01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Diagnostic preparations for clinical or medical laboratory use; Diagnostic reagents for clinical or medical laboratory use Pharmaceutical and veterinary preparations for the treatment or prevention of dermatological conditions, namely, eczema, inflammation, infection, warts, psoriasis, aging of the skin, ultra violet radiation and cancer; Pharmaceutical and veterinary preparations for the treatment of infections caused by bacteria, fungi, viruses and rheumatoid arthritis; Pharmaceutical and veterinary preparations for the treatment of diseases, disorders and conditions in the area of oncology
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Diagnostic preparations for clinical or medical laboratory use; Diagnostic reagents for clinical or medical laboratory use Pharmaceutical and veterinary preparations for the treatment or prevention of dermatological conditions, namely, eczema, inflammation, infection, warts, psoriasis, aging of the skin, ultra violet radiation and cancer; Pharmaceutical and veterinary preparations for the treatment of infections caused by bacteria, fungi, viruses and rheumatoid arthritis; Pharmaceutical and veterinary preparations for the treatment of diseases, disorders and conditions in the area of oncology
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
Goods & Services
Chemical substances for use in the manufacture of pharmaceutical preparations for the treatment of dermatological conditions and for the treatment of infections and diseases; chemical substances for use in research and development of pharmaceuticals for the treatment of dermatological conditions and for the treatment of infections and diseases; diagnostic preparations for scientific clinical use; diagnostic reagents for clinical or medical laboratory use Pharmaceutical and veterinary products and preparations for the treatment and prevention of dermatological conditions, namely, eczema, inflammation, infection, warts, psoriasis, aging of the skin, ultra violet radiation and cancer; Pharmaceutical and veterinary products and preparations for the treatment and prevention of infections caused by bacteria, fungi, viruses, and rheumatoid arthritis; Pharmaceutical and veterinary products and preparations for the treatment and prevention of diseases, disorders and conditions in the area of oncology; Pharmaceutical and veterinary products and preparations for the treatment and prevention of diseases, disorders and conditions in the area of gastroenterology; Pharmaceutical and veterinary products and preparations for the treatment and prevention of diseases, disorders and conditions in the area of neurology; Pharmaceutical and veterinary products and preparations for the treatment and prevention of diseases, disorders and conditions in the area of gynecology; Pharmaceutical and veterinary products and preparations for the treatment and prevention of diseases, disorders and conditions in the area of urology; Pharmaceutical and veterinary products and preparations for the treatment and prevention of diseases, disorders and conditions in the area of cardiology; Pharmaceutical and veterinary products and preparations for the treatment and prevention of diseases, disorders and conditions in the area of endocrinology; Pharmaceutical and veterinary products and preparations for the treatment and prevention of diseases, disorders and conditions in the area of nephrology; Pharmaceutical and veterinary products and preparations for the treatment and prevention of diseases, disorders and conditions in the area of hematology; Pharmaceutical and veterinary products and preparations for the treatment and prevention of diseases, disorders and conditions in the area of allergy; Pharmaceutical and veterinary products and preparations for the treatment and prevention of diseases, disorders and conditions in the area of immunology; Pharmaceutical and veterinary products and preparations for the treatment and prevention of diseases, disorders and conditions in the area of psychiatry; Pharmaceutical and veterinary products and preparations for the treatment and prevention of diseases, disorders and conditions in the area of anesthesiology; Pharmaceutical and veterinary products and preparations for the treatment and prevention of diseases, disorders and conditions in the area of rheumatology; all of the aforesaid for prescription only Research and development services for third parties in the field of chemical substances, pharmaceutical and veterinary products and preparations
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Pharmaceutical preparations and substances for the treatment of infectious diseases, for the treatment of dermatological disorders, for the treatment of gastrointestinal diseases, for the treatment of neurological diseases, for the treatment of cardiovascular diseases, and for the treatment of gynecological diseases
6.
Process for the manufacture of isavuconazole or ravuconazole
The invention relates to a process for the manufacture of diastereomerically and enantiomerically enriched triazole compounds isavuconazole and ravuconazole, comprising a Reformatsky reaction between a ketone and a 2-halozincpropionate ester, followed by a resolution step, preferably an enzymatic resolution with an esterase enzyme.
5 together represent methylenedioxy; and pharmaceutically acceptable derivatives thereof. Methods of treatment of neoplastic and autoimmune diseases with these compounds we also disclosed.
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
C12Q 1/48 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving transferase
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
05 - Pharmaceutical, veterinary and sanitary products
40 - Treatment of materials; recycling, air and water treatment,
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
(1) Pharmaceutical preparations for the prevention and/or treatment of: dermatological conditions, namely, skin pigmentation diseases, acne, infection, warts, psoriasis, aging of the skin, ultra violet radiation, cancer, and infectious diseases and disorders caused by bacteria, fungi and viruses, namely, skin infections, skin structure infections, diabetic foot infections, eye infections, respiratory tract infections, soft tissue infections, urinary tract infections, biliary infections, intra-abdominal infections, genital infections, bone infections, joint infections, nail infections, osteomyelitis, septicemia, pneumonia, bacterial endocarditis, meningitis, otitis media; pharmaceutical preparations for the prevention and treatment of rheumatoid arthritis; pharmaceutical preparations for the prevention and treatment of cancer; pharmaceutical preparations for use in oncology; antibiotic preparations; anti-inflammatory preparations; anti-fungal pharmaceutical preparations; Chemical, biological and diagnostic reagents for medical laboratory use and clinical laboratory use (1) Manufacturing of chemicals, pharmaceutical preparations, and veterinary products to the order and specification of others
(2) The provision of research and development services to others in the area of chemicals, pharmaceutical and veterinary products and preparations
(3) Operation of a pharmaceutical company
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
40 - Treatment of materials; recycling, air and water treatment,
42 - Scientific, technological and industrial services, research and design
44 - Medical, veterinary, hygienic and cosmetic services; agriculture, horticulture and forestry services
Goods & Services
(1) Pharmaceutical preparations for the prevention and/or treatment of: dermatological conditions, namely, skin pigmentation diseases, acne, infection, warts, psoriasis, aging of the skin, ultra violet radiation, cancer, and infectious diseases and disorders caused by bacteria, fungi and viruses, namely, skin infections, skin structure infections, diabetic foot infections, eye infections, respiratory tract infections, soft tissue infections, urinary tract infections, biliary infections, intra-abdominal infections, genital infections, bone infections, joint infections, nail infections, osteomyelitis, septicemia, pneumonia, bacterial endocarditis, meningitis, otitis media; pharmaceutical preparations for the prevention and treatment of rheumatoid arthritis; pharmaceutical preparations for the prevention and treatment of cancer; pharmaceutical preparations for use in oncology; antibiotic preparations; anti-inflammatory preparations; anti-fungal pharmaceutical preparations; Chemical, biological and diagnostic reagents for medical laboratory use, clinical laboratory use and medical research use (1) Manufacturing of chemicals, pharmaceutical preparations, and veterinary products to the order and specification of others
(2) The provision of research and development services to others in the area of chemicals, pharmaceutical and veterinary products and preparations
(3) Operation of a pharmaceutical company
10.
Use of BUBR1 as a biomarker of drug response to furazanobenzimidazoles
Use of BUBR1 as a biomarker for predicting the response to a compound, preferably resistance of a disease such as cancer in a subject, wherein the compound is a compound of general formula I
and pharmaceutically acceptable derivatives thereof. Methods of treatment of neoplastic and autoimmune diseases with these compounds are also disclosed.
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
Disclosed is a novel principle for dosing a specific anti-cancer drug compound of formula (I), a prodrug thereof or a pharmaceutically acceptable salt of said drug compound or prodrug thereof as described, wherein said drug compound, prodrug thereof or pharmaceutically acceptable salt of said drug compound or prodrug thereof is intravenously administered to a cancer patient according to a specific dosage frequency and a specific treatment cycle at a dose being below the maximum tolerated dose (MTD) defined for said dosage frequency and treatment cycle of said drug, prodrug thereof or pharmaceutically acceptable salt of said drug compound or prodrug thereof but providing at least the same exposure of the tissue of the cancer from which said cancer patient is suffering, to said drug as provided by the MTD at the same dosage frequency and treatment cycle.
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
13.
Process for the manufacture of isavuconazole or ravuconazole
The invention relates to a process for the manufacture of diastereomerically and enantiomerically enriched triazole compounds isavuconazole and ravuconazole, comprising a Reformatsky reaction between a ketone and a 2-halozincpropionate ester, followed by a resolution step, preferably an enzymatic resolution with an esterase enzyme.
The antibacterial compound of formula I
X5 represents C—H or C—(C1-C6alkyl), C-halogen; A1, A2, A3, R1 and R4 represent various substituents, G represents aryl or heteroaryl, which is unsubstituted or substituted which compounds show good activity against pathogenic bacteria.
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
C07D 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 409/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 405/12 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
C07D 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
The present invention relates to antibacterial compounds of formula I:
wherein all variable substituents are defined as described herein, which are useful for the treatment of bacterial infections.
C07D 491/052 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered
C07D 491/147 - Ortho-condensed systems the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
Crystalline (6R,7R)-7-{2-(5-amino-[1,2,4] thiadiazol-3-yl)-2-[(Z)-trityloxyimino]-acetylamino}-3-[(R)-1′-tert-butoxycarbonyl-2-oxo-[1,3′]bipyrrolidinyl-(3E)-ylidenemethyl]-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester; its manufacture and use
A solid DMSO solvate of a compound of formula (I) is described, which is a useful intermediate for preparing the broad spectrum antibiotics Ceftobiprole and Ceftobiprole Medocaril.
C07D 501/54 - Methylene radicals, substituted by hetero rings with the 7-amino radical acylated by an araliphatic carboxylic acid, which is substituted on the aliphatic radical by hetero atoms
The application relates to the macrolide compound of the formula (I): wherein * indicates a stereocentre which is in (R) or (S) configuration, or a pharmaceutically acceptable salt or ester thereof and their use as PDE4 inhibitors.
C07H 17/08 - Hetero rings containing eight or more ring members, e.g. erythromycins
A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
Use of BUBR1 as a biomarker for predicting the response to a compound, preferably resistance of a disease such as cancer in a subject, wherein the compound is a furazanobenzimidazole compound of general formula (I).
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/41 - 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 is nitrogen, e.g. tetrazole
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
G01N 33/00 - Investigating or analysing materials by specific methods not covered by groups
19.
PROCESS FOR THE MANUFACTURE OF ISAVUCONAZOLE OR RAVUCONAZOLE
The invention relates to a process for the manufacture of diastereomerically and enantiomerically enriched triazole compounds isavuconazole and ravuconazole, comprising a Reformatsky reaction between a ketone and a 2-halozincpropionate ester, followed by a resolution step, preferably an enzymatic resolution with an esterase enzyme.
Use of glu-tubulin as a biomarker for predicting the response to a compound, preferably resistance of a disease such as cancer in a subject to said compound, wherein the compound is a furazanobenzimidazole compound of general formula (I).
The invention relates to novel Rauwolfia alkaloid derivatives of formula (I) combinations of Rauwolfia alkaloid derivatives and a mitochondrial inhibitor, e.g. metformin, and the use of Rauwolfia alkaloid derivatives in combination with mitochondrial inhibitor for the treatment of cancer and for achieving clinical immunosuppression. The invention also relates to a fluorescence-based method for predicting the sensitivity of a cancer cell towards a compound of formula (I).
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
Goods & Services
(1) Chemical preparations for use in the pharmaceutical industry as well as chemical preparations for research and development of pharmaceutical preparations; pharmaceutical preparations for the prevention and / or treatment of: dermatological conditions, namely, dermatitis, skin pigmentation diseases, acne, eczema, inflammation, infection, warts, psoriasis, aging of the skin, ultra violet radiation and cancer; infectious diseases and disorders, namely, rheumatoid arthritis and infectious diseases and disorders caused by bacteria, fungi, and viruses; diseases, disorders and conditions in the area of oncology; antibiotic preparations; anti-inflammatory preparations; anti-fungal pharmaceutical preparations; anti-microbial pharmaceutical preparations. (1) The provision of scientific and technological research services and scientific and technological development services to others in the area of chemicals, pharmaceutical and veterinary products and preparations.
23.
Use of acetylated tubulin as a biomarker of drug response to furazanobenzimidazoles
Use of acetylated tubulin as a biomarker for predicting the response to a compound, preferably resistance of a disease such as cancer in a subject to said compound, wherein the compound is a furazanobenzimidazoles compound of general formula (I).
A61K 31/41 - 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 is nitrogen, e.g. tetrazole
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
Compounds of formula (I), wherein A1 represents -0-, -S- or -CH2-; A2 represents -CH2- or -0-; A3 represents C3-C8cycloalkylene; saturated or unsaturated 4 to 8-membered heterocyclodiyl with 1, 2 or 3 heteroatoms selected from nitrogen or oxygen, which group A3 is unsubstituted or substituted; A4 represents C1-C4alkylene, -C(=0)-; G represents aryl or heteroaryl, which is unsubstituted or substituted; X1 represents a nitrogen atom or CR1; R1 represents a hydrogen atom or a halogen atom; R2 represents a hydrogen atom; m is 0 or 1; n is 1; the -(CH2)n- group is unsubstituted or substituted; p is 0 or 1; or pharmaceutically acceptable salts thereof are valuable for use as a medicament for the treatment of bacterial infections.
C07D 491/147 - Ortho-condensed systems the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
26.
Furazanobenzimidazoles as prodrugs to treat neoplastic or autoimmune diseases
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
27.
USE OF PHOSPHO-AKT AS A BIOMARKER OF DRUG RESPONSE
Use of phospho-Akt as a biomarker for predicting the response, such as resistance, to a compound, wherein phospho-Akt is Akt that has been phosphorylated on one or more residues, with the proviso that for Akt1, Akt2, and Akt3 the designation phospho-Akt is used to indicate phosphorylation at a site other than T308, T309 or T305 respectively, wherein the compound is a compound of general formula (I) wherein R represents phenyl, thienyl or pyridinyl wherein phenyl is optionally substituted by one or two substituents independently selected from alkyl, halo-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, acyloxy-lower alkyl, phenyl, hydroxy, lower alkoxy, hydroxy-lower alkoxy, lower alkoxy-lower alkoxy, phenyl-lower alkoxy, lower alkylcarbonyloxy, amino, monoalkylamino, dialkylamino, lower alkoxycarbonylamino, lower alkylcarbonylamino, substituted amino wherein the two substituents on nitrogen form together with the nitrogen heterocyclyl, lower alkylcarbonyl, carboxy, lower alkoxycarbonyl, cyano, halogen, and nitro; and wherein two adjacent substituents are methylenedioxy; and wherein pyridinyl is optionally substituted by lower alkoxy, amino or halogen; X represents a group C=Y, wherein Y stands for oxygen or nitrogen substituted by hydroxy or lower alkoxy; R1 represents hydrogen, lower alkylcarbonyl, hydroxy-lower alkyl or cyano-lower alkyl; R2, R3 and R6 represent hydrogen; R4 and R5, independently of each other, represent hydrogen, lower alkyi or lower alkoxy; or R4 and R5 together represent methylenedioxy; and pharmaceutically acceptable derivatives thereof; or wherein R represents phenyl or pyridinyl wherein phenyl is optionally substituted by one or two substituents independently selected from alkyi, halo-lower alkyi, hydroxy-lower alkyi, lower alkoxy-lower alkyi, acyloxy-lower alkyi, phenyl, hydroxy, lower alkoxy, hydroxy-lower alkoxy, lower alkoxy-lower alkoxy, phenyl-lower alkoxy, lower alkylcarbonyloxy, amino, monoalkylamino, dialkylamino, lower alkoxycarbonylamino, lower alkylcarbonylamino, substituted amino wherein the two substituents on nitrogen form together with the nitrogen heterocyclyl, lower alkylcarbonyl, carboxy, lower alkoxycarbonyl, formyl, cyano, halogen, and nitro; and wherein two adjacent substituents are methylenedioxy; and wherein pyridinyl is optionally substituted by lower alkoxy, amino or halogen; X represents oxygen; R1 represents hydrogen, lower alkylcarbonyl, hydroxy-lower alkyi or cyano-lower alkyi; R2, R3 and R6 represent hydrogen; R4 and R5, independently of each other, represent hydrogen, lower alkyi or lower alkoxy; or R4 and R5 together represent methylenedioxy; and pharmaceutically acceptable derivatives thereof. Methods of treatment of neoplastic and autoimmune diseases with these compounds are also disclosed.
C12Q 1/48 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving transferase
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
28.
USE OF ACETYLATED TUBULIN AS A BIOMARKER OF DRUG RESPONSE TO FURAZANOBENZIMIDAZOLES
Use of acetylated tubulin as a biomarker for predicting the response to a compound, preferably resistance of a disease such as cancer in a subject to said compound, wherein the compound is a furazanobenzimidazoles compound of general formula (I).
Use of stathmin as a biomarker for predicting the response, such as resistance, to a compound, wherein the compound is a furazanobenzimidazole compound of general formula (I).
Use of glu-tubulin as a biomarker for predicting the response to a compound, preferably resistance of a disease such as cancer in a subject to said compound, wherein the compound is a furazanobenzimidazole compound of general formula (I).
Use of BUBR1 as a biomarker for predicting the response to a compound, preferably resistance of a disease such as cancer in a subject, wherein the compound is a furazanobenzimidazole compound of general formula (I).
3 are independently of one another hydrogen, F or Cl; or a pharmaceutically acceptable acid addition salt thereof, and (b) a carrier comprising a solubilizer component for the antifungally effective component (a).
A01N 55/02 - Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen and sulfur containing metal atoms
A01N 43/64 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
A61K 31/41 - 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 is nitrogen, e.g. tetrazole
A61K 31/555 - Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
Compound of formula (I): wherein A1 represents -O-, -S- or -N-R3; A2 represents -CH2-, -O-, -N-R4, -C(=O)- or -CH(O-R4)-; A3 represents C3-C8cycloalkylene; saturated and unsaturated 4 to 8-membered heterocyclodiyl with 1, 2 or 3 heteroatoms selected from nitrogen, oxygen and sulphur, which group A3 is unsubstituted or substituted; A4 represents C1-C4alkylene, C2-C4alkenylene, >C=O or a group selected from - C2H4NH-, -C2H4O-, and -C2H4S- being linked to the adjacent NR5-group via the carbon atom; and G represents aryl or heteroaryl, which is unsubstituted or substituted and R1 and R2 independently of one another, represent hydrogen or a substituent selected from hydroxy, halogen, mercapto, cyano, nitro, C1-C6alkyl, C1-C6alkoxy, C1-C6alkylthio, C1-C6alkylcarbonyloxy, C1-C6alkylsulfonyloxy, C1-C6heteroalkylcarbonyloxy, C5-C6heterocyclylcarbonyloxy, C1-C6heteroalkoxy, wherein heteroalkyl, heteroalkoxy groups or heterocyclyl comprise 1, 2 or 3 heteroatoms selected from nitrogen, oxygen and sulphur, in which substituents the alkyl moieties are unsubstituted or further substituted; R3, R4 and R5 independently of one another, represent hydrogen or C1-C6alkyl; X1 and X2 independently of one another, represent a nitrogen atom or CR2, with the proviso that at least one of Xl and X2 represents a nitrogen atom; m is 1; and the (CH2)m moiety is optionally substituted by C1-C4alkyl; halogen, carboxy, hydroxy, C1-C4alkoxy, C1-C4-alkylcarbonyloxy, amino, mono- or di-(C1-C4alkyl)amino or acylamino n is 0, 1 or 2 or pharmaceutically acceptable salt thereof are valuable for use as a medicament for the treatment of bacterial infections.
A61K 31/4741 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having oxygen as a ring hetero atom, e.g. tubocuraran derivatives, noscapine, bicuculline
A61K 31/4743 - QuinolinesIsoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having sulfur as a ring hetero atom
Crystalline (6R,7R)-7-{2-(5-amino-[1,2,4] thiadiazol-3-yl)-2-[(Z)-trityloxyimino]-acetylamino}-3-[(R)-1′-tert-butoxycarbonyl-2-oxo-[1,3′]bipyrrolidinyl-(3E)-ylidenemethyl]-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester; its manufacture and use
A solid DMSO solvate of a compound of formula (I) is described, which is a useful intermediate for preparing the broad spectrum antibiotics Ceftobiprole and Ceftobiprole Medocaril.
A61K 31/545 - Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula , e.g. cephalosporins, cefaclor, cephalexine
C07D 501/04 - Preparation from compounds already containing the ring or condensed ring systems, e.g. by dehydrogenation of the ring, by introduction, elimination or modification of substituents
C07D 501/54 - Methylene radicals, substituted by hetero rings with the 7-amino radical acylated by an araliphatic carboxylic acid, which is substituted on the aliphatic radical by hetero atoms
The invention relates to macrolide compounds of formula (I), the use of said compounds as medicaments, in particular for the treatment or prevention of inflammatory and allergic diseases, pharmaceutical compositions containing said compounds and to processes for their preparation. The invention relates in particular to macrolide compounds with antiinflammatory activity mediated primarily through inhibition of phosphodiesterase 4 (PDE4) which makes them useful for the treatment and/or prevention of inflammatory and allergic diseases such as chronic obstructive pulmonary disease (COPD), asthma, rheumatoid arthritis, atopic dermatitis or inflammatory bowel disease or proliferative diseases such as cancer.
A61K 31/4433 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
A compound of formula (II) wherein (a) represents a divalent benzene residue which is unsubstituted or substituted by one or two additional substituents independently selected from lower alkyl, halo-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, acyloxy-lower alkyl, phenyl, hydroxy, lower alkoxy, hydroxy-lower alkoxy, lower alkoxy-lower alkoxy, phenyl-lower alkoxy, lower alkylcarbonyloxy, amino, mono(lower alkyl)amino, di(lower alkyl)amino, mono(lower alkenyl)amino, di(lower alkenyl)amino, lower alkoxycarbonylamino, lower alkylcarbonylamino, substituted amino wherein the two substituents on nitrogen form together with the nitrogen heterocyclyl, lower alkylcarbonyl, carboxy, lower 15 alkoxycarbonyl, cyano, halogen, and nitro; or wherein two adjacent substituents can be methylenedioxy; or a divalent pyridine residue (Z = N) which is unsubstituted or substituted additionally by lower alkyl, lower alkoxy, lower alkoxy-lower alkoxy,amino, optionally substituted by one or two substituents selected from lower alkyl, lower alkenyl and alkylcarbonyl, halo-20 lower alkyl, lower alkoxy-lower alkyl, or halogen; R1 represents hydrogen, lower alkylcarbonyl, hydroxy-lower alkylor cyano-loweralkyl; and R2 represents a group selected from: (b), (c) and (d); or pharmaceutically acceptable salts thereof.
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
Compounds of formula (I) wherein X1, X3; X4 and X6, each independently of the others, represents a nitrogen atom or CR2, with the proviso that at least one of X1, X3; X4 and X6 represents a nitrogen atom; X2 represents C-H, C-(C1-C6alkyl), C-(C1-C6alkoxy), C-halogen, C-COOH; X5 represents C-H or C-(C1-C6alkyl), C-halogen; R1 and R2, independently of one another, represent hydrogen or a substituent selected from hydroxy, halogen, carboxy, amino, C1-C6alkylamino, di(C1-C6alkyl)amino, mercapto, cyano, nitro, C1-C6alkyl, C1-C6alkoxy, C1-C6alkylthio, C1-C6alkylamino- carbonyloxy, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkylcarbonyloxy, C1-C6alkyl- sulfonyloxy, C1 -C6heteroalkylcarbonyloxy, C5-C6heterocyclylcarbonyloxy, C1-C6heteroalkyl, C1-C6heteroalkoxy, wherein heteroalkyl, heteroalkoxy groups or heterocyclyl comprise 1, 2 or 3 heteroatoms selected from nitrogen, oxygen and sulphur, in which substituents the alkyl moieties are unsubstituted or further substituted by halogeno, cyano, hydroxy, C1-C4alkoxy, C1-C4alkylcarbonyl, C1-C4alkoxycarbonyl, unsubstituted or substituted phenoxy or phenylcarbonyl, unsubstituted or substituted C5-C6heterocyclyl or carboxy; A1 represents a divalent group of one of the formulae -O-(CH2)m-(CH2)-, -S-(CH2)m-(CH2)- or -(C=O)O-(CH2)m-(CH2)-, wherein the (CH2)m moiety is optionally substituted by C1-C4alkyl, C2-C4alkenyl, C3-C6cycloalkyl, C3-C6cycloalkylmethyl, morpholinomethyl, halogen, carboxy, hydroxy, C1-C4alkoxy; C1 -C4alkoxyC1 -C4alkyl, C1 -C4alkoxy(C1 -C4alkylenoxy)C1 -C4alkyl, benzyloxyC1 - C4alkyl, amino, mono- or di-(C1-C4alkyl)amino or acylamino, in which substituents the alkyl moieties can be further substituted by 1 or more fluoro atoms m is 0, 1 or 2, provided that the number of atoms in the direct chain between the two terminal valencies of A1 is at least 3, which group A1 is linked to A2 via the terminal (CH2)-moiety; A2 is a group selected from C3-C8cycloalkylene; saturated and unsaturated 4 to 8- membered heterocyclodiyl with 1, 2 or 3 heteroatoms selected from nitrogen, oxygen and sulphur, which group A2 is unsubstituted or substituted; R4 represents hydrogen or C1 -C4alkyl; A3 represents C1-C4alkylene, C2-C4alkenylene, >C=O, -C(O)C1-C3alkylene-, -C(=O)NH-, or a group selected from -C2H4NH-, -C2H4O-, and -C2H4S- being linked to the adjacent NR4-group via the carbon atom; and G represents aryl or heteroaryl, which is unsubstituted or substituted and n is 0, 1 or 2; or a pharmaceutically acceptable salts, hydrates or solvates thereof are valuable antibacterial agents.
C07D 405/12 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 409/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
C07D 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
A61K 31/4375 - 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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
A compound of formula (I) in a crystalline form, which has a X-ray diffraction pattern comprising, when measured using Cu- Kα1 radiation, a diffraction line, having a relative intensity (rl) of 100 percent at about 11.6, 12.9, 14.7, 22.0, 23.1 or 24.5, given in degrees 2 Theta [2θ]. Five corresponding polymorphic crystal forms (Polymorph A; B; C; D or E) have been characterized by means of their XRPD and have been isolated.
C07D 501/00 - Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula: , e.g. cephalosporinsSuch ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
A61K 31/549 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one sulfur as the ring hetero atoms, e.g. sulthiame having two or more nitrogen atoms in the same ring, e.g. hydrochlorothiazide
Disclosed is a process for the manufacture of a compound of formula (I)
2 represent, independently from one another, hydrogen or Hal; in which process a compound of formula (II)
is converted to a corresponding alkyl, fluoroalkyl or aryl sulfonic acid ester, which is then reacted with an alkali metal nitrite in the presence of a suitable crown ether in a polar non-nucleophilic solvent at a temperature of −10 to 50° C. to give the compound of formula (I).
C07D 277/24 - Radicals substituted by oxygen atoms
41.
CRYSTALLINE (6R,7R)-7-{2-(5-AMINO-[1,2,4]THIADIAZOL-3-YL)-2-[(Z)-TRITYLOXYIMINO]-ACETYLAMINO}-3-[(R)-1'-TERT-BUTOXYCARBONYL-2-OXO-[1,3']BIPYRROLIDINYL-(3E)-YLIDENEMETHYL]-8-OXO-5-THIA-1-AZA-BICYCLO[4.2.0]OCT-2-ENE-2-CARBOXYLIC ACID BENZHYDRYL ESTER; ITS MANUFACTURE AND USE
A solid DMSO solvate of a compound of formula (I) is described, which is a useful intermediate for preparing the broad spectrum antibiotics Ceftobiprole and Ceftobiprole Medocaril.
C07D 501/54 - Methylene radicals, substituted by hetero rings with the 7-amino radical acylated by an araliphatic carboxylic acid, which is substituted on the aliphatic radical by hetero atoms
A61P 31/00 - Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
A61K 31/546 - Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula , e.g. cephalosporins, cefaclor, cephalexine containing further heterocyclic rings, e.g. cephalothin
The invention relates to macrolide compounds of formula (I),the use of said compounds as medicaments, in particular for the treatment or prevention of inflammatory and allergic diseases, pharmaceutical compositions containing said compounds and to processes for their preparation. The invention relates in particular to macrolide compounds with anti-inflammatory activity mediated primarily through inhibition of phosphodiesterase 4 (PDE4) which makes them useful for the treatment and/or prevention of inflammatory and allergic diseases such as chronic obstructive pulmonary disease (COPD), asthma, rheumatoid arthritis, atopic dermatitis or inflammatory bowel disease or proliferative diseases such as cancer.
C07H 17/08 - Hetero rings containing eight or more ring members, e.g. erythromycins
A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
Macrolides of Formula (I) or (I-A): and wherein the residues R1, R2, R3, R4, R12, R13 and R14 have certain meanings defined in this application are useful for treating or preventing inflammatory or allergic diseases or. cancer in animals and humans.
A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
A process for the production of a compound of formula (I) wherein ALINKERB represents a linker moiety of formula (V): A[G1 - G2*- G3]B; wherein A and B indicate the orientation of the group of formula (V) in formula (I); G1, G2 and G3 have specific meanings described herein and may be present or absent, with the proviso that at least one of G1 or G3 is present; which linker group may furthermore optionally contain one or more groups of formula (VI); and/or other substituents; and R1 represents hydrogen or a C1-C4-alkyl group; R2 represents hydrogen or a C1-C4-alkyl group; R3 independently at each occurrence, represents hydrogen or a C1-C4-alkyl group; x is 0 or 1; y is 0 or 1; z independently at each occurrence, is 0 or 1; and (- -) represents a single bond between a primary, secondary or tertiary carbon atom of the moiety ALINKERB and the adjacent nitrogen atom; in which process (A) a compound of formula (II) is reacted with a compound of formula (III) wherein Pr represents an amino protecting group selected from t-butyloxy carbonyl (t-Boc), 1-methyl-1-(4-biphenylyl)ethyloxy carbonyl (Bpoc), 1-(1-adamantyl)-1-methylethyloxy carbonyl (Adpoc), 1-(3,5-di-t-butylphenyl)-1-methylethyloxy carbonyl (t-Bumeoc), 1-adamantyloxy carbonyl (Adoc), p-methoxybenzyloxy carbonyl (Moz), o,p-dimethoxybenzyloxy carbonyl, ALINKERB has the same meaning as in formula (I) with the exception that one or more of the optional groups of formula (VII) may be replaced by a group of formula (VII) and R1; R2; R3; x; y; z and (--), at each occurrence, have the same meaning as in formula (I) and Pr is as defined above; in a dipolar aprotic solvent in the presence of a base to obtain a compound of formula (IV) wherein Pr; ALINKERB; R1; R2; R3; x; y; z; and (- -), at each occurrence, have the same meaning as in formula (III); which compound is then (B) deprotected by reaction with formic acid or a mixture of formic acid or acetic acid with hydrochloric acid or hydrobromic acid, to give the compound of formula (I) as well as the compounds of the aforementioned formula (IV).
A process for manufacturing a compound of Formula (I) which has cis-conformation and wherein R1 represents a 1-phenyl-C1-C4alkyl or 1-naphthyl-C1-C4alkyl group, wherein the phenyl or naphthyl moiety of R1 is unsubstituted or substituted with one or more C1-C4alkoxy groups and the carbon atoms in 2-, 3-, and/or 4-position of the alkyl part of R1 are, independently of the phenyl or naphthyl moiety of R1 and independently of one another, unsubstituted or substituted with C1-C4alkoxy and/or silyloxy or, preferably, are unsubstituted or substituted with one C1-C4alkoxy group and/or silyloxy group per carbon atom, and R2 represents a C1-C6alkyl group or an unsubstituted or substituted benzyl group, in which process a compound of Formula (II) wherein R3 represents a C1-C6alkyl group or an unsubstituted or substituted benzyl group, and R1 and R2 have the same meaning as in formula (I); is treated with a base at a temperature of 0°C or less in a liquid aprotic solvent for a time period sufficient to obtain the compound of formula (I).
C07C 237/20 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton containing six-membered aromatic rings
A pharmaceutical composition for oral administration which is self-emulsifying on contact with an aqueous phase, in particular gastrointestinal fluids, and which comprises: (a)an antifungally active compound of formula (I) wherein R1, R2 and R3 are independently of one another hydrogen, F or Cl; or a pharmaceutically acceptable acid addition salt thereof, and (b)a carrier comprising a solubilizer component for the antifungally effective component (a).
Use of a monobactam antibiotic of formula (I) wherein the oxyimino group i.e. ᡶC=N-O- has Z-orientation, or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for the treatment of a bacterial infection in combination with a carbapenem antibiotic or a pharmaceutically acceptable salt thereof.
A61K 31/427 - Thiazoles not condensed and containing further heterocyclic rings
A61K 31/4436 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
Goods & Services
Chemical preparations (for use in the pharmaceutical
industry as well as chemical preparations for research and
development of pharmaceutical preparations). Pharmaceutical preparations. Scientific and technological research services and
scientific and technological development services.
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
Goods & Services
Chemicals used in industry; chemicals used in science
(except for medical or veterinary use). Pharmaceutical preparations; chemical preparations for
pharmaceutical use; chemical-pharmaceutical preparations;
chemical preparations for the investigation and the
development of pharmaceutical preparations. Scientific and technical research services as well as
scientific and technical development services.
50.
NEW MACROLIDES USEFUL AGAINST INFLAMMATORY AND ALLERGIC DISSEASES
Macrolide compounds of formula I: with PDF4 inhibiting activity are described, wherein R1 is a residue -Y-X-Q; Y is S, SO or SO2; X is a bond or a linear group consisting of hydrogen atoms and with up to 9 atoms selected from C, N, O and/or S, of which up to 2 atoms can be N and one atom can be O or S, one carbon atom can appear as a CO group and the sulphur atom can appear as an SO2 group and two adjacent C atoms can be present as - CH=CH- or -C≡C- and which group X is unsubstituted or is substituted with - COO-W or -CONH-W; Q is a residue -V-A1-L- A2-W or, if X does not represent a bond, may also be -NR6R7; V is a divalent aromatic or heterocyclic group; W is aryl or heterocyclyl; or in a group -V-A1-L- A2-W, wherein at least one of the groups A1; L or A2 is present, can also be a monovalent substituted or unsubstituted, saturated or unsaturated linear group with up to 5 atoms consisting of C, N, O and/or S of which one carbon can appear as a CO group one sulphur atom can appear as an SO2 group, A1, A2 are independently of each other either absent or a C1-C4alkylene group; L is -0-, -S-, -SO2-, -NH-, -CO-, -(CO)O-, -O(OC)-, -(CO)NH-, -NH(CO)-, -(SO2)NH-, -HN(SO2)-, -HN(CO)NH-, -0(CO)NH-, -NH(CO)O-, or can also be absent if Al and/or A2 are present; R2 is hydrogen and R3 is and 0R4 or R2, R3 taken together form a C=O group; R4 is hydrogen or an saturated or unsaturated aliphatic group with 1 to 6 carbon atoms; R6, R7 are independently selected from aryl; aralkyl; heterocyclyl and heterocyclylalkyl; and one of R6 and R7 can also be a group -L-W; and * indicates a chiral centre which is in the (R) or (S) form.
C07H 17/08 - Hetero rings containing eight or more ring members, e.g. erythromycins
A61K 31/7048 - Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
Goods & Services
Chemical substances for use in the pharmaceutical industry and in research and development of pharmaceuticals. Prescription only pharmaceutical and veterinary preparations; sanitary preparations for medical purposes; dietetic substances adapted for medical use, food for babies; plasters, materials for dressings; material for stopping teeth, dental wax; disinfectants; preparations for destroying vermin; fungicides, herbicides. Research and development services for third in the field of chemical substances, pharmaceutical and veterinary products and preparations.
