(C1=CC=C(C=C1)N1CCNCC1)=O CAYXRIBDDOLHBR-UHFFFAOYSA-N 0.000 description 1
- GKSBLGJAXZOORS-UHFFFAOYSA-N methyl 4-piperidin-4-ylbenzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1CCNCC1 GKSBLGJAXZOORS-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000004452 microanalysis Methods 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 201000006938 muscular dystrophy Diseases 0.000 description 1
- PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].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.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 201000001245 periodontitis Diseases 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 201000004409 schistosomiasis Diseases 0.000 description 1
- 238000013077 scoring method Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
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- A—HUMAN NECESSITIES
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- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
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- A—HUMAN NECESSITIES
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Tropical Medicine & Parasitology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Communicable Diseases (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pulmonology (AREA)
- Oncology (AREA)
- Transplantation (AREA)
- Neurology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Hydrogenated Pyridines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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GBGB0003111.2A GB0003111D0 (en) | 2000-02-10 | 2000-02-10 | Organic compounds |
Publications (1)
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ZA200206218B true ZA200206218B (en) | 2003-08-05 |
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ZA200206218A ZA200206218B (en) | 2000-02-10 | 2002-08-05 | Dipetide nitrile cathepsin K inhibitors. |
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US (4) | US6642239B2 (zh) |
EP (1) | EP1254124B1 (zh) |
JP (1) | JP3942895B2 (zh) |
KR (1) | KR100544553B1 (zh) |
CN (2) | CN1183122C (zh) |
AR (1) | AR029466A1 (zh) |
AT (1) | ATE402930T1 (zh) |
AU (1) | AU764334B2 (zh) |
BR (1) | BR0108118A (zh) |
CA (1) | CA2396158C (zh) |
CO (1) | CO5261578A1 (zh) |
CZ (1) | CZ20022721A3 (zh) |
DE (1) | DE60135087D1 (zh) |
ES (1) | ES2310177T3 (zh) |
GB (1) | GB0003111D0 (zh) |
HK (1) | HK1050197A1 (zh) |
HU (1) | HUP0300148A3 (zh) |
IL (1) | IL150406A0 (zh) |
MX (1) | MXPA02007768A (zh) |
MY (1) | MY122826A (zh) |
NO (1) | NO20023780D0 (zh) |
NZ (1) | NZ519940A (zh) |
PE (1) | PE20020220A1 (zh) |
PL (1) | PL200119B1 (zh) |
PT (1) | PT1254124E (zh) |
RU (2) | RU2265601C2 (zh) |
SK (1) | SK11462002A3 (zh) |
TR (1) | TR200201752T2 (zh) |
TW (1) | TWI258473B (zh) |
WO (1) | WO2001058886A1 (zh) |
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Families Citing this family (44)
Publication number | Priority date | Publication date | Assignee | Title |
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GB9723407D0 (en) * | 1997-11-05 | 1998-01-07 | Ciba Geigy Ag | Organic compounds |
KR100688740B1 (ko) | 1999-03-15 | 2007-02-28 | 액시스 파마슈티컬스 인코포레이티드 | 프로테아제 억제제로서의 n-시아노메틸 아미드 |
GB0003111D0 (en) * | 2000-02-10 | 2000-03-29 | Novartis Ag | Organic compounds |
US7148197B2 (en) * | 2000-08-24 | 2006-12-12 | The Regents Of The University Of California | Orally administered small peptides synergize statin activity |
US7723303B2 (en) * | 2000-08-24 | 2010-05-25 | The Regents Of The University Of California | Peptides and peptide mimetics to treat pathologies characterized by an inflammatory response |
US7199102B2 (en) * | 2000-08-24 | 2007-04-03 | The Regents Of The University Of California | Orally administered peptides synergize statin activity |
JP2004523506A (ja) | 2000-12-22 | 2004-08-05 | アクシス・ファーマシューティカルズ・インコーポレイテッド | カテプシン阻害剤としての新規な化合物と組成物 |
US7030116B2 (en) | 2000-12-22 | 2006-04-18 | Aventis Pharmaceuticals Inc. | Compounds and compositions as cathepsin inhibitors |
EP1436255A1 (en) | 2001-09-14 | 2004-07-14 | Aventis Pharmaceuticals, Inc. | Novel compounds and compositions as cathepsin inhibitors |
KR20050044497A (ko) | 2001-11-14 | 2005-05-12 | 아벤티스 파마슈티칼스 인크. | 올리고펩티드 및 카텝신 s 억제제로서 이를 포함하는조성물 |
WO2003075836A2 (en) * | 2002-03-05 | 2003-09-18 | Merck Frosst Canada & Co. | Cathepsin cysteine protease inhibitors |
CA2506114A1 (en) * | 2002-12-05 | 2004-06-24 | Axys Pharmaceuticals, Inc. | Cyanomethyl derivatives as cysteine protease inhibitors |
US7405229B2 (en) * | 2003-06-30 | 2008-07-29 | Merck Frosst Canada & Co. | Cathepsin cysteine protease inhibitors |
PE20050328A1 (es) * | 2003-07-21 | 2005-06-16 | Novartis Ag | Combinaciones de un bisfosfonato y un inhibidor de catepsina k |
JP2007511548A (ja) * | 2003-11-19 | 2007-05-10 | ノバルティス アクチエンゲゼルシャフト | 重篤な骨量減少疾患におけるカテプシンk阻害剤の使用 |
US7915300B2 (en) | 2004-01-08 | 2011-03-29 | Medivir Ab | Cysteine protease inhibitors |
CN101065137A (zh) * | 2004-09-16 | 2007-10-31 | 加利福尼亚大学董事会 | 用于改善动脉粥样硬化和其它病变的g型多肽和其它剂 |
US7579319B2 (en) * | 2004-12-06 | 2009-08-25 | The Regents Of The University Of California | Methods for improving the structure and function of arterioles |
GB0427380D0 (en) * | 2004-12-14 | 2005-01-19 | Novartis Ag | Organic compounds |
US20080125442A1 (en) * | 2005-01-19 | 2008-05-29 | Michael David Percival | Cathepsin K Inhibitors and Atherosclerosis |
US20090005323A1 (en) * | 2005-01-19 | 2009-01-01 | Michael David Percival | Cathepsin K Inhibitors and Obesity |
US20080293639A1 (en) * | 2005-04-29 | 2008-11-27 | The Regents Of The University Of California | Peptides and peptide mimetics to treat pathologies characterized by an inflammatory response |
GB0517637D0 (en) * | 2005-08-30 | 2005-10-05 | Novartis Ag | Organic compounds |
JP3975226B2 (ja) * | 2006-01-11 | 2007-09-12 | 生化学工業株式会社 | シクロアルキルカルボニルアミノ酸誘導体及びその製造方法 |
WO2007080884A1 (ja) | 2006-01-11 | 2007-07-19 | Seikagaku Corporation | シクロアルキルカルボニルアミノ酸エステル誘導体及びその製造方法 |
JP4047365B2 (ja) | 2006-01-11 | 2008-02-13 | 生化学工業株式会社 | シクロアルカンカルボキサミド誘導体及びその製造方法 |
WO2007137149A2 (en) * | 2006-05-22 | 2007-11-29 | Velcura Therapeutics, Inc. | Use of cathepsin k antagonists in bone production |
GB0614044D0 (en) * | 2006-07-14 | 2006-08-23 | Amura Therapeutics Ltd | Compounds |
GB0614053D0 (en) * | 2006-07-14 | 2006-08-23 | Amura Therapeutics Ltd | Compounds |
GB0614046D0 (en) | 2006-07-14 | 2006-08-23 | Amura Therapeutics Ltd | Compounds |
CN101970007A (zh) | 2007-06-08 | 2011-02-09 | 日本化学医药株式会社 | 脑动脉瘤的治疗或预防药 |
BRPI0702541A2 (pt) | 2007-06-21 | 2009-02-10 | Petroleo Brasileiro Sa | processo de craqueamento catalÍtico para produÇço de diesel a partir de sementes de oleaginosas |
US7893067B2 (en) | 2007-06-27 | 2011-02-22 | Medivir Ab | Cysteine protease inhibitors |
US20100331545A1 (en) | 2007-10-24 | 2010-12-30 | Nippon Chemiphar Co., Ltd. | Regulator for signaling toll-like receptor, which comprises cathepsin inhibitor as active ingredient |
WO2009076490A1 (en) * | 2007-12-12 | 2009-06-18 | Velcura Therapeutics, Inc. | Use of cathepsin l antagonists in the treatment of bone disease |
JP5587790B2 (ja) | 2008-01-09 | 2014-09-10 | アミュラ セラピューティクス リミティド | 化合物 |
EP2262783A2 (en) * | 2008-02-21 | 2010-12-22 | Sanofi-Aventis | Covalently binding imaging probes |
GB0817425D0 (en) * | 2008-09-24 | 2008-10-29 | Medivir Ab | Protease inhibitors |
US20100298507A1 (en) * | 2009-05-19 | 2010-11-25 | Menschig Klaus R | Polyisobutylene Production Process With Improved Efficiencies And/Or For Forming Products Having Improved Characteristics And Polyisobutylene Products Produced Thereby |
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