- Design and synthesis of 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3- dihydroisobenzofuran-5-carbonitrile (citalopram) analogues as novel probes for the serotonin transporter S1 and S2 binding sites
-
The serotonin transporter (SERT) is the primary target for antidepressant drugs. The existence of a high affinity primary orthosteric binding site (S1) and a low affinity secondary site (S2) has been described, and their relation to antidepressant pharmacology has been debated. Herein, structural modifications to the N, 4, 5, and 4′ positions of (±)citalopram (1) are reported. All of the analogues were SERT-selective and demonstrated that steric bulk was tolerated at the SERT S1 site, including two dimeric ligands (15 and 51). In addition, eight analogues were identified with similar potencies to S-1 for decreasing the dissociation of [3H]S-1 from the S1 site via allosteric modulation at S2. Both dimeric compounds had similar affinities for the SERT S1 site (Ki = 19.7 and 30.2 nM, respectively), whereas only the N-substituted analogue, 51, was as effective as S-1 in allosterically modulating the binding of [3H]S-1 via S2.
- Banala, Ashwini K.,Zhang, Peng,Plenge, Per,Cyriac, George,Kopajtic, Theresa,Katz, Jonathan L.,Loland, Claus Juul,Newman, Amy Hauck
-
supporting information
p. 9709 - 9724
(2014/01/06)
-
- Small molecule thienopyrimidine-based protein tyrosine kinase inhibitors
-
Various thienopyrimidine-based analog compounds are able to selectively inhibit the Src family of tyrosine kinases. These compounds are useful in the treatment of various diseases including hyperproliferative diseases, hematologic diseases, osteoporosis, neurological diseases, autoimmune diseases, allergic/immunological diseases, or viral infections.
- -
-
Page/Page column 40
(2010/02/15)
-
- PHENYL OR HETEROARYL AMINO ALKANE DERIVATIVES AS IP RECEPTOR ANTAGONIST
-
The present invention relates to a phenyl or heteroaryl amino alkane derivatives which are useful as an active ingredient of pharmaceutical preparations. The phenyl or heteroaryl amino alkanes of the present invention have IP receptor antagonistic activity, and can be used for the prophylaxis and treatment of diseases associated with IP receptor antagonistic activity. Such diseases include urological diseases or disorder as follows: bladder outlet obstruction, overactive bladder, urinary incontinence, detrusor hyper-reflexia, detrusor instability, reduced bladder capacity, frequency of micturition, urge incontinence, stress incontinence, bladder hyperreactivity, benighn prostatic hypertrophy (BPH), prostatitis, urinary frequency, nocturia, urinary urgency, pelvic hypersensitivity, urethritis, pelvic pain syndrome, prostatodynia, cystitis, or idiophatic bladder hypersensitivity. The compounds of the present invention are also useful for treatment of pain including, but not limited to inflammatory pain, neuropathic pain, acute pain, chronic pain, dental pain, premenstrual pain, visceral pain, headaches, and the like; hypotension; hemophilia and hemorrhage; and inflammation, since the diseases also is alleviated by treatment with an IP receptor antagonist.
- -
-
-
- Deprotection of pinacolyl boronate esters by transesterification with polystyrene-boronic acid
-
A mild, efficient method for the deprotection of pinacolyl organoboronate esters is described. Treatment of the organoboronate ester with excess polystyrene-boronic acid followed by filtration and evaporation of the solvent provides the corresponding organoboronic acid. Mild deprotection of pinacolyl boronate esters to the corresponding boronic acids was achieved in the presence of excess polystyrene-boronic acid via a transesterification process. The procedure allows for the cleavage of pinacolyl boronate esters in the presence of sensitive functional groups. Crown Copyright
- Pennington, Thomas E.,Kardiman, Cynantya,Hutton, Craig A.
-
p. 6657 - 6660
(2007/10/03)
-
