公开(公告)号：US07713950B2

公开(公告)日：2010-05-11

申请号：US12038105

申请日：2008-02-27

Applicant: Dale E. Shuster ,  Scott J. Hecker ,  Tomasz W. Glinka ,  Rajeshwar Singh ,  Zhuoyi Su

Inventor： Dale E. Shuster ,  Scott J. Hecker ,  Tomasz W. Glinka ,  Rajeshwar Singh ,  Zhuoyi Su

IPC: A61K31/165 ,  C07F9/09

CPC classification number: C07F9/094 ,  A61K31/165 ,  A61K31/661 ,  C07C317/32 ,  C07F9/091 ,  Y02A50/475

Abstract: Novel florfenicol compounds having the chemical structure: or a pharmaceutically-acceptable salt thereof or a solvate thereof, or prodrug thereof, wherein R1 is CHCl2, CHClF, CHF2, CHBrCl, CH3, CH2N3, CH2CN, CH(R2)NH2 or CHX1X2; where R2 is H, CH3 or CH2OH, and X1 and X2 are independently selected halogens; and R3 is CH2Cl, CH2F, CHF2, CHCl2 or CH2OH are disclosed. The compounds are useful for the treatment and/or prevention of bacterial infections in a broad range of patients such as, without limitation, birds, fish, shellfish and mammals.

Abstract translation: 具有化学结构的新型氟苯尼考化合物：或其药学上可接受的盐或其溶剂合物或其前药，其中R 1为CHCl 2，CHClF，CHF 2，CHBrCl，CH 3，CH 2 N 3，CH 2 CN，CH（R 2）NH 2或CHX 1 X 2; 其中R2是H，CH3或CH2OH，X1和X2是独立选择的卤素; 和R 3是CH 2 Cl，CH 2 F，CHF 2，CHCl 2或CH 2 OH。 该化合物可用于治疗和/或预防广泛范围的患者中的细菌感染，例如但不限于鸟类，鱼类，贝类和哺乳动物。

公开(公告)号：US06982260B1

公开(公告)日：2006-01-03

申请号：US10130843

申请日：2000-11-03

Applicant: Mark Robert Barvian ,  Ellen Myra Dobrusin ,  James Stanley Kaltenbronn ,  Peter L. Toogood ,  Roy Thomas Winters ,  Inderjit S. Sidhu ,  Rajeshwar Singh ,  Yadagiri Bathini ,  Ronald George Micetich

Inventor： Mark Robert Barvian ,  Ellen Myra Dobrusin ,  James Stanley Kaltenbronn ,  Peter L. Toogood ,  Roy Thomas Winters ,  Inderjit S. Sidhu ,  Rajeshwar Singh ,  Yadagiri Bathini ,  Ronald George Micetich

IPC: C07D239/84 ,  C07D239/78 ,  C07D239/80 ,  C07D403/12 ,  A61K31/517

CPC classification number: C07D239/78 ,  C07D239/80 ,  C07D239/84 ,  C07D401/12

Abstract: This invention provides quinazolines that are useful for treating cell proliferative diseases and disorders, such as cardiovascular diseases, infections, cancers, autoimmune diseases, gout, kidney disease, and neurodegenerative diseases and disorders such as Alzheimer's disease. We have now discovered a group of 2-arylamino-7-(alkyl)oxy-8-alkylquinazolines and 8-alkyl-2-arylamino-quinazoline 2,7-diamines that are potent inhibitors of cyclin-dependent kinases (cdks). The compounds are readily synthesized and can be administered by a variety of routes, including orally, and have sufficient bioavailability. This invention also provides pharmaceutical formulations comprising at least one of the quinazoline compounds together with a pharmaceutically acceptable carrier, diluent, or excipient therefor. The invention further provide useful intermediates generated during the production of the quinazoline compounds.

Abstract translation: 本发明提供了可用于治疗细胞增殖性疾病和疾病如心血管疾病，感染，癌症，自身免疫疾病，痛风，肾脏疾病和神经变性疾病和疾病如阿尔茨海默氏病的喹唑啉。 我们现在已经发现了一组2-芳基氨基-7-（烷基）氧基-8-烷基喹唑啉和8-烷基-2-芳基氨基 - 喹唑啉2,7-二胺，它们是细胞周期蛋白依赖性激酶（cdks）的有效抑制剂。 这些化合物容易合成，并且可以通过多种途径施用，包括口服，并具有足够的生物利用度。 本发明还提供药物制剂，其包含至少一种喹唑啉化合物及其药学上可接受的载体，稀释剂或赋形剂。 本发明还提供了在制备喹唑啉化合物期间产生的有用的中间体。

公开(公告)号：US06569847B1

公开(公告)日：2003-05-27

申请号：US09958141

申请日：2001-10-05

Applicant: Rajeshwar Singh ,  Andhe V. Narender Reddy ,  Jadwiga Kaleta ,  Ronald G. Micetich ,  Mark Whittaker ,  Philip Huxley

Inventor： Rajeshwar Singh ,  Andhe V. Narender Reddy ,  Jadwiga Kaleta ,  Ronald G. Micetich ,  Mark Whittaker ,  Philip Huxley

IPC: C07D205085

CPC classification number: C07D401/12 ,  A61K31/397 ,  C07D205/085 ,  C07D403/12 ,  C07D417/12 ,  Y02A50/414

Abstract: This invention relates to substituted azetidin-2-ones and to pharmaceutical compositions containing such compounds. Their use in medicine as inhibitors of cysteine proteases, particularly the cathepsins is also described. The invention includes a compound of formula (I), Y represents —C(O)— or —S(O2)—; R represents an allyl (ie CH2═CHCH2—) group or a radical. R1 represents —OCOR5, —OR5, —SR5, —S(O)R5, or —S(O)2R5; R2 represents a radical. R3 represents —OR5 or R5; or a pharmaceutically acceptable salt, hydrate or solvate thereof.

Abstract translation: 本发明涉及取代的氮杂环丁烷-2-酮和含有这些化合物的药物组合物。 还描述了它们在医学中作为半胱氨酸蛋白酶抑制剂，特别是组织蛋白酶的用途。 本发明包括式（I）化合物，Y代表-C（O） - 或-S（O 2） - ; R表示烯丙基（即CH 2 = CHCH 2 - ）基团或基团。 R 1表示-OCOR 5，-OR 5，-SR 5，-S（O）R 5或-S（O）2 R 5; R2代表一个基团。 R3表示-OR5或R5; 或其药学上可接受的盐，水合物或溶剂化物。

公开(公告)号：US06362181B1

公开(公告)日：2002-03-26

申请号：US09637949

申请日：2000-08-11

Applicant: Albert Kudzoi Amegadzie ,  Maureen Elizabeth Carey ,  John Michael Domagala ,  Liren Huang ,  Ronald George Micetich ,  Joseph Peter Sanchez ,  Rajeshwar Singh ,  Michael Andrew Stier ,  Arkadii Vaisburg

Inventor： Albert Kudzoi Amegadzie ,  Maureen Elizabeth Carey ,  John Michael Domagala ,  Liren Huang ,  Ronald George Micetich ,  Joseph Peter Sanchez ,  Rajeshwar Singh ,  Michael Andrew Stier ,  Arkadii Vaisburg

IPC: A61K31535

CPC classification number: C07D221/14 ,  C07D401/04 ,  C07D491/06 ,  Y02P20/55

Abstract: Benzo[de]isoquinoline-1,3-diones which are selective inhibitors of bacterial DNA gyrase and DNA topoisomerase useful in antibacterial agents are described as well as methods for their preparation and formulation. Novel intermediates useful in the preparation of the final products are also described.

Abstract translation: 描述了作为细菌DNA促旋酶的选择性抑制剂和可用于抗菌剂的DNA拓扑异构酶的苯并[de]异喹啉-1,3-二酮以及其制备和制剂的方法。 还描述了可用于制备最终产品的新型中间体。

公开(公告)号：US06331538B1

公开(公告)日：2001-12-18

申请号：US09508796

申请日：2000-03-15

Applicant: John Michael Domagala ,  Edmund Lee Ellsworth ,  Liren Huang ,  Thomas Eric Renau ,  Rajeshwar Singh ,  Michael Andrew Stier

Inventor： John Michael Domagala ,  Edmund Lee Ellsworth ,  Liren Huang ,  Thomas Eric Renau ,  Rajeshwar Singh ,  Michael Andrew Stier

IPC: C07D23996

CPC classification number: C07D403/04 ,  C07D239/96 ,  C07D471/04 ,  C07D471/06

Abstract: The invention is a series of 7-substituted quinazolin-2,4-diones useful as antibacterial agents, processes for the preparation of the compounds, and a pharmaceutical composition containing one or more of the compounds.

Abstract translation: 本发明是用作抗菌剂的一系列7-取代喹唑啉-2,4-二酮，用于制备化合物的方法和含有一种或多种化合物的药物组合物。

公开(公告)号：US6034077A

公开(公告)日：2000-03-07

申请号：US283297

申请日：1999-04-01

Applicant: Rajeshwar Singh ,  Nian E. Zhou ,  Enrico O. Purisima ,  Ronald G. Micetich

Inventor： Rajeshwar Singh ,  Nian E. Zhou ,  Enrico O. Purisima ,  Ronald G. Micetich

IPC: A61K38/55 ,  A61K31/00 ,  A61K38/00 ,  A61P9/10 ,  A61P11/00 ,  A61P13/12 ,  A61P19/02 ,  A61P19/10 ,  A61P21/04 ,  A61P25/28 ,  A61P27/12 ,  A61P29/00 ,  A61P31/04 ,  A61P31/10 ,  A61P33/00 ,  A61P33/06 ,  A61P35/00 ,  A61P43/00 ,  C07K5/06 ,  C07K5/065 ,  A61K31/395

CPC classification number: C07K5/06078 ,  A61K31/00 ,  A61K38/00

Abstract: In accordance with the present invention, there are provided 4-substituted-3-(2-amino-2-cycloalkyl methyl)-acetamido azetidin-2-one derivatives of the formula: ##STR1## wherein n is 1, 2 or 3; in which R.sub.1, R.sub.2 and R.sub.3 are as defined herein, and salts thereof, which exhibit excellent cysteine proteinase inhibitory activity and which can be used for treatment of different diseases such as muscular dystrophy, myocardial infarction, bone resorption, arthritis, cancer metastasis, pulmonary emphysema, septic shock, cerebral ischemia, memory function, Alzheimer and cataract, malaria, glomerular basement membrane degradation, bacterial infection, inflammatory diseases, parasitic infections, and viral infections.

Abstract translation: 根据本发明，提供下式的4-取代-3-（2-氨基-2-环烷基甲基） - 乙酰胺基吖丁啶-2-酮衍生物：其中n为1,2或3; 其中R 1，R 2和R 3如本文所定义，及其盐，其表现出优异的半胱氨酸蛋白酶抑制活性并且可用于治疗不同疾病如肌营养不良症，心肌梗塞，骨吸收，关节炎，癌症转移，肺 肺气肿，败血性休克，脑缺血，记忆功能，阿尔茨海默病和白内障，疟疾，肾小球基底膜降解，细菌感染，炎性疾病，寄生虫感染和病毒感染。

公开(公告)号：US5986108A

公开(公告)日：1999-11-16

申请号：US925459

申请日：1997-09-08

Applicant: Rajeshwar Singh ,  Nian En Zhou ,  Deqi Guo ,  Ronald G. Micetich

Inventor： Rajeshwar Singh ,  Nian En Zhou ,  Deqi Guo ,  Ronald G. Micetich

IPC: A61K38/55 ,  A61K38/00 ,  A61P35/00 ,  A61P43/00 ,  C07K5/06 ,  C07K5/065 ,  C07K5/087 ,  C07D205/00

CPC classification number: C07K5/0812 ,  C07K5/06043 ,  C07K5/06078 ,  A61K38/00 ,  Y02P20/55

Abstract: Disclosed herein are azetidin-2-one compounds which exhibit excellent cysteine proteinase inhibitory activity. The compounds are 4-substituted-3-{1 or 2 amino acid residue}-azetidin-2-ones of forumula I ##STR1## wherein AAR is a 1 or 2 acid residue, and R.sub.1 and R.sub.2 are as defined herein. The compounds can be used in the treatment of various diseases such as muscular dystrophy, bone resorption disorders, myocardial infarction and cancer metastasis.

Abstract translation: 本文公开了显示出优异的半胱氨酸蛋白酶抑制活性的氮杂环丁烷-2-酮化合物。 所述化合物是其中AAR是1或2个酸残基，并且R 1和R 2如本文所定义的哌啶-1-基的4-取代-3- {1或2个氨基酸残基} - 吖丁啶-2-酮。 该化合物可用于治疗各种疾病，如肌营养不良症，骨吸收障碍，心肌梗死和癌症转移。

公开(公告)号：US5905076A

公开(公告)日：1999-05-18

申请号：US831250

申请日：1997-04-08

Applicant: Rajeshwar Singh ,  Nian E. Zhou ,  Degi Guo ,  Alan Cameron ,  Jadwiga Kaleta ,  Enrico Purisima ,  Robert Menard ,  Ronald George Micetich

Inventor： Rajeshwar Singh ,  Nian E. Zhou ,  Degi Guo ,  Alan Cameron ,  Jadwiga Kaleta ,  Enrico Purisima ,  Robert Menard ,  Ronald George Micetich

IPC: C12N9/99 ,  A61K31/00 ,  A61K38/00 ,  A61P9/00 ,  A61P9/10 ,  A61P19/00 ,  A61P19/10 ,  A61P21/00 ,  A61P25/00 ,  A61P31/00 ,  A61P35/00 ,  A61P35/04 ,  C07D503/00 ,  C07K5/06 ,  C07K5/065 ,  C07K5/078 ,  C07K5/08 ,  A61K31/395 ,  C07D487/08

CPC classification number: C07K5/06191 ,  C07D503/00 ,  C07K5/06026 ,  C07K5/06034 ,  C07K5/06043 ,  C07K5/06078 ,  C07K5/06165 ,  A61K38/00

Abstract: Novel 6-substituted amino-4-oxa-1-azabicyclo�3,2,0!heptan-7-one compounds, as well as the pharmaceutically acceptable salts thereof and diastereoisomers thereof, of formula I, ##STR1## are disclosed, which exhibit excellent cysteine protease inhibitory activity and may be used for treatment of different diseases such as muscular dystrophy, arthritis, myocardial infarction, Alzheimer's disease, bacterial infection, common cold, osteroporosis and cancer metastasis.

Abstract translation: 公开了新颖的6-取代的氨基-4-氧杂-1-氮杂双环[3,2,0]庚-7-酮化合物及其药学上可接受的盐和非对映异构体，其表现出优异的半胱氨酸 蛋白酶抑制活性，可用于治疗肌肉营养不良，关节炎，心肌梗塞，阿尔茨海默氏病，细菌感染，感冒，卵巢疏松和癌症转移等不同疾病。

公开(公告)号：US5888998A

公开(公告)日：1999-03-30

申请号：US840608

申请日：1997-04-24

Applicant: Samarendra N. Maiti ,  Eduardo L. Setti ,  Oludotun A. Phillips ,  Andhe V. Narender Reddy ,  Ronald G. Micetich ,  Rajeshwar Singh ,  Fusahiro Higashitani ,  Chieko Kunugita ,  Koichi Nishida ,  Tatsuya Uji

Inventor： Samarendra N. Maiti ,  Eduardo L. Setti ,  Oludotun A. Phillips ,  Andhe V. Narender Reddy ,  Ronald G. Micetich ,  Rajeshwar Singh ,  Fusahiro Higashitani ,  Chieko Kunugita ,  Koichi Nishida ,  Tatsuya Uji

IPC: A61K31/44 ,  A61K31/4436 ,  A61K31/4439 ,  A61K31/54 ,  A61P31/04 ,  C07D401/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D205/085 ,  A61K31/395

CPC classification number: C07D409/14 ,  A61K31/44 ,  A61K31/54 ,  C07D413/14 ,  C07D417/14

Abstract: A compound of formula (I) ##STR1## wherein R.sub.1 is selected from the group consisting of 2-thienyl, 2-furyl, 2-pyrrolyl, 1-methyl-2-pyrrolyl, 2-amino-1-thiazolyl and 5-isothiazolyl;R.sub.2 is selected from the group consisting of: ##STR2## and M is hydrogen or a pharmaceutically acceptable cation; wherein the oxyimino fragment (.dbd.N--OR.sub.2) in formula (I) is in the `anti` orientation.

Abstract translation: 式（I）化合物其中R 1选自2-噻吩基，2-呋喃基，2-吡咯基，1-甲基-2-吡咯基，2-氨基-1-噻唑基和 5-异噻唑基; （a）（b）（c）（d）（e）（f）（g ），M为氢或药学上可接受的阳离子; 其中式（I）中的氧亚氨基片段（= N-OR2）处于“反”取向。

公开(公告)号：US5652234A

公开(公告)日：1997-07-29

申请号：US513803

申请日：1995-10-06

Applicant: Rajeshwar Singh ,  Tomohiro Yamashita ,  Charles Fiakpui ,  George Thomas ,  Chan Ha ,  Hiroshi Matsumoto ,  Toshio Otani ,  Shinji Oie ,  Ronald Micetich

Inventor： Rajeshwar Singh ,  Tomohiro Yamashita ,  Charles Fiakpui ,  George Thomas ,  Chan Ha ,  Hiroshi Matsumoto ,  Toshio Otani ,  Shinji Oie ,  Ronald Micetich

IPC: C07D503/00 ,  A61K31/42 ,  A61P35/02 ,  A61K31/395

CPC classification number: A61K31/42

Abstract: The present invention relates to the use of 3-(7-oxo-1-aza-4-oxabicyclo[3.2.0]hept-3-yl)alanine derivatives of formula (I) or a pharmaceutically acceptable salt thereof, as antitumor agents. ##STR1## Wherein R is: hydrogen or COOR.sub.2 wherein R.sub.2 is C.sub.1 -C.sub.3 alkyl group which may be substituted with aryl group.Wherein R.sub.1 is:hydrogen or C.sub.1 -C.sub.3 alkyl group which may be substituted with one or two aryl groups.

Abstract translation: PCT No.PCT / GB95 / 00023 Sec。 371日期1995年10月6日 102（e）日期1995年10月6日PCT 1995年1月6日PCT PCT。 公开号WO95 / 18611 PCT 日期：1995年7月13日本发明涉及式（I）的3-（7-氧代-1-氮杂-4-氧杂双环[3.2.0]庚-3-基）丙氨酸衍生物或其药学上可接受的盐 作为抗肿瘤剂。 （I）其中R为：氢或COOR 2，其中R 2为可被芳基取代的C 1 -C 3烷基。 其中R1是：可被一个或两个芳基取代的氢或C1-C3烷基。