Unlock instant, AI-driven research and patent intelligence for your innovation.
Novel amide derivs. as growth hormone secretagogues
What is Al technical title?
Al technical title is built by PatSnap Al team. It summarizes the technical point description of the patent document.
A technique of halogens, compounds, applied in the field of synthetic peptidomimetics
Inactive Publication Date: 2002-05-01
KAKEN PHARMA CO LTD +1
View PDF74 Cites 0 Cited by
Summary
Abstract
Description
Claims
Application Information
AI Technical Summary
This helps you quickly interpret patents by identifying the three key elements:
Problems solved by technology
Method used
Benefits of technology
Problems solved by technology
[0012] Many of these compounds have been reported to be more effective in promoting the release of endogenous growth hormone in humans, however, they still have problems with oral bioavailability, specificity and safety
Method used
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more
Image
Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
Click on the blue label to locate the original text in one second.
Reading with bidirectional positioning of images and text.
Smart Image
Examples
Experimental program
Comparison scheme
Effect test
preparation example Construction
[0072] The preparation of compounds of formula I and intermediates 8, 9 can also be carried out according to the centralized synthetic routes depicted in synthetic schemes 4, 5, 6, 7, 8, 9, 10, 11 or 12. In some cases, protected amino acid derivatives 10 are commercially available where Z is protected 1 is for example a Boc or CBZ or Fmoc group. Other protected amino acid derivatives 10 can be prepared by a number of methods well known in the literature. Intermediates 11, 12, or 13 were prepared by coupling protected amino acid derivatives 10 with diamino derivatives 5, 6, or 7.
[0073] Synthetic Scheme 4
[0074] As shown in Synthetic Scheme 5, by removing the protecting group Z 1 (CBZ, Boc, Fmoc, formyl, etc.) to convert 11, 12, or 13 into intermediates 14, 15, or 16. CBZ and Boc are widely used in such syntheses and the conditions for their removal are known to those skilled in the art. For example, the CBZ group can be removed by various methods known in the art; f...
Embodiment 1
[0152] The structures of the compounds were confirmed by nuclear magnetic resonance (NMR) or mass spectroscopy (MS). NMR shifts (δ) are given as parts per million (ppm) and shifts are given for selected peaks only. Column chromatography was performed on Shin-Etsu Chemical silica gel using the technique described by W. C. Still et al. in J. Org. Chem. 1978, 43, 2923-2925. The compounds used as starting materials are known compounds, or compounds which can be easily produced by methods known per se. [Example 1] (Method I) N-(3-amino-2-hydroxypropyl)-2(R)-[1-(2-ethylbutyryl)pyrrolidine-2(S)-carbonylamino] -3-Naphthalen-2-yl-propionamide hydrochloride
[0153] Under cooling in an ice-water bath, 216 mg (1.6 mmol) of HOBt and 216 mg (1.6 mmol) of EDC 306 were added successively to a DMF solution (7 ml) of 337 mg (1.58 mmol) of N-(2-ethylbutyryl)-2(S)-pyrrolidinecarboxylic acid. mg (6 mmol), 589 mg of tert-butyl D-3-(2-naphthyl)alanyl-3-amino-2-hydroxypropylcarbamate, and conti...
Embodiment 35
[0175] Compounds of Examples 36, 37, 110-117 were synthesized in a similar manner to Example 30. [Example 35] (Method IV) N-(3-methylamino-2-hydroxypropyl)-2(R)-[1-(2-ethylbutyryl)pyrrolidine-2(S)-carbonyl Amino]-3-naphth-2-ylpropionamide hydrochloride
[0176] Under ice-water bath cooling, N-(2-propenyl)-2(R)-[1-(2-ethylbutyryl)pyrrolidine-2(S)-carbonylamino]-3-naphthalene-2- A solution of m-chloroperbenzoic acid 142 mg / dichloromethane 2 ml was added dropwise to a dichloromethane solution (4 ml) of 200 mg (0.44 mmol) of propionamide, and stirred overnight at room temperature. The reaction mixture was washed successively with saturated sodium bicarbonate solution, water, and dried over anhydrous sodium sulfate. Dichloromethane was removed by evaporation.
[0177] To a solution of the above residue in methanol (3 ml) was added a solution of 300 mg of methylamine in 40% methanol, and stirring was continued at room temperature overnight. Solvent was removed by evaporation. ...
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More
PUM
Login to View More
Abstract
Disclosed are the novel compounds as growth hormone secretagogues represented by structural Formula (I), wherein R<1 >is, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl, or substituted or unsubstituted amino, X is -CO- or -SO<2>-, Y is Formula (II), wherein n is an integer from 0-4, R<4 >is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, R<5 >and R<6 >are independently selected from hydrogen, substituted or unsubstituted alkyl, or R<5 >and R<6 >or R<4 >and R<5 >are taken together to form substituted or unsubstituted alkylene, R<2 >is hydrogen, or substituted or unsubstituted alkyl, R<3 >is substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, D is substituted or unsubstituted amino, substituted or unsubstituted alkoxy, or substituted or unsubstituted alkylthio, * represents an asymmetric center, and pharmaceutically acceptable salts and individual isomers thereof, which have growth hormone releasing activity in humans or animals.
Description
field of invention [0001] The present invention relates to synthetic peptidomimetics having growth hormone releasing activity in humans or animals, and their use in the treatment of human diseases due to growth hormone deficiency, or in increasing the speed and extent of growth in animals , or in increasing milk or wool production in animals, or in treating animal diseases. Background of the invention [0002] Growth hormone, secreted by the pituitary gland, stimulates the growth of all tissues in the body that are capable of growing. In addition, growth hormone is known to have the following basic effects on the body's metabolic processes: 1) increase the rate of protein synthesis in body cells; 2) decrease the rate of carbohydrate utilization in body cells; 3) increase the activity of fatty acids and the rate of fatty acid production of energy use. [0003] Artificially manipulating growth hormone levels has proven to have significant therapeutic utility. Supplementatio...
Claims
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More
Application Information
Patent Timeline
Application Date:The date an application was filed.
Publication Date:The date a patent or application was officially published.
First Publication Date:The earliest publication date of a patent with the same application number.
Issue Date:Publication date of the patent grant document.
PCT Entry Date:The Entry date of PCT National Phase.
Estimated Expiry Date:The statutory expiry date of a patent right according to the Patent Law, and it is the longest term of protection that the patent right can achieve without the termination of the patent right due to other reasons(Term extension factor has been taken into account ).
Invalid Date:Actual expiry date is based on effective date or publication date of legal transaction data of invalid patent.
Login to View More 
Login to View More