HL 752: A potent and long-acting antispasmodic agent
Ester analogues of methyl-2-(4-(2-piperidinoethoxy)benzoyl)-benzoate hydrochloride (pitofenone) ( 2) were prepared with an aim to find a more potent and metabolically stable antispasmodic compound. The compounds were evaluated for their in vitro and in vivo antispasmodic activity, and stability to i...
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| Published in: | Bioorganic & medicinal chemistry Vol. 5; no. 7; pp. 1381 - 1387 |
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| Main Authors: | , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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Elsevier Ltd
01-07-1997
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| Abstract | Ester analogues of methyl-2-(4-(2-piperidinoethoxy)benzoyl)-benzoate hydrochloride (pitofenone) (
2) were prepared with an aim to find a more potent and metabolically stable antispasmodic compound. The compounds were evaluated for their in vitro and in vivo antispasmodic activity, and stability to in vitro enzymatic hydrolysis. Of the compounds synthesised, HL 752 (
21) showed the most potent and long-lasting antispasmodic activity and was selected as the candidate for clinical development.
From a series of ester analogues, the most potent and long-acting antispasmodic compound, HL 752 (R = isopropyl), was chosen for development. |
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| AbstractList | Ester analogues of methyl-2-(4-(2-piperidinoethoxy)benzoyl)-benzoate hydrochloride (pitofenone) (
2) were prepared with an aim to find a more potent and metabolically stable antispasmodic compound. The compounds were evaluated for their in vitro and in vivo antispasmodic activity, and stability to in vitro enzymatic hydrolysis. Of the compounds synthesised, HL 752 (
21) showed the most potent and long-lasting antispasmodic activity and was selected as the candidate for clinical development.
From a series of ester analogues, the most potent and long-acting antispasmodic compound, HL 752 (R = isopropyl), was chosen for development. Ester analogues of methyl-2-(4-(2-piperidinoethoxy)benzoyl)-benzoate hydrochloride (pitofenone) (2) were prepared with an aim to find a more potent and metabolically stable antispasmodic compound. The compounds were evaluated for their in vitro and in vivo antispasmodic activity, and stability to in vitro enzymatic hydrolysis. Of the compounds synthesised, HL 752 (21) showed the most potent and long-lasting antispasmodic activity and was selected as the candidate for clinical development. |
| Author | Ghate, Anil V. Subbarayan, Palakodety Bhedi, Dilip N. Mishra, Anil K. Kulkarni, Anjali V. Punekar, Narayan S. Rajagopalan, Ramanujam Bal-Tembe, Swati |
| Author_xml | – sequence: 1 givenname: Swati surname: Bal-Tembe fullname: Bal-Tembe, Swati – sequence: 2 givenname: Dilip N. surname: Bhedi fullname: Bhedi, Dilip N. – sequence: 3 givenname: Anil K. surname: Mishra fullname: Mishra, Anil K. – sequence: 4 givenname: Ramanujam surname: Rajagopalan fullname: Rajagopalan, Ramanujam – sequence: 5 givenname: Anil V. surname: Ghate fullname: Ghate, Anil V. – sequence: 6 givenname: Palakodety surname: Subbarayan fullname: Subbarayan, Palakodety – sequence: 7 givenname: Narayan S. surname: Punekar fullname: Punekar, Narayan S. – sequence: 8 givenname: Anjali V. surname: Kulkarni fullname: Kulkarni, Anjali V. |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/9377098$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1055/s-1985-31098 10.1021/jo01014a066 10.1021/bi00427a020 10.1016/S0040-4039(00)72435-X 10.1016/S0076-6879(85)12031-8 10.1016/S0076-6879(57)03413-8 |
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| References | Barry, Bram, Decodts, Loupy, Orange, Petit, Sansoulet (BIB4) 1985 Walsh (BIB5) 1979 BIB8 Layne (BIB10) 1957; 3 Allen, Abeles (BIB6) 1989; 28 Parish, Stock (BIB2) 1965; 30 Eckert, Badian, Gantz, Maaβ (BIB1) 1986 Shaw, Kunerth, Sherry (BIB3) 1973 Bickel, Bal-Tembe, Blumbach, Dohadwalla, Lal, Palm, Rajagopalan, Rupp, Schmidt, Volz-Zang (BIB7) 1990; 18 Markowitz, Archibald, Downie (BIB12) 1964 The Staff of the Department of Pharmacology, University of Edinburgh (BIB11) 1970 Bodor (BIB9) 1985; 112 Walsh (10.1016/S0968-0896(97)00067-9_BIB5) 1979 Bickel (10.1016/S0968-0896(97)00067-9_BIB7) 1990; 18 Markowitz (10.1016/S0968-0896(97)00067-9_BIB12) 1964 Parish (10.1016/S0968-0896(97)00067-9_BIB2) 1965; 30 Allen (10.1016/S0968-0896(97)00067-9_BIB6) 1989; 28 Bodor (10.1016/S0968-0896(97)00067-9_BIB9) 1985; 112 Layne (10.1016/S0968-0896(97)00067-9_BIB10) 1957; 3 The Staff of the Department of Pharmacology, University of Edinburgh (10.1016/S0968-0896(97)00067-9_BIB11) 1970 Eckert (10.1016/S0968-0896(97)00067-9_BIB1) 1986 Shaw (10.1016/S0968-0896(97)00067-9_BIB3) 1973 Barry (10.1016/S0968-0896(97)00067-9_BIB4) 1985 |
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| Snippet | Ester analogues of methyl-2-(4-(2-piperidinoethoxy)benzoyl)-benzoate hydrochloride (pitofenone) (
2) were prepared with an aim to find a more potent and... Ester analogues of methyl-2-(4-(2-piperidinoethoxy)benzoyl)-benzoate hydrochloride (pitofenone) (2) were prepared with an aim to find a more potent and... |
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| SubjectTerms | Animals Benzoates - chemical synthesis Benzoates - metabolism Benzoates - pharmacology Benzophenones - chemical synthesis Benzophenones - metabolism Benzophenones - pharmacology Dogs Drug Stability Esters - metabolism Esters - pharmacology Female Guinea Pigs Hydrolysis Ileum - drug effects In Vitro Techniques Male Parasympatholytics - chemical synthesis Parasympatholytics - metabolism Parasympatholytics - pharmacology Piperidines - chemical synthesis Piperidines - metabolism Piperidines - pharmacology |
| Title | HL 752: A potent and long-acting antispasmodic agent |
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