EP0511271A1 - Thiazole derivatives - Google Patents

Thiazole derivatives

Info

Publication number
EP0511271A1
EP0511271A1 EP91902805A EP91902805A EP0511271A1 EP 0511271 A1 EP0511271 A1 EP 0511271A1 EP 91902805 A EP91902805 A EP 91902805A EP 91902805 A EP91902805 A EP 91902805A EP 0511271 A1 EP0511271 A1 EP 0511271A1
Authority
EP
European Patent Office
Prior art keywords
ppm
bromo
phthalimidoalkan
formula
preparation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP91902805A
Other languages
German (de)
English (en)
French (fr)
Inventor
John Charles Eriks
Geert Jan Sterk
Henderikus Van Der Goot
Hendrik Timmerman
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Cedona Pharmaceuticals BV
Original Assignee
Cedona Pharmaceuticals BV
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Cedona Pharmaceuticals BV filed Critical Cedona Pharmaceuticals BV
Publication of EP0511271A1 publication Critical patent/EP0511271A1/en
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
    • C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D277/38—Nitrogen atoms
    • C07D277/40—Unsubstituted amino or imino radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—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 C07D415/00
    • C07D417/02—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 C07D415/00 containing two hetero rings
    • C07D417/06—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 C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—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 C07D415/00
    • C07D417/02—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 C07D415/00 containing two hetero rings
    • C07D417/12—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 C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • Thiazole derivatives which are: a substituted 4- or 5-( ⁇ -aminoalkyl)thiazole with formula 1, wherein X represents a nitrogen atom and Y represents a sulphur atom or alternatively X represents a sulphur atom and Y represents a nitrogen atom, n is 1-6, R 1 represents a straight or branched alkyl group containing 1-4 carbon atoms and R 2 represents an amino group.
  • the invention also relates to the acid addition salts of the compounds with the formula 1.
  • Histamine receptors are classified according to the presentt knowledge into three categories which are described, mainly for historical reasons, with the qualifications of H 1 -, H 2 - and H 3 -receptor.
  • Each of these classes of receptors presumably has its own and biologically specific function, in as far as they are present and dependent on the locating of such a receptor type in the organism involved.
  • a treatment with endogenous or exogenous compounds may be necessary which may stimulate (agonistic activity) or inhibit (antagonistic activity) the receptor system.
  • histamine H 2 -receptor (pharmacological) point of view, but also in therapeutic respect notably the stimulation of the histamine H 2 -receptor offers wide perspectives for the treatment of congestive heart diseases, accompanied by heart failure, and certain allergic disorders so that there exists a large interest from within the pharmaceutical industry for the development and application of selective, histamine H 2 -receptor active, compounds.
  • the invention also relates to a process for the preparation of a ⁇ -aminoalkylthiazole derivative in which one prepares a histamine H 2 -receptor active compound.
  • Certain alkylaminothiazoles are known from the literature. Examples are described in several patent applications, e.g. FR 76 24 496, US 26 36 037, GB 15 26 038 and GB 11 49 110. None of these patent applications reveal the now claimed compounds, whereas the method of preparation of the alkylaminothiazoles described in the aforementioned patent applications also differs from the process now claimed.
  • Several authors have incidentally reported about examples of certain alkylamino-thiazoles: G.J. Durant et al describe in J.Med.Chem.
  • the 2- amino-5-(2-aminoethyl)-4-methylthiazole (3) can be displaced competitatively by cimetidine, while the intrinsic activity (related to the chronotropic effect) is equal to that of histamine, thus rendering it to be a full agonist for the H 2 - receptor with an activity twice as high as that of histamine.
  • the 2-amino-5-(3-aminopropyl)-4-methylthiazole (10b) is a full H 2 -receptor agonist with an activity 30 times as high as that of the corresponding 4(5)-3-aminopropyl)-imidazole.
  • the 2-amino-5-(2-aminoethyl)-4-methylthiazole (3) shows however contrary to histamine (4), in the testing systems used not a single activity towards the E 1 and H 3 -receptors.
  • the 4- or 5-( ⁇ -aminoalkyl) thiazole derivatives mentioned in the introduction with formula 1 may be obtained using a process not previously described in the literature in high yields by ring closure of a 3-bromo- ⁇ -phthalimidoalkan-2-one (8) with thiourea in dimethylformamide under mild conditions, followed by hydrazinolysis or hydrolysis with diluted hydrochloric acid of the resulting phthalimido derivatives (9) as depicted in reaction scheme A.
  • the preparation of the 3-bromo- ⁇ -phthalimidoalkan-2-ones (8) as indicated in reaction scheme (A) takes place by selective bromination with bromine in carbon tetrachloride of the corresponding ⁇ -phthalimidoalkan-2-ones (7) which may be obtained according to a process described in the Dutch patent application 8800998.
  • the necessary ⁇ -haloketones (6) which are to be used for the preparation of the 3-bromo- ⁇ -phthali- midoalkan-2-ones (8) are either commercially available or may be obtained in good yield according to a process described in the literature such as for example the process described in the Dutch patent application 65 11581.
  • the invention also relates to a medicament or a scientific (pharmacological) adjuvant which contains as the active ingredient a compound according to one of the formula 1 or an acid addition salt thereof.
  • a medicament or a scientific (pharmacological) adjuvant which contains as the active ingredient a compound according to one of the formula 1 or an acid addition salt thereof.
  • Melting points were determined by a Mettler FP 5 device for the determination of melting points.
  • Mass spectra are determined on a Varian Mat CH 5 spectrometer or on a Mat 90 (Finnigan Mat, San Jose, U.S.A.).
  • 6-Bromo-2-hexanone (6a) is prepared according to a modified process as described in Dutch patent application 6511581 dated March 7,1966, cf. Chem. Abstr. 65, P20151d.
  • a mixture of 552 g (4 mole) of particulated anhydrous potassium carbonate, 404 g (2 mole) of freshly distilled 1,3- dibromopropane, 260g (2 mole) of freshly distilled acetyl acetic ester and 700 ml of absolute ethanol is heated with vigorous stirring until circa 60°C. After the mild exothermal reaction beginning at circa 50°C, the reaction mixture is refluxed for circa 5 hours. After cooling the reaction mixture the inorganic salts are filtered off and the residue is rinsed with absolute ethanol. The combined filtrates are subsequently vacuum concentrated, thereafter to the residue circa 250 ml of demineralized water is added. Subsequently it is extracted with toluene. The collected toluene phases are combined, dried on anhydrous sodium sulfate, filtered and subsequently vacuum concentrated.
  • Mass spectrum M/Z (intensity in %). 180(0.14): 178(0.11);
  • the 4-phthalimido-2-butanone (7a) was prepared according to a modified process by H. Irai et al., Kogyo Kagaku
  • the 5-phthalimido-2-pentanone (7a) is prepared according to Dutch patent application 8800998, April 18,1988.
  • the 6-phthalimido-2-hexanone (7b) is prepared as described for the 5-phthalimido-2-pentanone (7a) in Dutch patent application 8800998, April 18,1988.
  • Mass spectrum M/Z (intensity in %): 171(28.9); 154(75.1); 127(100); 115(9.7).

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pulmonology (AREA)
  • Immunology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
EP91902805A 1990-01-19 1991-01-18 Thiazole derivatives Withdrawn EP0511271A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
NL9000132 1990-01-19
NL9000132A NL9000132A (nl) 1990-01-19 1990-01-19 Nieuwe thiazoolderivaten.

Publications (1)

Publication Number Publication Date
EP0511271A1 true EP0511271A1 (en) 1992-11-04

Family

ID=19856444

Family Applications (2)

Application Number Title Priority Date Filing Date
EP91902805A Withdrawn EP0511271A1 (en) 1990-01-19 1991-01-18 Thiazole derivatives
EP91902804A Withdrawn EP0511270A1 (en) 1990-01-19 1991-01-18 New thiazole derivatives

Family Applications After (1)

Application Number Title Priority Date Filing Date
EP91902804A Withdrawn EP0511270A1 (en) 1990-01-19 1991-01-18 New thiazole derivatives

Country Status (9)

Country Link
EP (2) EP0511271A1 (xx)
JP (2) JPH05503096A (xx)
AU (2) AU7058191A (xx)
CA (2) CA2074180A1 (xx)
IE (2) IE910172A1 (xx)
IL (2) IL96997A0 (xx)
NL (1) NL9000132A (xx)
WO (2) WO1991010657A1 (xx)
ZA (2) ZA91418B (xx)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1713780B1 (en) * 2004-02-05 2012-01-18 Probiodrug AG Novel inhibitors of glutaminyl cyclase

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2636037A (en) * 1947-10-10 1953-04-21 Sharp & Dohme Inc 2-amino-4-piperidinoethyl-thiazole
FR2073427A1 (en) * 1969-11-28 1971-10-01 Sogeras 4-methyl-5-ethyl-n-heterocyclic thiazoles - with antianoxic activity
FR2361111A1 (fr) * 1976-08-11 1978-03-10 Roussel Uclaf Nouveaux derives de 5-thiazole alkylamine, un procede pour leur preparation et leur application comme medicaments
US4166860A (en) * 1977-10-11 1979-09-04 William H. Rorer, Inc. Imidazole amidinoureas for stimulating H2 -receptors
US4474794A (en) * 1982-03-19 1984-10-02 Eli Lilly And Company N-Thiazolylmethylthioalkyl-N1 -alkenyl (or alkynyl)guanidines and related compounds
NL8601585A (nl) * 1986-06-19 1988-01-18 Vereniging Voor Christelijk Wetenschappelijk Onderwijs N-(2-gesubstitueerde alkyl)-n-imidazol-4-yl alkyl guanidine.
NL8800998A (nl) * 1988-04-18 1989-11-16 Cedona Pharm Bv Werkwijze voor het bereiden van een al of niet gesubstitueerd 4(5)-(omega-aminoalkyl) imidazool.

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9110656A1 *

Also Published As

Publication number Publication date
ZA91419B (en) 1991-10-30
NL9000132A (nl) 1991-08-16
WO1991010657A1 (en) 1991-07-25
AU7058191A (en) 1991-08-05
JPH05503694A (ja) 1993-06-17
AU7064491A (en) 1991-08-05
CA2074175A1 (en) 1991-07-20
WO1991010656A1 (en) 1991-07-25
IE910172A1 (en) 1991-07-31
IL96998A0 (en) 1992-03-29
IE910171A1 (en) 1991-07-31
CA2074180A1 (en) 1991-07-20
IL96997A0 (en) 1992-03-29
JPH05503096A (ja) 1993-05-27
EP0511270A1 (en) 1992-11-04
ZA91418B (en) 1991-10-30

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