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COMPOUNDS AND METHOD OF TREATMENT HAVING AGONIST-LIKE ACTIVITY SELECTIVE AT ALPHA 2B OR 2B/2C ADRENERGIC RECEPTORS

机译:具有在ALPHA 2B或2B / 2C肾上腺素受体上具有类似激动剂活性的选择性治疗的化合物和方法

摘要

Coumpounds having adrenergic activity which are selective agonists for one or both of the alpha 2B and alpha 2C adrenoceptor receptor subtypes in preference to the alpha 2A adrenoceptor receptor subtype; the active compound being selected from the group consisting of compounds having formula (I) wherein the dotted lines represent optional bonds provided that two double bonds may not share a common carbon atom; R is H or lower alkyl; X is S or C(H)R1, wherein R1 is H or lower alkyl, but R1 is absent when the bond between X and the ring represented by formula (a) is a double bond; Y is O, N, S, (CR12)y, wherein y is an integer of from 1 to 3, -CH=CH- or -Y1CH2-, wherein Y1 is O, N or S; x is an integer of 1 or 2, wherein x is 1 when R2, R3 or R4 is bound to a saturated carbon atom and x is 2 when R2, R3 or R4 is bound to a saturated carbon atom; R2 is H, lower alkyl, halogen, hydroxy or lower alkoxy, or, when attached to a saturated carbon atom, R2 may be oxo; R3 and R4 are, each, H, lower alkyl, hydroxy, lower alkoxy, or phenyl or, together, are -(C(R2)x)z-; -Y1(C(R2)x)z'-; -Y1(C(R2)x)yY1-; -(C(R2)x)-Y1-(C(R2)x)-; -(C(R2)x)-Y1-(C(R2)x)-(C(R2)x)- and -Y1-(C(R2)x)-Y1-(C(R2)x)- wherein z is an integer of from 3 to 5, z' is an integer of from 2 to 4 and x and y are as defined above, and further either end of each of these divalent moieties may attach at either R3 or R4 to form a condensed ring structure and the rings formed may be totally unsaturated, partially unsaturated, or totally saturated; and being useful for treating muscle spasticity including hyperactive micturition, diarrhea, diuresis, withdrawal syndromes, pain including neuropathic pain, neurodegenerative diseases, memory and cognition deficits, psychoses including manic disorders and anxiety, hypertension, cardiac ischemia, congestive heart failure, and nasal congestion without sedating or cardiovascular side effects.
机译:具有肾上腺素能活性的化合物,它是α2B和α2C肾上腺素能受体亚型之一或两者的选择性激动剂,优先于α2A肾上腺素能受体亚型。所述活性化合物选自具有式(I)的化合物,其中虚线表示任选的键,条件是两个双键可以不具有共同的碳原子; R为H或低级烷基; X为S或C(H)R 1,其中R 1为H或低级烷基,但是当X与式(a)表示的环之间的键为双键时,R 1不存在。 Y为O,N,S,(CR 1 2)y,其中y为1至3的整数,-CH = CH-或-Y 1 CH 2-,其中Y 1为O, N或S; x为1或2的整数,其中当R 2,R 3或R 4与饱和碳原子键合时,x为1,而当R 2,R 3或R 2为x时,x为2。 R 4与饱和碳原子键合; R 2是H,低级烷基,卤素,羟基或低级烷氧基,或者当连接至饱和碳原子时,R 2可以是氧代; R 3和R 4各自为H,低级烷基,羟基,低级烷氧基或苯基,或一起为-(C(R 2)x)z-。 -Y 1((C(R 2>)x)z'-; -Y <1>(C(R <2>)x)yY <1>-; -(C(R 2)x)-Y 1-(C(R 2)x)-; -(C(R 2)x)-Y 1-(C(R 2)x)-(C(R 2)x)-和-Y 1- 2)x)-Y 1-(C(R 2)x)-其中z是3至5的整数,z'是2至4的整数,x和y为这些二价部分的每一个的另一端可以在R 3或R 4处连接形成稠合的环结构,并且形成的环可以是完全不饱和的,部分不饱和的或完全饱和的;对治疗包括痉挛性尿毒症,腹泻,利尿,戒断综合症,包括神经性疼痛,神经退行性疾病在内的疼痛,记忆力和认知能力低下,包括躁狂症和焦虑症在内的精神病,高血压,心脏缺血,充血性心力衰竭和鼻充血等肌肉痉挛没有镇静或心血管副作用。

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