Halogen Or Acyclic Nitrogen Bonded Directly To The -c(=x)- Group Patents (Class 544/390)
  • Publication number: 20080146572
    Abstract: Compounds having the formula are apoptosis promoters. Also disclosed are methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.
    Type: Application
    Filed: February 26, 2008
    Publication date: June 19, 2008
    Applicant: ABBOTT LABORATORIES
    Inventors: Steven W. Elmore, Cheol-Min Park, Xilu Wang
  • Publication number: 20080139565
    Abstract: Therapeutically active anthranilic acid derivatives of Formula (I) wherein R1, R2, W, Y and Z are as defined in the specification, processes for the preparation of said derivatives, pharmaceutical formulations containing the active compounds and the use of the compounds in therapy, particularly in the treatment of diseases in which under-activation of the HM74A receptor contributes to the disease or in which activation of the receptor will be beneficial, are disclosed.
    Type: Application
    Filed: February 14, 2006
    Publication date: June 12, 2008
    Inventors: Matthew Campbell, Andrew McMurtrie Mason, Ivan Leo Pinto, Ian Edward David Smith
  • Patent number: 7381822
    Abstract: Piperidine or piperazine compounds useful for treating neurodegenerated diseases characterized by the lack of dopamine neurons activity or for imaging the dopamine neurons are provided.
    Type: Grant
    Filed: March 31, 2004
    Date of Patent: June 3, 2008
    Assignee: The General Hospital Corporation
    Inventors: David R. Elmaleh, Choi Songwoon, Alan J. Fischman
  • Publication number: 20080119477
    Abstract: The present invention relates to certain biarylz and arylheteroaryl piperazine derivatives of Formula (Ia) that are modulators of the 5HT2c receptor. Accordingly, compounds of the present invention are useful for the treatment of 5HT2c receptor associated diseases or disorders, such as, obesity, Alzheimer Disease, erectile dysfunction and related disorders.
    Type: Application
    Filed: December 9, 2005
    Publication date: May 22, 2008
    Inventors: Brian M. Smith, Vincent J. Santora, Rena Hayashi, Jason B. Ibarra, Jeffrey A. Schultz, Scott A. Estrada
  • Patent number: 7323563
    Abstract: A method for the treatment of bacterial infections in humans and non-human mammals, which comprises inhibiting bacterial growth by administering to a subject an antibacterially effective dose of a compound of formula (I) or a pharmaceutically or veterinarily acceptable salt thereof:
    Type: Grant
    Filed: August 22, 2005
    Date of Patent: January 29, 2008
    Assignee: British Biotech Pharmaceuticals Ltd.
    Inventors: Michael George Hunter, Paul Raymond Beckett, John Martin Clements, Mark Whittaker, Zoe Marie Spavold
  • Patent number: 7211670
    Abstract: The present invention describes a method for the synthesis of enantiomerically pure 3-amidinophenylalanine derivatives, which are used as pharmaceutically effective urokinase inhibitors, by starting from 3-cyanophenylalanine derivatives. The methods of manufacture comprising only one synthesis step lead to new intermediates, namely 3-hydroxyamidino- and 3-amidrazonophenylalanine derivatives. These intermediates or their acetyl derivatives can be reduced into the desired 3-amidinophenylalanine derivatives under gentle conditions (H2 or ammonium formiate, Pd/C (approx. 10%), ethanol/water, room temperature, normal pressure or also H2, Pd/C, AcOH or HOI/ethanol, 1–3 bar) in excellent yields and in an enantiomeric excess of up to 99.9%.
    Type: Grant
    Filed: February 28, 2003
    Date of Patent: May 1, 2007
    Assignee: Wilex AG
    Inventors: Hugo Ziegler, Peter Wikstroem
  • Patent number: 7208497
    Abstract: A novel class of substituted piperazines and diazepanes, pharmaceutical compositions comprising them and use thereof in the treatment of diseases and disorders related to the histamine H3 receptor. More particularly, the compounds are useful for the treatment of diseases and disorders in which an interaction with the histamine H3 receptor is beneficial.
    Type: Grant
    Filed: June 27, 2002
    Date of Patent: April 24, 2007
    Assignee: Novo Nordisk A/S
    Inventors: Florencio Zaragoza Dorwald, Knud Erik Andersen, Jan Lindy Sørensen
  • Patent number: 7208496
    Abstract: Disclosed are novel heterocyclic compounds having the structure which are useful for the treatment of various disease states, in particular cardiovascular diseases such as atrial and ventricular arrhythmias, intermittent claudication, Prinzmetal's (variant) angina, stable and unstable angina, exercise induced angina, congestive heart disease, and myocardial infarction. The compounds are also useful in the treatment of diabetes.
    Type: Grant
    Filed: June 7, 2004
    Date of Patent: April 24, 2007
    Assignee: CV Therapeutics, Inc.
    Inventors: Jeff Zablocki, Elfatih Elzein, Tim Marquart
  • Patent number: 7030115
    Abstract: Compounds having the formula are apoptosis promoters. Also disclosed are methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.
    Type: Grant
    Filed: March 21, 2003
    Date of Patent: April 18, 2006
    Assignee: Abbott Laboratories
    Inventors: Steven W. Elmore, Cheol-Min Park, Xilu Wang
  • Patent number: 7019003
    Abstract: Novel PDF inhibitors and novel methods for their use are provided.
    Type: Grant
    Filed: March 1, 2002
    Date of Patent: March 28, 2006
    Assignee: Smithkline Beecham Corporation
    Inventors: Jia-Ning Xiang, Siegfried B. Christensen, IV, Jinhwa Lee, Daniel J. Mercer
  • Patent number: 6992190
    Abstract: A method for the treatment of bacterial infections in humans and non-human mammals, which comprises inhibiting bacterial growth by administering to a subject an antibacterially effective dose of a compound of formula (I) or a pharmaceutically or veterinarily acceptable salt thereof:
    Type: Grant
    Filed: June 26, 2002
    Date of Patent: January 31, 2006
    Assignee: British Biotech Pharmaceuticals Ltd.
    Inventors: Michael George Hunter, Paul Raymond Beckett, John Martin Clements, Mark Whittaker, Zoe Marie Spavold
  • Patent number: 6906074
    Abstract: A 2-phenylpiperazine derivative represented by the formula (I) or a pharmaceutically acceptable salt, hydrate, or complex thereof: wherein each of X1 and X3 is oxygen or two hydrogen atoms, X2 O, NH, NCH3, or CH2, n is an integer of 0 or 1, R1 is hydrogen or lower alkyl and R2 is hydrogen, cyano, tetrazolyl, aminotriazolyl , mesyl, t-butoxycarbonyl, or a lower alkyl which may be optionally substituted, R3 is hydrogen, halogen, lower alkyl or lower alkoxy, each of R4 and R5 is hydrogen, lower alkoxy or trifluoromethyl, and a broken line indicates a single or double bond. The derivative may be used as a tachykinin antagonist in the treatment of diseases of the digestive system, nervous system and respiratory system, inflammation, allergy, carcinoid syndrome, chronic pain, headache, Crohn disease, depression and vomiting.
    Type: Grant
    Filed: February 20, 2003
    Date of Patent: June 14, 2005
    Assignee: Nippon Zoki Pharmaceutical Co., Ltd.
    Inventors: Takashi Ogino, Yukari Konishi, Kunihiko Higashiura, Kazuhito Furukawa
  • Patent number: 6903092
    Abstract: Compounds having the general formula wherein R1, R2, R3, R4, R5, X1 and X2 are as defined in the specification, methods of using such compounds for the treatment of diseases and pharmaceutical composition comprising such compounds.
    Type: Grant
    Filed: April 5, 2001
    Date of Patent: June 7, 2005
    Inventor: Peter Bernstein
  • Patent number: 6897209
    Abstract: A complex of a radiometal or paramagnetic metal ion with a metal chelating agent such as a diaminedioxime has attached thereto a substituent of formula (Y)m-A-NHR)k can function as a substrate for the fibrin-stabilizing Factor XIIIa. The complex is useful for the diagnosis or therapy of thrombosis, embolism, atherosclerosis, inflammation or cancer.
    Type: Grant
    Filed: August 22, 2003
    Date of Patent: May 24, 2005
    Assignee: GE Healthcare Limited
    Inventors: Alan Michael Forster, Peter Knox, Marivi Mendizabal, Timothy Charles Richardson, Anthony Eamon Storey, Ian Andrew Wilson, Susan Champion, Alex Gibson, Benedicte Guilbert
  • Patent number: 6861435
    Abstract: The invention relates to the compounds of general formula (I), that are present with respect to R1 as racemates as well as L- or D-configured compounds and as E/Z mixtures as well as E or Z isomers and in which the various symbols are defined as in the description and the claims, as well as to the salts thereof, for use as therapeutic agents and for diagnostic purposes. The inventive compounds can be processed to medicaments or to diagnostic agents that are used for the diagnosis, therapy and prevention of urokinase- or urokinase-receptor associated diseases, for example for the treatment of tumors. The compounds are highly efficient in inhibiting growth and/or spread of malign tumors, for example tumor spread of pancreatic cancer, tumor growth of breast cancer and the formation of tumor metastases. The compounds of formula (I) and the salts thereof can be produced by conventional methods.
    Type: Grant
    Filed: March 19, 2002
    Date of Patent: March 1, 2005
    Assignee: Pentapharm AG
    Inventor: Hugo Ziegler
  • Patent number: 6723730
    Abstract: Disclosed are diaryl piperazines and related compounds of the following Formula: wherein the variables are as defined in the specification. These compounds are selective modulators of capsaicin receptors, including human capsaicin receptors, that are, therefore, useful in the treatment of a chronic and acute pain conditions, itch and urinary incontinence. Methods of treatment of such disorders and well as packaged pharmaceutical compositions are also provided. Compounds of the invention are also useful as probes for the localization of capsaicin receptors and as standards in assays for capsaicin receptor binding and capsaicin receptor mediated cation conductance. Methods of using the compounds in receptor localization studies are given.
    Type: Grant
    Filed: July 20, 2001
    Date of Patent: April 20, 2004
    Assignee: Neurogen Corporation
    Inventors: Rajagopal Bakthavatchalam, Alan Hutchinson, Robert W. DeSimone, Kevin J. Hodgetts, James E. Krause, Geoffrey G. White
  • Patent number: 6683184
    Abstract: The present invention relates to a novel compound of formula (I) and its pharmaceutically acceptable acid addition salt, and process for the preparation thereof, which have strong antitumor activities and very low toxicity: wherein R1 and R2 are independently hydrogen, C1-C4 alkyl, C1-C4 alkylcarboxyl, C1-C4 alkylcarbonyl, C1-C4 alkoxy, C1-C4 hydroxyalkyl, C1-C4 aminoalkyl or C1-C4 hydroxyiminoalkyl, or R1 and R2 are fused to form C3-C4 unsaturated ring; R3, R4, R5, R6 and R7 are independently hydrogen, halogen, hydroxy, nitro, amino, C1-C4 alkyl, C1-C4 alkylcarboxyl, C1-C4 alkylcarbonyl, C1-C4 alkoxy, C1-C4 thioalkoxy; R8 is C1-C4 alkyl; Y is oxygen, sulphur, amino, subsitituted amino or C1-C4 thioalkyl; Z is C1-C4 alkoxy, C1-C4 alkyl, C1-C4 alkylamino or C1-C4 thioalkoxy; X1 and X2 are independently CH or nitrogen; and —N═C— and —C═Y— may form a single bond or a double bond provided that if —N═C— forms a single bond, —C═Y&md
    Type: Grant
    Filed: March 26, 2002
    Date of Patent: January 27, 2004
    Assignee: Samjin Pharmaceutical Co., Ltd.
    Inventors: Eui-Hwan Cho, Sun-Gan Chung, Sun-Hwan Lee, Ho-Seok Kwon, Dong-Wook Kang, Jeong-Ho Joo, Young-Hee Lee
  • Patent number: 6673799
    Abstract: This application relates to a piperazino-substituted novel cyanophenyl derivative in which a substituted carbamoyl or substituted sulfamoyl group having an aryl, heterocyclic or the like group that may have a substituent group is bonded to one nitrogen atom on the piperazine ring. The compound of this application has an anti-androgen action and is useful in preventing or treating prostatic cancer, benign prostatic hyperplasia and the like diseases.
    Type: Grant
    Filed: March 21, 2001
    Date of Patent: January 6, 2004
    Assignee: Yamanouchi Pharmaceutical Co. Ltd.
    Inventors: Nobuaki Taniguchi, Isao Kinoyama, Takashi Kamikubo, Akira Toyoshima, Kiyohiro Samizu, Eiji Kawaminami, Masakazu Imamura, Hiroyuki Moritomo, Akira Matsuhisa, Masaaki Hirano, Yoji Miyazaki, Eisuke Nozawa, Minoru Okada, Hiroshi Koutoku, Mitsuaki Ohta
  • Patent number: 6653299
    Abstract: A complex of a radiometal or paramagnetic metal ion with a metal chelating agent such as a diaminedioxime has attached thereto a substituent of formula —(Y)m—A—NHR, can function as a substrate for the fibrin-stabilizing Factor XIIIa. The complex is useful for the diagnosis or therapy of thrombosis, embolism, atherosclerosis, inflammation or cancer.
    Type: Grant
    Filed: October 4, 1999
    Date of Patent: November 25, 2003
    Assignee: Nycomed Amersham PLC
    Inventors: Alan Michael Forster, Peter Knox, Marivi Mendizabal, Timothy Charles Richardson, Anthony Eamon Storey, Ian Andrew Wilson, Susan Champion, Alex Gibson, Benedicte Guilbert
  • Patent number: 6593327
    Abstract: The present invention relates to novel N-cyanomethyl amides which are cysteine protease inhibitors, the pharmaceutically acceptable salts and N-oxides thereof, their uses as therapeutic agents and the methods of their making.
    Type: Grant
    Filed: December 14, 2001
    Date of Patent: July 15, 2003
    Assignee: Axys Pharmaceuticals, Inc.
    Inventors: Clifford M. Bryant, James T. Palmer, Robert M. Rydzewski, Eduardo L. Setti, Zong-Qiang Tian, Shankar Venkatraman, Dan-Xiong Wang
  • Patent number: 6462046
    Abstract: Compounds having the structure are peroxisome proliferator-activated receptor-gamma (PPAR-gamma) selective agonists and as such are useful in the modulation of blood glucose and the increase of insulin sensitivity in mammals. This activity of the piperazine derivatives of the invention make them particularly useful in the treatment of those conditions selected from the group consisting of diabetes, atherosclerosis, hyperglycemia, hyperlipidemia, obesity, syndrome X, insulin resistance, hypertension, heart failure and cardiovascular disease in mammals.
    Type: Grant
    Filed: December 11, 2000
    Date of Patent: October 8, 2002
    Assignee: Advanced SynTech, LLC
    Inventors: Boliang Lou, Adnan M. M. Mjalli
  • Patent number: 6362174
    Abstract: The present invention provides novel N-type calcium channel blockers, compositions comprising them, and methods of their use. The compounds of the invention are useful in the treatment of stroke, cerebral ischemia, pain, epilepsy, and head trauma.
    Type: Grant
    Filed: August 9, 2001
    Date of Patent: March 26, 2002
    Assignee: Warner-Lambert Company
    Inventors: Michael Francis Rafferty, Yuntao Song
  • Publication number: 20020016298
    Abstract: Compounds according to the formula: 1
    Type: Application
    Filed: December 21, 2000
    Publication date: February 7, 2002
    Inventors: Bruce A. Hay, Anthony P. Ricketts, Bridget M. Cole
  • Patent number: 6316440
    Abstract: The present invention provides novel N-type calcium channel blockers, compositions comprising them, and methods of their use. The compounds of the invention are useful in the treatment of stroke, cerebral ischemia, pain, epilepsy, and head trauma.
    Type: Grant
    Filed: December 27, 1999
    Date of Patent: November 13, 2001
    Assignee: Warner-Lambert Company
    Inventors: Michael Francis Rafferty, Yuntao Song
  • Patent number: 6255120
    Abstract: A combinatorial chemical library comprising a plurality of members of the Formula [S]—C(O)—L′-Z containing hydroxyamides is disclosed, in which [S] represents a solid support and L′-Z is a linker/compound residue. In this library, Z is and Y is —NR3R4 or —OR9. R3 and R4 are independently selected from the group consisting of H, alkyl, aralkyl, heteroarylalkyl, heterocycloalkyl, —CH(R5)CH(R6)OH, —CH(R5)C(O)NHR6 and —CH(R5)C(O)NHCH(R6)C(O)NHR7. R3 and R4 together are wherein X=O or NR8 and R9 is aryl, aralkyl or R7CH═CH(CH2){overscore (n)}. The combinatorial library can be optionally encoded with identifiers T′-L, which are covalently attached to the solid support. The methods of synthesizing such a library are described. The use of such library in assays to discover biologically active compounds is also disclosed.
    Type: Grant
    Filed: May 15, 1998
    Date of Patent: July 3, 2001
    Assignee: Pharmacopeia, Inc.
    Inventors: Roland Ellwood Dolle, III, Cullen Lee Cavallaro, Timothee Felix Herpin
  • Patent number: 6211242
    Abstract: This invention relates to new benzamide derivatives having a vasopressin antagonistic activity, etc. and represented by the general formula (I): wherein R1 is aryl optionally substituted with lower alkyl, etc., R2 is lower alkyl, etc., R3 is hydrogen, etc., R4 is aryl, etc., X is CH or N, and Y is CH or N, and pharmaceutically acceptable salts thereof, to processes for the preparation thereof and to a pharmaceutical composition comprising the same.
    Type: Grant
    Filed: January 30, 1998
    Date of Patent: April 3, 2001
    Assignee: Fujisawa Pharmaceutical Co., Ltd.
    Inventors: Hiroyuki Setoi, Takehiko Ohkawa, Tatsuya Zenkoh, Keiji Hemmi, Hirokazu Tanaka
  • Patent number: 6114325
    Abstract: A 1,2-di-substituted benzene-carboxamide derivative or a salt thereof expressed by the following Formula (I); ##STR1## wherein each of A and B is R.sup.1 or --(CH.sub.2)n-NR.sup.2 R.sup.3, wherein when A is R.sup.1, B is --(CH.sub.2)n-NR.sup.2 R.sup.3 and when A is --(CH.sub.2)n-NR.sup.2 R.sup.3, B is R.sup.1 ; Z is --O--, --OCO--, --OCONR.sup.6 -- or --NR.sup.6 --; R.sup.1 is a hydrocarbon group of C.sub.10-30 ; R.sup.2 and R.sup.3 individually represent a hydrogen atom, a lower alkyl group, a phenyl group or a benzyl group, or together represent a heterocyclic ring having 3-7 members; when A is --(CH.sub.2)n-NR.sup.2 R.sup.3, R.sup.2 may be a hydrogen atom, a lower alkyl group, a phenyl group or a benzyl group, and R.sup.3 and R.sup.5 together may represent a heterocyclic ring of 6 or 7 members including two nitrogen atoms; when --Z--B is --OCONR.sup.6 --(CH.sub.2)n-NR.sup.2 R.sup.3 or --NR.sup.6 --(CH.sub.2)n-NR.sup.2 R.sup.3, R.sup.
    Type: Grant
    Filed: October 22, 1998
    Date of Patent: September 5, 2000
    Assignee: Shiseido Co., Ltd.
    Inventors: Hirotada Fukunishi, Kenichi Umishio, Masahiro Tajima, Koji Kobayashi
  • Patent number: 6080860
    Abstract: Novel methods for the synthesis of substituted ureas and guanidines including Terazosin, Prazosin, Doxazosin, Tiodazosin, Trimazosin, Quinasin and Bunazosin (exemplary of 2-amino substituted Quinazolines), Meobentine and Bethanidine and novel intermediates suitable for use in such methods of synthesis are taught.
    Type: Grant
    Filed: September 29, 1997
    Date of Patent: June 27, 2000
    Assignee: Brantford Chemicalss Inc.
    Inventors: Khashayar Karimian, Keshava Murthy, Darren Hall
  • Patent number: 6028195
    Abstract: The present invention relates to novel compound having strong antimumor activities of the general formula(I) ##STR1## wherein R.sub.1 and R.sub.2 are independently hydrogen, substituted or unsubstituted C.sub.1 -C.sub.8 alkyl, substituted or unsubstituted C.sub.3 -C.sub.6 cycloalkyl, substituted or unsubstituted C.sub.2 -C.sub.8 unsaturated alkyl, ketone, substituted or unsubstituted aryl, substituted or unsubstituted C.sub.1 -C.sub.4 alkoxy, substituted or unsubstituted arylhydroxy, substituted or unsubstituted amino, C.sub.1 -C.sub.4 lower ester, C.sub.1 -C.sub.4 lower thioester, thiol, substituted or unsubstituted carboxyl, epoxy, substituted or unsubstituted C.sub.1 -C.sub.4 lower thioalkoxy; or R.sub.1 and R.sub.2 are fused to form C.sub.3 -C.sub.4 saturated or unsaturated chain; R.sub.3, R.sub.4, R.sub.5, R.sub.6 and R.sub.7 are independently hydrogen, halogen, hydroxy, nitro, C.sub.1 -C.sub.4 lower ester, C.sub.1 -C.sub.4 lower alkyl, C.sub.1 -C.sub.4 lower thioalkyl, substituted or unsubstituted C.
    Type: Grant
    Filed: February 27, 1998
    Date of Patent: February 22, 2000
    Assignee: Samjin Pharmaceutical Co., Ltd.
    Inventors: Eui-Hwan Cho, Sun-Gan Chung, Sun-Hwan Lee, Ho-Seok Kwon, Jae-Eung Lee, Dong-Wook Kang, Jeong-Ho Joo, Young-Hee Lee
  • Patent number: 5981531
    Abstract: The invention concerns acid derivatives of formula IR.sup.1 --CON(R.sup.2)--N(R.sup.3)CO--X.sup.1 --Q--X.sup.2 --Gand pharmaceutically acceptable metabolically labile esters or amides thereof, and pharmaceutically acceptable salts thereof, in which R.sup.1, R.sup.2, R.sup.3, X.sup.1, Q, X.sup.2 and G have the meanings given in the specification. The invention also concerns processes for the preparation of the acid derivatives of formula I, pharmaceutical compositions containing them and their use as inhibitors of the binding of fibrinogen to glycoprotein IIb/IIIa.
    Type: Grant
    Filed: May 29, 1998
    Date of Patent: November 9, 1999
    Assignee: Zeneca Limited
    Inventors: Andrew George Brewster, Peter William Rodney Caulkett, Alan Wellington Faull, Robert James Pearce, Richard Eden Shute
  • Patent number: 5952503
    Abstract: Optically-active 2-piperazinecarboxylic acid derivatives are produced through diastereomer salt resolution using optically-active acidic amino acid derivative as the resolving reagent. In this method, the recovery of the resolving reagent used is high, and the production efficiency to produce the optically-active products is high. As the optically-active acidic amino acid derivatives, usable are optically-active, N-acylated acidic amino acid derivatives and optically-active, N-sulfonylated acidic amino acid derivatives.
    Type: Grant
    Filed: August 26, 1998
    Date of Patent: September 14, 1999
    Assignee: Toray Industries, Inc.
    Inventors: Toshihiro Fujino, Haruyo Sato
  • Patent number: 5945534
    Abstract: Optically active piperazine-2-carboxylic acid derivatives of the general formula: ##STR1## in which X is alkoxy or a (substituted) amino group, are prepared by asymmetric hydrogenation of the corresponding pyrazinecarboxylic acid derivatives, catalyzed by optically active rhodium complexes. The compounds of the formula I are intermediates for the preparation of pharmaceutical active substances, for example, HIV protease inhibitors.
    Type: Grant
    Filed: April 14, 1997
    Date of Patent: August 31, 1999
    Assignee: Lonza AG
    Inventor: Rudolf Fuchs
  • Patent number: 5925762
    Type: Grant
    Filed: September 15, 1997
    Date of Patent: July 20, 1999
    Assignee: Boehringer Ingelheim (Canada) Ltd.
    Inventor: Bounkham Thavonekham
  • Patent number: 5922873
    Abstract: A process for preparing a N-tert-butyl-2-pyrazinecarboxamide having the formula (2): ##STR1## which comprises reacting a cyanopyrazine having the formula (1): ##STR2## with tert-butyl alcohol in the presence of sulfuric acid and a process for preparing a N-tert-butyl-2-piperazine-carboxamide having the formula (3): ##STR3## which comprises hydrogenating of said N-tert-butyl-2-pyrazinecarboxamide having the formula (2) in the presence of Raney nickel or Raney cobalt.
    Type: Grant
    Filed: January 20, 1998
    Date of Patent: July 13, 1999
    Assignee: Koei Chemical Co., Ltd.
    Inventors: Nanao Watanabe, Sadao Asahi, Hideki Kuranishi
  • Patent number: 5908843
    Abstract: Novel piperazine derivatives of formula I:Y--(C.sub.m H.sub.2m --CHR.sup.1).sub.n --CO--(NH--CHR.sup.2 --CO).sub.r -- Zwherein ##STR1## R.sup.1, R.sup.2 and R.sup.7 are each, independently, --C.sub.t H.sub.2t --R.sup.9, benzyl, hydroxybenzyl, imidazolylmethyl or indolylmethyl;R.sup.3 is H or H.sub.2 N--C(.dbd.NH)--;R.sup.4 and R.sup.6 are each, independently, (H,H) or .dbd.O;R.sup.5 is H, H.sub.2 N--C(.dbd.NH)-- or H.sub.2 N--C(.dbd.NH)--NH;R.sup.8 is OH, OA or NHOH;R.sup.9 is H, OH, NH.sub.2, SH, SA, COOH, CONH.sub.2 or NH--C(.dbd.NH)--NH.sub.2 ;A is in each case, independently, alkyl having 1-4 C atoms;m and t are each, independently, 0, 1, 2, 3 or 4;n and r are each, independently, 0 or 1; andp is 0, 1 or 2,inhibit the binding of fibrinogen to the fibrinogen receptor and can be used for the treatment of thrombosis, apoplexy, cardiac infarctus, inflammation, arteriosclerosis and tumors.
    Type: Grant
    Filed: January 31, 1994
    Date of Patent: June 1, 1999
    Assignee: Merck Patent Gesellschaft mit Beschrankter Haftung
    Inventors: Joachim Gante, Peter Raddatz, Horst Juraszyk, Sabine Bernotat-Danielowski, Guido Melzer
  • Patent number: 5892038
    Abstract: Compounds of Formula I ##STR1## are disclosed as inhibitors of plasmepsin and cathepsin D. The compounds are therefore useful to treat diseases such as malaria. In preferred compounds of formula I, Y is the residue of an N-acylated amino acid, a substituted 4-aminoproline or a substituted piperazinealkanoic acid. Intermediates in the solid phase synthesis of compounds of formula I, in which the compounds are attached to a solid support, are also disclosed.
    Type: Grant
    Filed: December 8, 1997
    Date of Patent: April 6, 1999
    Assignee: Pharmacopeia, Inc.
    Inventors: Roland Ellwood Dolle, III, Hitesh K. Patel
  • Patent number: 5886181
    Abstract: Optically active piperazine-2-carboxylic acid derivatives of the general formula: ##STR1## wherein R.sup.1 and R.sup.2 are inter alia hydrogen, alkyl or acyl and X is alkoxy or a (substituted) amino group, are prepared by asymmetric hydrogenation of the corresponding 1,4,5,6-tetrahydropyrazines, catalyzed by optically active rhodium, ruthenium or iridium complexes. The compounds of the Formula 1 are intermediates for the preparation of pharmaceutical active ingredients, for example, HIV protease inhibitors.
    Type: Grant
    Filed: May 23, 1996
    Date of Patent: March 23, 1999
    Assignee: Lonza, Ltd.
    Inventors: Rudolf Fuchs, Jean-Paul Roduit
  • Patent number: 5872262
    Abstract: Compounds of Formula I ##STR1## are disclosed as inhibitors of plasmepsin and cathepsin D. The compounds are therefore useful to treat diseases such as malaria. In preferred compounds of formula I, Y is the residue of an N-acylated amino acid, a substituted 4-aminoproline or a substituted piperazinealkanoic acid. Intermediates in the solid phase synthesis of compounds of formula I, in which the compounds are attached to a solid support, are also disclosed.
    Type: Grant
    Filed: December 8, 1997
    Date of Patent: February 16, 1999
    Assignee: Pharmacopeia, Inc.
    Inventors: Roland Ellwood Dolle, III, Hitesh K. Patel, Theodore O. Johnson, Jr., Carolyn DiIanni Carroll, Shiwei Tao
  • Patent number: 5866609
    Abstract: Disclosed herein are substituted vinylurea derivatives represented by the following general formula (1): ##STR1## wherein R.sup.1 and R.sup.3 are independently a phenyl group which may be substituted, R.sup.2 is a phenyl group which may be substituted, or a cycloalkyl group, and wave lines mean that the bonding state may be either E or Z, with the proviso that the cases where R.sup.1, R.sup.2 and R.sup.3 are unsubstituted phenyl groups, and where R.sup.1 and R.sup.2 are unsubstituted phenyl groups and R.sup.3 is a 4-ethoxyphenyl group are excluded, or salt thereof, and medicines comprising such a derivative as an active ingredient as well as a method of preventing and treating arteriosclerosis with such a medicine. The derivatives or salts thereof selectively and strongly inhibit ACAT in macrophages and are hence useful as prophylactic and therapeutic agents for arteriosclerosis.
    Type: Grant
    Filed: July 24, 1997
    Date of Patent: February 2, 1999
    Assignee: SS Pharmaceutical Co., Ltd.
    Inventors: Yoshihiko Kanamaru, Hiroyuki Hirota, Akihiro Shibata, Teruo Komoto, Hiroyuki Naito, Koichi Tachibana, Mari Ohtsuka, Fumio Ishii, Susumu Sato
  • Patent number: 5861512
    Abstract: Intermediates of structural formula ##STR1## can be made by reacting a primary or secondary amine with glycosidol or an activated derivative thereof. The process and intermediates are useful for synthesizing HIV protease inhibitor compounds.
    Type: Grant
    Filed: September 16, 1997
    Date of Patent: January 19, 1999
    Assignee: Merck & Co., Inc.
    Inventors: David Askin, Kai Rossen, Paul Reider, Richard J. Varsolona, Ralph P. Volante, Kenneth M. Wells
  • Patent number: 5856485
    Abstract: A process for preparing 2-piperazinecarboxamides in the form of their enantiomers or their enantiomer mixtures of the general formula: ##STR1## wherein R.sub.1 is (a) unsubstituted or substituted alkyl or (b) --OR.sub.4, wherein R.sub.4 is unsubstituted or substituted alkyl, alkenyl or aryl, or (c) --NR.sub.5 R.sub.6, wherein R.sub.5 is hydrogen or alkyl and R.sub.6 is alkyl, and R.sub.2 and R.sub.3 are identical or different and are hydrogen, unsubstituted or substituted alkyl, alkenyl or aryl, or the radical of an amino acid or an amino acid ester. A 2-piperazinecarboxylic acid of the formula: ##STR2## or a salt thereof, is first converted into an N-acyl derivative of the general formula: ##STR3## where R.sub.1 and R.sub.4 are as defined above. This compound is then cyclized in a second stage in the presence of a halogenating agent to form a piperazinecarboxylic anhydride of the general formula: ##STR4## where R.sub.
    Type: Grant
    Filed: December 23, 1996
    Date of Patent: January 5, 1999
    Assignee: Lonza AG
    Inventors: Walter Brieden, Jean-Paul Roduit
  • Patent number: 5840896
    Abstract: There is disclosed a process for preparing (l)-(-)-2-aminocarbonyl)-N-(4-amino-2,6-dichlorophenyl)-4-?5,5-bis(4-fluor ophenyl)pentyl!-1-piperazineacetamide which comprises the steps of (a) cyclizing (-)-(S,S)-N.sup.1,N.sup.
    Type: Grant
    Filed: April 18, 1995
    Date of Patent: November 24, 1998
    Assignee: Janssen Pharmaceutica, N.V.
    Inventors: Herman Van Belle, Willy Joannes Carolus Van Laerhoven
  • Patent number: 5811462
    Abstract: Peptide analogs containing norbornene are HIV protease inhibitors. These compounds are useful in the prevention or treatment of infection by HIV and in the treatment of AIDS, either as compounds, pharmaceutically acceptable salts, pharmaceutical composition ingredients, whether or not in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of treating AIDS and methods of preventing or treating infection by HIV are also described.
    Type: Grant
    Filed: May 2, 1997
    Date of Patent: September 22, 1998
    Assignee: Merck & Co., Inc.
    Inventors: Randall W. Hungate, Joseph P. Vacca, Byeong Moon Kim
  • Patent number: 5807856
    Abstract: This invention relates to certain novel compounds and derivatives thereof, their synthesis, and their use as selective alpha 1a adrenergic receptor antagonists. One application of these compounds is in the treatment of benign prostatic hyperplasia. These compounds are selective in their ability to relax smooth muscle tissue enriched in the alpha 1a receptor subtype without at the same time inducing orthostatic hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia are achieved.
    Type: Grant
    Filed: November 12, 1996
    Date of Patent: September 15, 1998
    Assignee: Merck & Co., Inc.
    Inventors: Marg G. Bock, Michael A. Patane
  • Patent number: 5801175
    Abstract: Novel compounds of Formula ##STR1## are disclosed. Also disclosed is a method of inhibiting Ras function and therefore inhibiting the abnormal growth of cells. The method comprises administering a compound of the above formula to a biological system. In particular, the method inhibits the abnormal growth of cells in a mammal such as a human being.
    Type: Grant
    Filed: September 13, 1996
    Date of Patent: September 1, 1998
    Assignees: Schering Corporation, Pharmacopeia, Inc.
    Inventors: Adriano Afonso, John J. Baldwin, Ronald J. Doll, Ge Li, Alan K. Mallams, F. George Njoroge, Dinanath F. Rane, John C. Reader, Randall R. Rossman
  • Patent number: 5792869
    Abstract: Process for preparing optically active 2-piperazine-carboxylic acid derivatives, particularly S-enantiomer thereof, in high yield and high optical purity on industrial scale. As the optical resolving agents, easily accessible sulfonamides derived from selected optically active amino acids, such as N-tosyl-L-phenylalanine, N-tosyl-D-phenylglycine, N-tosyl-L-alanine or N-tosyl-L-valine, give excellent results. These resolving agents are stable and easily recovered from the reaction mixture and reused. Resolved 2-piperazinecarboxylic acid derivatives are preferably isolated as 4-t-butoxycarbonyl (Boc) derivatives. Diastereomeric salts (an example being shown below) formed as the intermediates of resolution are novel. ##STR1## ?In the formula "Ar" stands for a phenyl or naphthyl group which may be substituted with one to three C1-C6 alkyl groups, halogen atoms, nitro or alkoxy groups; and n=0 or 1.
    Type: Grant
    Filed: November 2, 1995
    Date of Patent: August 11, 1998
    Assignee: Yamakawa Chemical Industry Co., Ltd
    Inventors: Hisamichi Murakami, Shoko Satoh, Tadashi Tobiyama, Ken'ichi Sakai, Hiroyuki Nohira
  • Patent number: 5756504
    Abstract: Compounds of the formula X--Y--R, or the pharmaceutically acceptable salts and esters thereof, wherein X is ##STR1## Y is --SO.sub.2 --, --(CH.sub.2).sub.p -- or --CO--(CH.sub.2).sub.p --; R is unsubstituted or substituted phenyl where said substitutents are one or more of R.sup.5, R.sup.6 or R.sup.7 ; R.sup.1 is hydrogen, cyano, phenyl, --CONHR.sup.2, --CONR.sup.2 R.sup.2, --(CH.sub.2).sub.m --OR.sup.2, --(CH.sub.2).sub.p --S(O).sub.r --R.sup.2, --(CH.sub.2).sub.m --CO.sub.2 R.sup.2, --(CH.sub.2).sub.m --N.sub.3, --(CH.sub.2).sub.m --NH.sub.2 or --(CH.sub.2).sub.m --NR.sup.2 R.sup.2 ; R.sup.2 is hydrogen, C.sub.3-8 cycloalkyl or C.sub.1-5 alkyl; R.sup.5 and R.sup.6 are each independently selected from hydrogen, C.sub.1-5 alkoxy, halogen or --(CH.sub.2).sub.n --N(R.sup.2)--C(O)--R.sup.18 ; R.sup.7 is hydrogen or ##STR2## R.sup.11 is selected from hydrogen, C.sub.1-5 alkyl-carbonyl, --Z--R.sup.13, ##STR3## or substituted C.sub.
    Type: Grant
    Filed: September 23, 1996
    Date of Patent: May 26, 1998
    Assignee: Merck & Co., Inc.
    Inventors: Mark G. Bock, Ben E. Evans, J. Christopher Culberson, Kevin F. Gilbert, Kenneth E. Rittle, Peter D. Williams
  • Patent number: 5734055
    Abstract: A process for preparing a N-tert-butyl-2-pyrazinecarboxamide having the formula (2): ##STR1## which comprises reacting a cyanopyrazine having the formula (1): ##STR2## with tert-butyl alcohol in the presence of sulfuric acid and a process for preparing a N-tert-butyl-2-piperazine-carboxamide having the formula (3): ##STR3## which comprises hydrogenating of said N-tert-butyl-2-pyrazinecarboxamide having the formula (2) in the presence of Raney nickel or Raney cobalt.
    Type: Grant
    Filed: July 20, 1995
    Date of Patent: March 31, 1998
    Assignee: Koei Chemical Co. Ltd.
    Inventors: Nanao Watanabe, Sadao Asahi, Hideki Kuranishi, Takashi Kurahashi
  • Patent number: 5734054
    Abstract: Compounds of Formula I ##STR1## are disclosed as inhibitors of plasmepsin and cathepsin D. The compounds are therefore useful to treat diseases such as malaria. In preferred compounds of formula I, Y is the residue of an N-acylated amino acid, a substituted 4-aminoproline or a substituted piperazinealkanoic acid. Intermediates in the solid phase synthesis of compounds of formula I, in which the compounds are attached to a solid support, are also disclosed.
    Type: Grant
    Filed: November 5, 1996
    Date of Patent: March 31, 1998
    Assignee: Pharmacopeia, Inc.
    Inventors: Roland Ellwood Dolle, III, Theodore O. Johnson, Jr., Carolyn DiIanni Carroll
  • Patent number: 5721365
    Abstract: There are disclosed N-substituted piperazine NONOate compounds having the structure: ##STR1## wherein M is a pharmaceutically acceptable cation, x is the valence of the cation, and R is selected from the group consisting of: an unsubstituted or substituted C.sub.1 -C.sub.20 straight chain alkyl, an unsubstituted or substituted C.sub.3 -C.sub.20 branched chain alkyl,an unsubstituted or substituted C.sub.2 -C.sub.20 straight chain alkenyl, an unsubstituted or substituted C.sub.3 -C.sub.20 branched chain alkenyl, a group of formula, ##STR2## a group of formula, ##STR3## a group of formula R.sup.4 --SO.sub.2 --, or a group of formula R.sup.5 --O--N.dbd.N(O)--. The compounds are potent nitric oxide releasing compounds.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: February 24, 1998
    Inventors: Larry Kay Keefer, Joseph E. Saavedra, Joseph Anthony Hrabie