Fully synthetic macrocycles with constrained conformation
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 technology for compounds and compositions, applied in the field of conformationally constrained fully synthesized macrocyclic compounds, capable of solving complex quality control and development process issues
Active Publication Date: 2018-09-25
POLYPHOR AG
View PDF2 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
[0014] - Complex quality control and development processes
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
Embodiment 1
[0943] Data of Example 1: C 31 h 40 FN 3 o 7 Si (613.7). LC-MS (Method 7):
[0944] R t =1.45(41), 614([M+H] + ); 1.47(44), 614([M+H] + ).
[0947] Synthesis of protected macrocyclic lactam embodiment 2
[0948] Over 2 hours, T3P (50%, in EtOAc, 0.75 mL, 1.27 mmol) and iso-Pr 2 NEt (0.36 mL, 2.2 mmol) in anhydrous CH 2 Cl 2 (20mL) solution was added amino acid 98 (250mg, 0.43mmol) in anhydrous CH 2 Cl 2 (730 mL) solution. The solution was stirred at room temperature for 20 h, then washed with saturated Na 2 CO 3 Aqueous extraction. Dry the organic phase (Na 2 SO 4 ), filtered and concentrated. FC(CH 2 Cl 2 / MeOH 100:0 to 95:5), providing Example 2 (187 mg, 77%).
[0949] Data of Example 2: C 30 h 36 FN 3 o 7 (569.6) LC-MS (Method 7):
[0950] R t =1.35(62), 570([M+H] + ); 1.39(15), 570([M+H] + )
[0960] Data of Example 3: C 33 h 41 FN 4 o 8 (640.7). HPLC (30%CH 3 CN): R t =3.20(96). LC-MS (Method 9c): R t =2.06,641([M+H] + ). 1 H-NMR (CDCl 3 ): 7.45-7.32 (m, 5H), 7.06 (m, 1H), 6.94-6.88 (m, 2H), 5.57 (dd, J=2.8, 12.6, 1H), 5.42 (width m, 1H), 5.26 ( d, J=12.2, 1H), 5.15(d, J=12.2, 1H), 4.90(dd, J=2.5, 11.0, 1H), 4.34(d, J=17.2, 1H), 4.35-4.11(m, 3H), 3.82 (width t, J about 8.5, 1H), 3.65 (d, J=17.3, 1H), 3.29 (t, J about 8.8, 1H), 3.14 (s, 3H), 2.65 (s, 3H) , 2.51-1.98 (several m, 5H), 1.76 (td, J=8.2, 12.7, 1H), 1.36 (s, 9H).
[0961] Synthetic acid embodiment 4:
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
The invention relates to conformation-constrained entirely-synthetic macrocyclic compounds. A conformation-constrained, space-defined 12-30-member macrocyclic system (I) which is as shown in the description comprises three different constitution units: an aromatic template a, a confor1ation regulator b and a spaced part c, which are illustrated in the description and the claims. The macrocyclic compounds (I) can be easily prepared according to a parallel synthesis method or a combinatorial chemistry method, and are designed for realizing interaction with a specific biological target. Particularly, the compounds show agonistic or antagonistic activity to the following matters: a motilin receptor (MR), a 5-hydroxytryptamine receptor (5-HT2B receptor) of a subtype 5-HT2B, and a prostaglandin F2alpha receptor (FP receptor). Thus, the compounds are effectively used for treating gastrointestinal tract hypomotility disorder such as diabetic gastroparesis and constipation-predominant irritable bowel syndrome, CNS-related diseases such as migraine, schizophrenia, psychosis and depression, ocular hypertension such as glaucoma-related ocular hypertension, and premature delivery.
Description
[0001] This application is a divisional application whose parent application is Chinese invention patent application 200980160767.8. technical field [0002] Macrocyclic natural and synthetic products are in the development of new drugs, especially anti-infectives (see Review: F. von Nussbaum, M. Brands, B. Hinzen, S. Weigand, D. Angew.Chem.Int.Ed.Engl.2006,45,5072-5129; D.Obrecht,J.A.Robinson,F.Bernardini,C.Bisang,S.J.DeMarco,K.Moehle,F.O.Gombert,Curr.Med.Chem.2009 , 16,42-65), as anticancer drugs and in other therapeutic areas (C.E.Ballard, H.Yu, B.Wang, Curr.Med.Chem.2002,9, 471-498; F.Sarabia, S.Chammaa , A.S.Ruiz, L.M.Ortiz, F.J.Herrera, Curr.Med.Chem.2004, 11, 1309-1332) play a key role. They often show significant biological activity, and many macrocycles or their derivatives have been successfully developed as drugs (L.A.Wessjohann, E.Ruijter, D.Garcia-Rivera, W.Brandt, Mol.Divers. 2005,9,171 -186; D.J. Newman, G.M. Gragg, K.M. Snader, J. Nat. Prod. 2003, 66, 1022-...
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